Pagei

UltrasoundinMedicine

Pageii

UltrasoundinMedicine,TheThirdMayneordPhillipsSummerSchool
StEdmundHall,Oxford,June1997

Pageiii

UltrasoundinDedicine,TheThirdMayneordPhillipsSummerSchool
StEdmundHall,Oxford,June1997

1VictorHumphrey

8JeffBamber

15DarkoGroev

22JohnTruscott

2ElizabethMoore

9NadinePay

16SandyMather

23FrancisDuck

3BarryWard

10JimWilliams

17TimSpencer

24AndrzejJastrzebski

4MatthewReilly

11AndersOlsson

18MikeHalliwell

25FrankRakebrandt

5KatDixon

12BenKhoo

19PhilBurford

26PanagiotisTsiganos

6JimGreenleaf

13MalcolmSperrin

20MegWarner

27GarethPrice

7OsiyahPapayi

14ElvinNix

21TonyWhittingham

28KitHill

Pageiv

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ThePhysicsandRadiobiologyofFastNeutronBeams
DKBewley
MedicalPhysicsandBiomedicalEngineering
BHBrown,RHSmallwood,DRHose,PVLawfordandDCBarber
RehabilitationEngineeringAppliedtoMobilityandManipulation
RACooper
PhysicsforDiagnosticRadiology,2ndedition
PPDendyandBHHeaton
LinearAcceleratorsforRadiationTherapy,2ndedition
DGreeneandPCWilliams
HealthEffectsofExposuretoLowLevelIonizingRadiation
WRHendeeandFMEdwards(eds)
MonteCarloCalculationsinNuclearMedicine
MLjungberg,SEStrandandMAKing(eds)
IntroductoryMedicalStatistics,3rdedition
RFMould
RadiationProtectioninHospitals
RFMould
RPLDosimetryRadiophotoluminescenceinHealthPhysics
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SWebb(ed)
ThePhysicsofThreeDimensionalRadiationTherapy
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Pagev

MedicalScienceSerice

UltrasoundinMedicine
Editedby
FrancisADuck
RoyalUnitedHospital,BathandUniversityofBath,UK
AndrewCBaker
ChristianMichelsenResearchAS,Bergen,Norway
formerlyUniversityofBath
HazelCStarritt
RoyalUnitedHospital,Bath,UK
BasedonInvitedLecturespresentedatthe
ThirdMayneordPhillipsSummerSchool1997
sponsoredby
InstituteofPhysicsandEngineeringinMedicine
BritishInstituteofRadiology
InstituteofPhysics
BritishMedicalUltrasoundSociety
InstituteofPhysicsPublishing
BristolandPhiladelphia

Pagevi

IOPPublishingLtd1998
Allrightsreserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystemortransmittedinanyformorbyanymeans,electronic,mechanical,
photocopying,recordingorotherwise,withoutthepriorpermissionofthepublisher.Multiplecopyingispermittedinaccordancewiththetermsoflicencesissuedby
theCopyrightLicensingAgencyunderthetermsofitsagreementwiththeCommitteeofViceChancellorsandPrincipals.
TheEditorsandIOPPublishingLtdhaveattemptedtotracethecopyrightholdersofallmaterialreproducedinthispublicationandapologizetocopyrightholdersif
permissiontopublishinthisformhasnotbeenobtained.
BritishLibraryCataloguinginPublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
ISBN0750305932
LibraryofCongressCataloginginPublicationDataareavailable
SeriesEditors:
RFMould,Croydon,UK
CGOrton,KarmanosCancerInstituteandWayneStateUniversity,Detroit,USA
JAESpaan,UniversityofAmsterdam,TheNetherlands
JGWebster,UniversityofWisconsinMadison,USA
CoverillustrationcourtesyofAndrewBakerandMarkCahill
PublishedbyInstituteofPhysicsPublishing,whollyownedbyTheInstituteofPhysics,London
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USOffice:InstituteofPhysicsPublishing,ThePublicLedgerBuilding,Suite1035,150SouthIndependenceMallWest,Philadelphia,PA19106,USA
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Pagevii

TheMedicalScienceSeriesistheofficialbookseriesoftheInternationalFederationforMedicalandBiologicalEngineering(IFMBE)andthe
InternationalOrganizationforMedicalPhysics(IOMP).
IFMBE
TheIFMBEwasestablishedin1959toprovidemedicalandbiologicalengineeringwithaninternationalpresence.TheFederationhasalonghistoryofencouraging
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TheIFMBEhaspublishedthejournalMedicalandBiologicalEngineeringandComputingforover34years.AnewjournalCellularEngineeringwas
establishedin1996inordertostimulatethisemergingfieldinbiomedicalengineering.InIFMBENewsmembersarekeptinformedofthedevelopmentsinthe
Federation.ClinicalEngineeringUpdateisapublicationofourdivisionofClinicalEngineering.TheFederationalsohasadivisionforTechnologyAssessmentin
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Everythreeyears,theIFMBEholdsaWorldCongressonMedicalPhysicsandBiomedicalEngineering,organizedincooperationwiththeIOMPandtheIUPESM.
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TheadministrativecounciloftheIFMBEmeetsonceortwiceayearandisthesteeringbodyfortheIFMBE.ThecouncilissubjecttotherulingsoftheGeneral
Assemblywhichmeetseverythreeyears.

Pageviii

ForfurtherinformationontheactivitiesoftheIFMBE,pleasecontactJosAESpaan,ProfessorofMedicalPhysics,AcademicMedicalCentre,Universityof
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IFMBE@amc.uva.nl.WWW:http://vub.vub.ac.be/~ifmbe.
IOMP
TheIOMPwasfoundedin1963.Themembershipincludes64nationalsocieties,twointernationalorganizationsand12000individuals.MembershipofIOMP
consistsofindividualmembersoftheAdheringNationalOrganizations.Twootherformsofmembershipareavailable,namelyAffiliatedRegionalOrganizationand
CorporateMembers.TheIOMPisadministeredbyaCouncil,whichconsistsofdelegatesfromeachoftheAdheringNationalOrganizationregularmeetingsof
CouncilareheldeverythreeyearsattheInternationalConferenceonMedicalPhysics(ICMP).TheOfficersoftheCouncilarethePresident,theVicePresidentand
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3891.Fax:(46)907851588.Email:Hans.Svensson@radfys.umu.se.

Pageix

CONTENTS.
ContributingAuthors

xvii

Glossary

xix

Introduction
FrancisADuck

xxv

Acknowledgments

xxx

References

xxx

Part1
ThePhysicsofMedicalUltrasound

1
UltrasonicFields:StructureandPrediction
VictorFHumphreyandFrancisADuck

1.1CircularplaneSources
1.1.1PressureVariationontheAxis

1.1.2PressureVariationOfftheAxis

1.2PulsedFields

10

1.3FocusedFields

13

1.4SourceAmplitudeWeighting

15

1.5RectangularSources

17

1.6Conclusion

20

References

21

2
NonlinearEffectsinUltrasoundPropagation
AndrewCBaker

23

2.1NonlinearPropagationinMedicalUltrasound

24

2.2ConsequencesofNonlinearPropagation

27

2.2.1ExperimentalMeasurements

27

2.2.2TheoreticalPredictions

31

2.2.3ClinicalSystems

34

References
3
RadiationPressureandAcousticStreaming
FrancisADuck
3.1Radiationpressure

36
39

39

Pagex

3.2LangevinRadiationPressure,PLan

40

3.3RadiationStressTensor

43

3.3.1TheExcessPressure
3.4RayleighRadiationPressure,PRay

44

3.5AcousticStreaming

46

3.5.1MethodsofMeasuringAcousticStreaming
3.6ObservationsinVivoofRadiationPressureEffects

50
52

3.6.1Streaming

52

3.6.2ObservedBiologicalEffectsApparentlyRelatedtoRadiation
Pressure

52

3.7Discussion

53

References

54

4
UltrasonicPropertiesofTissues
JeffreyCBamber
4.1BasicConcepts

57

57

4.1.1Attenuation,Absorption,ScatteringandReflection

57

4.1.2SpeedofSound

61

4.1.3Nonlinearity

61

4.1.4TransducerDiffractionField

61

4.1.5PulseEchoImaging,SpeckleandEchoTexture

62

4.1.6ReceiverPhaseSensitivity

64

4.2MeasurementMethods

64

4.2.1MeasurementoftheAbsorptionCoefficient

64

4.2.2MeasurementoftheAttenuationCoefficient

65

4.2.3MeasurementofSoundSpeed

68

4.2.4MeasurementofScattering

70

4.2.5MeasurementofNonlinearity

72

4.3UltrasonicPropertiesofTissues

73

4.3.1AbsorptionandAttenuation

73

4.3.2SoundSpeed

76

4.3.3Scattering

78

4.3.4Nonlinearity

83

References

83

Part2
TechnologyandMeasurementinDiagnosticImaging

89

5
TransducerArraysforMedicalUltrasoundImaging
ThomasLSzabo

91

5.1PiezoelectricTransducerElements
5.1.1ABasicTransducerModel

43

91
91

Pagexi

5.1.2TransducerElementsasAcousticResonators

93

5.1.3TransducerArrayStructures

95

5.1.4TransducerModels

96

5.1.5TransducerDesign

99

5.2Imaging

102

5.3BeamForming

103

5.4OtherImagingModes

108

5.5Conclusion

109

References

109

6
CurrentDopplerTechnologyandTechniques
PeterNTWells
6.1TheDopplerEffect

113

6.2TheOriginoftheDopplerSignal

114

6.3TheNarrowFrequencyBandTechnique

116

6.3.1TheContinuousWaveDopplerTechnique

116

6.3.2ThePulsedDopplerTechnique

118

6.4FrequencySpectrumAnalysis

120

6.5DuplexScanning

120

6.6ColourFlowImaging

121

6.6.1BasicPrinciples

121

6.6.2AutocorrelationDetection

123

6.6.3OtherDopplerFrequencyEstimators

123

6.6.4TimeDomainProcessing

124

6.6.5ColourCodingSchemes

125

6.6.6ThreeDimensionalDisplay

126

6.7ContrastAgentsandSecondHarmonicImaging

126

References

127

7
ThePurposeandTechniquesofAcousticOutputMeasurement
TAWhittingham

113

129

7.1WhyMeasureAcousticOutputs?

129

7.2UltrasoundDamageMechanismsandtheirBiologicalSignificance

129

7.2.1Heating

130

7.2.2Cavitation

131

7.3TrendsinAcousticOutputs

133

7.4RegulationsandStandards

134

7.4.1FDA510(k)Regulations

135

7.4.2AIUM/NEMAOutputDisplayStandard

135

7.4.3IEC61157

136

7.5IsThereaNeedforIndependentMeasurements?

137

7.6WhichOutputParametersshouldbeMeasured?

137

Pagexii

7.7TheNewcastlePortableSystemforAcousticOutputMeasurementsat
HospitalSites
7.7.1TheHydrophoneandPreAmplifier

138

7.7.2VariableAttenuator,PowerAmplifierandPowerMeter

140

7.7.3Oscilloscope

141

7.7.4OscilloscopeCamera,PCandDigitisationTablet

141

7.7.5TheMeasurementTank

141

7.7.6TheHydrophonePositioningSystem

142

7.7.7TheProbeMountingSystem

142

7.7.8CalibrationandAccuracy

142

7.8TheNPLUltrasoundBeamCalibrator

142

7.9MeasurementofAcousticPower

143

7.10FindingWorstCaseValues

145

7.10.1WorstCaseIsptaofStationaryBeams,e.g.PulsedDoppler
Mode

145

7.10.2WorstCaseIsptaforScannedBeamModes,e.g.BMode

146

7.11Conclusions

146

References

147

Part3
UltrasoundHyperthermiaandSurgery

149

8
UltrasoundHyperthermiaandthePredictionofHeating
JeffreyWHand

151

8.1UltrasoundHyperthermia

151

8.1.1Introduction

151

8.1.2UltrasoundIntensity,AttenuationandAbsorption

152

8.1.3TransducersforHyperthermia

154

8.1.4HighIntensityShortDurationHyperthermia

163

8.2PredictionofHeating

165

8.2.1ThermalConduction

165

8.2.2Pennes'BioheatTransferEquation

166

8.2.3OtherApproachestoThermalModelling

168

8.3Summary

171

Acknowledgments

172

References

172

9
FocusedUltrasoundSurgery
GailRterHaar
9.1MechanismsofLesionProduction

138

177

178

9.1.1ThermalEffects

178

9.1.2Cavitation

179

Pagexiii

9.2LesionShapeandPosition

179

9.3SourcesofUltrasound

179

9.4ImagingofFocusedUltrasoundSurgeryTreatments

182

9.4.1UltrasoundTechniques

182

9.4.2MagneticResonanceImaging

182

9.5ClinicalApplications

182

9.5.1Neurology

182

9.5.2Ophthalmology

183

9.5.3Urology

183

9.5.4Oncology

184

9.5.5OtherApplications

184

9.6Conclusion

184

References

184

10
AcousticWaveLithotripsy
MichaelHalliwell
10.1PercutaneousContinuousWaveSystems

189

10.2ExtracorporeallyInducedLithotripsy

190

10.2.1TypesofPressureWaveTransducer

190

10.2.2PositioningSystems

191

10.2.3FieldMeasurement

192

References

196

Part4
UltrasoundandBubbles

197

11
AnIntroductiontoAcousticCavitation
TimothyGLeighton

199

11.1TheAcousticPropertiesoftheBubble

189

199

11.1.1StiffnessandInertia

199

11.1.2Resonance

200

11.1.3InertialCavitation

201

11.2TypesofCavitation

206

11.3TheImplicationsoftheOccurrenceofOneTypeofCavitationforthe
OccurrenceofAnother

210

11.3.1AlterationoftheBubbleSizebyRectifiedDiffusion

210

11.3.2AlterationoftheAcousticPressureFieldattheBubbleby
RadiationForces

212

11.3.3Nucleation

214

11.3.4PopulationEffects

214

11.4TheImplicationsoftheOccurrenceofOnetypeofCavitationfor
CausingChangetotheMedium

217

11.5Conclusion

219

References

219

Pagexiv

12
EchoEnhancing(UltrasoundContrast)Agents
DavidOCosgrove
12.1NonBubbleApproaches

225

12.2MicrobubbleAgents

226

12.2.1History

226

12.2.2SafetyofContrastAgents

229

12.2.3BasicPrinciples

230

12.2.4ClinicalApplications

230

12.2.5QuantificationandFunctionalStudies

233

12.2.6NewUses:AgentsandTechniques

234

12.3Conclusion

236

References

236

13
SonochemistryandDrugDelivery
GarethJPrice

241

13.1CavitationanditsEffects

243

13.2WhatCanUltrasounddoforChemists?

245

13.3BioEffectsandDrugDelivery

252

References

256

Part5
ResearchTopicsinMedicalUltrasound

261

14
ImagingElasticPropertiesofTissue
JamesFGreenleaf,RichardLEhman,MostafaFatemiandRaja
Muthupillai

263

14.1Introduction

263

14.1.1ExogenousTransverseWaves:ImagingwithMRE

263

14.1.2StimulatedAcousticEmission:ImagingwithUSAE

264

14.2MagneticResonanceElastography(MRE)

264

14.2.1Theory

264

14.2.2Methods

265

14.2.3MREResults

266

14.3UltrasoundStimulatedAcousticEmission(USAE)

270

14.3.1TheoryofUSAE

270

14.3.2USAEResults

272

14.4Conclusions

275

14.4.1MRE

275

14.4.2USAE

276

Acknowledgments

276

References

276

15
TheSignaltoNoiseRelationshipforInvestigativeUltrasound
ChristopherRHill
References

225

279

286

Pagexv

16
ChallengesintheUltrasonicMeasurementofBone
JohnGTruscottandRolandStrelitzki
16.1Bone

288

16.2UltrasonicMeasurementsSuitableforBone

289

16.2.1SpeedofSound(SOS)

291

16.2.2Attenuation

292

16.2.3Problems

295

16.3EffectofStructureonBroadbandUltrasonicAttenuation

295

16.4ProblemsintheMeasurementofSpeedofSound

297

16.4.1TimeDomain(ZeroCrossingPointMeasurement)

297

16.4.2FrequencyDomainMeasurements

300

16.5Discussion

303

Acknowledgment

305

References

305

Index

287

307

Pagexvii

CONTRIBUTINGAUTHORS
DrAndrewCBaker
ChristianMichelsenResearchAS
Fantoftvegen38,Postboks6031
5020Bergen
Norway
(FormerlyDepartmentofPhysics,
UniversityofBath,UK)
Andrew.Baker@cmr.no
DrJeffreyCBamber
JointDepartmentofPhysics
TheRoyalMarsdenNHSTrust
DownsRoad
Sutton
SurreySM25PT
UK
jeff@icr.ac.uk
ProfessorDavidOCosgrove
DepartmentofRadiology
HammersmithHospital
DuCaneRoad
LondonW120NN
UK
dcosgrov@rpms.ac.uk
DrFrancisADuck
MedicalPhysicsDepartment
RoyalUnitedHospital
CombePark
BathBA13NG
UK
f.duck@bath.ac.uk
ProfessorJamesFGreenleaf
BiodynamicsResearchUnit
DepartmentofPhysiologyand
Biophysics
MayoFoundation
RochesterMN55905
USA
jfg@mayo.edu
DrMichaelHalliwell
MedicalPhysicsand
Bioengineering
BristolGeneralHospital
GuineaStreet
BristolBS16SY
UK
mike.halliwell@bris.ac.uk
DrJeffreyWHand
RadiologicalSciencesUnit
DepartmentofImaging
HammersmithHospital
DuCaneRoad
LondonW120NN
UK
jhand@rpms.ac.uk
ProfessorChristopherRHill
StoneyBridgeHouse
CastleHill
Axminster
DevonEX135RL
UK
(FormerlyPhysicsDepartment,
RoyalMarsdenHospital,UK)

Pagexviii

DrVictorFHumphrey
DepartmentofPhysics
UniversityofBath
ClavertonDown
BathBA27AY
UK
v.f.humphrey@bath.ac.uk
DrTimothyGLeighton
FluidDynamicsandAcoustics
Group
InstituteofSoundandVibration
Research
UniversityofSouthampton
Highfield
SouthamptonSO171BJ
UK
tgl@isvr.soton.ac.uk
DrGarethJPrice
DepartmentofChemistry
UniversityofBath
ClavertonDown
BathBA27AY
UK
g.j.price@bath.ac.uk
DrHazelCStarritt
MedicalPhysicsDepartment
RoyalUnitedHospital
CombePark
BathBA13NG
UK
h.c.a.starritt@bath.ac.uk
DrThomasLSzabo
HewlettPackard
ImagingSystemsDivision
3000MinutemanRoad
Andover,MA18101099
USA
tom.szabo@
hp.andover.om3.om.hp.com
DrGailterHaar
JointDepartmentofPhysics
TheRoyalMarsdenNHSTrust
DownsRoad
Sutton
SurreySM25PT
UK
gail@icr.ac.uk
DrJohnGTruscott
CentreforBoneandBody
CompositionResearch
InstituteofPhysicalScience
DepartmentofClinicalMedicine
WellcomeWing
LeedsLS13EX
UK
j.g.truscott@leeds.ac.uk
ProfessorPeterNTWells
MedicalPhysicsand
Bioengineering
BristolGeneralHospital
GuineaStreet
BristolBS16SY
UK
peter.wells@bris.ac.uk
DrTonyWhittingham
RegionalMedicalPhysics
Department
NewcastleGeneralHospital
WestgateRoad
NewcastleUponTyne
NE46BE
UK

Pagexix

GLOSSARY
Thefollowingsummaryincludessubstantiallyallthedefinedsymbolsandacronymswhichhavebeenusedthroughoutthebook.Whereverpossiblethesamesymbol
hasbeenuseduniquelyforaparticularquantity.Onthefewoccasionswhenthishasprovedtobeimpossible,localuseisidentifiedinthetext.Converselywhen,
rarely,ithasbeennecessarytousethesamesymbolindifferentchaptersfordifferentquantities,thisisnotedinthelist.Onoccasionssubscriptshavebeenusedinthe
texttodefinethematerial(wforwater,tfortissueandsoon).Thislevelofdetailisexcludedfromthelistofsymbols.Thelistalsoincludesseveralsymbolswhich
havebeenusedarbitrarilyasconstantswithinparticularequations.
A
a,b

constantsinequationforbubblebehaviour

backscatteredsignalamplituderadiatingarea

A(f)

amplitudespectrum

ACF

autocorrelationfunction

AL

acousticlossfactor

B
B/A

nonlinearityparameter

constantrelatingtemperaturerisetotime

BUA

broadbandultrasonicattenuation

C
c

acousticwavevelocity

cc c

meanpulsevelocity

elasticstiffnessconstant(clamped)

cg

acousticgroupvelocity

cp

acousticphasevelocity

C0

capacitance(clamped)

D
d

beamdiameter

piezoelectricelementthickness

d3

3dBfocalzonewidth

radiationforce(drag)coefficient

effectivebeamdiameter

dielectricdisplacement

DIFF(z)

diffractioncorrectionfactor

E
E0
E

energydensity
timeaveragedenergydensity

Pagexx

Ep

pulseenergy

EL

electriclossfactor

F
f

acousticfrequency

fD

Dopplershiftedfrequency

f opt

optimalfrequencyforhyperthemia

fr

resonantfrequency(bubble)

radiationforce

FEM

finiteelementmodelling

FUS

focusedultrasoundsurgery

G
g

gravitationalacceleration

g(x,y)

amplitudebeamprofile

geometricfactorforacousticstreaming

amplitudefocusinggain

G(t)

magneticfieldgradient

H
h

heightofliquidcolumn

depthofsphericaltransducersurface

apiezoconstant

h(x,y,z)

pointspreadfunction

forwardpropagationoperator

H*

backwardpropagationoperator

I
i

electricalcurrent

acousticintensity

I(z)

axialintensitydistribution

I,Ita

timeaveragedintensity

Ipa

plusaveragedintensity

Isp

spatialpeakintensity

Isppa

spatialpeakpulseaveragedintensity

Ispta

spatialpeaktimeaveragedintensity

I.3

'derated'intensity

I0

sourceintensity

IR

intensityatthecentreofcurvatureofasphericalsource

K
k

wavenumber

thermalconductivity

k eff

effectivethermalconductivity

kT

electromechanicalcouplingcoefficient

constantrelatingtothermalequilibrium

timeaveragedkineticenergydensity

L
ld

discontinuitylength

lv

lengthofvessel

l3

3dBfocalzonelength

perfusionlength

M
m

mass

MI

mechanicalindex

Pagexxi

MR

magneticresonance

MRE

magneticresonanceelastography

O
ODS

OutputDisplayStandard

P
p

acousticpressure

complexpressure

p0

acousticpressureamplitudeatsourceorforplanewave

pc

acousticpressureatpeakcompression

pr

acousticpressureatpeakrarefaction

pf

acousticpressureatthefocus

pn

acousticpressureamplitudeatharmonicn

popt

leastpeakrarefactionpressurecausinginertialcavitation

p()

probabilitydensity

prf

pulserepetitionfrequency

excesspressure

PE

excesspressure(Euleriancoordinates)

excesspressure(Lagrangiancoordinates)

generalisedpropertyvalueoftissuei

PLan

Langevinradiationpressure

PRay

Rayleighradiationpressure

PII

pulseintensityintegral

PPSI

pulsepressuresquaredintegral

PSF

pointspreadfunction

PVDF

polyvinylidenefluoride

PZT

leadzirconatetitanate

Q
Q

heatflux

Qfactoratresonance

QBF

heattermtoaccountforbloodflow

Qe

electricalQ

R
r

vesselradius

ra

radiusofacircularsource

rz

radialdistanceatdepthz

r(t)

postionvectorofthemovingspin

reflectioncoefficient

radiusofcurvature

RA

radiationresistance

Ropt

criticalbubbleradiusforinertialcavitation

R0

bubbleradius

RF

radiofrequency

S
s

specificheatcapacity

s( t)

crosscorrelationfunction

area

specklecellsize

S,Sij

radiationstress(tensor)

Si

generalisedsignalvalueassociatedwithtissuei

Pagexxii

SAR

specificabsorptionrate

SNR

signaltonoiseratio

T
t

time

tp

pulseperiod

temperature

strain

T(x,y,z)

tissuebackscatterimpulseresponse

TI

thermalindex

TIB

boneatfocusthermalindex

TIC

cranialthermalindex

TIS

softtissuethermalindex

TOA

timeofarrival

TOF

timeofflight

U
u

particlevelocity

u0

particlevelocityamplitude(sinewave)

complexparticlevelocity

USAE

ultrasoundstimulatedacousticemission

V
streamingvelocity

wavevelocityofpiezoelectricmaterial
vectorvelocityofsourceorobserver

volume

voltage
V

timeaveragedpotentialenergydensity

W
w

perfusionvolumeflowrate

W,WA

acousticpower

WE

electricalpower

W.3

'derated'acousticpower

W1

acousticpowerfroma1cmlengthofarray

Wv

absorbedpowerperunitvolume

X
x,y

dimensionsorthogonaltothebeamaxis

reactance

XA

radiationreactance

Xeq

vesselthermalequilibriumlength

X6

6dBbeamwidth

dimensionparallelwithacousticaxis

Z
zf

focaldistance

Z,ZA

acousticimpedance

Z(f)

Fouriertransform

Z(f)*

complexconjugateFouriertransform

ZT

electricalimpedance
amplitudeattenuationcoefficient

amplitudeabsorptioncoefficient

a0

amplitudeabsorptioncoefficientat1MHz

amplitudescatteringcoefficient

Pagexxiii

nonlinearityparameter
Kroneckerdelta

ij

acousticMachnumber
S

dielectricconstant(clamped)
gyromagneticratio
Gol'dbergnumber

k,k0

adiabaticbulkcompressibility
wavelength
constantassociatedwiththermal

contactbetweenvesselandtissue

intensityattenuationcoefficient

intensityabsorptioncoefficient

intensityscatteringcoefficient

bs

backscatteringcoefficient

ds

differentialscatteringcoefficient

kinematicviscosity
angleofrefraction

phaseoffset
(f)

phasespectrum

( )

transversemagnetisationphase
shearviscosity

equilibriumdensity
standardvariation

shockparameter
m

nonlinearpropagationparameter

( , )

differentialscatteringcrosssection
timeshift

peakdisplacementofspin
beamprofilephasefunction
tissueorientationangle
angularfrequency
solidangle

Pagexxv

INTRODUCTION
FrancisADuck
Theweatheroftheweekof7June1997wasalmostperfectinOxford.ThevenuefortheThirdMayneordPhillipsSummerSchool'UltrasoundinMedicine'hadbeen
chosentobeStEdmundHall,Oxfordonlyonprecedent:thetwoearlierMedicalPhysicsSummerSchoolshadbeensuccessfullyheldthere.Intheevent,theweek
turnedouttobeaveryspecialoccasionforthefortyorsolecturersandstudentswhoattendeduniqueandmemorable(frontispiece).ApartfromthelossofBarry's
glassesduringthepuntingexpedition,thememoriesoftheweekremainverypositive,aweekoflearningandcompanionship,andnewandrenewedfriendships.
ThisbookisoneoutcomeofthatSummerSchool.AllthelecturerswhocontributedtotheSchoolhavepreparedchapters,eachbasedaroundthetopicoftheirown
lecture.InanumberofcasesthechapterhasbeenlimitedtothematerialcontainedwithinthelectureinOxford,whileotherauthorshaveextendedtheirmaterialto
includedetailsmoreeasilypresentedinaprintedform.Moredetailsofthebook'scontentandstructurearedescribedbelow.Initially,however,ashortbackgroundto
theMayneordPhillipsMemorialTrustwillbegiven,sincewithoutitsestablishment,thisSummerSchool,andthisbook,wouldnothavebeencreated.
TheMayneordPhillipsMemorialTrustwasestablishedin1994,thefirstTrusteesrepresentingthethreefoundingbodies:theBritishInstituteofRadiology,the
InstituteofPhysicsandtheInstituteofPhysicalSciencesinMedicine(nowtheInstituteofPhysicsandEngineeringinMedicine).OneoftheoriginalTrustees,
ProfessorKitHill,isawelcomecontributortothisbook.TheTrustdeedidentifiedoneobjectiveas'thefurthering,forthebenefitofthepublic,theknowledgeand
understandingofallaspectsandallapplicationsofmedicalphysicsandkindredsciences...bytheorganisationofeducationalmeetingstobecalledtheMayneord
PhillipsSummerSchools'.InadditiontheTrusteesshould'arrangeforthepublicationeitherinfullorinpartofanysuchSchools'.TheTrusteesdecidedthattheThird
Schoolshouldtakethetopic'UltrasoundinMedicine'andtousetheSchoolandsubsequentpublicationtoexploreabroadranging

Pagexxvi

studyofmedicalultrasound,includingultrasoundpropagation,interactionwithtissue,andanexplorationofanumberofcontemporaryinnovationsintheapplicationof
ultrasoundinmedicine.Giventhisbackground,itisclearthatthecontentofbothSchoolandpublicationwasandisrathernarrowerthanthetitlemightimply.The
focusisspecificallyonthescienceandtechnology,thephysicsandtheengineering,ratherthanontheclinicalapplications.Thisisnottosaythatclinicalapplications
areabsent,sinceitisthenatureofapplyingphysicstomedicinethatthelinkbetweenscientificandengineeringdevelopmentandclinicalapplicationmustbefirmly
made.Neverthelesstheemphasisalwaysremainsthus:todrawfromthebasicsciencesthoseaspectswhichrelatemostcloselytothechallengeofapplyingthisscience
toaparticularclinicalneed:andtoreviewagainsttheclinicalneednowsuccessfultechnologicalinnovationhasbeeninusingnaturalsciencetoimprovemedical
diagnosisandtreatment.
WVMayneordandCESPhillipsweretwooutstandingpioneersoftheapplicationsofphysicstomedicine.Intheirnatureaspioneerstheybothhadastrong
concerntohelpandencourageyoungercolleaguestodeveloptheirowninterestsandexpertise.Thefollowingparagraphsbrieflysummarisetheirlivesand
contributionstomedicalphysics.Furtherdetailsmaybefoundelsewhere[1,2].
MajorPhillipshasbeendescribedasthefirstBritishmedicalphysicist.Bornin1871,hisearlyexperimentswithdischargetubesledtohisdescriptionofthe'Phillips'
phenomenon',therotationofaluminousringinanelectricaldischargetubewithinastaticmagneticfield.In1897,hepublishedacompletebibliographyofXray
literature,probablythelastoccasionwhenthiswasapossibility.Hisworkonradiationstandardsduringthefirstdecadeofthetwentiethcenturyledhimtobe
commissionedtopreparethreeradiumstandardsfortheRoentgenSociety.HebecamethephysicisttotheXRayCommitteeoftheWarOfficeduringthe191418
war.HeworkedwiththeradiologistRobertKnoxashonoraryphysicistattheCancerHospital(nowtheRoyalMarsdenHospital)uptohisretirementin1927,during
whichtimehehelpedtodevelopthescientificbasisofradiotherapy,handlingradioactivematerials,andradiationprotection.
ValMayneordwas22yearsoldwhenhegainedhisfirstjobasamedicalphysicistatStBartholomew'sHospitalin1924.VerysoonaftermovingtotheCancer
HospitalonPhillips'retirement,Mayneordstartedmakingmajorcontributionstoradiationdosimetry.UnlikePhillips,whopublishedlittle,Mayneordwasaprolific
writer.Hisfirstbook[3],publishedbeforehis30thbirthday,remainsoneoftheclearestearlydiscussionsofthescientificrealitiesofmedicalradiationtherapyand
protection.Hisyear'ssecondmenttoCanadabytheUKgovernmentafterthewaronlyfiredhisenthusiasmonhisreturnfortheapplicationofphysicstoawiderange
ofmedicalproblems.Perhapsevenmoreimportantthanhisownpersonalscientificachievementswashisbuildingupofadepartmentofphysicsappliedtomedicineat
the

Pagexxvii

RoyalMarsdenHospital,whichearneditselfaninternationalreputationforworknotonlyinradiotherapy,butalsoinnuclearmedicine,diagnosticultrasoundand
severalotherareasofmedicalphysics.Heachievedthisbyunderstandingthatgoodmedicinemustbebasedongoodscience,andthatgoodphysicalscientistsneeda
strongandstimulatingenvironmentinwhichtothrive.Thisisastruenowasitwasthen.
Ultrasoundhasbeenalatestarterinitsapplicationtomedicine.EvenduringtheperiodofvigorousgrowthinapplyingphysicstomedicalproblemswhichVal
Mayneordandhiscontemporariesexperiencedfollowingthewar,ultrasoundstillhadasomewhatsecondaryplacetotheinnovationsinnuclearmedicine,diagnostic
radiologyandradiotherapy.Interestingly,acoustics,thestudyofthescienceofsoundwaves,andtheknowledgeofpiezoelectricitybothsubstantiallypredatethe
discoveryofXraysandofradioactivityduringthelastdecadeofthenineteenthcentury.PerhapsitwastheastonishingbreadthofLordRayleigh'sbook'TheTheory
ofSound'[4],firstpublishedin1877,whichdiscouragedothersfromattemptinganydeeperstudy.Maybethedramaticoverturnofclassicaltheoriesofphysicsatthe
turnofthecenturycausedacousticstobecomeapoorrelationinphysics.Ormaybeitrequiredanappropriatepracticalobjectivetodrawtogetheracousticscience
andtransducertechnologytowardstheexploitationwhichcharacterisesmedicalultrasoundattheendofthetwentiethcentury.
TheCuriesrediscoveredpiezoelectricphenomenaincrystalsfollowingBecquerel'sworkearlierinthenineteenthcentury[5],whichwasitselfbasedonworkbyHauy
inthelate1700s.TheCuries'workseemstohavegeneratedinterestmostlyamongscientistsratherthanpracticalpeople(bothRoentgenandKelvinshowedactive
interestinthephenomenon).Nevertheless,theonlypracticaloutcomeoftheirobservationsofthereversepiezoelectriceffectofquartz[6]seemstobethe'Quartz
pizolectrique'[7]whichwasusedsoeffectivelybyMarieandPierreCurieintheircarefulexperimentalstudiesoftheradioactivityofradium.ItwaslefttoLangevin,
whohadpreviouslybeenastudentoftheCuries,toexploitthestrongpiezoelectricpropertiesofquartzasaresonantelectroacoustictransducerforunderwater
echolocationfordepthsoundingandsubmarinedetection[8].Whileacousticdepthsoundinghadbeensuggestedintheearlypartofthenineteenthcentury,itwas
Langevin'sworkduringtheFirstWorldWarwhichestablishedtwokeyelementsforitssuccess.Firstly,herecognisedthecompromiserequiredintheselectionofthe
optimumfrequency,balancingresolutionagainstpenetration.Thisledhimtoidentifythepotentialadvantageofusingfrequenciesabovetheaudiblelimit(about20
kHz)forunderwaterecholocation.ShortlyaftertheTitanicdisaster,LewisFryRichardsonhadtakenoutapatentfortheuseof100kHzsoundforthesame
purpose[9],butthedeviceseemsnevertohavebeenimplemented.Richardsonisbetterknownforhisbookonthemathematicalprediction

Pagexxviii

ofweather.Langevinrealisedhoweverthattomakesuchadevicework,greatersensitivitywasrequired.Hissecondinnovationwastoexploittheelectronicmethods
alreadyavailableforradiocommunicationtodevelopresonantmodesoftransmissionandreception,sosubstantiallyenhancingtheoutputpower,andthedetection
sensitivityofhisquartztransducers.(Asafootnote,Langevinalsodescribesclearlythemeasurementofacousticpowerusingaradiationforcemethod.)Itliesoutside
thescopeofthisintroductiontotracefurtherthedevelopmentfromthisearlyuseofultrasonicechodetectiontotheextremesophisticationofmodernmedical
diagnosticsystems.Muchoftheearlymedicalwork,duringthe1940sand1950s,hasbeenwelldescribedelsewhere[10,11].
Intheremainingparagraphsabriefoverviewwillbegivenofthechapterscontainedinthebook,andofthewayinwhichtheyrelatetooneanother.
Ultrasoundisrapidlybecomingtheimagingmethodofchoiceformuchofdiagnosticmedicine,andinsomespecialistareasithasallbutreplacedotherdiagnostic
methods.Ithasbeenestimatedthataquarterofallmedicalimagingstudiesworldwideisnowanultrasoundstudy[12].ThisissupportedbyUKDepartmentof
HealthdatawhichsuggestthatinNHSTrustsinEnglandalone,over4millionultrasoundimagingstudieswerecarriedoutinoneyear,ofwhichabout1.7millionwere
obstetricscans(1996/97figures).Eventhishugenumberexcludesthestudiescarriedoutinprimarycare(GPpractices)andintheprivatesector.Itrepresentsthree
scansforeachlivebirth.Thisastonishinggrowthhasbeenencouragedinpartbecauseultrasoundisperceived,itmustbesaidwithgoodreason,tobeadiagnostic
methodwithnoriskoverhead.Theassertionthatmedicalultrasoundissafehasbecomeatruism,andmanyofthedevelopmentsindiagnosticultrasound,especially
thoseusingDopplermethodsanddescribedbyPeterWellsinChapter6,weremadepossiblebecauseofthisview.Thiswastrueinspiteoftheconsiderable
increasesinintensityandacousticpowerrequiredforsomeapplications,andthesearereviewedbyTonyWhittingham(Chapter7).Undoubtedlymanyofthe
advanceshavecomeaboutbecauseofthedevelopmentoftechniquesinarraytechnologywhicharedescribedbyTomSzaboinChapter5.Thesehaveallowed
paralleloperationinDopplerandpulseechomodessoastofullyexploittheabilityofultrasoundtoimagebothstructure(throughpulseechoscanning)andblood
perfusion(throughDoppler).Miniaturisationofarraysnowgivesaccesstodeepstructuresbyarrayinsertionintotherectum,oesophagusandvagina,andeven
throughthevasculartreeasfarasthecardiacarteries.Thedevelopmentofveryhighfrequencyminiatureprobesisanexcitingdevelopmentareawhich,sadly,isone
activitynotcoveredhere.Vascularultrasoundisbecomingfurtherenhancedbydevelopmentsinechoenhancingcontrastmaterials.DavidCosgroveintroducesthis
rapidlygrowingclinicalareainChapter12.
Bycomparison,therapeuticandsurgicalusesofultrasound,someofwhichpredatedthediagnosticmethods[13],havedevelopedinparallelbuthave

Pagexxix

failedthusfartoexerttheimpactonmedicinethatwaspromisedfromtheearlywork.Perhapsthishasbeeninpartbecauseinsufficientemphasishasbeenplacedon
theproperscientificdevelopmentofthesemethods,includingafullrecognitionofthecareneededinacousticdesign,andinestablishingamorecomplete
understandingoftheinteractionbetweenultrasonicwavesandtissue.Fromrecentsuccessesinhyperthermiaandfocusedsurgery,discussedfullybyJeffHandin
Chapter8,andGailterHaarinChapter9,andalsotheuseofavarietyofultrasonicapproachestolithotripsydescribedbyMichaelHalliwellinChapter10,itmaybe
confidentlypredictedthatultrasoundwillindeedfindavaluableplaceinthesurgicalandtherapeuticarmouryofthefuture,perhapscomparablewiththatachieved
alreadybydiagnosticultrasound.
However,strongandsuccessfulapplicationsonlydevelopfromastrongunderstandingofthebasicscience.Itissurprisinghowofteninsufficientattentionisplacedin
standardmedicalultrasoundtextsonthedifficultiesindescribingfullythepropagationofdiagnosticultrasoundpulsesthroughtissue.Eventhedescriptionofpulse
propagationinafocusednearfieldunderlinearconditionsinalosslessfluidposessomedifficulties,andthesearedescribedcarefullyinChapter1byVictor
Humphrey.Therealityoffiniteamplitudeeffectsandnonlinearacousticpropagationisnowknowntobenotanesotericsideissuebutcentraltoallmeaningful
discussionsofmedicalultrasound.AndyBakerintroducessomeaspectsofthisdifficulttopicinChapter2,whileFrancisDuck'ssubsequentchapterdescribestwo
practicalnonlinearphenomena,acousticpressureandacousticstreaming.Chapter4byJeffBambergivesacompleteoverviewofasubjectwhichiscentraltoall
discussionsofultrasoundinmedicine,theacousticpropertiesoftissue.Attenuation,absorption,scattering,soundspeed,nonlinearparameter,andtheirfrequency
dependenciesarealldescribed.
Anunderstandingofbiophysicalprocessesisimportantintheinterpretationoftissue/ultrasoundinteractions,bothforanunderstandingofultrasounddosimetryin
therapyandsurgery,andinsafetydiscussions.Thermalprocesseshavealreadybeennoted(Chapter8)ashasstreaming(Chapter3).Thethirdprocessisacoustic
cavitation,whichisdescribedbyTimLeightoninChapter11.Oftenacousticcavitationseemstobeatopicontheboundariesofinterestinmedicalapplications,but
theuseofcontrastmaterials(Chapter12)hasbroughtanewinterestinthetopic,inadditiontoitsimportanceinultrasoundsurgeryandinsafety.Cavitationis
howevercentraltotheuseofultrasoundinchemicalprocessing,andGarethPricedescribeshowthisscientificcousinmayinstructandilluminateapplicationsin
medicine,forexampleindrugdelivery(Chapter13).
ThepurposeoftheSummerSchoolwasnotonlytoreviewtopicswhicharepartofpresentclinicalpractice,butalsotoallowanexplorationofsomeresearchtopics
wherenewdevelopmentsareactive.Itisrarelypossibletoseparatefullystateoftheartapplicationsfromnewdevelopments,but

Pagexxx

thelastthreechaptersinthebookeachrepresentinonewayoranothernewstepsforward.Linkingtheexcitingcapabilitiesforimagingpresentedbymagnetic
resonanceimaging,JimGreenleafandhiscolleaguesdescribemethodsofgreatoriginalityforstudyingthemechanicalpropertiesoftissue,whichhavefascinating
potentialindiagnosticmedicine.KitHillreturnstoafundamentalissueindiagnosticultrasoundimaging,signaltonoiseratio.JohnTruscottreviewscriticallysomeof
themethodscurrentlybeingusedtoinvestigateboneusingultrasound,andsuggestsalternativemethodswhichmayhavethepotentialofimprovedprecision.
Allthechaptersinthisbookhavebeenpreparedwithaviewtobridgingthegapbetweenthetutorialtextswidelyavailableforsonographerandmedicaltraining,and
booksofacousticswhichcontainfewlinksbetweentheoreticalacousticsandtheapplicationsofultrasoundtomedicine.Somematerialwhichisverywelladdressedin
standardmedicalultrasoundtextshasbeendeliberatelyomittedforexamplethedescriptionofbasicpulseechoandimagingmethods,qualityassurancetestsusing
phantoms,artefactgenerationandavoidanceandsoon.Readersaredirectedtowardsoneofmanytextswhichnowincludethismaterial.Thepresentbookisoffered
asauniquecollectionofchapterscontainingwellreferencedmaterialofdirectrelevancetoanystudentwishingtoexploremedicalultrasoundatdepth.Wherespace
limitedthescopeofanychapter,amplereferencingwillallowtheseriousstudenttodiscoveramuchwiderbaseofknowledge.Itishopedthatthesepages,which
havebeenpreparedwiththespiritofMayneordandPhillipsinmind,willservetoilluminateandinstructanywhowishtolearnatgreaterdepthofthescienceand
technologyintheapplicationofultrasoundtomedicine.
Acknowledgments
Iwouldliketoaddmyheartfeltthankstoallthelecturersandauthorswhowerecajoledintotakingpartinthisenterprise,moreorlesswillingly.Ialsoacknowledge
theenormoussupportgivenbyAndyBakerandHazelStarritt,coorganisersoftheSummerSchool,andcoeditorsofthisbook,whosewarmandsteadysupport
wasessentialinthesuccessofbothprojects.AndfinallywewouldliketodedicatethebooktoallthosewhoattendedtheSummerSchoolwho,notknowingwhat
theywerelettingthemselvesinfor,enjoyeditanyway.
References
[1]HillCRandWebbS1993TheMayneordPhillipsSummerSchools:BackgroundtotheSchoolsandShortProfilesoftheTwoPioneeringPhysicists
(SuttonandLondon:InstituteofCancerResearchandRoyalMarsdenHospital)

Pagexxxi

[2]SpiersFW1991WilliamValentineMayneordBiographicalMemoirsoftheRoyalSociety3734164
[3]MayneordWV1929ThePhysicsofXRayTherapy(London:Churchill)
[4]Rayleigh,Baron:StruttJW1877TheTheoryofSound(London:Macmillan)
[5]BecquerelAC1823Expriencessurledveloppementdel'lectricitparlapressionloisdecedveloppementAnnalesdeChimieetdePhysique22534
[6]CurieJandCurieP1881ContractionsetdilatationsproduitespardestensionslectriquesdanslescristauxhmiedresafacesinclinesCompteRenduAcad.
Sci.Paris93113740
[7]CurieJandCurieP1893QuartzpizolectriquePhil.Mag.(5thSer.)363402
[8]LangevinP1924TheemploymentofultrasonicwavesforechosoundingHydrographicRev.IINo1,Nov1924,5791
[9]RichardsonLF1912ApparatusforwarningashipatseaofitsnearnesstolargeobjectswhollyorpartlyunderwaterUKpatent11125
[10]WhiteDN1976HistoricalsurveyUltrasoundinMedicalDiagnosisedDWhite(Kingston:Ultramedison)pp136
[11]LeviS1997Thehistoryofultrasoundingynaecology19501980UltrasoundMed.Biol.23481552
[12]WFUMB1997WFUMBNews4(2)UltrasoundMed.Biol.23followingp974
[13]BergmannL1938UltrasonicsandTheirScientificandTechnicalApplications(NewYork:Wiley)

Page1

PART1
THEPHYSICSOFMEDICALULTRASOUND

Page3

Chapter1
UltrasonicFields:
StructureandPrediction.
VictorFHumphreyandFrancisADuck
Introduction
Pulsedultrasoundbeamssuchasthoseuseddailyduringmedicalexaminationshaveacousticstructuresofconsiderablecomplexity.Thisistrueevenwhenconsidering
theirpropagationsimplythroughanidealisedacousticallyuniformmediumwithnoloss.Propagationthroughtheacousticinhomogeneitiesofbodytissuesresultsin
furtheralterationsintheacousticfield,bothfromscatteringatsmallscaleandfromlargescaleinterfaceeffects.Thepurposeofthischapteristodiscussthefactors
whichcontroltheacousticbeamsusedformedicalapplications,andtodescribethesebeamsandthemethodsfortheirprediction.Thepropagationmodelsusedwill
belimitedtothosewherethebeamisassumedtobeofsufficientlysmallamplitudethatlinearassumptionsmaybemadeabouttheacousticwavepropagation.While
thisisaninvalidassumptionforverymanymedicalultrasoundbeamsinpractice,itallowsinstructiveanalysestobedeveloped.Someofthebeamcharacteristics
whichariseduetofiniteamplitudeeffectsaredescribedinChapter2.Thesecondbroadlimitationinthischapteristhatconsiderationislimitedtoalosslessliquid
mediumwhichisacousticallyhomogeneous.Aswillbeseen,theuseofthesetwoassumptionsallowsthepropagationoftheultrasoundwavetobedescribedinterms
ofonlytwoacousticquantities,thewavenumberandtheacousticimpedance,togetherwithinformationaboutthesourcegeometry.Considerationofthesourceofthe
ultrasoundwave,thetransducer,isgiveninChapter5.
Forthemajorityofdiagnosticapplicationsofultrasoundtherangeoffrequenciesusedisquitenarrow,210MHz,wheretheparticularfrequencyisselectedinorder
toachievethebestcompromisebetweenspatialresolutionanddepthofpenetration.Higherfrequenciesareonly

Page4

usedinspecialisedapplicationssuchasophthalmology,skinimagingandintravascularinvestigations,reachingexperimentallyashighas100MHzormore.
Frequenciesbelow2MHzareusedinDopplersystemsforfetalheartmonitoring,andthelowerpartoftheultrasonicspectrumisalsousedfortherapeuticand
surgicalapplicationssuchaslithotripsy(Chapter10)orhyperthermiaandfocusedultrasoundsurgery(Chapters8and9).Sonochemistry(Chapter13)andsomebio
effectsstudiesuseultrasonicfrequenciesbelow100kHzthischapterwillnotconsidertheparticularissuesassociatedwithbeamsusingsuchlongwavelengths.
Havingestablishedthesimplifyingassumptions,severalcomplicatingfactorsofparticularrelevanceinmedicalapplicationsofultrasoundareintroduced.Itis
recognisedthatitispulsedratherthancontinuouswaveultrasoundbeamswhichareofmostinterest.Inordertoachievegoodspatialresolution,theultrasoundpulses
arelessthan1mminlength.Thevelocityofsoundthroughsofttissues,ct,liesintherangeapproximately14501600ms1(seeChapter4),sotherangeofacoustic
wavelengths, (=ct/f),isabout0.15to0.75mm.Thepulsesthemselvesarethuscommonlylessthan1slongandconsistofveryfewacousticcycles:theyareall
endandnomiddle.Thisfactresultsinsignificantdifferencesbetweenthebeamprofilesinsuchpulsedbeamsandthoseatasinglefrequencyfromthesamesource.A
secondimportantpracticalconsiderationisthatmedicalultrasoundpracticeusuallycouplesthetransducerdirectlytothetissuetobeinvestigated.Thismeansthat
signalsarereturnedfromthe'nearfield'ofthetransducer,inaregionwhichmaybestronglyinfluencedbythesizeandshapeofthetransduceritself.Theanalysisof
thenearfieldisthereforeofsignificance.
Symmetryisofconsiderableimportanceinthestructureofacousticfields.Theanalysisofbeamswithcircularsymmetryhasbeenwelldevelopedintheliterature,and
thiswillbedescribedbelow.Howeverthemajorityofmodernscannersdonotusecircularsourcesofultrasound,linear,curvilinearand'phased'arraysbeingalmost
universallyused.Forthisreason,theanalysisofrectangularsourcesisveryimportant.Thefinalsignificantfactoristhatallpracticalmedicalultrasoundtransducersvary
inbothamplitudeandphaseovertheiraperture:thatistheyareapodisedandtheyarefocused.
Recognisingthesecomplexities,thischapterwillcommencewithasimpledescriptionofthebeamfromacircularplanepistonsourceofultrasound,andproceedto
describethewayinwhicheachofthemorecomplexfeatureswhicharerelevanttothedescriptionofthestructureofmedicalultrasoundbeamshavebeenaddressed.
1.1
CircularPlaneSources
Itiscommonfirsttoconsidertheacousticfieldgeneratedbyaplanecircular'piston'sourcewhichisvibratingwithasinusoidalmotiononlyinadirection

Page5

Figure1.1.
Asimplifiedaxialsectionoftheacousticfield
fromaplanecircularsinglefrequency
sourcewhosediameterissignificantlygreater
thantheacousticwavelengthinthe
propagatingmedium.

perpendiculartoitssurface.Theanalysisofthisfieldisincludedinmanytexts(Wells1977,Kinsleretal1982).Thisfieldhasparticularcharacteristicswhicharise
fromtheveryspecifictemporalandspatialsymmetriesofthesource.Inpractice,thebeamsfrommanyphysiotherapytransducersapproximateinstructuretothe
followingdescription.
Thesimplestviewofthefieldofacirculartransducerwouldconsiderthefieldtobeaplanewaveofthesamediameterasthetransducerinthenearfield(theFresnel
region)andthentobeanexpandingsphericalwaveinthefarfield(Fraunhoferregion).Thisisshowninfigure1.1.
ThetransitionoccursattheRayleighdistancezR,where

whereaisthetransducerradius, isthewavelengthandk(=2 / )isthewavenumber.

Thismodelisconceptuallysimple,anduseful.Itispossible,forexample,tocalculatetheapproximateRayleighdistanceforatypical1MHzphysiotherapytransducer
witha=12.5mminwatertobeabout33cm,demonstratingthatforsuchatransducer,alltreatmentoccursinthenearfield.Neverthelessthissimplemodeldoesnot
allowfordiffractionandinterferenceandfurtherdevelopmentisrequired.
Consideraplanar,circular,transducermountedinarigidbaffle(surface)andradiatingintoafluid.Inordertocalculatethefieldduetothetransducerassumethat
eachsmallelementdSofthetransducersurfacevibratescontinuouslywiththesamevelocityunormaltothesurface(thex,yplane)where

TheneachelementdSgivesrisetoasphericalwavecontributinganelementalpressurecontributiondpataranger'of

Page6

Figure1.2.
Thegeometryforthecalculation
ofthepressurefieldp(r, ,t)atan
observerpointO,duetoaplanecircular
pistonsource.

where 0isthedensityofthefluid.Theresultantfieldofthetransducercanbeevaluatedbyaddingupallofthecontributionsduetothesmallelements.Inthelimitthis
summationbecomesanintegralandtheresultantpressurefieldp(r, ,t)isgivenby

Thesurfaceintegralisboundedbythecondition a,where istheradialpositionofthesurfaceelementdS(seefigure1.2).Theexpressioninequation(1.4)is

oftenknownastheRayleighintegral.
Ingeneralitisonlypossibletofindsimpleclosedformsolutionstothisintegralforspecialsituations,thatisalongthesymmetryaxisofthetransducerandinthefar
field.Otherwisealternativenumericalstrategiesareneeded.Forexample,StepanishenandBenjamin(1982)andWilliamsandMaynard(1982)havedeveloped
methodsforthepredictionofacousticfieldsusingaspatialFouriertransformapproach,recognisingthatthefarfieldbeampatternistheFouriertransformofthe
aperturefunction.Thisapproachcanbeofconsiderablevalueininvestigatingthefarfieldofnoncircularsources,suchastherectangularsourcesdiscussedinsection
1.5.Inprinciplesuchmethodscanbefastandaccurate,providedthatthespatialgridisfineenoughtopreventspatialaliasing.Forthenearfieldthetimedomain
numericmethodsusedbyZemenek(1971)havebeenveryeffectiveinevaluatingthediffractionintegral.
1.1.1
PressureVariationontheAxis
Theaxialpressurevariationmaybederivedfromequation(1.4).Geometricalconsiderationsgive:

Page7

whered istheincrementalwidthofasurfaceannulusofradius .Substitutioninequation(1.4)gives

thatis,theintegrandisaperfectdifferential.Substitutingandevaluatingat =aand =0givestheaxialcomplexpressurep(r,0,t):

Thepressureamplitudeisthemagnitude(i.e.therealcomponent)ofp(r,0,t).Expressedinrectangularcoordinates,replacingrbyz,thedistancealongthebeamaxis
perpendiculartothesource,theaxialvariationofthepressureamplitudep(z)is

Thisvariationisshowninfigure1.3,fromwhichitmaybeseenthattheaxialpressurevariationinthenearfieldischaracterisedbyaseriesofunequallyspaced
r
pressuremaxima,withvalue2r 0cu0,separatedbylocalisedfieldnullswherethepressureiszero.Sincethepressureamplitudeatthesource,p0,is 0cu0,thenearfield
pressuremaximahaveanamplitude2p0.Inthoseregionswherethesineisnegativethephaseofthepressurewaveisreversed.
Thepositionsofthemaximaandminimamaybecalculatedfromtheconditionsgivingthesinefunctioninequation(1.10)valuesof1(maxima)and0(minima).That
is,

wherethepositionsofthemaximaarisewhenmisodd(m=1,3,5,...)andthepositionsofthenullsarewhenmiseven(m=2,4,6,...).Themost

Page8

Figure1.3.
Thecalculatedvariationofacousticpressureontheaxis
ofaplanecirculartransducerof38mmdiameterat2.25MHz.
Thepressureisnormalisedtop0,thepressureatthesource.

distantmaximumfromthesourceiscommonlyreferredtoasthe'lastaxialmaximum'itsposition,zlam,maybecalculatedapproximatelybysettingm=1inequation
(1.11),andassumingthata<<z,whenzlam=a2/ .Similarlytheapproximatepositionofthelastaxialnullisa2/2 ,halfthedistancetothelastaxialmaximum.
Ithasbecomeconventionaltoconsiderthatthedistancezlammarkstheboundarybetweenthenearandfarfieldsforplanecircularsources.Aswillbeshownbelow,
thisdefinitionbecomeslessmeaningfulwhenconsideringsourceswhichdonothaveradialsymmetry,forexamplerectangularsourcesfromarraytransducers,andfor
focusedbeamswherethepositionofthe'lastaxialmaximum'iscontrolledasmuchbythefocusinggeometryasbythediffractionpatternfromthesource.Comparison
withequation(1.1)showsthattheRayleighdistancezR= zlamfortheexamplecitedofa1MHzphysiotherapysource,a=12.5mm,thelastaxialmaximumis
approximately11cmfromthetransducerface.
Referringagaintoequation(1.10),itispossibletoapproximatetheaxialbehaviourinthefarfieldbyconsideringconditionswhenz/a>>ka,whenequation(1.10)
reducesto

whereSistheareaofthesource.Equation(1.12)showsthattheaxialpressureinthefarfieldreduceswith1/(distance).

Page9

Figure1.4.
Contourplotofthenormalisedacousticpressure
(p/p0)foracirculartransducerofradiusa=5 .
Theaxialdistanceisnormalisedtoa2/ .

1.1.2
PressureVariationOfftheAxis
Atpositionsofftheaxisofsymmetrytheultrasoundpressurefieldhasconsiderablecomplexity.Acalculatedexampleofthenormalisedpressurefieldamplitudep/p0
foracircularapertureofradiusa=5 isshowninfigure1.4,usinganumericalapproach(seeZemanek1971).Thecompletepressurefieldmaybethoughtofas
beingformedbyrotatingthisradialsectionaroundthezaxis,andconsistsofringsofhigheracousticpressurewhosenumberandradialfrequencyincreaseasthe
sourceisapproached.Itmayalsobeseenthatthe6dBbeamwidthatzlam(a2/ )isonlyabout0.4thatattheaperture,demonstratingthesocalled'selffocusing'of
aplanesource.
Thealternativerepresentationofthenearfieldpatternshowninfigure1.5emphasisesanalternativeapproachtotheanalysisoftheultrasonicnearfield,originallyused
bySchoch(1941).Heshowedthatthefieldcouldbeconsideredasaconvolutionbetweentwoparts,oneaplanewavepropagatingnormallyfromthesource,and
theotherawavefromitsboundary.Theinterferencebetweenthesetwowavesmaybeclearlyseeninthefieldpatternshowninfigure1.5.Thisviewofthefieldas
beingcomposedofaplanewaveandan'edgewave'isparticularlyusefulwhenconsideringthecharacteristicsofpulsedultrasonicbeams(seebelow).
InthefarfieldtheoffaxisacousticpressurepqmaybeexpressedintermsofitsdirectivityfunctionDq:

Page10

Figure1.5.
Spatialdistributionofthenormalisedacoustic
pressure(p/p0)foracirculartransducerofradiusa=5 .
Theaxialdistanceisnormalisedtoa2/ .

andJ1isBessel'sfunctionofthefirstkind.J1(kasin )=0whenkasin =3.83,7.02,10.17,13.32etc.Thatisthefieldisformedofacentrallobe,andsidelobes.

Theboundaryofthecentrallobeoccurswhere =sin1(0.61 /a).
1.2
PulsedFields
Theimportanceofthedifferencesbetweenthesinglefrequencyandbroadbandpulsedbeamscannotbeoveremphasised.Severalauthorshavereviewedthe
structureofpulsedfields(Friedlander1958,Harris1981a,Wells1977,Duck1980,KrautkramerandKrautkramer1990).Whilethefarfieldmainlobeisnotmuch
affected,thespatialvariationsinthepressurenearfieldbecomesmaller,andsidelobesmaydiminishinamplitudeandmerge.Inadditionthepressurepulsewaveform,
anditsspectrum,varywithposition,includingthepotentialforpulsesplitting.Thesealterationsbecomeimportantoncethepulselengthreducestolessthansixcycles
ofoscillation(KrautkramerandKrautkramer1990).Theyarethusimportantforallmedicalpulseechoultrasoundbeams,andalsoformanypulsedDoppler
applicationswhenshorterpulselengthsareused(DuckandMartin1992).
Oneapproachtotheanalysisofapulsedfieldistoconsideritasasummationofthecomponentfieldsofallthespectralcomponentscomprising

Page11

thepulsespectrum(PapadakisandFowler1971).Foranysourceradius,thepositionsofnearfieldmaximaandminimadependonthewavenumberk(seeequation
(1.11)),andhenceonthefrequency.Summationofallthespectralcomponentswillthusresultinasmearingofthelocalspatialvariationsinacousticpressure.This
approachhasbeenvaluableinitsabilitytointroduceattenuativelossintothecalculationofthepulsedacousticfield,withitsassociatedfrequencydependence.
However,itisnecessarytogenerateasufficientsamplingofthefrequencydependentfieldstoavoiderrors,andgenerallythismethodmayonlybeexpectedtogive
goodapproximationsratherthanexactsolutionstothepredictionofthepulsedacousticfield.
Awidelyusedalternativemethodhasdevelopedfromtheanalysisofthetemporalimpulseresponseofasource.Thisallowsthepressurep(r,t)tobecalculatedfrom
theconvolutionbetweenasourcefunctionandthepressureimpulseresponsefunctionh(r,t):

where*indicatesatemporalconvolution.Sinceh(r,t)isafunctiononlyofthesourceshape,andu0(t)isafunctionofthesourcevibrationonly,equation
(1.15)givesapowerfulgeneralapproachtotheanalysisofavarietyofsourcegeometries,inadditiontothecircularpistonsourcewhichhasbeen
consideredsofar.FollowingStepanishen'soriginalpublicationsforthecircularpiston(Stepanishen1971,1974,Beaver1974),expressionsforh(r,t)
foranumberofothersourcegeometrieshavebeenpublished:includingthoseforrectangularsources(LockwoodandWillette1973),shallowbowl
(focused)sources(PenttinenandLuukkala1976a),andsourceswithavarietyofapodisingfunctions(Harris1981b).
Anexampleofacalculationofthepressurewavefrontinthenearfieldofaplanepistonsource,excitedusingasinglesinusoidalcycle,isshowninfigure1.6(a=8
mm,f=4MHz,z=40mm).Thetimescaleisexaggeratedinordertoemphasisethepulsestructureacrossthebeam.Thepulsewaveformontheaxisconsistsoftwo
componentsseparatedintime.Thefirstisthatfromtheplanewavepropagatedfromthesource.Thesecondoccursfromtheconstructiveinterferenceoftheedge
wave,andhasbeentermeda'replicapulse'.Itarrivesontheaxisatatimedelay

Itsphaseisinverted,anditsamplitudeisthesameasthatoftheplanewave.Offtheaxistherearetworeplicapulseswithloweramplitudes,becauseofincomplete
constructiveinterferencebetweentheedgewavecomponents.

Page12

Figure1.6.
Calculatedpulsepressureprofile
foracircularpistonsource,radius
8mm,vibratingwithonecycleat4MHz.
c=1500ms1z=40mmanda2/
=170mm.

Intheregionoutsidetheprojectionofthesourcearea,theplanewavecomponentisabsent,andonlythetwoedgewavecomponentsexist.Inthisexampleitisonlyat
thelateralboundariesofthebeamthatthereisoverlapbetweentheedgewaveandtheplanewave.Asthewavepropagates,sothedelaybecomessmallerbetween
theplanewavecomponentanditsreplicapulse(seeequation(1.16)).Interferencebetweenthetwocomponentscanonlyoccuratdistanceswherethetimedelay t
hasbecomelessthanthepulselength,andonlybeyondthisdistancedoesonaxisvariationinpulsepressureamplitudeappear.Experimentalobservationsofedge
wavesandreplicapulseshavebeendemonstratedby,forexample,WeightandHayman(1978).
Othermethodsappropriatetothecalculationofbothpulsedandsinglefrequencybeamsarefiniteelement/boundaryelementmethods,andfinitedifferencemethods.
Finitedifferencemethodshavefoundmosteffectiveapplicationinthepredictionofbeamswithinwhichfiniteamplitudeeffectsareimportant,givingrisetononlinear
acousticbehaviour.Becauseoftheimportanceoftheseeffectsinmedicalultrasound,theyaredealtwithseparatelyinChapter2.

Page13

Figure1.7.
Geometryofasphericalfocusingsource.

1.3
FocusedFields
Formanymedicalapplicationsofultrasoundtheneedarisestoreducethebeamwidth,ortoincreasethelocalpressureamplitude,orboth,fromthevalueswhichare
easilyachievedusingplanetransducers.Thisrequiresthebeamstobefocused,soachievingimprovedspatialresolutionforimaging,orintensitiesofsufficient
magnitudetodestroytissue(seeChapter9).UsefulanalyseshavebeenpublishedbyO'Neil(1949),Kossoff(1979)andLucasandMuir(1982).
Thesimplestmeansforfocusingabeamisbytheuseofasphericalcap,orbowltransducer(seefigure1.7).
TheamplitudegainGforabeamfromasourcewithradiusofcurvatureRcanbecalculatedapproximatelyby

Itiscommontoconsiderthreetypesoffocusedbeam,categorisedbytheirdegreeoffocusing.Theseare:
weakfocus:0<G 2
mediumfocus:2<G 2
strongfocus:G>2 .
Diagnosticbeamsaregenerallyofmediumfocus,whilethoseusedforhyperthermiaandtherapyarecommonlyofstrongfocus(seeChapters8and9).Whileitis
commoninacousticstospecifyfocusingintermsoftheamplitudegainofabeam,itissometimesusefultospecifytheintensityorpowergain,especiallywhenenergy
deliveryisrequired,aswithhyperthermia.Intensitygainmaythereforebequoted,whichisG2.
Forasinglefrequency,continuouswave,focusedsourcethereareaxialpressurevariationssimilartothoseinthebeamfromaplanesource.Themaindifferencesare
thatthemaximavaryinmagnitude,thespacingbetweenthemaximaandminimaaredifferent,andforstronglyfocusedfields,

Page14

Figure1.8.
Axialvariationofnormalisedacoustic
pressure(p/p0)insphericallyfocusedfields
withdifferentfocalgains(a)G=2and4
(b)G=6,8,and10.Thedistanceisnormalised
tothegeometricfocallength,R.

onaxisminimamayoccurbeyondthefocus.Examplesofaxialprofileswithamplitudefocalgainsof2,4,6,8,and10areshowninfigure1.8(a)and(b).Theaxes
arenormalisedtothesourcepressurep0andtotheradiusofcurvatureR.Theaxialvariationisgivenapproximatelyby

Page15

Atthegeometricfocus(infigure1.8wherez/R=1),thepressurepR0=Gp0.However,themaximumaxialpressurealwaysexceedsthisvalue,andthemaximum(i.e.
theacousticfocus)isalwaysreachedatapositionclosertothesourcethanthegeometricfocus.Furthermore,thisseparationbetweenthegeometricandacousticfoci
decreasesasthefocusinggainincreases.Whileagainof10isassociatedwithanapproximate10%shiftinposition,foragainof4(usedinsomediagnosticsystems)
theacousticfocusmayoccuronlyatabout0.7R.Ithasbecomeconventionalinpulseddiagnosticbeamstogivethefocallengthintermsoftheacousticfocus,where
thebeamintensityreachesamaximum(seeChapter7).Inspectionoffigure1.8a,balsodemonstratesthatthelengthofthefocalzonedecreasesasthegainandpR0/p0
increases.TheradialpressurevariationinthefocalplanepR(y)isgivenapproximatelyby

whereyistheoffaxisdistance.pR(y)reducesto3dBofitsaxialvaluewheny=1.62R/ka.Inotherwordsthe3dBbeamwidthatthefocus,d3,is

Pulsedfocusedbeamsdifferfromsinglefrequencybeamsinamannercomparablewiththedifferencesforplanesources.Impulseresponsefunctionshavebeen
developedforsphericalbowlsources(PenttinenandLuukkala1976a),forfocusinglenses(PenttinenandLuukkala1976b)andforconicalradiators(Pattersonand
Foster1982).Figure1.9demonstratesacomputedpulseprofileforacircularbowlsource,radiusofcurvature80mm,underconditionsotherwisesimilartothose
usedforfigure1.6.Theedgewavecomponentisstillvisible,buttheplanewaveisnowasphericalwaveconvergingtowardsthegeometricfocus.
1.4
SourceAmplitudeWeighting
ThetheoreticaldevelopmentinalltheprecedingsectionshasassumedthatmovementofallelementsdSoverthesourcehasbeenofequalamplitude.Focusingcanbe
consideredsimplyasthealterationoftherelativephaseofthemovementoftheelements.Howevermostrealtransducersarenottrue'piston'sources,thatis,thereis
somevariationinthesourceamplitudeoverthesourcearea.Thismaycomeaboutdeliberately,ashappenswithsomearraysforwhichweighting,orapodisation,is
appliedacrossthearray.Itmayoccurbecauseofthephysicalmountingofthetransducer,forexampleiftheedgesarelessfreetomovethanthecentreofa
piezoelectricelement,

Page16

Figure1.9.
Calculatedpulsepressureprofilefor
acircularsphericalbowlsource,
radius8mm,vibratingwithonecycleat4MHz.
c=1500ms1z=40mm.
Comparewithfigure1.6.

or,whenusingalens,fromthetransmissionlosswhichvariesfromthelensaxistoitsedge.Smallerscalevariationsacrossthesourceareamayalsooccur.These
occurbecauseoftheconstructionofanarrayandmayalsocharacterisethebehaviourofaphysiotherapytransducerdrivenatitsthirdharmonic.
Eachoftheseexamplesindicatesthatfieldsfromrealtransducersmaywelldifferfromthedescriptionderivedfromtheformaltheorysetoutinthischapter.Inpractice
itisquitecommontoapodiseanarrayusedinadiagnosticscanner,forexampleusingaGaussianamplitudeweightingfunction(DuandBreazeale1985).Figure1.10
showstheoutcomeofGaussianapodisationforaplanesinglefrequencycircularsourcewitha=5 .Theeffectofapodisationistoreducethepressurevariationsin
thenearfield,andtoreducethesidelobelevelinthefarfield.AmorecompletedescriptionoftheeffectsofradialweightingonpulsedfieldshasbeengivenbyHarris
(1981b).
Foraplanecircularsourcetheeffectofapodisationcausedbyedgetetheringistoalterslightlythepositionofthelastaxialmaximum.Forthisreasonitiscommonto
considerthesourceashavinganeffectiveradiusaeffsuchthatthemeasuredlastaxialmaximumliesat(aeff)2/ .

Page17

Figure1.10.
Calculatedsinglefrequencyvariation
inpeakpressureamplitude,
foraGaussiansourceapodisation
witha=5 :(a)axialpressure
variation(b)offaxispressure
variation.

1.5
RectangularSources.
Theradialsymmetryassociatedwithbothplaneandsphericallyfocusedcircularsourceshasaparticulareffectonthebeamsproduced,particularlyalongthebeam
axis.Thisistruewhethersinglefrequencyorimpulsebehaviourisconsidered,andalsoforpracticalapplicationsusingbroadbandpulses.Anyalterationfromthe
circularsymmetryofthesourceservestoalterthegeometricconditionsandhencethebeam.Ofparticularpracticalinterestformedicalapplicationsisthebehaviourof
rectangularsourcesofultrasound,becauseoftheircommonuseinthearraysusedfordiagnosticimagingandassociatedDopplerapplications.Thedesignand
fabricationofsucharraysisdescribedingreaterdetailinChapter5.Herewewillbeconcernedonlywiththetheoreticalconsiderationsoftheacousticbeams
generatedbysuchrectangularsourcesofultrasound.
Whilecircularlysymmetricbeamsmaybeanalysedintermsofonlytwo(rectangular)coordinates(y,z),anyothershapeofsource,includingrectangular,requires
three(x,y,z)(figure1.11).Insimpletermsthebeamformation,bothintermsofthelengthofthenearfieldandthedivergenceinthefarfield,iscontrolledseparately
bythetwoorthogonaldimensionsofthesource,2aand2b.Ifa<<bthentherewillbeashorterregionin

Page18

Figure1.11.
Coordinatesystemforarectangularsource.

whichthereisoffaxisamplitudemodulationintheydirectionthaninthexdirection,andthebeamwilldivergemorestronglybeyondthisregion.Ifa=b,thesource
willbehavesomewhatlikeacircularsourcewithradiusa,andtherewillbeamaximumontheaxisatz a2/ ,althoughthenearfieldamplitudemodulationwillnotbe
sopronounced.
Figure1.11showsanobservationpointOat(x,y,z)andasourceelementdS=dx 0dy0at(x 0,y0).Geometricconsiderationsgive
(r')2=z2+(xx 0)2+(yy0)2
andusingabinomialexpansionr'canbeapproximatedby

Further,substitutingintheequationfortheRayleighintegral(equation(1.4))andreplacingthe1/r'termwith1/rwehave

Substitutingg=x 0 (2/z )g0=b (2/z )h=y0 (2/z )h0=a (2/z )anddefiningtheaspectratiooftherectangleN=a/bsoh0=b/N (2/z )wehaveonaxis

Page19

Figure1.12.
Axialvariationinnormalisedacoustic
pressureamplitude(p/p0)forasquare
transducer.Comparewithfigure1.3fora
circularsource.

Figure1.13.
Axialvariationinnormalisedacoustic
pressure(p/p0)forarectangularsource
withaspectratio1:2.

Thetwointegralsontherighthandsideofequation(1.23)giveanamplitudedependencyonb2/z anda2/z .Therelativelocationsoftheacousticfeaturesinthe

beamwilldependontheaspectratioN.
Thecalculatedaxialpressurevariationisshownforasquaretransducerinfigure1.12andforarectangularaperturewithaspectratioN=1:2infigure1.13.Pressure
maximaandminimavariationsarereducedforthesquaretransducer,andlargelyabsentfortherectangulartransducer.Inadditionthemaximumpressureamplitudeon
axisislessthan2p0,whichisreachedtheoreticallyontheaxisinthenearfieldofaplanecircularsource.
Figure1.14showsthepulsepressureprofileat40mmfromasquare

Page20

Figure1.14.
Calculatedpulsepressureprofilefor
asquarepistonsource,side2a=16mm,
vibratingwithonecycleat4MHz.c=
1500ms1z=40mm.Compare
withfigure1.6.

source,a=8mm,operatingforasinglecycleat4MHz,calculatedusingtheimpulseresponsefunctionderivedbyLockwoodandWillette(1973).Theconditions
arethesameasthoseusedtocalculatetheprofileshowninfigure1.6foracircularsource,withwhichcomparisonmaybemade.Thisshowsthepresenceoffurther
replicapulsesbeingcausedbytheedgewavesfromeachofthefouredgesofthesource.
Medicalultrasonicscannersnotonlyuserectangulartransducers,butapplyastigmatic(cylindrical)focusing.Theanalysisofthesefocusedpulsedfieldsmustbecarried
outusingnumericalmethodssuchasthefinitedifferencemethodswhichwerementionedabove.
1.6
Conclusion
Thischapterhasshownthatitispossibletodescribetheacousticpressurefieldstructurefromavarietyofsourcegeometries,usingappropriateapproximations.The
adventofpowerfulcomputershasenablednumericalmethodstobeappliedtopreviouslyintractableanalyses.Theparticularsymmetryassociatedwiththeacoustic
fieldfromanidealcircularpistonsourcevibratingwithasinglefrequencyisnotsharedbyothermorepractical

Page21

ultrasoundbeamsusedformedicalapplications.Apodisation,pulsingandtheuseofrectangularsourcesallservetosmoothoutthepressurevariations,resultingin
beamswithlowamplitudemodulationinthenearfield,andlowacousticsidelobeamplitudes.Thefullanalysisandpredictionofthefieldgeneratedbyapulsed
rectangularsourcewithastigmaticfocusingandapodisation,propagatingnonlinearlythroughaninhomogeneousabsorbingandscatteringmedium,remainsachallenge.
References
BeaverWL1974SonicnearfieldsofapulsedpistonradiatorJ.Acoust.Soc.Am.5610438
DuGandBreazealeMA1985TheultrasonicfieldofaGaussiantransducerJ.Acoust.Soc.Am.7820836
DuckFA1980ThepulsedultrasonicfieldPhysicalAspectsofMedicalImagingedBMMooresetal(London:Wiley)
DuckFAandMartinK1992Exposurevaluesformedicaldevices,inUltrasonicExposimetryedsMZiskinandPLewin(BocaRaton:CRC)
FriedlanderF1958SoundPulses(Cambridge:CambridgeUniversityPress)
HarrisGR1981aReviewoftransientfieldtheoryforabaffledplanarpistonJ.Acoust.Soc.Am.701020
1981bTransientfieldofabaffledplanarpistonhavinganarbitraryvibrationamplitudedistributionJ.Acoust.Soc.Am.70186204
KinslerLE,FreyP,CoppensABandSandersJV1982FundamentalsofAcoustics3rdedition(NewYork:Wiley)
KossoffG1979AnalysisoffocusingactionofsphericallycurvedtransducersUltrasoundMed.Biol.535965
KrautkramerJandKrautkramerH1990UltrasonicTestingofMaterials4thedition(Berlin:Springer)pp8792
LockwoodJCandWilletteJG1973HighspeedmethodforcomputingtheexactsolutionforthepressurevariationsinthenearfieldofabaffledpistonJ.Acoust.
Soc.Am.5373541
LucasBGandMuirTG1982ThefieldofafocusingsourceJ.Acoust.Soc.Am.72128996
O'NeilHT1949TheoryoffocusingradiatorsJ.Acoust.Soc.Am.2151626
PapadakisEPandFowlerKA1971Broadbandtransducers:radiationfieldandselectedapplicationsJ.Acoust.Soc.Am.5072945
PattersonMSandFosterSF1982AcousticfieldsofconicalradiatorsIEEETrans.SonicsUltrasonicsFreq.Contr.SU298392
PenttinenAandLuukkalaM1976aTheimpulseresponseandpressurenearfieldofacurvedultrasonicradiatorJ.Phys.D:Appl.Phys.9154757
1976bSoundpressurenearthefocalareaofanultrasoniclensJ.Phys.D:Appl.Phys.9192736
SchochA1941BetrachtungenuberdasSchallfeldeinerKolbenmembranAkust.Z.631826
StepanishenPR1971TransientradiationfrompistonsinaninfiniteplanarbaffleJ.Acoust.Soc.Am.49162938
1974AcoustictransientsinthefarfieldofabaffledcircularpistonusingtheimpulseresponseapproachJ.SoundVibr.32295310

Page22

StepanishenPRandBenjaminKC1982ForwardandbackwardprojectionofacousticfieldsusingFFTmethodsJ.Acoust.Soc.Am.7180312
WeightJPandHaymanAJ1978ObservationsofthepropagationofveryshortultrasonicpulsesandtheirreflectionbysmalltargetsJ.Acoust.Soc.Am.63396
404
WellsPNT1977BiomedicalUltrasonics(London:Academic)
WilliamsEGandMaynardJD1982NumericalevaluationoftheRayleighintegralforplanarradiatorsusingtheFFTJ.Acoust.Soc.Am.72202030
ZemanekJ1971BeambehaviourwithinthenearfieldofavibratingpistonJ.Acoust.Soc.Am.4918191

Page23

Chapter2
NonlinearEffectsinUltrasoundPropagation
AndrewCBaker
Introduction
Inafluid,ultrasoundpropagatesaslongitudinalwavesofalternatecompressionsandrarefactions.Toafirstapproximationthewavetravelsataconstantspeed(c)
andsoitsshaperemainsunchangedasitpropagates.Thislevelofapproximationcorrespondstothesimplestpossibleformofwaveequationandiswidelyapplicable
tomanyacousticsystems(e.g.normalsoundlevelsinairandmostsonarsystemsinwater).Themethodsoflinearsystemstheoryareappropriatetothesolutionsof
problemsinthesefieldsandgreatuseismadeofmethodssuchassuperpositionandlinearscalingofsolutions.Theintroductionofafrequencydependentabsorption
causesnogreatdifficultieseithersincethesystemislinear.Thelinearwaveequationdependsontwomainassumptions:firstlythattheparticlevelocity(u)ofthewave
isinfinitesimal(oratleastsmallcomparedtoc)andsecondlythatthepressuredensityrelationshipofthefluidislinear.
Iftheacousticamplitudeissufficientlyhighthenassumptionsoflinearityarenolongervalidandwillintroducesignificanterrors.Theresultingwavehascompressional
phasesthattravelataspeed(c+ u0),whichisfasterthanthespeedoftherarefactions(c u0) isaparametercharacterisingthenonlinearityofthemedium(the
nonlinearityparameterisoftenexpressedasB/A=2( 1):measurementmethodsandtypicalvaluesaregiveninChapter4).Notethatthefiniteparticlevelocityand
thenonlinearityofmediumbothproducethesameeffect.Thuswegetdistortionthatwillcauseawaveformthatisinitiallysinusoidaltobecomemorelikeasawtooth
(figure2.1).Theamountofdistortionwillincreasewithdistancepropagatedandshocklikewaveformsarecommonlyencountered,withanabruptincreasefrompeak
negativepressuretopeakpositivepressureasthewavepassesanypoint.Intermsoffrequencycontent,thewaveform

Page24

Figure2.1.
Initialwaveform(top, =0)
anddistortedwaveform(bottom,
= /2).

distortionisequivalenttoharmonicgenerationatintegermultiplesoftheoriginalfrequency.Thusenergyispumpedtohigherfrequencieswheretheabsorptionlosses
willbehighercausing,amongotherthings,increasedintensitylosswhichcanleadtoenhancedheatingandstreamingeffects.Inarealbeamofultrasoundtherewill
alsobediffractioneffectswhichinteractwithnonlinearityandabsorptiontofurthercomplicatematters.Ageneralhistoryofnonlinearityinfluidscanbefoundinthe
bookbyBeyer(1984).
2.1
NonlinearPropagationinMedicalUltrasound
Theuseofultrasoundinmedicineonlybecomeprevalentduringthe1960sandalthoughnonlinearacousticeffectshavebeenknownaboutsincetheeighteenth
century,itwas1980whenthefirstpapershighlightedtheimportanceofnonlineareffectsinmedicalultrasound.MuirandCarstensen(1980)andCarstensenetal
(1980)discussedthepotentialforshockformation,enhancedabsorptionduetoharmonicgenerationandbeambroadening,causedbythetransferofenergyfromthe
mainlobeofthefundamentalbeamtohigherharmonics.Oneofthemeasuresofthestrengthofnonlinearitytheyusedwastheplanewaveshockparameter = kz,
(=u0/c)istheacousticMachnumberwhereu0istheparticlevelocityamplitudeatthesource,k(=2 f/c)isthewavenumberandzisthedistance

Page25

thatthewavehastravelled.Avalueof =1indicatesthatashockisjuststartingtoform(i.e.averticaldiscontinuityisjustappearinginthepressurewaveform).At
thispointthedistancetravelled(z)isoftendenotedbytheplanewaveshockdistanceld=1/ k.Inthecaseofaplanewave,u0canbedeterminedfromtheacoustic
pressureamplitude,p0,usingtheplanewaveimpedancerelationu0=p0/p0cwherep0isthedensityofthemedium.When = /2thewaveisfullyshocked,witha
discontinuityfromthepeakpositivepressuretothepeaknegativepressure(figure2.1).Furtherdistortionleadstoreductionsofthepeakpositiveandnegative
pressuresasmoreofthewavemovesintotheshockedregion.Notethat isproportionaltoboththeacousticpressure(p0)andthedistancetravelled(z)henceitis
possibletodetermineexperimentallywhethernonlinearpropagationisoccurringinasystembynotingwhetherwaveformdistortiondecreasesaseitherdrivepressure
and/orobservationdistanceisdecreased.Inwaterat20C, =3.5,henceifwetakeultrasonicparametersthataretypicalofcurrentimagingsystems(e.g.f=3.5
MHz,p0=1MPaseeChapter7)wewillhaveaplanewaveshockdistanceld=43mm(assumingp=1000kgm3andc=1486ms1).Wewouldtherefore
expecttoobservenonlinearwaveformdistortionrelativelyeasilyatdistancesgreaterthanthis.Itshouldbenotedthatinclinicalsystemsfocusinganddiffractionwill
alsoaffecttheshockformationdistancesoldshouldonlybeusedasaroughestimateofnonlineareffectsinclinicalbeams.
Thesituationissimilarinhumantissueswhere valuesaretypicallyintherange4to6(Duck1990)withthehighervaluesduetofattytissues.However,attenuation
lossesarehigherintissuewhichtendstocounteractnonlineardistortion.ThisisindicatedbytheGol'dbergnumber =1/ld = k/ where isthelinearattenuation
coefficient(inneperm1).TheGol'dbergnumberaccountsforthefactthatabsorptioncounteractsnonlineargenerationsoitistheratioofthetwowhichisimportant.
MethodsofmeasuringthenonlinearityparameterandthepossibilityofmappingittoforminvivoimageshavebeenreviewedbyBjrn(1986).
Figure2.2representsthenonlinearpropagationofa3.5MHz,500kPaplanewaveinwater(i.e.theGol'dbergnumber =38).Wecanseethatatzerorangeonly
thefundamentalispresent.Theharmonicsbuildupwithdistanceandeventuallysettleinalmostconstantratiotothefundamental.Energyislostfromthefundamental
andispumpedintotheharmonics.Inthecaseofalinearwavewewouldexpectnoharmonicsandthefundamentaltoremainalmostconstantlinearabsorptionwould
onlyaccountforalossofafewpercentoverthissortofdistanceinwater.Arangeof85mmcorrespondsto =1forthiswaveanditcanbeseenthatthereis
appreciablesecondandthirdharmoniccontent.Onlythefirstfiveharmonicsareplottedherealthoughmanymorewillbepresentespeciallyatlongerranges.Ata
rangeof133mmwehave = /2andappreciableenergyhasbeenlostfromthefundamentaltothehigherharmonics.

Page26

Figure2.2.
Fundamentalandsecondtofifthharmonicsfor
anonlinearplanewaveinwater(f0=3.5MHz,
P0=500kPa, =38).

isausefulquantitywhentryingtoestimatethesignificanceofnonlinearityinagivensituationbutaplanewaverepresentsaratheridealisedcase.Inanattemptto
includetheeffectsoffocusing,Bacon(1984)proposedanonlinearpropogationparameter( m )whichtakesaccountofamplitudefocalgainG:

wherethefocalpressurepfisdefinedas(pc+pr)/2(pcandprarecompressionandrarefactionpressuremagnitudesatthefocaldistancezf),andfistheacoustic
frequency.Thisequationcanbeusedalsotocalculate atthefocusupto = /2.Abovethisvalue m nolongerdependslinearlyonsourceamplitude,andultimately
reachesasaturationvalueof2 .
Theinclusionofdiffractionandfocusinginthenonlinearproblemcausesphaseshiftsinwaveformsothatinsteadofresemblingasawtooth,anonlinearlydistorted
ultrasonicpulselooksmorelikethemeasurementsshowninfigure2.3.Thewaveformshownisarelativelylowamplitude2.25MHzpulsegeneratedbyaheavily
damped,shockexcitedtransducer.Thediffractivephaseshiftscausethetopbottomasymmetryofthedistortedpulse.
Diagnosticultrasoundtendstooperateovershorterdistancesthan600mmbutwithcorrespondinglyhigherdrivelevelsandfocusinggain,hencethedistorted
waveformshapeistypicalofthedistortedpulsesobservedfromclinicalsystems(DuckandStarritt1984).Eventhehighabsorptionoftissueisnotsufficientto
suppressnonlinearityhencesimilarwaveformdistortionandharmonicgenerationhavebeenobservedinbiologicaltissues(Starrittetal1985,1986).Anextensive
surveyoftheoutputofdiagnosticsystems(Ducketal1985)showedthatalmostallthesystemssurveyedwerelikelytobesubjecttononlinearpropagation.Amore
recentsurvey(Henderson

Page27

Figure2.3.
Initialpulse(top)andnonlineardistortion
ofpulse(bottom)afterpropagating600mm
inwater.

etal1995)indicatedthattheacousticoutputlevelsofnewdiagnosticsystemshadincreasedconsiderablyandthusnonlineareffectsarenowevenmoresignificant.
Othermedicalultrasoundsystemssuchaslithotriptersandhyperthermiasystemswillalsobesubjecttononlinearpropagationsincealthoughtheyusuallyhavelower
fundamentalfrequenciestheyalsohavehighacousticdrivelevels.
2.2
ConsequencesofNonlinearPropagation
2.2.1
ExperimentalMeasurements
Themostobviouspracticalconsequenceofnonlinearpropagationisthatanincreasedmeasurementbandwidthisnecessary.Thisistruebothforacousticfield
measurementswithhydrophones(seeChapter7)andforpulseechoimagingofharmonicbackscatterasisusedclinically,forexampleinharmonicimagingofcontrast
materials(seeChapter12).Figure2.4showsthefrequencycontentofthepulsesinfigure2.3.Theinitialpulsehasitsenergyconcentratedaroundthecentrefrequency
ofthetransducer(2.25MHz

Page28

Figure2.4.
Initialspectrum(top)andspectrum
ofdistortedpulse(bottom).

inthiscase).Thegrowthofdistortionleadstopeaksatmultiplesofthecentrefrequencyuptoabout25MHzwherethehydrophonebandwidthstartstolimitthe
widthofthespectrum.ThehydrophoneusedinthiscasewasaGECMarconibilaminarPVDF(polyvinylidenefluoride)membranedevicewhichhasasmooth
responseuptoitsmainresonanceatabout20MHz.Othervariantsofthisdevicehaveahigherresonantfrequencyprovidingevengreaterbandwidth(Bacon1982).
Untilthemembranehydrophonewasdevelopeditwasdifficulttoobservethedistortedwaveformsproducedbymedicalultrasoundsystems.In1980itwasnotedthat
'Althoughmicroprobeswithaflatresponseto10MHzhavebeenreported,theyaredifficulttoconstructandarenotcommerciallyavailable'(Carstensenetal1980).
ThechoiceofhydrophoneisanimportantonewhendealingwithsuchdistortedwaveformsandfewdevicescancurrentlyapproachtheGECMarconimembranein
termsofthewidthandsmoothnessoftheiroperationalfrequencyrange.Inrecentyearsthoughtherehavebeensomeimprovementsinneedleprobehydrophone
design,andthesedevicesusuallyhaveasignificantpriceadvantageovertheGECMarconimembranehydrophone.Neverthelessitisrecognisedthatthefrequency
responsemaybequitevariable,particularlyatlowerfrequencies,andneedlehydrophonesneedto

Page29

beusedcriticallyifhighfidelitymeasurementsarerequired(Preston1991).
Severalfactorsareimportantwhenhandlingdistortedwaveformsofthistypeincluding:
2.2.1.1
SystemBandwidth.
Thelossofhighfrequencycomponentsduetolimitedhydrophonebandwidth(orlimitedbandwidthinanypartofthesignalprocessingsystem)isparticularly
noticeableintheobservedpeakpositivepressurewhichcanappeartobesignificantlyreduced.Thechoiceofdigitisingfrequencymustalsobeappropriatetothe
systembandwidth.Itiscommontousedigitisingfrequenciesof100MHzorhigherforthecaptureoftypicalmedicalimagingpulseswhichhavetheircentre
frequenciesinthelowMHzrange.Caremustalsobetakentoavoidaliasingindigitisers.
2.2.1.2
HydrophoneCalibrationandFrequencyResponse
Thepresenceofnonlinearitymeansthatmeasurementscannotbescaledfromonedriveleveltoanother.Inalinearsystem,forexample,thedirectivityplotofan
acousticbeamdoesnotchangewithdrivelevelundernonlinearconditionsitwillchangewithdrivelevel.Itisthereforeusefultoknowtheacousticpressureatwhich
measurementsweremade.Thehydrophonecalibrationisalsoimportantinremovingwaveformartefactsduetohydrophoneresonances.Thefrequencyresponseofa
hydrophoneisusuallydeterminedbyoneormoreofitselectromechanicalresonanceswhichmaynotbeapparentinundistortedwaveforms.Adistortedwaveform
howevercanhavesufficientenergyathigherfrequenciestoexcitethehydrophoneresonanceshencetheobservedelectricalsignalisnotatruerepresentationofthe
pressurewaveformbeingmeasured.Itishardlyeverjustifiabletouseasinglefrequencycalibrationoverthebandwidthsrequired.
2.2.1.3
HydrophoneSize
Theharmonicbeampatternsarenarrowerthanthefundamentalbeam(figure2.5).Thusahydrophonechosentobesmallenoughtoavoidspatialaveragingproblems
atthefundamentalfrequencymaywellberatherlargeincomparisonwiththehigherharmonicbeams.Thiswillleadtounderestimatesofthepeakvalues(Smith1989,
ZeqiriandBond1992,Bakeretal1996).
2.2.1.4
HydrophoneAlignment
Thenarrowerbeamwidthsoftheharmonicsmakehydrophonealignmentmorecritical.Theharmonicamplitudebeamwidthsvaryas
wherenistheharmonic
number(ReillyandParker1989).Thehigherharmonics,however,canprovideausefulguidetoalignmentsincethepeakpositivepressureissensitivetotheir
presence.
2.2.1.5
HydrophoneLinearity
Theacousticpressuresaresufficientlyhighthatthehydrophoneitselfcangenerateharmoniccomponents.Themagnitudeofthesecomponentswillonlydependonthe
amplitudeof

Page30

Figure2.5.
Calculatedharmonicbeampatternsinfocal
planeoffocusedtransducer(f0=2.25MHz).

acousticfieldbeingmeasuredwhereasnonlinearityduetopropagationalsoaccumulateswithdistance.Itisthuspossibletodistinguishbetweenthesetwosourcesof
nonlinearitybymovingthehydrophoneclosetotheultrasonicsourcewherethepropagationnonlinearityshouldbenegligible.Careisstillneededastheultrasonic
sourcewilloftentransmitlowlevelsofharmonicdirectly.Theeffectofhydrophonenonlinearityanddirecttransmissionofharmonicsisnotusuallyserioussincethe
levelsaresmallincomparisonwiththeharmoniclevelsgeneratedbynonlinearpropagation(Prestonetal1983).
2.2.1.6
ChoiceofPropagatingMedium
Laboratorymeasurementsareinvariablymadeinwater,butthiscancreatedifficulties.Theabsorptionofultrasoundinwaterislow(relativetotissue)whichallowsa
greaterdegreeofnonlineardistortiontooccurandhenceincreasedsignalbandwidth.Itisnotasimplemattertotranslatewaterbasedmeasurementstoinvivo
values.The'derating'procedurewhichiscommonlyusedinstandards(AIUM/NEMA1992)isbasedonassumptionsoflinearpropagation.Christopherand
Carstensen(1996)concludethatapplyingthelinearderatingfactortostronglyshockedmeasurementsinwatercanleadtosignificantunderestimatesofthepressure
fieldintissue.
Theeffectofnonlinearpropagationcanalsobeobservedinmeasurementsofultrasonicpropertiessuchasabsorptioncoefficientwhichbecomedependentonthe
drivelevelandmeasurementgeometry(Zeqiri1992,Wu1996).Bothofthesestudiesconcludedthatitisadvisabletominimisethetransmitterreceiverseparationand
tokeeptheplanewaveshockparameter 0.1inordertoavoidsignificantnonlinearerrors.
Characteristicsforhydrophonesandguidanceformakingmeasurementsinthisfrequencyrangecanalsobefoundintherelevantinternationalstandards

Page31

(IEC1987,1991,1993)andPreston(1991).OtherpracticalaspectsoftheuseofhydrophonesforexposuremeasurementaregiveninChapter7,section7.7.
2.2.2
TheoreticalPredictions
Theoreticalmodelsforultrasoundpropagationareusefulinthedesignandanalysisofultrasoundsystems,especiallysinceinvivomeasurementsarenoteasytocarry
out.Themaindifficultyinmodellingisthepresenceofnonlinearitywhichrulesoutmostofthemethodsthatareapplicabletolinearsystems.Thecumulativenatureof
thedistortionwithdistanceanditsinteractionwithdiffractionandabsorptionmeanthatitisnotnormallypossibletocalculatetheamplitudeofasinglefieldpointata
distancefromthesourcewithoutcalculatingthefullfieldintheregionbetweenthefieldpointandthesource.Thusstraightforwardanalyticalsolutionscanonlybe
foundforrelativelysimplegeometriesandingeneralitisnecessarytousecomputationallyintensivenumericalmethods.Inadditiontocalculatingtheacousticfield,
thereisalsoarequirementtobeabletopredicteffectssuchasheating,streamingandcavitationsincethesearepotentialsourcesofbioeffectsandwilldependonthe
acousticfield.
Anumberofapproachestopredictingtheultrasonicfieldsofmedicalultrasoundsystemshavebeentriedbutthemethodthathasprobablyreceivedmostattentionto
dateisafinitedifferencesolutiontoanapproximatenonlinearwaveequation.ThewaveequationisknownastheKhokhlovZabolotskayaKuznetsov(orKZK)
equationanditaccountsfornonlinearity,absorptionanddiffraction(Kuznetsov1971).ThemostimportantassumptionintheKZKequation,inthiscontext,isthatthe
acousticenergypropagatesinafairlynarrowbeamthisisknownastheparabolicapproximationortheparaxialapproximation.Theparabolicapproximationisvalid
foracousticsourceswhicharemanywavelengthsacrossandforfieldpointsthatarenottooclosetothesourceortoofaroffaxis.Forcircularsourcesofultrasound
weneed(kra)2>>1whereraisthesourceradiusandtheminimumaxialdistanceisra(kra/2)1/3(NazeTjttaandTjtta1980).Inpractice,formostweaklyfocused
diagnosticbeams,theseconditionsdonotusuallyposeseriousdifficulties.AfinitedifferencesolutionfortheKZKequationwasdescribedbyAanonsen,Barkve,
NazeTjttaandTjttaoftheUniversityofBergen,Norway(Aanonsenetal1984).NazeTjttaandTjttahavebeenresponsiblefordevelopingmuchofthe
mathematicalbackgroundinthefieldofnonlinearsoundbeamstheresultingnumericalsolutionsandcomputerprogramsarenowwidelyknownastheBergencode.
TheapproachusedintheBergencodeistosubstituteaFourierseriesforthetimewaveformintotheKZKequationandsolvetheresultingsetofcoupleddifferential
equationsusingfinitedifferencemethods.
TheBergencodehasbeenappliedtoultrasonicsourcessimilartothosefoundinmedicalsystemsandhasprovedtobeareliablemodelofthebeam

Page32

Figure2.6.
ComparisonoftheKZKequation()withmeasurements
offundamentalandsecond,thirdandfourthharmonics
(+,x,*,)forafocusedultrasoundsourceinwater
(f0=2.25MHz,p0=68kPa,a=19mm).Theverticaldashed
lineindicatesthepositionofthefocalplane.

behaviourinwater.Planecircularsourcesofcontinuouswaveultrasoundhavebeenstudied(Bakeretal1988,TenCate1993,Nachefetal1995)aswellasfocused
sourcesasshowninfigure2.6(Baker1992,AverkiouandHamilton1995).
Figure2.6showsthatclosetothesourcetherearenoharmoniccomponents,onlythefundamental.Theharmonicsbuildupwithaxialrangewithvariousmaximaand
minimamirroringthoseinthefundamentaluntilthefinalaxialmaximasettleatroughlyconstantlevels(approximately1/n)relativetothefundamental.TheKZKsolution
doesnotshowtheexpectednearfieldoscillationsatveryshortranges,thisisaconsequenceofthestepsizeused.Smallerstepswouldhaveshownmoredetailatshort
rangesinsteadweseetheaveragevalueofthesolutioninthatregion.
TheBergencodemayalsobeinitialisedwithapulsespectrumhencepulsedfieldssimilartodiagnosticsystemshavebeenexamined(BakerandHumphrey1992,
Baker1991).Rectangulargeometrieshavealsobeenmodelled(Berntsen1990,Bakeretal1995).TheBergencodehasrecentlybeenappliedtoultrasoundsystems
withrectangulararrays(CahillandBaker1997a,b)anditwasfoundthatnonlinearitycaninteractwithdiffractiontocausetheregionofpeakintensitylosstomove
fromtheacousticaxis(atlowdrivelevels)tooffaxislocationsathighdrivelevels(figure2.7).Thisshiftiscontrarytothepredictionsoflineartheories.Thefirstpart
offigure2.7showsthelinear(lowdrivelevel)pressurefieldofasquareapertureaswouldbe

Page33

Figure2.7.
Nonlineargenerationalongthediagonalofaplanesquareaperture
(sidelength=20mm).Thebeampropagatesdownthepagefora
distanceof200mm(f0=2.25MHz).

measuredacrossitsdiagonaldiffractioneffectsarestrongestonthediagonalduetotheinteractionofedgediffractionfromthetwosides.Itcanbeseenthatinthe
linearcasethepeakamplitudeoccursontheacousticaxisatthebottomoftheplot.Thesecondplotcorrespondstothefundamentalwhenthesourcepressureis
increasedto1MPa.Theregionofpeakfundamentalamplitudenowoccursoffaxisandmuchclosertothesource.Thesecondharmonicisstrongestwherethe
fundamentalisstrongestsoittoohasitspeakvaluesoffaxisnearerthesource.Thesecondharmonicalsoshowstwiceasmanyfringesacrossthebeamwhen
comparedtothefundamentalthiseffectcanbeseeninfigure2.5.Thetenthharmonic(i.e.22.5MHz)hasasharplydefinededgetotheoffaxisregionandagain
exhibitsamaximumamplitudeoffaxis.Thishasconsequencesforthepredictionofpotentialbioeffectssincetheintensitylossfromthebeamdeterminestheheat
sourcedistributionforthermaleffectsandthedrivingforceforstreaming.
Computationalrequirementscanbecomeanissuefornonlinearmodelling.Thecontinuouswavecircularcaseatmoderatedrivelevelscanberunonapersonal
computer(e.g.aPentiumbasedPC)inamatterofminutes.TheBergencode,however,worksinthefrequencydomainandifthedrivelevelisincreased,more
harmonicsareneededinthesolutionwhichrequiresmore

Page34

memoryandmoreCPUtime.Theinclusionofpulsedwaveformsrequiresmorefrequencycomponentsintheinitialspectrumwhichagainrequiresmorememoryand
moreCPUtime.TherectangularcodeisanotherorderofmagnitudebiggerinitsrequirementsformemoryandCPUtime.TheresultsofCahillandBaker(1997b)
requiredabout500MBphysicalmemoryandtookoftheorderof40hoursCPUperrunonaDECAlpha8400computer.Somesavingsincomputereffortwere
madebyintroducinganartificiallyhighabsorptionfactorforthehighestharmonicswhichcanreducethetotalnumberofharmonicsrequiredinthesolution.Fourier
transformmethodsalsoenabledconsiderableCPUtimesavingsbycalculatingthenonlinearinteractionsinthetimedomain.Spatialresolutionsometimeshastobe
tradedforsavingsinruntime:themorecloselyspacedthegridpointsinthefinitedifferencescheme,themorememoryandCPUtimethatisrequired.
ApartfromtheBergencodeanumberofothermethodsofsolutionarealsofeasible.ChristopherandParker(1991)havedemonstratedanonlinearmodelwhich
operatesinthefrequencydomainbutusesaspatialFouriertransformmethodtocalculatediffractioneffects.Itisclaimedthatithasnorestrictionsonthepositionsof
fieldpointsanditsuseforlithotriptermodellinghasbeendemonstrated(Christopher1994).CurrentlythemaindrawbackoftheChristopherandParkermodel
appearstobeitslackofasinglemathematicalbasis.TheuseofFouriertransformmethodsfordealingwithdiffractioniswellestablishedbuttheinclusionof
nonlinearitydoesnotappeartohavebeenfullyjustifiedmathematically.
Othershavedevelopednonlinearsolutionswhichoperateentirelyinthetimedomain(Clevelandetal1996,LeeandHamilton1995).Timedomainmodelshavethe
advantagethatnonlineardistortionandpulsedfieldscanbeaccountedformoreeasilyhowever,attenuationbecomesaconvolutionoperatorinsteadofasimple
multiplyingfactorinthefrequencydomain.
Allnonlinearmodellingmethodsrequirethepropertiesofthemediumtobeknownoverawidefrequencyrangethisposesseriousrestrictionsforallbiologicaltissues
andfluids.Theonlymediumthatcouldbesaidtobewellcharacterisediswater.Currentlythemostcomprehensivecatalogueofacousticpropertiesofbiological
mediaisthatofDuck(1990)butevencommonlyusedultrasoundpathssuchasurineandamnioticfluidarerepresentedbyonlyafewdatapoints.Furtheruncertainty
arisessincemanyofthosemeasurementsweremadeatatimewhentheimportanceofnonlinearpropagationinmakingabsorptionmeasurementswasnotwidely
appreciated.
2.2.3
ClinicalSystems
Inpracticenonlinearitycanhaveanumberofbothusefulandunwantedsideeffectsfortheultrasoundsystem.Allclinicalultrasoundsystems(diagnosticand
therapeutic)areliabletosufferfromenhancedabsorptiondueto

Page35

Figure2.8.
Theeffectofnonlinearityonthepatternofintensityloss
forafocusedcircularsource.Thebeampropagates
downthepage(f0=2.25MHz,a=19mm,gain=6).

nonlinearitywhichcanleadtoacousticsaturation.Inasystemthathasbecomesaturatedanincreaseinacousticdriveleveldoesnotleadtoanincreaseintheacoustic
pressureatsomedistantfieldpoint.Theextraenergyisconvertedtoharmonicfrequenciesandbecomesabsorbed.Thesameeffectcanleadtoincreasedsidelobe
levelsasthemainlobeofthebeamwillsaturatebeforethesidelobeswhichhaveloweracousticamplitudes.Theenergypumpedintotheharmonicswillhaveagreater
contributiontobioeffectmechanismssuchasheating(BaconandCarstensen1990)andstreaming(Starrittetal1989).Anexampleofnonlinearpropagationis
observedinultrasonicsurgery(Watkinetal1996)wherethelesionsaregeneratedclosertotheultrasoundsourceasthedrivelevelisincreased.Anexplanationof
thiscanbeseeninfigure2.8.whichshowsthespatialdistributioninafocusedfieldoftherateofintensityloss I/ z
nthharmoniccomponent

wherepnistheamplitudeofthe

Page36

andmisthetotalnumberofharmonicsgenerated.Thisquantitycanbeconsideredasthesourcetermforthermalcalculations(orthedrivingforceforstreaming).
Whereasthemeasurementofalltheharmoniccomponentsoveranentirepressurefieldwouldbeverytimeconsuming,anumericalmodelcangeneratethesedata
relativelyeasily.Infigure2.8thesourceis38mmindiameterandispositionedatthetopofeachplot,thewidthoftheplotsisequaltothesourcediameterandthe
propagatingmediumiswater.Atthelowestdrivelevel(10kPa)theintensitylossfollowsthesamepatternasthelinearintensityplot.At100kPatheregionof
intensitylossismuchnarrowerandpeaksatagreateraxialrange.Notethateachplotisnormalisedtoitsmaximumintensitylossandthetotalintensitylossinthe
secondplotismuchhigherthanthefirstanditsspatialdistributionhaschanged.Atthehighestdrivelevel(200kPa)thepositionofpeaklosshasmovedevencloserto
thesource.Correspondingobservationsoftheshiftofpeakstreamingvelocity(Starrittetal1989)canbeexplainedbythesamemechanism(Baker1997).
Therearehoweverseveralpotentialbenefitsmanyofwhichcanbeachievedwithoutfurtherincreaseinultrasonicdrivelevels.Mostcurrentimagingsystemsusethe
sametransducerelementstotransmitandreceiveandthebandwidthisnotsufficienttocapturetheharmonicfrequenciespresentinthereturningecho.Animaging
systemwithawidebandreceivingarraywouldhavetheadvantageofhighersignaltonoiseratioandbetterresolutionduetotheinclusionoftheharmonics(Wardetal
1996,1997).Suchsystemsarenowbecomingwidelyavailablecommerciallyassocalled'harmonicimaging'modesonclinicalscanners.Evidenceofimproved
signaltoclutterratioshasbeenreportedduringtheirapplication.Muchinteresthasarisenrecentlyfromtheuseofultrasoniccontrastmediaincludingsecondharmonic
imaging,anditsbenefitsarebeingdemonstratedclinically.Nonlinearimageenhancementhasalsobeendemonstratedinthefieldofacousticmicroscopy.Calibration
techniqueshavealsobeenbasedonnonlinearpropagationwheretheincreasedsignalbandwidthisusedtocalibrateahydrophoneatseveralfrequenciesinasingleset
ofmeasurements(SmithandBacon1990).
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&NEMA)
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Page37

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Page38

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180921

Page39

Chapter3
RadiationPressureandAcousticStreaming
FrancisADuck
Introduction
Thischapterdealswithtwolinkedbutseparatephenomena,radiationforceandacousticstreaming,bothofwhichhavesomepracticalimportanceinmedical
applicationsofultrasound.Wewillstartwithsimplequalitativedescriptionsofthesephenomena,beforegivinganoutlineoftheirtheoreticalbasis,thendiscusssome
reportsintheliteratureoftheirappearanceinamedicalcontext,andspeculateaboutthedifficultiesstillremaining.
Whenasolidobjectisplacedinaprogressiveultrasoundwaveitexperiencesasmallforcewhichisdirectedalongthebeaminthedirectionofpropagation.Thisis
calledtheradiationforce.Ifthesolidtargetislargerthanthebeam,thisforceisproportionaltothetotalacousticpower.Asaresult,radiationforcehasbeenusedas
thebasisofwellestablishedmethodsformeasuringacousticpower.Whenanultrasoundwavepropagatesinafluid(liquidorgas),thefluidwithinthebeamflows
awayfromthetransducerinthedirectionofpropagation.Thisiscalledacousticstreaming.(Insomeoldertextsitisreferredtoas'quartzwind'.)
Thesetwophenomenabothexistbecauseoftheinherentnonlinearityofacousticwavepropagationinrealmedia.Whilethemagnitudeoftheforceonthetarget,orof
thestreamingvelocity,alsodependonanumberofotherfactors(absorptionandreflectioncoefficient,geometryofthebeamandtarget/containerandsoon)
streamingandradiationforcewouldnotexistifpressureanddensitywerelinearlyrelated(Beyer1997).
3.1
RadiationPressure
Thelinkbetweenradiationforceandacousticstreamingliesintheconceptofradiationpressure(Beyer1950,Borgnis1953,Beissner1985).Notethat

Page40

theradiationpressuredoesnotvarywithtimeinacontinuouswavebeam,unliketheacousticpressure.Itisasteady'dc'stresswhicharisesfromnonlinear
propagationeffects.
Thereareanumberofconfusionsintheliteratureinthediscussionsofradiationpressure,andthedetailsofthedebatewillnotbeenteredintohere.Whatisimportant
isabroadunderstandingofthephenomena,andapragmaticapproachtothemathematicswhichallowsthegeneralconceptstobelaiddownandsomeusefulresults
tobeseen.Thefirstsourceofconfusionstemsfromtheuseofthesameterm'radiationpressure'tomeantwodifferentthings.Thefirsthastodowiththeobserved
radiationforcewhichisexperiencedbyawallorinterfaceinabeamofsound,andisdeterminedbythewavealone.ThisistheLangevinradiationpressure.The
secondisduetoLordRayleigh,andhastodowiththefieldanditsconstraints.
3.2
LangevinRadiationPressure,PLan
TheLangevinradiationpressureisdefinedasthedifferencebetweenthemeanpressureatareflectingorabsorbingwallandthepressureimmediatelybehindthe
wall.Thederivationofthispressurehasbeendealtwithbyseveralauthors(see,forexample,HueterandBolt1955).Whilethepressurederivesfromtheinherent
nonlinearityofacousticwavepropagation,theradiationpressurePLanmaybeexpressedverysimply.
Foraplanewaveimpingingnormallyonaperfectabsorbertheradiationpressureonthesurfaceisequalinvaluetothetimeaveragedenergydensity E0 atthe
surface,orthetotalenergyperunitvolume,

wherep0isthepressureamplitudeofthewave, 0thefluiddensity,andcthesoundspeed.Iistheintensityofthewave.Inarealbeamthesurfaceofatargetwill
experiencearadiationpressurefieldwhichwillextendoveritssurfacewithaprofileidenticaltothe2Dintensityprofileofthebeam.
Ifthedimensionsofthetargetextendbeyondtheboundaryofthebeam,theradiationforceFonthetargetisgivenbytheintegraloftheradiationpressureoverthe
targetarea,S.Foranabsorbingtargettheforceis

whereWisthetotalacousticpower.Theradiationforceonthetargetisthereforeameasureofthetotalpowerinthebeam,theconstantofproportionalitybeingthe
acousticvelocityinthefluid.

Page41
Table3.1.ExamplesofradiationpressureforplanewaveswithenergydensityE0.

Physicalsituation

Energydensities
atinterface

Perfectabsorbernormaltosoundbeam

Front:E1=E0

CoefficientD
Radiationforce
F=DE0S
D=1

Back:E2=0
Perfectreflectornormaltosoundbeam

Front:E1=2E0

D=2

Back:E2=0
Perfectreflectoratangle tothebeam

Front:E1=2E0

D=2cos2

Back:E2=0
Nonreflectinginterfacenormaltobeam: Front:E1=E0
c1 c2
Back:E2=E0(1D)
Absorbingmedium,nointerface,Iz=
I0e2az( =amplitudeattenuation
coefficient)

(dE/dz)z=(dIz/dz)/c

D=1c1/c2forc1<c2,forceawayfrom
sourceforc1>c2,forcetowardssource
D=2 (dE/dz)=EzDCauses
streaminginfluidmedium

Inpracticetheproportionalitydependsnotonlyonthesoundspeedbutalsoonthesurfacematerialanditsreflectionorabsorptionproperties,andonthegeometryof
thesurface.Thecoefficientsforseveralsituationsaresetoutintable3.1.Anumberofdetailsaboutradiationpressureandforceshouldbenotedrelatingtotable3.1.
Firstlyatotallyreflectinginterfacedoublestheenergydensityatthesurfaceintheliquid,sodoublingtheforceonthetarget.ForatotallyabsorbingtargetD=1inthe
directionofthebeam,forallanglesofincidence.However,ifthebeamisincidentatanangle tothenormal,thecoefficientfortheradiationforcenormaltothe
surfaceiscos .Aradiationforcebalancewithanabsorbingtargetwillstillthereforebedependentontheangleofincidence(seeChapter7forfurtherremarkson
radiationforcebalances).
Theradiationforceexertedonawater/airinterfaceissufficienttoraisethewatersurfaceuntiltheheightisbalancedbythehydrostaticpressureinthecolumn
produced.Thisgeneratesasocalledacousticfountain.Theheightoftheliquidcolumnisgivenapproximatelyby

whereIisintensity, 0istheliquiddensity,cthespeedofsoundandgtheaccelerationduetogravity.Itshouldbenotedthattheprocessgeneratingthissurface
elevationisdistinctfromthatgeneratingstreaming,whichisdiscussedbelow.

Page42
Table3.2.Estimatedradiationforcesandpressuresina3MHzpulsedbeam,Ita1Wcm2andIpa500mWcm2,
beamarea10mm2.
Totallyabsorbingsurface

Timeaverageforce

65N

Timeaverageradiationpressure

6.5Pa

Pulseaverageforce

32.5mN

Pulseaverageradiationpressure

3.25kPa

Tissuelikeattenuatingmedium
Timeaverageforcegradient

0.2Nmm1

Timeaverageradiationpressuregradient

0.02Pamm1

Pulseaverageforcegradient

0.1mNmm1

Pulseaverageradiationpressuregradient

10Pamm1

Theradiationpressureonaninterfacebetweentwomediawithdifferentacousticspeeds,butzerotransmissionloss,causesainterestingresult.Whenc1>c2,the
radiationforceisbackwardstowardsthetransducer.Thiscounterintuitiveresultoccursbecausetheforceistowardstheregionoflowerenergydensity.Particularly
strongexamplesofthiseffectareshownbyBeyer(1978)andmorerecentlybyHertz(1993)forwater/carbontetrachloride,andwater/anilineinterfaces.
Thefinalexampleintable3.1notesthatitispossibletoextendthesimpleanalysistoincludepropagationthroughauniformattenuatingmedium.Underthese
conditionstheradiationpressureonanelementofthemediumdependsonitsattenuationcoefficient.Sincethereisnointerfacebetweenmedia,aradiationforceper
unitvolumeiscalculated.Thisisequivalenttoaradiationpressuregradientinthedirectionofthebeam.
Formeasurementsinwatertheradiationforceonanabsorbingtargetinabeamof1watttotalacousticpowerwouldbebalancedbyamassofapproximately69mg.
Diagnosticbeamshaveacousticpowerswhicharetypicallyintherange1200mW,andthereforeradiationforcebalancesofthetypedescribedinChapter7mustbe
verydelicatetoallowaccuratemeasurement.Table3.2givesestimatesofforces,pressuresandpressuregradientsinatypicaldiagnosticbeam,forbothtimeaverage
andpulseaveragecalculations.

Page43

3.3
RadiationStressTensor
Thesimpleanalysiswhichleadstoanequivalencebetweenradiationpressureandscaledenergydensityhassignificantdeficiencies,however.Oneexampleisthe
failuretoexplainwhytheforceonatargetalterswiththeanglebetweenthebeamandsurface(Herrey1955).Theradiationpressurecalculatedinthesimpleway
describedaboveisascalarquantity,andthusoperatesnormallyonasurface.Itisunfortunatethattheword'pressure'hasbeenusedtodescribewhatisstrictlya
stresstensor(Beyer1978,Brillouin1964).
TheproperrepresentationofthestressexertedonamediumsupportinganacousticwaveisbymeansoftheradiationstresstensorSij.Foraplanewave
propagatinginalosslessmediumthisis

where
isthetimeaveragedparticlevelocityproduct.Thesequantitiesaresecondorderquantities,andarenonzeroatthenonlinearlevel. ijisthe
Kroneckerdelta.Soforasoundwavetravellinginthexdirectionthestresstensoris

Thesignnotationusedreflectstheconventionthatatensionispositiveandacompressionnegative.
Thestresstensorisseentocomprisetwoelements:thetimeaveragedexcesspressureandtheterm
themomentumdensity 0u.

u2 .Thesecondtermrepresentsthetimeaveragedtransportof

3.3.1
TheExcessPressure
Theproblemwiththeuseoftheradiationstresstensorlieswiththecalculationofthetimeaveragedexcesspressure P .Expressionsfortheexcesspressuredepend
ontheframeofreference.ThismaybeeitherEulerian,thatisevaluatedatapointinspaceorLagrangian,thatisevaluatedataparticularparticle.Generallythese
aredifferent,althoughforthespecificcircumstanceofarigidreflectingwall,theyareidenticalatitssurface.
Beissner(1986)usefullysummarisestwoexpressionstermed'Langevin'sfirstandsecondrelations',whicharegoodapproximationstothesetwotimeaveraged
pressures.Langevin'sfirstrelationgivestheexcesspressureinLagrangiancoordinates.Itis

Page44

where V isthetimeaveragedpotentialenergydensityand K isthetimeaveragedkineticenergydensity.

Cisaconstantinspaceandtimeanddependsonthesystemconstraints.AccordingtoLeeandWang(1993),CiszerofortheLangevinradiationpressure,which
dependsonlyonthewave.Langevin'ssecondrelationgivestheexcesspressureinEuleriancoordinates:

Theradiationpressureexperiencedatawallis,ingeneral,Lagrangianthatisitisexperiencedbytheparticles.Theradiationpressureintheradiationstresstensorisat
apointinspaceandisthereforeEulerian.The1Dcaseclarifiesthelinkbetweenthesequantities.Theradiationstressis

Assumingparticlemotionisonlyinonedirection,thetimeaveragedkineticenergydensity K is

u2 /2,so

Sointhe1DcasetheexcesspressureexpressedinLagrangiancoordinatesisthenegativeoftheradiationstress.Thisisnotgenerallytrueforthe2or3Dcase.
3.4
RayleighRadiationPressure,PRay
Rayleigh(1902)originallyconcernedhimselfmorewithageneralfieldquantityratherthanwiththeactualpressureexperiencedatarealinterface.TheRayleigh
radiationpressurePRayisdefinedasthedifferencebetweentheaveragepressureatasurfacemovingwithaparticle
andthepressureexistingintheabsenceof
sound,withthefluidatrest.Itismoreoftheoreticalthanpracticalinterest.CalculationsofRayleighradiationpressuredependonthefieldconstraintsinawaythatthe
equivalentLangevinpressuresdonot,andgenerallyrequiretheconstantCtobeevaluated.Forplanewavepropagationinauniformlosslessmedium:

Page45

where E isthetimeaverageoftheenergydensityandB/Adescribesthematerialnonlinearity.Itmaybeconsideredtobethepressureonaninterfacebetweentwo
identicalmedia(LeeandWang1993).
Expressedintensorform,PRayis(Beyer1978)

TheRayleighradiationpressurecanbeconsideredtobeapropertyofthefield.Fordiffractivebeamsitvariesthroughoutthethreedimensionalextentofthefield
anditfollowsthereforethatthreedimensionalradiationpressuregradientscanbegenerated.
Hertz(1993)hasdescribedanelegantmethodformappingthevariationofradiationpressurethroughoutanacousticbeam.Notingthattheradiationpressureof1Pa
correspondstoasoundintensityof150mWcm2,verysensitivelocalpressuremeasurementisrequired.Hertzdevelopedabubbletechnique:theradiationpressure
istransferredtoairthroughabubbleattheendofanairfilledtubeplacedatthepointofmeasurement.Usingareferencetubeatapositionofknownpressure,
outsidetheultrasoundbeam,thedifferentialpressurebetweenthetubeswasmeasuredbyagaspressuretransducer.Themethodisindependentofthestaticpressure
duetosurfacetension,andmeasuresthedifferencebetweentheLagrangianpressure(exertedonthebubble)andtheEulerianpressuregivenbythereferencetube
outsidethebeam.Themethodcanoperateatradiationpressureslessthan40Pa,abovewhichthecalibrationceasestobelinear.Figure3.1showstheresultsof
measurementsmadeinthiswayinthefieldofaweaklyfocused1MHztransducerof16mmdiameter.Thefocalintensityisapproximately6Wcm2.
Thepresenceofcontinuousradiationforceonadiscretetargetmaycauseitsdisplacement.Whilethistargetmovementisnotedandusedinthemeasurementoftotal,
timeaveragedacousticpowerinsomeradiationforcebalancedesigns,thereisverylittleexperimentalevidenceofstraininhomogeneoustargets,norofintermittent
movementofmacroscopictargetsduringtheperiodofasinglepulse,bothofwhichmightbeexpectedathighenoughintensities.Slightdisplacementofagargelwas
reportedbyDyerandNyborg(1960)duringcontinuouswaveexposure,butunfortunatelythisstudywascarriedoutat25kHz,anditsextrapolationtohigher
frequenciesisuncertain.OfgreaterinterestperhapsisthereportgiveninthisvolumebyGreenleafetal(Chapter14)whichshowsacousticemissionfromatargetat
thepulserepetitionfrequency.Thisobservationwouldimplythatthetargetpositionisbeingmodulatedinthepresenceofapulsedacousticbeam,sodemonstratinga
localradiationforceeffect.

Page46

Figure3.1.
Measuredradiationpressurefieldfromaweakly
focused1MHztransducer.(FromHertz(1993)
withpermission.)

3.5
AcousticStreaming.
Asshownabove,acousticwavesarecapableofgeneratingradiationpressuregradientswithintheexposedmediumsupportingthewave.Ifthemediumisafluid,and
thereforefreetomove,itwilldoso.Theresultbulkflowoffluidiscalled'acousticstreaming',orinoldertexts,'quartzwind'.Anexampleofthevisualisationof
acousticstreamingisshowninfigure3.2.Thestreamwasgeneratedinwaterfromtheweaklyfocused1MHzbeamassociatedwiththeradiationpressurefield
mappedinfigure3.1.Itmaybenoticedthatthestreamcommencespredominantlyintheregionofthefocus,andnotatthesource,asobservedbyothers.Anumber
ofauthorshavelookedatthetheoreticalproblemofpredictingstreaminginplaneprogressivewaves,eitherwithinalimitingtubeorasafreestream,usingavarietyof
simplifications(Eckart1948,Markham1952,Tjtta1959,TjttaandNazeTjtta1993,Nyborg1998).Thedifficultiesstemfromtheoriginoftheforcecausingthe
stream,whichwehaveseentobearadiationstresstensorfieldwithacousticallynonlinearorigins,therangeofgeometriesbothforthebeamandfortheboundariesof
thefluid,andinthedegreeofnonlinearityassociatedwiththeultrasoundpropagation.However,thefollowingequationsummarisesthesituationadequatelytodescribe
manysituations:

wherevisthestreamingvelocity,Iistheintensity,cistheacousticspeed,visthekinematicviscosity= / , istheshearviscosity,disthebeamdiameterandGisa
geometricfactor.

Page47

Figure3.2.
Photographofstreamingmotioninducedin
waterbyaweaklyfocused1MHztransducer.
Theradiationpressurefieldisshowninfigure3.
1.Exposuretime1s.

Examinationofequation(3.11)showsthatthepressuregradientwhichdrivesthestreamisthatassociatedwiththeradiationpressurenotedearlier,2 I/cor
equivalently2 E0.Examplesoftheradialprofilesforacousticpressuregradientforanumberofmaterialsareshowninfigure3.3.Theseprofileswerederivedfrom
highresolutionmeasurementsofpulseaverageintensityina3MHzbeampropagatingtoahighdegreeofnonlineardistortionatitsfocusinwater.Theradiation
pressuregradientwasderivedfromthelinearsummationofthecontributionsfromalltheharmoniccomponentsusingequation(3.11),andtakingaccountofthe
frequencydependenceofattenuationineachofthematerials:water,amnioticfluid,bloodandaveragesofttissue.
Anyabsorptionmechanismcancontributeto (Nyborg1953),includingshearviscosity,bulkviscosityandrelaxation.Excessabsorptionfromstrongnonlinearityand
shockpropagationalsocontributestotheradiationpressuregradient(Starrittetal1989).Thepressuregradient,andhencethestreamingvelocity,arefrequency
dependentbecauseofthefrequencydependenceof .Inthiswayitdiffersfromtheradiationpressureonatotallyreflectingortotallyabsorbinginterface,whichhas
nodependenceonthefrequencyofthewave.Theretardingforceswhichlimitthemaximumvelocityarefromtwosources:firstlytheviscousdragofthefluiditself,
givenby1/vandsecondlythegeometryoftheboundariesofthefluidspace,representedbythefactorG.
Theequationinthisformrepresentsthesteadystate,inacontinuousbeamofuniformcrosssection.Anumberofotherconsiderationscomeintoplaywhenevaluating
streaminginbiologicalfluidsunderconditionsrelevantto

Page48

Figure3.3.
Radialprofilesofradiationpressuregradients
calculatedfrommeasuredpulseintensitiesat
thefocusofashocked,weaklyfocusedbeaminwater.
Frequency3MHzpulseaverageintensity118Wcm2.

medicalultrasound.Severalauthorshaveconsideredthetimetakenforthestreamtoreachasteadystate.Thiscanbeanimportantquantitywhenconsideringwhether
streamingmaybeestablishedwhenabeamisbeingmovedslowly.Inwater,Starrittetal(1989)reportedshorteststreamingrisetimesoftheorderoffewhundred
millisecondsforunscannedpulsedbeams,andofafewsecondsforscanned(imaging)beams.Workingathigherfrequencies(10and20MHz),withnarrowerbeams
andatacousticpowersaslowas3.5mW,Hartley(1997)recordedrisetimesinwaterof200ms,andinbloodof80ms.Theseobservationsconfirmthatacoustic
streamingcanreasonablybeexpectedtobeestablishedwithintheperiodoftypicalscanningdwelltimes.
Inpracticetheflowmaynotexistasasimplestreamlinewhenformedinalargevolume.Evidencefromvisualisationofstreams(Starrittetal1991)andlaser
anemometry(Mitomeetal1996),showsthatanominallysteadystreammayalterinpositionandmagnitude,probablycausedbythermalconvectioninthefluid
volume.Thiscanbeinduced,forexample,bythetransducerselfheating.Suchinstabilitiesareparticularlynoticeablewhenslowstreaminginlargebeamsisbeing
generated,forexampleinphysiotherapybeams.Converselythereissomeevidencefromlaseranemometrystudiesthatthestreamatthefocusofapulsedbeamhasa
disturbedaxialcomponentsurroundedbystreamlineflow.Fulltheoreticaldescriptionsofsuchflowsarenotyetpossible.
Equation(3.11)givesanexpressionforthestreamingvelocityinaplanepropagatingwave.Someauthors(WuandDu1993,Kamakuraetal1995,Nowickietal
1997)havedevelopedexpressionsappropriateforstreaminginweaklyfocusedbeams,whichadequatelypredictexperimentalmeasurementsofstreaminginwater
andotherfluids.Sincetheradiationpressuregradient

Page49

Figure3.4.
Attenuationcoefficient, ,forseveralbiologicalliquids,
expressedas =afbindBcm1MHzb.Thegraph
demonstratesthedecreaseofexponentfrom2(forwater)
to1(forsofttissue)astheattenuationat1MHzincreases.

dependsonintensity,thestreamingvelocitytendstobeamaximumataboutthefocus.Theimportanceofnonlinearpropagationeffectsbecomesmorerelevantin
focusedbeams(seeChapter2).Underconditionsofextremenonlinearity,suchasthosefoundindiagnosticpulsespropagatinginwater,theexcessattenuationfrom
shockpropagationaddstothatfromthefluidalone.Insuchbeamsthestreamingvelocityinwaterisconsiderablygreaterthanpredictedusingthesimpleformula
(Starrittetal1989).Thedegreeofenhancementfromthiscauseislessmarkedinotherfluids,however,atleastundertheconditionsappropriateinmedical
applications.Thiswouldseemtodependonthebalanceoflossmechanismsbetweenthatfromthefundamental,andtheexcesslossfromabsorptionoftheharmonics
generatedbynonlinearpropagationeffects(seeChapter2).Attenuationinbiologicalfluidsvariesbothinabsolutevalueandinfrequencydependence(seefigure3.4),
andthebalancebetweennonlinearpropagationandthermoviscouslosswillbecomplex.Inpulsedfieldsat3.5MHz(Zauharetal1998)andat10and20MHz
(Hartley1997)streamingvelocitieswereobservedtobelowerinbloodthaninwaterforagivensourcepower.Hartleyalsoobservedthatthestreamingvelocityin
bloodincreasedwithfrequency,suggestingthatnonlineareffectswerenotdominantundertheconditionsusedinhisexperiment.
Thestudiesreferencedabovehavedemonstratedthatpulseddiagnosticbeamswithpulselengthslessthan1scancausestreamingvelocitieswhichcanreach10cm
s1inwater.Furthermore,streamingcanbegeneratedindiagnosticimagingfieldsundersomecircumstances.Itmustbeinferredfromtheseobservationsthatthe
radiationpressuregradientassociatedwiththepassagethroughafluidofasinglediagnosticpulsecanbesufficientto

Page50

Figure3.5.
Acousticstreamingdemonstratedusingthymolbluefor
a3MHzpulsedbeam.(FromStarrittetal(1991),withpermission.)

causefluiddisplacement,sinceunlessonepulsegeneratesmovement,therecanbenointegratedeffecttoformastream.
3.5.1
MethodsofMeasuringAcousticStreaming
Fluidflowmaybevisualisedandmeasuredbyaremarkablywiderangeofmethods,manyofwhichhavebeenappliedtothestudyofacousticstreaming.Auseful
reviewofmethodsforevaluatingflowhasbeengivenbyMerzkirch(1987).Ifitisrequiredonlytovisualisethestream,anumberofmarkermethodshavebeenused.
Theseincludethesheetilluminationofthestreamwithlaserlight,incombinationwithseedingthefluidwithfineparticles(Mitomeetal1993,Hertz1993)(seefigure
3.2).Starrittetal(1989)usedasimpledyemethod,colouringthewaterwithpotassiumpermanganate.AusefulvisualisationmethodusesthepHsensitivedyethymol
bluewhichisorangeyellowatlowpHandbecomesblueabovepH=9.6.LocalpHisalteredbyelectrolysisadjacenttoaplatinumelectrodeacrosswhichthe
streampasses(Starrittetal1991).Anexampleofastreamformedinwaterfromamedicalultrasonictransducerisshowninfigure3.5.Recirculationmixingre
equilibratesthepH,sopreventingtheaccumulationofthebluecolour,allowingcontinualstudiesofstreamingtobecarriedoutoveranextendedperiod.

Page51

Figure3.6.
Acousticstreamprofilesmeasuredusingalaser
velocimeteratthefocusofa5MHzweaklyfocusedbeam.
Totalacousticpowerwas150mWinbothcases.
continuouswave,lowamplitudebeam
ostronglyshockedpulsedbeam,1.4spulselength,
10.1kHzprf,1.20Wcm2timeaverageintensity.
Thebeamwidthatthefocuswas2.5mm.

Markeranddyemethodsaredifficulttoquantifyhowever,requiringsequentialimagecaptureandofflineanalysis.Severalmeasurementmethodshavebeenexplored
toquantifystreamingvelocity.HotfilmanemometrywassuccessfullyusedbyStarrittetal(1989)forstudiesinwater,givingspatialresolutionoftheorderof1mm.
Howeverthemethodrequirescarefulcalibration,sincetheresponsetovelocityisnonlinear,anditcannotbeusedreliablyinanyfluidwhichmaycontaminatethe
surfaceofthesensorthisincludesmostfluidsofbiologicalinterest.Laseranemometryisaverypowerfultechniqueforflowmeasurementintransparentliquids,and
hasbeenusedtoexploreacousticstreaminginwaterandsometransparentbiologicalsolutions(Ducketal1993,Mitomeetal1993,Hertz1993).Themethodcan
achievespatialresolutionbetterthan1mmandspeedresolutionoftheorderof1mms1.Anexampleoftwostreamprofilesatthefocusofa5MHzbeamisshown
infigure3.6.Enhancementofthestreamvelocityfromtheuseofhighamplitude,nonlinearpulsesisdemonstrated.Neverthelesstheequipmentisfairlyexpensive,and
againtheobservationsarelimitedtotransparentliquids,soexcludingstudiesinblood.
UltrasoundDopplermethodspresentanobviousandattractivealternativeapproach.Thesehavebeenimplementedeitherbyusingthesamebeamtocausethestream
astomeasureit(Hartley1997,Nowickietal1997)orbyusingaseparatecontinuouswaveDopplerprobe(Zauharetal1998).Theseapproacheshaveadvantages
ofcheapnessandavailability,butsufferfrompoorspatialresolutionandlimitedsensitivitytolowstreamingvelocities.

Page52

Atpresent,though,allreportsofstreamingmeasurementinbloodhaveusedultrasonicmethods.Thefinalmethodwhichshouldbeeasilyavailablewithinamedical
environmentistheuseofmagneticresonance.Suchmethodsremaintobeexplored,butoffertheabilitytoevaluateflowinthreedimensions,withveryhighsensitivity,
withinopaquesubstances,andwithadequatespatialresolution.
3.6
ObservationsInVivoofRadiationPressureEffects
3.6.1
Streaming
Streaminginvivoseemstobearelativelywellnotedincidentalobservationinclinicaldiagnosticpractice,butonewhichispoorlydocumented(Duck1998).
Streaminghasbeennotedincystfluidinbreast,ovaryandtesticle,withinventricularhaemorrhageinaninfant,andwithinliquefiedvitreoushumour.Streaminghas
beensuggestedasadiagnosticaidtodistinguishfluidfromsolidlesions(Nightingaleetal1995).Streamingitselfinvivowouldnotappeartobehazardous.
Neverthelessitdemonstratesthepresenceofradiationpressuregradientswhichdeservestudyasamechanismforbiologicaleffectwithincellularstructures.
3.6.2
ObservedBiologicalEffectsApparentlyRelatedtoRadiationPressure
Literaturereportswhichrelateabioeffecttoradiationpressure,ratherthantoathermalorcavitationcause,fallbroadlyintotwocategories.Thefirstcategory
includesthosewhichsuggestabiologicaloutcomedirectlyfromcompressionortension.Lizzietal(1981)reportedtransientblanchingofthechoroidofarabbiteye
priortotheonsetofthermaldamage,inworkatintensitiesintendedtocauseretinallesions.Theblanchingwasnoticedmorereadilyathigherpulseamplitudes,andis
thereforeconsistentwiththeviewthatradiationstresscausedcompressionofthebloodvessels.Morerecently,instudiesdirectedattheeffectsofultrasound
exposureoncardiacfunction,Dalekietal(1997)reportedthatdirectexposureofafroghearttoalongultrasoundpulsecausedareductionincentralbloodpressure.
Thiscouldbemimickedbyexposinganabsorberontheoutermyocardialsurfacetothesamebeam.Itwasconcludedthatradiationforceexertedbyeitherultrasound
exposureorexternalapplicationgavesimilaroutcomes.
Thesecondclassofreportsrelatetoneurosensoryreactionstoultrasound.Dalekietal(1995)notedthatthepressuresensorsintheskincandetectpulsed
ultrasoundeitherdirectly,orviaanacousticabsorber.Theequivalenceofsensationbetweenthesetwomethodssuggestsaradiationforceeffect.Atsufficientlyhigh
pulseintensities,itispossibletostimulateothersensoryreceptors,whichincludehotandcoldskinreceptorsandpain

Page53
Table3.3.Summaryofpulsingregimesrequiredtogenerateacousticbioresponsesapparentlycausedbyradiation
pressure.
Effect

Pulselength

Numberofpulses

Choroidblanching(Lizzi)

100s

Tactilesensation(Daleki)

1ms

repetitive

Cardiacresponseinfrog(Daleki)

5ms

Fluidmovement(Starritt)

0.5s

receptorsbothattheskinandatdepth(Gavrilov1984).Howeverinthisseriesofstudies,carriedoutoverarangeoffrequencies,thethresholdforresponsewas
moststronglycorrelatedwithparticledisplacement,ratherthanintensityorradiationpressure.Severalauthorshaveexploredtheapparentdirectstimulationofthe
auditorynervebyultrasound.Exposureoftheauditorynervecanapparentlyresultinthesensationofhearingthepulserepetitionfrequency,althoughdirectbone
conductioncannotbeexcluded.MageeandDavies(1993)stimulatedtheauditorynerveusingapulsedDopplerbeamviatheforamenmagnum,apparentlyavoiding
thiscriticism.
Table3.3summarisesthepulsingregimesusedtogeneratesomeoftheseresponses.
3.7
Discussion
Thecompleteevaluationoftheinteractionoftheradiationstressfieldwithtissueischallenging.Thestressfieldvariesbothspatiallyandtemporally,anditmaybethat
spatialandtemporalgradientsinthestressfieldmayhavegreaterimportanceinaffectingtissuesthantimeaveragedorspatiallyaveragedvalues.Thevariationoftissue
attenuationcanalsogiverisetoalocalradiationpressuregradientcausinglocalstrain(seeChapter4).Radiationstressisexperiencedonlyduringthetimeapulseis
passingthroughtissueandthereisnostressbetweenpulses.Aproperevaluationoftheradiationstressfieldwithintissuescausedbydiagnosticpulses,andits
outcome,isasubstantialchallenge.
ThemagnitudeofthestressinmodessuchaspulseechoandpulsedDopplerdependsonthepulseaverageintensityratherthanthetimeaverageintensity.
Traditionally,bioeffectswhichshowadependenceontimeaverageintensityareinterpretedasbeingthermalinoriginandthosewhichdependonpulseaverage
intensityorpulseamplitudeareexplainedintermsofcavitation.Oncewestarttoconsiderradiationstressasapossiblemechanismitbecomesmoredifficultto
separatethedependenceonexposurefactors.Althoughradiationstresseffectsareexperiencedonlyduringapulse,andarethereforedependentonpulseamplitude
orpulseaverageintensity,

Page54

someoftheoutcomes,likestreamingandsomeofthesensoryeffects,relyonanintegrationofthestresses.Inthisrespecttheyresemblethermaleffects.Howeverthe
timescalescanbeverydifferent.Acousticstreamingforexampleisestablishedintimescalesoflessthanasecond,whereasthermaleffectstendstodevelopslowly,
generallyrequiringseveralminutestoreachequilibrium.
Table3.3showstheminimumpulselengthsandnumberofpulsesrequiredtoproducetheradiationstresseffectsdescribedinthepapersreviewedabove.Itshows
thatsomeeffectscanbeproducedandobservedfollowingasinglepulseofultrasound,whileothersrequirethestresstoberepeatedoveranumberofpulses.
Choroidblanchingoccurredwithasinglepulseabout100sindurationandthecardiacresponseinfrogswasalsoseenwithasinglelongpulse,5msinduration.In
ordertosenseultrasoundontheskinarepetitivestressisrequiredandsimilarly,whilelocalfluidmovementmustbeinducedbyasinglepulse,thereneedstobea
repeatedeffectbeforeitmanifestsitselfasbulkstreaming.
Itisincreasinglyrecognisedthatradiationforceeffectsprovideapossibleexplanationforultrasoundbioeffectswhichappeartobenonthermalandnoncavitational
innature.Inadulttissuetheradiationforcesarehighlyunlikelytobesignificantcomparedwiththetensilestrengthofthetissue.Howeverembryonictissuedoesnot
havethestructuralstrengthwhichitdevelopsinlaterfetalandadultlife.Itisnotknownwhatisthestressthresholdforpermanentcelldisplacementinsuchweakly
boundtissues.Untilthesemattersaremorefullyexplored,itisappropriatetocontinuetoexercisecautionintheuseofhighestexposuresduringultrasound
examinationsduringtheearlierstagesofpregnancy.
References
BeissnerK1985OnthetimeaverageacousticpressureAcustica5714
1986TwoconceptsofacousticradiationpressureJ.Acoust.Soc.Am.7916102
BeyerRT1950RadiationpressureinasoundwaveAm.J.Phys.18259
1978RadiationpressurethehistoryofamislabeledtensorJ.Acoust.Soc.Am.63102530
1997NonlinearAcoustics(Woodbury,NY:AcousticalSocietyofAmerica)(reprintofthe1974bookbyUSDepartmentoftheNavy)
BorgnisFE1953AcousticradiationpressureofplanecompressionalwavesRev.Mod.Phys.2565364
BrillouinL1964TensorsinMechanicsandElasticity(TrROBrennan)(NewYork:Academic)
DalekiD,ChildSZ,RaemanCHandCarstensenEL1995TactileperceptionofultrasoundJ.Acoust.Soc.Am.97316570
DalekiD,RaemanCR,ChildSZandCarstensenEL1997EffectsofpulsedultrasoundonthefrogheartIII:theradiationforceeffectUltrasound.Med.Biol.23
27585
DuckFA1998Acousticstreamingandradiationpressureindiagnosticapplications:whataretheimplications?SafetyofDiagnosticUltrasound,Progressin
Obstetrics&GynaecologySeriesedsSBBarnettandGKossoff(NewYork:Parthenon)pp8798

Page55

DuckFA,MacGregorSAandGreenwellD1993MeasurementofstreamingvelocitiesinmedicalultrasonicbeamsusinglaseranemometryAdvancesinNonlinear
AcousticsedHHobaek(Singapore:WorldScientific)pp60712
DyerHJandNyborgWL1960UltrasonicallyinducedmovementsincellsandcellmodelsIRETrans.Med.Electron.ME71635
EckartC1948VorticesandstreamscausedbysoundwavesPhys.Rev.736876
GavrilovLR1984UseoffocusedultrasoundforstimulationofnervestructuresUltrasonics221328
HartleyCJ1997CharacteristicsofacousticstreamingcreatedandmeasuredbypulsedDopplerultrasoundIEEETrans.UltrasonicsFerroelectr.Freq.Control
44127885
HerreyEMJ1955ExperimentalstudiesonacousticradiationpressureJ.Acoust.Soc.Am.278916
HertzTG1993ApplicationsofacousticstreamingPhDdissertation(LundUniversity,Sweden)
HueterTFandBoltRH1955Sonics(NewYork:Wiley)
KamakuraT,MatsudaK,KumamotoYandBreazealeMA1995AcousticstreaminginducedinfocusedGaussianbeamsJ.Acoust.Soc.Am.9727406
LangJ,ZanaR,GairardB,DaleGandGrosChM1978UltrasonicabsorptioninthehumanbreastliquidsUltrasoundMed.Biol.412530
LeeCPandWangTG1993AcousticradiationpressureJ.Acoust.Soc.Am.941099109
LizziFL,ColemanDJ,DrillerJ,FranzenLAandLeopoldM1981EffectsofpulsedultrasoundonoculartissueUltrasoundMed.Biol.724552
MageeTRandDaviesAH1993AuditoryphenomenaduringtranscranialDopplerinsonationofthebasilararteryJ.UltrasoundMed.1274750
MarkhamJJ1952Secondorderacousticfields:streamingwithviscosityandrelaxationPhys.Rev.86497502
MerzkirchW1987FlowVisualisation2ndedition(London:Academic)
MitomeH,IshikawaA,TakedaHandKyomaK1993EffectsofattenuationofultrasoundasasourceofdrivingforceofacousticstreamingAdvancesinNonlinear
AcousticsedHHobaek(Singapore:WorldScientific)pp58994
MitomeH,KozukaTandTuziutiT1996MeasurementoftheestablishmentprocessofacousticstreamingusinglaserDopplervelocimetryUltrasonics3452730
NarayanaPA,OphirJandMakladNF1984TheattenuationofultrasoundinbiologicalfluidsJ.Acoust.Soc.Am.7614
NightingaleKRetal1995Anovelultrasonictechniquefordifferentiatingcystsfromsolidlesions:preliminaryresultsinthebreastUltrasoundMed.Biol.2174551
NowickiA,SecomskiWandWojcikJ1997Acousticstreaming:comparisonoflowamplitudelinearmodelwithstreamingvelocitiesmeasuredby32MHzDoppler
UltrasoundMed.Biol.2378391
NyborgWL1953AcousticstreamingduetoattenuatedplanewavesJ.Acoust.Soc.Am.256875
1998AcousticstreamingNonlinearAcousticsedsMFHamiltonandDTBlackstock(NewYork:Academic)pp20731
Rayleigh,Lord1902OnthepressureofvibrationsPhil.Mag.333846
StarrittHC,DuckFAandHumphreyVF1989AnexperimentalinvestigationofstreaminginpulseddiagnosticultrasoundfieldsUltrasoundMed.Biol.1536373
StarrittHC,DuckFAandHumphreyVF1991ForcesactinginthedirectionofpropagationinpulsedultrasoundfieldsPhys.Med.Biol.36146574
TjttaS1959OnsomenonlineareffectsinsoundfieldswithspecialemphasisonthegenerationofvorticityandtheformationofstreamingpatternsArch.Math.
Naturvidensk55168

Page56

TjttaSandNazeTjttaJ1993AcousticstreaminginultrasoundbeamsAdvancesinNonlinearAcousticsedHHobaek(Singapore:WorldScientific)pp6016
VermaPK1994personalcommunication
WuJandDuG1993AcousticstreaminggeneratedbyfocusedGaussianandfiniteamplitudetoneburstsUltrasound.Med.Biol.1916776
ZauharG,StarrittHCandDuckFA1998StudiesofacousticstreaminginbiologicalfluidswithanultrasoundDopplertechniqueBr.J.Radiol.71297302

Page57

Chapter4
UltrasonicPropertiesofTissues
JeffreyCBamber
Introduction.
Thepropertiesthatinpracticeareusedforprovidinginformationaboutthestructureofbiologicaltissues,andwhichcontributetothephysicallycomplicatedprocess
offormationofmedicalultrasoundimages,areacousticspeed,impedance,absorption,scatteringandattenuation.Inaddition,foracousticpressureamplitudesusedin
manymedicalapplications,thenonlinearityofsoundwavepropagationbecomesimportant.Knowledgeofthesecharacteristics,andtheirvariationwithfrequency,
amplitude,temperature,age,pathology,etc,isimportantforathoroughunderstandingandoptimumuseofpresentandpotentialultrasonicdiagnostictechniques.They
alsoplayanimportantroleindeterminingthenatureandmagnitudeofthebiologicaleffectsofultrasound,whichformthebasisbothforultrasoundtherapeutic
proceduresandconcernforthecontinuedsafeuseofmedicalultrasound.Thenaturalvariationoftheacousticalcharacteristicsofbiologicalmediaisoftenverybroad
andthisrangeisfurtherbroadenedbydifficultyinmakingaccuratemeasurements.Asaconsequenceitisalsodifficulttospecifyindetailthewavemediuminteraction
mechanismsthatareresponsiblefortheobservedacousticalcharacteristics.
4.1
BasicConcepts
4.1.1
Attenuation,Absorption,ScatteringandReflection
Inbiologicaltissuesbothscattering(whichincludesrefractionandreflection)andabsorptioncontributetotheattenuationofaplanesoundwave

Page58

propagatinginthepositivezdirection:

wherecisthespeedofsoundofangularfrequency ,tistimeandthewaveamplitude,u0,ismodifiedbyaconstantfactor, ,perunitpathlength,z.Practical

situations,however,rarelyinvolveperfectlyplanewavesandtherearealmostalwaysadditionallosses(orgains)ofacousticintensityduetothediffractionfieldofthe
soundsource.Diffractioncorrections,tocompensatefordiffractionlossesorassociateddiffractionphasechanges,arerequiredforaccuratemeasurementof
attenuation,scatteringorsoundspeed.
Scatteringandabsorptionbybiologicalmediaaredescribedintermsofbulkcoefficients,sanda,whichareintensitycrosssectionsperunitvolume[1].Ifitwere
possibletoidentifyindividualscatterersorabsorbers(whichisalmostneverthecase)thenthebulkscatteringcoefficientwouldbe(intheabsenceofmultiple
scattering)
giventhatthenumberdensitydistributionofindividualscatterercrosssectionsisdescribedbynsi( si).Asimilarrelationshipwouldholdfor
theabsorptioncoefficientandforaplanewaveofpowerW,thetotalpowerincrementeitherabsorbedorscattered,dWs+dWa,inapathlengthdz,wouldbesWdz
+aWdz.Integrationofthisrelationshipgives

Thesumoftheintensityscatteringandabsorptioncoefficients(s+a)iscalledtheintensityattenuationcoefficient,.Whenexpressedintermsoftheratiooftwo
measuredpowers,

typicallytakesunitsofcm1.Theamplitudeattenuation,absorptionandscatteringcoefficients( , a,and s,respectively)areexpressedsimilarlyastheratiooftwo

measuredwaveamplitudesandalsohaveunitsofcm1,sothat=2 .If,however,theratiosofeitherpoweroramplitudeareexpressedintermsofdecibelsthen
and becomenumericallyequal,takingunitsofdBcm1.Itiscommontousethesymbol whenexpressingtheattenuationcoefficientindBcm1,whichistherefore
equalto4.343timesincm1and8.686times incm1.
Forindividualscatterersthedifferentialscatteringcrosssection, ds( , ),definestheratioofthepowerscatteredinaparticulardirection,Ws( , ),totheincident
intensity,I,perunitsolidangle :

Page59

Figure4.1
Geometricalvariablesusedwhendefining
scatteringcoefficients(adaptedfrom[91]).

wherefigure4.1definesthegeometricalvariables.Foramediuminwhichthescatteringisincoherent(i.e.whenthereisnomeasurablespatialcorrelationinthe
scatteringproperties)thepowerscatteredwillbeproportionaltothenumberofscatterers,orthevolumeofthemedium.Foramediumofdiscretescatterersa
differentialscatteringcoefficientmightthenbedefined,similarlytothescatteringcoefficient,as
Ingeneral,however,thescattering
strengthasafunctionofscatteringangle( , )isdescribeddirectlybythedifferentialscatteringcoefficientds( , )=(ds/d )( , ),definedasthepowerscattered
perunitincidentintensity,perunitvolume,perunitsolidangle.Animportantspecialcaseofthisisthebackscatteringcoefficient,bs=(ds/d )( ,0).
Thescatteringcoefficientandthedifferentialscatteringcoefficientarerelatedby

Forscatteringwithazimuthalsymmetrythisreducesto

Ifthescatteringiscompletelyisotropic(sphericalsymmetry)thisreducesfurtherto

Unlikes,theunitsfords( , )andbsmayonlybelength1solidangle1(usuallycm1sterad1)thereisnodecibelequivalent.

Page60

Therearecoherentandincoherentcomponentstothescatteringfromtissues,therelativecontributionsdependingontherandomnessofthescatteringmediumandthe
ratioofeitherthewavelengthorthesizeofthescatteringvolumetothetypicalspacingofscatteringstructures.Patternsofscatteringobservedasafunctionof
measurementvariablessuchasangle,orientation,frequencyorspatialposition,commonlydisplayaveragelargescaletrendsonwhicharesuperimposedfiner
fluctuationsduetointerferenceeffects.Ifthesoundisscatteredincoherently(i.e.frommanyrandomlydistributedscatteringsources)thenthesefinerfluctuations,
althoughdeterministicallyrelatedtothescatteringstructure,representmultiplicativenoiseasfarasmeasuringanaveragescatteringcoefficientisconcerned.The
probabilityofthescatteredamplitudeisthendescribedbyaRayleighdistributionwithastandarddeviation0.52ofthedesiredmeanvalueandthetypicalscaleofthe
fluctuationsinthescatteringcoefficientbeingdeterminedbytheparametersoftheexperiment(e.g.beamwidth,pulselength)ratherthanbythetissuestructure.Semi
periodicinterferencefluctuationsduetocoherentscatteringmaybeobservedifthereisunderlyingregularitytothetissuestructure.Alternatively,thepropertiesofthe
finescaleinterferencefluctuationsinthescatteringpatternmaybecomemorecharacteristicofthetissuestructureiftheyarisefromcoherentscatteringstructurethat
hasaspatialscaleapproaching,orgreaterthan,thesizeofthescatteringvolume.Thusinformationaboutthescatteringstructureispotentiallyavailablefromeither
componentofthescatteringpattern:theaveragetrendduetoincoherentscatteringorthelocalfluctuationsduetothecoherentcomponent,butnotthelocal
fluctuationsduetotheincoherentscattering.
Interference,ordiffraction,patternsmaybeobservedasfluctuationsinthevaluesofvarious'instantaneous'differentialscatteringcoefficientswithchangingscattering
angle( , ),wavelength,ortissueorientationangle, .Ontheotherhand,inordertostudytheaverageangularororientationdependenceofscattering,orindeedto
usesuchdatatoestimatesanditsfrequencydependence,itisnecessarytocomputetheaverageofanumberofstatisticallyindependentscatteringpatternsobtained
byalteringsomesuitableindependent(orassumedtobeindependent)variable,suchasthespatialpositionwithinthetissueor,forisotropictissues,tissueorientation.
Thisprocessisinvariablyacompromiseandusuallyresultsinlossofresolutionofsomekind,whetherthisbespatial,spectral,angularorabilitytoresolvespatial
anisotropy.
Reflectionisessentiallygeometricalscatteringfromstructuresmuchlargerthanthewavelength.ForplaneinterfacesSnell'slawofrefractionapplies.Theintensity
reflectioncoefficient,R,foraplanewaveincidentatanangle onaplaneinterfacebetweentwofluidsofcharacteristicacousticimpedanceZ1andZ2,(whereZ1=
oc)andemergingatanangleofrefraction ,istheratioofthereflectedtotheincidentintensityandisequalto

Page61

butthisexpressionwillnotadequatelydescribethesituationatinterfacesinvolvingsolids,whereconversionbetweenlongitudinalandshearwavesmaytakeplace.
4.1.2
SpeedofSound
Althoughbothgroupandphasespeedsmaybedefined,andsoundspeediswaveamplitudedependent,thefieldofmedicalultrasonicshasadoptedthesimplistic
viewpointofasinglevaluedsoundspeedwhichcanbemeasuredforeachmedium,givenby

where 0isthemeandensityandkistheadiabaticbulkcompressibility.
4.1.3
Nonlinearity
Theassumptionthatdensityandacousticpressurearelinearlyrelatedisanapproximationresultingfromtheuseofonlythefirstterminaseriesexpressionbetweenthe
two.Extensionofthetheorytothenextorderofsmallquantitiesbyinclusionofthenext(quadratic)termresultsinasecondorder,ornonlinear,relationshipbetween
densityandpressure.Thephasespeedmaythenbewritten

whereuistheparticlevelocity,Ais 0c2,andtheratioB/Aisknownasthenonlinearityparameter,whichvarieswiththemediumandwithtemperature[24].The
dependenceofsoundspeedonparticlevelocity,andhenceacousticpressure,describedbyequation(4.10)producesawavewhichchangesshape,becoming
progressivelysteeperduringthefallfromthehightothelowpressurecycles,asitpropagates.Theseandothermattersassociatedwithnonlinearpropagationare
coveredmorefullyinChapter2.
4.1.4
TransducerDiffractionField
Theacousticalcharacteristicsofbiologicalmediaaredefinedintermsofplanewavepropagation(seechapter1)butdiffractionfromthesourceoftencontributes
substantiallytothemeasuredvalues,whichmustthereforebecorrectedtoyield(planewave)valuesthatareindependentofthe

Page62

Figure4.2.
Diffractionlossandphaseshiftfroma
circularpistonsourceofradiusa,
seenbyanidenticalreceiver,
asafunctionofnormaliseddistance
(unitsof /a2)betweenthetwo
(adaptedfrom[85,86]).

measurementsystem.Diffractioncorrectionsmaybeappliedtoanyacousticfieldparameter(intensity,pressure,etc)asafunctionofbothspace(threedimensions)
andtime(orfrequencyspectrum).Forasinglefrequencycomponent,theapparentmagnitudeandphaseofthesignalreceivedinalosslessmediumbyaplane
circulartransducerofidenticalsizeandshapetoatransmittingtransducerdecayandfluctuatewithtransducerseparation(figure4.2.)Diffractionloss(or'gain')curves
ofthiskindwillvarywiththesizeandshapeofeitherofthetransducers,andwiththedisplacementphase/amplitudeprofilesofeitherthesourceorthereceiver(i.e.
theirfocusing/apodisationcharacteristics).Furthermore,modernmedicalultrasoundimagingsystemsuseelectronicallyfocusedtransducerarraysinwhichthereceived
aperturesize,apodisationandfocallengthmayallvarywithdistance.
4.1.5
PulseEchoImaging,SpeckleandEchoTexture
ABscanisformedfromthemagnitudeofthebackscatteredsignal(|A|)asafunctionofthespatialpositionofthescatteringvolume.Itdepictsthespatialvariationin
backscatteringcoefficient,smoothedbytheshapeoftheresolutioncellorpointspreadfunction(determinedbythelateralextentofthebeamandaxialextentofthe
pulseenvelope)andmodifiedbyanumberoffactorswhichincludethesourceacousticspectrum,thediffractionfieldofthesource,theattenuationofsoundinthe
tissueandthegeometryof

Page63

thereceiver.However,superimposedonthisaveragescatteringmagnitudearefinescalefluctuationsduetointerferenceeffects.MathematicallytheBscanisobtained
fromthemagnitudeofacoherentconvolutionbetweenaspatiallyvariant,objectdependentradiofrequency(RF)pointspreadfunctionh(x,y,z)andthetissue
backscatteringimpulseresponseT(x,y,z)[5,6]:

T(x,y,z)isrelated,bywhichevermodelforscatteringisfavoured,tothespatialrateofchangeindensityand/orcompressibilityinthemedium.Biologicalmedia
containstructuresoveraverywiderangeofspatialfrequenciesandtheechomagnitudeforasingleimagepointwillresultfromthecoherentsumofechoesduetoa
numberofstructurespresentwithintheresolutioncellsurroundingthatpoint.Suchinterferenceeffectsstronglyinfluencethefinedetail,ortexture,ofBscanimages.
Foranyuniformregionofthemediumcontainingalargenumberdensity(morethanabout10perresolutioncell)ofsmall(<< ),randomlydistributed(incoherent)
scatteringsources,theimagemagnitude,althoughdeterministic,variesapparentlyrandomlywithposition.Theresult,knownasaspecklepattern,isthemultiplicative
noisediscussedinsection4.1.1andhas(intheabsenceofnonlinearsignalprocessing)predictablestatisticalproperties.Anydeparturefromthissituation,suchasthe
introductionofanisolatedcoherentscatterer,theexistenceofdistributedcoherentscatteringfromanonrandom(periodic)distributionofscatterers,areductionofthe
numberdensityofscatterers,ortheexistenceofatransitionfromaregionofonebackscatteringcoefficienttoanother,willresultinachangeinthesestatistical
properties.Theprobabilitydensityfunction,p(|A|),offullydevelopedspeckleisaRayleighdistribution[7]:

where A2 isthemeansquarescatteringamplitude.Thesecondorderstatisticalpropertiesofspecklearedescribedbythefactthattheautocorrelationfunctionof
speckleisdeterminedonlybytheautocorrelationfunctionoftheinterrogatingpointspreadfunction,inturndeterminedbythetransduceraperture,centrefrequency,
focallengthandbandwidth.Theaveragespecklecellsizes(orspecklecorrelationlength),inthedirectionsparallelto(Scz)andperpendicularto(Scx)thepulse
propagation,aregivenforthefocaldistance,zf,ofanapertureofdiameterDandaGaussianpulsewithhalfpowerbandwidth, f,by

wherefisinMHzanddimensionsinmillimeters.Estimationofscattering(andattenuation)coefficientsfrombackscatteredsignals,whichisaformof

Page64

specklereduction,requiresaveraging.Forspatialaveraging,equation(4.13)definesthedistancesbetweensamplesrequiredforindependentestimates.Duetothe
phaseintegratingnatureofthereceiver(seesection4.1.6),however,thespeckleinthenearfield(Fresnelzone)andbeyondthefocalzoneofafocusedaperture
possessesamuchshortercorrelationlengththatisdifficulttopredictanalytically[8].Thephenomenonofspecklealsooccursinothercoherentsystemssuchas
imagingwithlaserlightandradar.Fortheacousticcase,however,opportunitiesexistforinterferenceeffectstooccurfromsourcesotherthanthesimpleconvolutional
modeldefinedbyequation(4.11),e.g.multiplescattering,phasereversalatscatteringboundariesandwaverefractionordistortionduetosoundspeedinhomogeneity
ofthemedium.
4.1.6
ReceiverPhaseSensitivity
Unlikeopticaldetectors,whichareenergysensitive,acousticreceiversarephasesensitive.Forscatteredwavesreceivedundernearfieldconditions(e.g.fromoutside
thefocalplane),orifthewavepropagatesthroughanaberratingmedium,phasevariationsacrossthereceiverwillcausedestructiveadditionacrossthewave,resulting
infurtherfinescalevariation(i.e.speckle)andunderestimationofthesignalmagnitude.Thismaycauseunderestimationofscatteringcoefficients,overestimationof
attenuation,lossofsignalinimagingandadditionalvariationsinestimatedsoundspeed.
4.2
MeasurementMethods.
Thereaderisreferredtopreviousreviews(e.g.[1,4,9,91])formorecompletedescriptionsofmethodsofmeasuringultrasonicpropagationpropertiesoftissues.
4.2.1
MeasurementoftheAbsorptionCoefficient
Athermocoupleprobemaybeusedtomeasurethatportionoftheultrasonicenergyabsorbedlocallyandtransformedintothermalenergy[4,911].Themethodmay
beappliedinsitu,invivoandinsmalllocalstructuressuchasthemousespinalcord[12,13]andisspecifictoaverylocalregionoftissue.Athermocouplejunction
ofdiametersmallrelativetotheultrasonicwavelengthisimplantedinthesampleunderstudyandexposedtoshortburstsofsound.Ariseintemperatureduringthe
first0.1s,duetoviscousmotionabsorptionbythewires,istobeignored,butatfrequenciesbelowabout300kHzthistendstoobscureaccurateobservationofthe
subsequent,relativelylinear,rateoftemperaturerisewhichisduetoabsorptioninthesample.Calculationofaisfromthedensity,specificheatandacoustic

Page65

intensityusinganiterativetechniqueinwhichaninitialvalue,calculatedusinganapproximatemeasuredincidentintensity,I,isusedasavaluefortoestimatethetrue
valueofIknowingthepathlengthinthesample.SuccessivebetterestimatesofaandIarethenobtained.Itisdifficulttoproducebroadplanewavesandsmall
thermocouplesforhighfrequencyworkandconvergenceofadoesnotoccurifistoolarge.Measurementsupto7MHzhavebeenmadeintissues,withatotal
uncertaintyoftheorderof1015%[14].Analternativeapproachemploystherateofcoolingofthetissuearoundthethermocouplefollowingashort(lessthan0.1s)
soundpulse[15].
4.2.2
MeasurementoftheAttenuationCoefficient
Theattenuationcoefficient,,maybemeasuredusingsystemsthatarenarrowbandorbroadband[1].Afurtherdistinctionisbetweenfixedpathandvariable
pathinstrumentsthepathlengthbeingthatbetweenthetransmitterandreceiver.Variablepathsystems,whichmeasuretherateofchangeofreceivedsignalwiththe
positionofthereceiver/reflector,provideabsolutevaluesofbutdiffractioncorrectionsarerequired,whichareproportionatelyworseatlowfrequencies(below3
MHztheaccuracybecomesworsethan5%).Above12MHzmillilitresamplevolumescanbemeasuredwithoutappreciablediffractioncorrections.Accuraciesof
0.5%arepossiblewithgoodtemperaturecontrol,homogeneity,calibrationofelectronicamplification,distancemeasurementandtransducer/reflectoralignment.
Variablepathmethodshavebeenusedtostudysolutionsandliquids(e.g.water[16]),orhomogenisedtissues,atfrequenciesuptoabout200MHz.
Thesubstitution[17]orinsertion[18]techniquesarefixedpath,makingdiffractioncorrectionslessimportantandalignmenttoleranceslessstringent,butthe
measurementsarerelativetotheattenuationcoefficientofareferenceliquid(oftenwater).Inthesubstitutionmethod,suitableformeasurementsdownto0.3MHz
(errorsaslowas2%)onliquidsorgroundtissuesinsuspension,thetransmittingandreceivingtransducersaremechanicallylinkedsothattheymovesimultaneously:
onethroughthereferenceliquid,theotherthroughthetestmedium.Thetwomediaareseparatedbyanacousticallytransparentwindowandonlytheproportionofthe
acousticpathlengthoccupiedbythereferenceandtestliquidsisvaried.Theinsertiontechnique,whichhasbeenappliedtosolidtissuesatfrequenciesfrombelow
onemegahertzuptomanyhundredsofmegahertz,involvesusingequation(4.3)todeterminefromtheratioofthepowersinthesignalreceivedwithandwithoutthe
tissuebetweenthetransmitterandreceiver.Areferencemediumseparatesthetransducersfromthesample,asshowninfigure2.3,reducingtheerrordueto
diffractionlossesbyreducingtherelativechangeinoverallpathlengthwhenthetissueisinserted.Neglecting

Page66

forwardscattering

wherewistheattenuationcoefficientofthereferencemedium(e.g.water),dzisthetissuethickness,WandW'arethepowersreceivedwithandwithoutthetissue
present,andRisthereflectioncoefficientatthetissue/waterinterface.Itisdifficulttoaccuratelycutandmountparallelsidedtissueslabsandmeasurementerrorscan
beupto10%.Thesemaybereducedbyrepeatingmeasurementsonmultipletissueslabsofdifferentthicknessorbyusingcuttingandmountingproceduresdesigned
toreducespecimenthicknesserrorsto~2%[19].
Ultrasonicinterferometersandreverberationchambersneedtobecalibratedwithareferenceliquidbutverysmallvolumes(e.g.10ml)ofliquidsorsuspensionsmay
bestudied,withaccuraciesoftheorder10%[20],overawidefrequencyrange(e.g.0.2to10MHzorhigher).
Broadbandtechniquesusespectralanalysisofmodulatedacousticsignalstoobtainasafunctionoffrequencywithinthebandwidthofthesystem[1].For
example,usingequation(4.3),(f)maybeobtainedfromthelogarithmofthepowerspectrumofthepulsetransmittedthroughthespecimendividedbythepower
spectrumofthereferencepulse.Whencombinedwiththefixedpathinsertiontechnique,thesemethodsarepopularforstudyingsolidtissuesbuttheexperimental
difficultiesareeasilyunderestimatedandunderstandingoftheerrorsisincomplete.Diffractioncorrections,whilesmall,varywithfrequencyandmaybeimportant
whenmeasuringmediawithverylowattenuation.Spectralprocessingnecessitatestheuseofphasesensitivereceiverswhichsufferfromphasecancellationartefacts
andtheuseofshortpulseswithrelativelyhighpeakacousticpressuresmayresultinadditionallossesduetononlinearpropagation.
Invivomeasurementpresentsmoreproblems.Completethroughpropagationispossibleforonlyafeworgans(e.g.thefemalebreast)butifregionsoftissue
sufficientlylargeandhomogeneouscanbelocated,estimatesofmaybeobtainedfromtheaveragerateofdecreaseofthesignalbackscatteredbythetissuewith
depthofpropagation[1].Ifcommercialultrasoundimaginginstrumentationisemployedcorrectionsmustbeappliedfornonlinearsignalprocessing[21].Theseare
variablepathmethodsandthereforerequire(frequencydependent)diffractioncorrections,butthediffractionlossasafunctionofdistance(seesection4.1.4)is
unknownsincefrequencydependentattenuationandtheinhomogeneousnatureofthepropagationmediumwillalterthediffractionfield,andthediffractionloss
dependsonthenatureofthereceivingtransducerwhichinthiscaseisdeterminedbythescatteringstructure.Theuseofdifferentmodelsforthediffractionloss
producesdifferentresultsfortheattenuation

Page67

estimate.Fixedpathmethodsthereforeoffergreateradvantagesforinvivoworkandmaybeimplementedbyamethodanalogoustothesubstitutiontechnique:the
pulseechotransduceriscoupledtothetissuebyawaterbathandismovedtowardsorawayfromthetissuesoastoensurethateachestimateofthebackscattered
signalisobtainedatthesamepositioninthediffractionfield[22].
References[1]and[91]providediscussionsoferrorsinattenuationmeasurement.Errorspresentevenforhomogeneousmediaincludethoseassociatedwith:the
forwardscatteredpartofs,whichcausesunderestimationoftoadegreedependentonmeasurementgeometry(whichcouldbe20%forsofttissuesorhigherfor
stronglyscatteringtissuessuchaslungorbone),thetissuepathlength,thefrequencyf,linearityofvoltagesignalscorrespondingtoWandW',linearityoftransduction
orsoundpropagation,reflectionatspecimenboundaries,signallossinthereferencemedium,anddifferencesinsoundspeedbetweenthetissueandcouplingmedium
(diffractionlossesandrefractionorphasecancellationduetomisalignmentornonparallelismofthespecimen).
Theacousticalinhomogeneityoftissuesgivesrisetoadditionalerrorsduetorefraction,diffractivescatteringandphasecancellation.Phasecancellationlossesarise
becausethepowerdependentsignalisobtainedfromthevoltagesignalsquared,proportionaltotheintegralofthesquaredpressureacrossthereceiver,whereasits
truevalueistheintegralofthereceiver,whereasitstruevalueistheintegralofthesquaredpressuredistribution.Ifthephaseofthewavereceivedisnotconstantover
thereceiverthenWwillbeunderestimated.Distortedwavefrontsmaybecausedbyvariationsintissuesoundspeedorspecimenthickness.Theerrormaybe
eliminatedbyusingpowersensitivereceiverssuchastheradiationforcebalance[23]oracoustoelectricreceivers[24],andreducedbytheuseofthin,evenlycut
specimens,acouplingmediumwhosesoundspeedismatchedtothatofthespecimen,anarrowsoundbeaminthevicinityofthespecimen,andareceiverofsize
and/ordistancefromthespecimenadjustedaccordingtothespatialcoherenceofthedistortedwave.Afocusedtransmitterandreceiver,withthespecimenatthejoint
focalplane,helpstoreducephasecancellationwithoutincreasingrefractionlosses.
Theconditionsunderwhichtissuesaremeasuredmaysubstantiallyinfluencetheirobservedacousticalcharacteristics.Reviewsofthistopicmaybefoundelsewhere
[1,91]buttheimportantfactorsmayincludetheambienttemperature,timesincedeath,temperatureofstorage,mediumofstorage,chemicalpreservation(fixation),
freezing,mediumofmeasurement(e.g.pH,concentration),unwantedgasinclusionorproduction,andinherentbiologicalvariationwithinorbetweenspecimens.
Factorswhichmayinfluencetherelationshipbetweentheacousticalcharacteristicsinvitroandinvivoare:bloodflowandothertissuemovement,blood
pressure/volume,differencebetweenbloodandthemediumofmeasurement,surroundingtissuesandorgans(e.g.tensionsuppliedbyconnection),temperature,tissue
orientation

Page68

(foranisotropictissues)andanyfactorsspecifictothedeathofparticularcellsandtissues.
Performanceofanattenuationmeasurementsystemmaybeassessedbymeasurementofastandardmaterialwhichhasknown,orwidelyagreedupon,characteristics.
Forabsolutemeasurementsinliquidsthedataforwater[16]areoftenemployed,whileforrelativemeasurementsthesoundspeedandattenuationcoefficientofcastor
oil[1,25,91]aresuitablysimilartothoseofmanysofttissuesinthelowMHzrangeoffrequencies.
4.2.3
MeasurementofSoundSpeed
Priorreviewsprovidesummariesofthemethodsofmeasuringsoundspeed[2,4,9,27,91].Mostattenuationmeasurementmethodsarealsocapableofproviding
simultaneousdataonsoundspeed.Theyhavesimilarlimitationswithregardtotheirapplicabilitytotissuesversusliquids,andcoversimilarfrequencyrangestothose
describedinsection4.2.1.Themostcommonabsolutemeasurementmethodsarevariantsofageneraltransittime,ortimeofflight(TOF),measurement,initially
developedasavariablepathtechniqueforliquids[28].SoundspeedisobtainedeitherfromthevariationinTOFwithpathlengthorfromtheTOFforaknownfixed
pathlength.TherehavebeenmanyapproachestodeterminingtheTOFinthe'singaround'system,separatetransmittingandreceivingtransducersareused,the
receivedpulseisshapedtobefedbackasatriggerforthetransmittingtransducerandtheresultingpulserepetitionperiodprovidesaselfadjustingmeasurementof
TOF.Accuraciesof~0.1%havebeenclaimedusingsuchmethods[29],orevenbetteraccuraciesusingcontinuouswaveultrasonicinterferometers[30].
Forsolidtissuesrelativemethodsaremoresuitable,thereferencemediumusuallybeingwaterorsaline.AcommonapproachisanothervariationofthepulseTOF
method,usingtheinsertiongeometrydescribedbyfigure4.3,eitherwithasingletransducerplusreflectororwithseparatetransmittingandreceivingtransducers.The
average(group)speedofsoundinthetissue,ct,maythenbecalculatedfrom

wherecwisthespeedofsoundinthereferencemediumatknowntemperatureand tisthemeasuredtimeshiftinthepositionofthereceivedsoundpulsewithand
withoutthetissuespecimeninplace.Iflongpulsesareemployedvelocitydispersioncanbeobserved.Itisalsopossibletomeasurephasespeedanddispersionin
shortpulseTOFsystemsbysubtractingthephasespectrumofthereceivedsoundpulse(obtainedbyFouriertransformation)fromthatofthepulsewhichtravelled
throughreference

Page69

Figure4.3.
Typicalexperimentalarrangementforattenuation
andsoundspeedmeasurementbytheinsertion
technique,andbackscatteringmeasurementbythe
substitutionmethod.Hereasingletransducer
actsasbothtransmitterandreceiverbutaseparate
receivermayalsobeused,inplaceofthereflector
(adaptedfrom[1]).

mediumonly[31].Thesubstitutionmethod[17]describedinsection4.2.1canprovidephasespeedbynotingthevariationinthedifferenceinphasebetweenthe
receivedsignalandthatofthesourceasrelativepathlengthisvaried.Similarapproachestophasecomparison,althoughwithfixedrelativepathlengths,areemployed
whenmakingrelativemeasurementsofsoundspeedusingacousticmicroscopes.
Forinvivomeasurement,wheneverconventionaltransmissionmeasurementisimpossible,methodsthatusesignalsbackscatteredbythetissueinclude(i)theuseof
misregistrationbetweenmultipleimagesofthesametissuestructuretoestimatethebeamrefractionthatoccurswhensoundentersthebodyfromaknowncoupling
medium[32](ii)statisticalestimationofTOFoverapathincludingscatteringfromaregionoftissuedefinedbyoverlappingbeamsfromtransmittingandreceiving
transducers[33,35]and(iii)findingthesoundspeedwhich,whenusedtoreconstructaphasedarrayimage,producesthesharpestimageofaspecifiedstructure
[34].Mostofthesemethodscanprovideaccuraciesandprecisionsof0.51%underlaboratoryconditionsbutinvivotissueinhomogeneityisaproblem.
Errorsarereviewedelsewhere[27,91]butnotethatintherelativemeasurementoffigure4.3apathlengtherrorof10%translatestoasoundspeederrorofless
than1%,ifthereferencemediumiswateranditstemperatureisknown.Also,pulsetimeofarrival(TOA)canbedifficulttodefineitiscommontoemploythetime
whenthereceivedsignalisfirstdetectableabovenoiseortheoccurrenceofoneofthezerocrossings,butthesemeasureswillbeinerrorifthepulsechangesshape
afterpropagationthroughthetissue.Accountmustbetakenofattenuation

Page70

relatedpulseamplitudechangesandpulsestretchingduetofrequencydependentattenuation[27].TOAofthecentreofthepulse,e.g.estimatedusingcross
correlationmethods,isthoughttobebetteralthoughearliestTOAisadvantageousifthereismultipathpropagation.PhasecancellationmayseriouslyaffectTOF
measurementsandprovidesfurtherjustificationforcorrelationtechniques.Diffractionphasecorrections,madeinvariablepathandinterferometricsystemsatlow
frequencies,mayormaynotbenegligiblefortheinsertiontechnique.Theeffectsofmeasurementconditions,wheretheyareknown,followarelatedpatterntotheir
effectsonattenuation[27,91].
Water[30],saline[36]andwaterethanolmixtures[37]maybeusedforcheckingtheaccuracyandprecisionofasoundspeedmeasurement[27,91].
4.2.4
MeasurementofScattering
Acompletespecificationofultrasonicscatteringbytissue,reviewedelsewhere[3840,91],requiresmeasurementofmanydifferentscatteringcoefficients,someof
whichweredefinedinsection4.1.1,andmeasurementofthevariationofanyscatteringcoefficientwithoneoftheexperimentalvariables(frequency,scatteringangle,
orientation,spatialposition,etc)involvesaveragingoveroneormoreoftheothervariables.
Bothdirectandindirectestimatesofs(f)arepossible.Indirectmeasurementshaveresultedfrom:
thedifferencebetweentheattenuationcoefficientandtheabsorptioncoefficienta[15,41],althoughbothmeasurementshaverarelybeenmadeonthesame
specimensandtheresultislikelytobeinaccurate
subtractingfromameasurementofforanintacttissue,thevaluemeasuredaftergrindingthetissuetoremovethescatterers[42](butitisdifficulttodothiswithout
alteringa[27,91])
makinguseofchangesinbsand,measuredsimultaneously,whenthetissueismodifiedinsomeway[91].Ifthemodificationdoesnotaltertheangularscattering
distributionbswillbeproportionaltos.Thisisparticularlyusefulifitcanbeassumedthataisconstant,inwhichcasetheratioofs/maybeobtainedfromthe
ratioofthefractionalchangeintothatinbs.
Directmeasurementofs(f)wouldinvolveintegratingoverallanglesthemeasuredaverageangulardependenceofds( , ).Inpracticemeasurementsaremadeover
alimitedrangeofanglesandequations(4.6)or(4.7)usedeventhoughthelevelofisotropyofscatteringisingeneralunknown[4345].Themeasurementof
scatteringcoefficientsrequirescorrectionforattenuationandforthescatteringvolume,whichmayvarywithscatteringangle.Amoreestablishedliteratureis
associatedwithbsbut,althoughitissimplertomeasure,therearestillavarietyofapproaches.

Page71

Forthearrangementinfigure4.3,thepowerbackscatteredbythetissue,Wbs,maybederivedinasimilarmannertothe'weatherradarequation'[46]anddividedby
thepower,Wref,receivedfromaplaneinterfaceofreflectioncoefficient,Rref,positionedperpendiculartothesoundbeamtothesoundbeamatdistancez0[91].This
substitutiontechniqueyields

where isthesolidanglesubtendedatthereceiverbythecentreofthescatteringvolumeatdistancez0,wistheintensityattenuationcoefficientofthecoupling
medium(water),istheintensityattenuationcoefficientofthetissue,z1isthedistancefromthetissuesurfacetothebeginningofthescatteringvolume, zisthelength
ofthescatteringvolume(definedbyconvolvingtheacousticpulsewiththesignalgate)andtheincidentbeamisassumedtohavethehighlysimplifiedstructureofa
constantcrosssection(alongthelengthofthescatteringvolume)ofuniformmagnitudeandphasewithinspecifiedboundaries,outsidewhichtheincidentintensityis
zero.Thistechniqueisdesignedtocorrectfordiffractionlosses,thetransmittedacousticpowerandthecrosssectionalareaofthescatteringvolumemanyversions
havebeenderivedsincethefirstmeasurementofbsforblood[47],theleastrestrictiveappearingtobethatofreference[38].
Manyoftheerrorsinscatteringmeasurementsareassociatedwiththenormalisationinthesubstitutionmethod,whichisanareaofdiscrepancybetweeninvestigators
[44,48,49,91].Equation(4.16)describesasimpleapproachanditsdeficienciesincludethefactthattheincidentbeamdirectivityisnotarectangularfunction.The
effectofthisdependsonthenatureofthereflector,inparticularthedegreeofcoherenceinthescattering,butforaplaneinterfaceatthefocalplaneofaconcave
transducertheerroristhoughttobeoftheorderof1dB[91].Inprinciple,however,completespecificationofthetransmittedfieldcanbeusedtonormalisefor
reliableestimatesofbsatalmostanypositioninthefieldofeitherfocusedorunfocusedsources[38].
Otherpotentialuncertaintiesareassociatedwithfactorsanalogoustothoseinattenuationmeasurement,e.g.linearityofreceivedsignalamplification,uncertaintyin
attenuatingtissuepathlength,beamrefractionbythespecimenandphasecancellation.Inadditionbsestimatesareaffectedbyuncertaintyinthevalueoftheareaof
thereceivingtransduceraperture,andthevaluesofcorforthetissuespecimen.Phasecancellationisreducedbyensuringthatobservationsaremadeunderfarfield
conditionsbutevenenergysensitivedetectionwouldrequireaveragingofdiffractivefluctuations,withasufficientnumberofuncorrelatedinstantaneousestimates.
Errorsfortissuesarenotknownbutmaybeashighas70%[91]andscatteringmeasurementsmaybeevenmoreseverelyinfluencedbytheconditionofthetissue
thanattenuation[1,91].

Page72

Testsofscatteringmeasurementsystemsarelessstraightforwardthanforattenuation,duetothelackofavailabilityofanidealstandardmaterial.Asaplanereflectora
water/CCl4interfacemaybeused,forwhichequation(4.8)showsRtobe48dBat20C(althoughstronglytemperaturedependent),andrandomdistributionsof
microscopicglassspheresingelatinearepopularincoherentscatteringmodelsforwhichdscanbecomputedasafunctionofbothfrequencyandangle.
4.2.5
MeasurementofNonlinearity
TherearetwomainmethodsfordeterminingB/A.Thefiniteamplitudemethod[5053]isbasedonthemeasurementoftheamplitudeofthesecondharmonic
generatedduringpropagationofasinusoidalwave.Twotransducersareused,asinvariablepathattenuationmeasurement.Thesecondharmonicpressurep2(z),asa
functionofpropagationdistancez,is

wherep1(0)istheacousticpressureoutputofthetransmittingtransduceratthefundamentalfrequency, a1and a2aretheabsorptioncoefficientsofthemeasured

mediumatthefundamentalandsecondharmonicfrequencies,andDIFF(z)isthediffractioncorrection.Byanalogywiththeinsertionmethodofattenuation
measurement,normalisationforp1(0)andDIFF(z)isachievedbycomparisonofp2(z)determinedforthesamplewiththatofareferencemedium(10%NaClsolution)
ofknownB/Aandanacousticimpedancesimilartothatofthesample.Thethermodynamic(or'pressurejump')methodrequiresmeasurementoftherateofchange
insoundspeedinthesamplewithambientpressure,p,whenthepressureisdecreasedrapidly(atabout510MPas1)toapproximateanadiabaticdepressurisation
[53,54]

Thefiniteamplitudeandthermodynamicmethodshavesourcesoferrorincommonwiththoseforattenuationandsoundspeedestimation,respectively.Thetotal
systematicerroris~8%forthefiniteamplitudemethodand~5%forthethermodynamicmethod(butworseifsamplesareinhomogeneous)[55].Forliquids,
relativethermodynamicmeasurementsofB/Acanbeachievedwithaprecisionbetterthan0.3%[56].Temperatureappearstobeimportantbutthereappearstobe
nosignificantdifferencebetweeninvivoandinvitrovalues[57].

Page73

4.3
UltrasonicPropertiesofTissues
Thissectionprovidesasummaryofmaterialinpreviousreviews[1,4,27,5863,91].
4.3.1
AbsorptionandAttenuation
4.3.1.1
MolecularSpecies.
Asillustratedinfigure4.4,adependsstronglyonthestructuralcomplexityofthemedium.Althoughbodytissuescontainover60%waterthecontributionofthe
absorptionbywatertointissuesisnegligibleatlowmegahertzfrequenciesbut,becauseofthef 2dependence,thiscontributionmayprovetobemoresubstantial
above100MHz.Smallmolecules,suchasaminoacidsinaqueoussolution,barelymodifya(f)ofwaterbutwhenassembledintowholebiopolymers,suchas
proteins,theycontributesignificantlytoa.Forbiopolymers,amayincreasewithmolecularweight,butnotalwaysandthedependenceisnotwellunderstood[64].
Absorptionisoftencharacteristicofinteractionbetweenmacromolecules,havinganonlinearconcentrationdependenceandbeingincreasedbychemicalfixativesthat
promotecrosslinkages.
Thefrequencydependenceofultrasonicabsorptionforbiopolymers(typicallybetweenf 1andf 1.4)suggestsadistributionoftimeconstantsforrelaxationprocesses,
butthespecificrelaxationmechanismsandtheirnumberareunknown.Relaxationistheprocessbywhichtheacousticwavemayrepeatedlyperturbsomephysicalor
chemicalequilibriuminthemedium.Thewaveenergyiscyclicallyredistributedbetweentranslational,molecularvibrationalandstructural,orlatticevibrationaland
structuralstates,butwithatimelagforreturntotheoriginalenergydistribution,sothatwaveenergydegradestoheat.Thefrequencydependenceofasinglerelaxation
processhasageneralformdescribedby

whereARisaconstant(therelaxationamplitude)andf Ristherelaxationfrequencycorrespondingtothetimeconstantfortheprocess.Atfrequencieswellbelowf R,R

f 2,whichdescribesthebehaviourofwateratmedicalfrequenciesduetothe'classical'processesofshearviscosityandthermalconductivity.Absorptioninsolutions
ofbiopolymershasbeenmodelledbysummingmultiplerelaxationprocessesandtheclassicalabsorptionduetoshearviscosity, ,(neglectingthermallosses):

Page74

Figure4.4.
Generaltrendsforthevariationofthe
attenuationcoefficientwithfrequency
andtissue(after[1],whichalsocontains
thereferencestotheoriginalsourcesofdata).

ItisthoughtthatatphysiologicalpHthedominantrelaxationmechanismsarisefromperturbingthehydrationlayersofmacromolecules,i.e.structuralrelaxation
betweenthenumberofwatermoleculesatanyinstantinafreeorboundstate.
4.3.1.2
Tissues
Despitethedifficulty,frompublisheddata,ofdistinguishingthebiologicalvariationofofmanytissuesfromsystematiceffects,thefollowingobservationsmaybe
made.
Formosttissues,thecontributionofscatteringtoattenuationisunknown.Scatteringhasnotbeenobservedatmedicalfrequenciesfromsomeuniformmediasuchas
amnioticfluid,aqueoushumour,vitreoushumour,andcystliquids(althoughnotall).Theveryhighvalueforininflatedlung(seefigure4.4)ispredominantlydueto
scatteringbygasbubblesandsomemodelsattributethefrequencydependenceandhighvalueinbone,whichmaybebetween2and20timesthatforsofttissue,to
scattering

Page75
Table4.1.Selectionofpublishedestimatesforthecontributionofscatteringtoattenuation.
Species

Director
indirect

Angulardistributionofds

Human

Direct

19.00 47

[44]

Angulardistributionofds

Calf

Direct

2.00 37

[43]

Measurementofa and

Beef

Indirect

18.00 5.60

[15]

Changesinbsand

Human

Indirect

916

4.00

[1]

Changeinondestructionoftissuestructure
(knownoverestimation,seetext)

Beef

Indirect

30.00 110

Frombsassumingisotropicscattering

Human

Indirect

0.10.6

515

[90,44]

Angulardistributionofds

Human

Direct

0.10.5

47

[44]

Method

s/(%)

Freq.(MHz)

Reference

(i)Liver

[42]

(ii)Blood

fromanisotropicgrainlikestructures.BoneisdiscussedingreaterdetailinChapter16ofthisvolume.
Anintactcellularstructureappearstoberesponsibleforabout19%oftherelativelylowattenuationcoefficientofbloodandhighlevelstructureaccountsforabout
30%ofattenuationinliver[42].Howeverinneithercasearethesenecessarilythecontributionsofscatteringtoattenuation,sincehighlevelstructuremaycontributeto
absorptionthroughmechanismssuchasviscousrelativemotion,wheredampingofthesoundwavemayoccurduetorelativemotionbetweenastructureandthe
surroundingviscousmedium,whenthedensityofthestructureisdifferentfromthatofthemedium.Thereisacyclictransferofmomentumbetweenthestructural
inhomogeneitiesandtheembeddingmedium,whichtakesplaceatafiniterateresultinginafrequencydependenceofabsorptionnotunlikethatforrelaxation
phenomenabutwheretheequivalentoftherelaxationfrequencyisitselfafunctionoffrequency.Thefrequencydependentfunctionisspecifictotheshapeofthe
inhomogeneityandhasbeenevaluatedonlyforsimpleshapessuchasspheresandcylinders.Afrequencydependenceforthissourceofattenuationintissuemaybe
obtainedbysumminganumberofprocessesinvolvingadistributionofsizesandshapesofinhomogeneity.Itisthoughtthatviscousmotionallossescouldaccountfor
10%ofattenuationinbloodandthatonly1%atmaximumcanbeaccountedforbylongitudinalwavescattering[65].Insolidsofttissuetheevidenceforthe
contributionofscatteringtoattenuationisinconsistent.Innormalliver,thetissuemostoftenstudied,viscousrelativemotionlosseshavebeencalculatedtobeashigh
as60%of.Table4.1summarisespublishedresultsfrombothdirectandindirectestimatesofs/.

Page76
m

Thefrequencydependenceof,asshowninfigure4.4,isoftendescribedoverlocalfrequencyrangesbythemodel=bf .Mostsofttissuesandbodyliquids
exhibitavalueofmalittlegreaterthanunityandthishasbeenobserved,forsometissues,toextendtof>100MHz.Atstillhigherfrequenciesonemightexpectthe
f 2dependenceofabywatertobegintodominate.Thewidevariationinpublishedresultsforanyparticularsofttissuedoesnotingeneralpermitanadequate
evaluationofcompetinghypotheses,intermsofscatteringorabsorptionmodels,fortheobservedfrequencydependenceofattenuation.Apossibleexceptionis
muscle,forwhichthedatahavebeensaidtosuggesttheexistenceofastrongrelaxationregionat~40kHz,inadditiontomechanismsatotherfrequencies.
Insofttissuesisacomplexfunctionoftemperature,T.ForT=640C,andf>2MHz,d/dTisnegativeanddecreasesbothwithTandf.Asfdecreasesone
findsafrequencyatwhichd/dT~0,belowwhichd/dTmaybepositive.Above40C,d/dTbecomespositiveandirreversible,evenathighfrequencies,
consistentwithheatdenaturationofmacromolecules.Thisbehaviourisnotunderstood,beingpartiallyconsistentwitheithermolecularrelaxationorviscousrelative
motion.
Thestructuralproteincollagenhasaparticularlyhighvalueofelasticmodulusandisthoughttoplayakeyroleindeterminingattenuationandscatteringcharacteristics
ofmanytissues.Thedatainfigure4.4exhibitthetrendthatincreasingcorrelateswithincreasingcollagencontent.Forparenchymaltissues,whichintheirnon
diseasedstatecontainrelativelylittlecollagen,dependsmainlyontheoverallproteincontent,i.e.isinverselyrelatedtothewatercontent.Variousdiseasesand
woundsmaycausealocalincreaseincollagencontentwhich,intheabsenceofanincreaseinfluidcontent,invariablyresultsinanincreaseinattenuationand
scattering.Forsometissuesand/ordiseaseconditions,fatcontentisalsoimportant.Soundisscatteredstronglyatfat/nonfatinterfacesduetoalowsoundspeedin
fat.Iftheinterfacesarepresentinsufficientnumber,suchasinnormalhumanbreastorfattydiseasedliver,thentheymaycontributetoraisingandsinthesetissues.
Otherdiseases,sometypesofcancerforexample,raisethewatercontentandconsequentlylowerandsalthoughthesituationiscomplicatedsincetissuechanges
usuallyinvolvethesimultaneousalterationofmanysuchproperties.
4.3.2
SoundSpeed
Figure4.5providesexamplesoftherangesofcthathavebeenmeasuredinvariousmammaliantissues,withsomenonbiologicalmediaforcomparison.Excluding
lungandbone(leftofthefigure)thetotalrangeintissuesis~10%ofthemean,andspatialvariationsaregenerallyneglectedinthedesignofmostmedicalimaging
systems.Thelargedifferencesinvaluesforcand 0oneithersideofboundariesbetweenasofttissueandgas

Page77

Figure4.5.
Rangesofvaluesforspeedofultrasound
intissuesfortemperatures2037C
(leftandmiddle)andexamplesofthe
temperaturedependenceofsoundspeed
(farright).Sourcesofdataasreviewed
in[27],exceptwhereindicatedby*,
inwhichcasetheyarefrom[54]
(after[91]).

orbonegiverisetoveryhighlevelsofscatteringwhich,combinedwiththeassociatedhigh,makeitdifficult(oftenimpossible)toobtainusefulultrasonicimages
throughbone,lungorothergas.
Forsofttissuesinthemiddlesectionoffigure4.5,variationincisdeterminedlargelyatthemolecularlevel,ratherthanbythepresenceofintactcellsorhigherlevel
structure.Frequencydispersion(studiedupto100MHz)isverysmall,thelargestreportedvariationbeinggreaterthan0.5%increaseincperdecade,whichisclose
tothatpredictedfrombothrelaxationtheoryandgeneralrelationshipsbetweenattenuationanddispersion[66].Thetemperaturedependence,however,isstrong
enoughtohaveaccountedforsomeofthevariabilityofearlyresultsinvitro.Forfatdc/dTisstronglynegativeandfornonfattytissuesitispositive,which

Page78

givesrisetounpredictabletemperaturedependenciesincomplextissuessuchasbreast,aminimuminsoundspeedinadultbrainat15C[66],aslightnegative
temperaturedependenceinfattyliver[54]andastrongtemperaturedependenceofscatteringfromfat/nonfatinterfaces.Forfattytissuechasalsobeenobservedto
dropabruptlywithtemperatureinassociationwithasolid/liquidphasetransition,althoughitisnotclearthatmeltingcausedtherapidchangeinc[92].Heat
denaturationorcoagulationoftissuesproducesasmallbutmeasurabledecreaseinsoundspeed[67].TheshapesofthecurvesofcversusTfornonfattytissues,with
amaximumintheregionof4070Caresimilartothoseforwaterandaqueoussaltsolutions,whereasfatbehavesmorelikemostotherliquids.Thelowsoundspeed
forfatatbodytemperaturemakesitanacousticallyimportanttissuecomponent,accountingforsomeoftheobservedvariationincbetweentissues.Increasingsound
speedalsocorrelateswithincreasingproteincontent,particularlythestructuralproteincollagenpresentinskin,cartilageandtendon,andwithdecreasingwater
content.Fortissuessuchasliver,whichcontainonlymoderateamountsofcollagen,normalandpathologicalvariationsinsoundspeedarelargelyexplainedby
simultaneousvariationofboththewaterandfatcontent.Invivomeasurementofcinanorgansuchasthelivermayenableuniqueidentificationofincreasedfat
contentasthecauseofincreasedattenuationorscatteringwhichmightotherwisebeduetofibrosis.Highwatercontentisbelievedtoexplaintheresultsforfetalbrain
(figure4.5,right).
Thehighsoundspeedandattenuationinskullboneisaccompaniedbyarelativelylargedispersion,believedtobeassociatedwithscattering.Bonemayalso
propagatetransversewavesandbehighlyanisotropic,dispersionoflongitudinalsoundspeedvarying~112%,over13MHz,dependingonthebonetypeand
directionofpropagation.Transversewavespeedalsovarieswithdirectionbutfallsintherange18002200ms1.
Muscleisalsoanisotropicbuttherearedifferingobservationsforwhethercishighestalongoracrossthefibres[27],anddifferentauthorshaveobservedsoundspeed
toincreaseanddecreasewithmusclecontraction(althoughanincreasehasonlybeenobservedinvivowherefactorssuchasbloodcontentvaryduringcontraction).
4.3.3
Scattering
Thescatteringpropertiesoftissueshavebeenreviewedbyvariousauthors[5,68,91].Mostpublishedresultsareforbs(figure4.6)andthedataexhibitawide
variationforsometissues,makingitdifficulttoevaluatemodelsfortheirscatteringstructure.
The'simplest'ofthescatteringtissuesisblood,forwhichgoodagreementhasbeenobtainedbetweenexperimentalresultsandtheoreticalpredictionsbasedon
modellingbloodasacollectionofsmall(radius,r,about3m)fluid(aqueoushaemoglobinsolution)spheresofthesamevolumeasredbloodcells.Experimentswith
redcell'ghosts'havedemonstratedthat

Page79

Figure4.6.
Examplesoftrendsforvariation
ofultrasonicbackscatteringcoefficient
withfrequencyandbiologicalmedium.Key:
a,b,c,d,i,j,k,l,asreviewedin[68]
butexcludingcalflivere[48]
g[87]h[73]i[88]m[88]
(adaptedfrom[91]).

thereisnegligiblecontributiontoscatteringfromthecellmembrane.When >~20r,Rayleighscatteringtheoryappliesand[70]

whereVeisthevolumeofaredcell,k e, eandk f, farethecompressibilityandmassdensityofredcellsandthesurroundingfluidrespectively.Thusthescattered

powerwillvaryasf 4(observedinflowingbloodorredcellssuspendedinsaline)andthesquareoftheredcellvolume(observedbyutilisingthespeciesdependence
ofredcellsize).Thepredictedangularscatteringdistribution(predominantlybackward,fromthesumofthemonopolecompressibilityanddipoledensityterms)
agreeswellwithmeasureddistributionsalthoughamodelthatincludestheeffectoffluidviscosityonthedipoleterm,providesabetterfit[71].Thereisalinear
relationshipbetweenbsandredcellconcentrationonlyforhaematocrit<8%.Dilutebloodisexceptionalinthat sand dsforindividualscatterers

Page80

canbecalculated[68].Fornormalwholeblood,redcellsdonotbehaveaseitherindependentorsmallscatterers:
bspercelldecreasesuntilitpeaksathaematocrit=13%
redcellsaggregateintolargerunitsthatscattermorestrongly,accordingtheV2dependence.Aggregationisreducedbyshearingforcessothat bsisinverselyrelated
toflowratehencevenousbloodismoreechogenicthanarterialblood
bscorrelateswithbotherythrocytesedimentationrateandtheconcentrationofplasmaproteinsassociatedwithclotting
forwholebloodthefrequencydependenceisreducedfromf 4atlowflowrates.
Turbulentflowalsoincreasesthescatteringfrombloodandbloodclotsaremoreechogenicthanunclottedblood.Bloodstructureisspatiallycorrelatedandmaythus,
atanyinstant,actlikesolidtissuestoproducepartiallycoherentscattering,toadegreedependentonthehaematocrit[70].
Identificationandmodellingofthescatteringstructureoftissuesmorecomplexthanbloodhasprovendifficult.Apopularmodelforthescatteringstructureoftissuesis
theinhomogeneouscontinuummodelinwhichmassdensityandcompressibilityareassumedtofluctuatecontinuouslybysmallamountsabouttheirmeanvalues, 0and
k 0,andinamannerdescribedstatisticallybyspatialautocorrelationfunctions(ACF)inbothquantities.BothGaussianandexponentialACFshavebeenemployed.A
furthersimplification,butonethatisdisputed,isthatfluctuationsindensityarenegligiblebycomparisonwiththoseincompressibility.Analternativeassumption,that
andkfluctuationsareinverselyrelated,leads(foraGaussianACFinboth andk)to[44]

wherea*isthecorrelationdistanceoftheACF,describingthescaleofasinglecharacteristicscatteringstructure(inverselyrelatedtomeanspatialfrequency).The
frequencydependenceofbackscatteringfrommyocardium(figure4.6)forexampleappearstobequitewelldescribedbyafitsomewhereintherangef 2.7f 3.3,
consistentwitharelativelysimplecharacteristicstructureclosetothecellularlevel.Liverhasacomplexstructure:bsincreaseswithffrom~f 0at1MHztoaboutf 3at
7MHz,suggestingthatasimplemodelwithonecorrelationlength(whichpredictsadecreasingfrequencydependence)isinadequate.Compositemodelswithtwoor
threecorrelationlengthsgiveabetterfit[72]andwouldalsoseemtobeappropriateforothertissuessuchasbrain[73]andkidney[74].It

Page81

Figure4.7.
Polarplotsoftheangulardependenceofthe
differentialscatteringcoefficientat6MHzforblood,
liverandskeletalmuscle[44].

thereforeseemsthatinsuchtissues(figure4.6)mostofthescatteringatlowfrequencies(12MHz)arisesfromrelativelylargestructures,suchassmallvesselsand
liverlobules(~1mm).Asfincreasestheslopeofthefrequencydependenceincreasesandeventuallyapproachesthatforblood,indicatingthatathigherfrequencies
thescatteringfromthecellularstructure(~20m)dominates.Itmaybeanticipatedthatathigherfrequenciesthefrequencydependenceofscatteringshouldbeginto
decreaseagain,unlessscatteringfromsubcellularstructuresbeginstodominatethetotalscatteredpower.
Theaverageangularscatteringpatternoftissues[43,44]hasalsobeenusedtoestimatethecharacteristicsizeofthescatteringstructuresandtheresultsareconsistent
withtheaboveobservationthatthesizeofthedominantscatteringstructuredecreaseswithincreasingfrequency.Figure4.7showsangularscatteringdata[44]from
whichitwasestimated,byfittingequation(4.22),thatat6MHz'effectivescatteringstructures'existwithinblood,skeletalmuscle(perpendiculartothefibres)and
liverwithcorrelationlengthsof81m,745mand618m,andwithdensityfluctuationsof50%,28%and15%ofthecompressibilityfluctuations,respectively.
Methodsofmeasuringthevariouskindsofdshavegivenrisetoapproachestoparametricimagingthatpermitamodelbasedanalysisoftissuestructurebyfitting,to
theexperimentaldata,thevariationofdswithagivenmeasurementvariablepredictedfromagivenmodelofthetissuestructure,descriptionsofthetissuemaybe
providedintermsofparametersofthemodel.Withinthisapproach,effective'scatterersize'isavailablefromtheaverage(incoherent)frequencyorangular
dependenceofds[75,76,93].Effective'scattererspacings'havebeenestimatedfrom

Page82

Figure4.8.
ExamplesofthenonlinearityparameterB/A,
atatmosphericpressure.Key:a[3]b[50]
c[55]d[89]e[85]f[54]g[53](after[91]).

interference(diffraction)patternsassociatedwiththecoherentcomponentofscattering,asafunctionoffrequency[77],tissueorientation[73,78]andspatialposition
[79,80].Forliver,observedfluctuationsareconsistentwithscattererspacings~1mm.'Structuralanisotropy'isavailablefromtheaverage(incoherent)orientation( )
dependenceofdstheouterregionofthekidney,thecortex,hasaradialpatternofcollectingsystemsandexhibitsstronganisotropyofbs,asdoesscatteringfrom
muscle[81].SuchscatteringhasbeenmodelledusingatwodimensionalanisotropicGaussianACFandhasassistedintheidentificationoftwodominantscattering
structuresintherenalcortex:bloodvessels/tubulesandglomeruli[75].
Fromtheabovediscussionitmaybenotedthatdifferencesinthescatteringcoefficientsfordifferenttissues(figure4.6)mayarisefromacombinationofatleastfive
tissueproperties:thecompressibilityanddensityvariationsthatcausethescatteringthecharacteristicsizeofthescatteringstructurestheircharacteristicspacing
(numberdensity)theirdegreeofalignmentandtheirpreferentialorientationifstronglyaligned.Tissueechogenicityisoftenrelatedtoconnectivetissuecontentsince
thecompressibilityanddensityofstructuralproteinssuchascollagenandelastinareverydifferent

Page83

fromthoseofothertissuecomponents[82].Strongscatteringisthereforeobservedfromskin,whichisrichinrelativelylarge(50100m)stronglyalignedbundlesof
collagenfibres,andcollagenrichpathologysuchasinfarctedmyocardium.Attheotherextreme,bloodisanisotropiccellularscatterercontainingnostructuralprotein.
Becauseofthelowsoundspeedinfatatbodytemperaturestrongscatteringoccursintissuessuchasbreast,whichcontainslargefat/nonfatinterfaces,and
backscatteringfromdiffuselydiseasedliverishighlycorrelatedwithpercentagefatcontent.Increasedwatercontent,dilutingthenumberdensityofscatterers,is
associatedwithreducedbackscatterinliverandnonfibrouslivertumours[78].Lackofalignmentandthesmallsizeofcollagenfibresappearstoaccountforreduced
backscattering,relativetodermis,insomehighlycollagenousskintumours[83].Thetemperaturedependenceofscatteringcoefficientsisunknownbutheat
coagulationofliverslightlydecreasesthebackscatteringcoefficient[67].
4.3.4
Nonlinearity
ExamplesofreportedvaluesforB/Aareprovidedinfigure4.8.Forwaterfrom0to40C,solutionsofmacromoleculesandmosttissues,B/Aincreasesslightlywith
increasingsoundspeedandtemperature.B/Aforfat,however,isgreaterthanforaqueousmediaandothertissues(cf.soundspeed,wherethereverseistrue)and,as
temperatureincreases,B/Aandcvaryinaninversemannerforfattyliver[54].Thisbehaviourissimilartothatseeningeneralforpurenonbiologicalmediawhere
B/Aisinverselycorrelatedtosoundspeed[3,84].ForsolutionsofbiologicalcompoundsB/Adependsontheconcentrationandonthetypeofsolutebutis
independentofmolecularweight.Solutesolventinteractionsarethereforeregardedasthemostlikelysourceofnonlinearityinsuchmedia,ratherthaninteror
intramolecularinteractions,withthesolutehydrationshellstructureplayinganimportantrole[56].B/Ahasbeenshowntoresultfromalinearcombinationof
contributionsfromvariouschemicalcomponents,andsimultaneousmeasurementofcandB/Aenableschemicalcompositiontobepredictedintermsofthevolume
fractionsofwater,fatandresidualcomponentssuchasproteinsandcarbohydrates[54].ValuesforwholeandhomogenisedliversuggestthatB/Aisinfluencedbythe
presenceoflargescalestructureintissue[53]aftersubtractingthecontributionduetowatertheremainingcontributionstoB/Aappeartobe26%fromcellcell
adhesiveforce,20%fromhepatocytecellularstructureand15%fromsecondary/tertiaryproteinstructure.
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[92]JohnsonSAetal1977NonintrusivemeasurementofmicrowaveandultrasoundinducedhyperthermiabyacoustictemperaturetomographyUltrasonics
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[93]MercerJ1997UltrasoundscatterersizeimagingofskintumourspotentialandlimitationsPhDThesis,UniversityofLondon

Page89

PART2
TECHNOLOGYANDMEASUREMENTINDIAGNOSTICIMAGING

Page91

Chapter5
TransducerArraysforMedicalUltrasoundImaging
ThomasLSzabo
Introduction.
Thetransduceristheindispensiblepartofadiagnosticultrasoundimagingsystem.Phasedandlineararraysfocusandelectronicallyscanelasticwavesintothebody,
andgathertheechoesfromtissuesforgeneratingrealtimeimagesofthebody.Overthelast30years,transducershavecontinuedtoevolve:providingimagesof
betterclaritydetail,andfidelitygoingwherenoarrayhasgonebefore(newapplicationsandorifices),andproducingnewinformationaboutorganfunctionandtissue
viability.
Theroleofthetransducerintheimagingprocessisexaminedhereinacomprehensiveway.Beginningwithindividualpiezoelectricelements,inthefirsthalf,weshall
coverarraystructures,designchallenges,transducermodellingandmaterials,andachievableperformance.Inthesecondhalf,thebeamformingfunctionsofanarray
inconjunctionwithanimagingsystemareexamined.Arrayconfigurations,beamsteeringandfocusing,apodisation,achievableresolutionandnonidealarray
performancearealsoincluded.Referencesareprovidedtomoredetailedworksforthosewishingtopursueanytopicinmoredepth.
5.1
PiezoelectricTransducerElements
5.1.1
ABasicTransducerModel
Ultrasoundtransducersformedicalpurposes(Huntetal1993)employpiezoelectricelementsthatconvertelectricalsignalstomechanicalforces

Page92

andviceversa.Thebasiccharacteristicsofapiezoelectrictransducercanbedescribedbyasimplemodel.Thetransducerisessentiallyacapacitorthatconverts
electricalsignalsintoacousticwaves.Thisabilitycanbeexpressedasapiezoelectricstressequation(Auld1990),

whereSisstressTisstrainDisdielectricdisplacementCDiselasticstiffnessconstantobtainedunderconditionsofconstantDandhisapiezoelectricconstant.The
piezoelectricelementcanbethoughtofasasingingcapacitorofareaAandthicknessd,C0= SA/d,asillustratedinfigure5.1,whereC0istheclampedcapacitance
and Sistheclamped(zerostrain)dielectricconstant.Whenavoltage,V,isappliedacrossthetwoelectrodedfacesofthecapacitor,oppositelysignedstresses
appearonthesesidesthroughthepiezoelectriceffect.Thesestressescanberepresentedasimpulsiveforcesoneachelectrodedface:

underaclampedconditionofzerostraincausedbytheloadingofeachfacebymedia.Inthisexample,theloadimpedanceZAisequaltothetransduceracoustic
impedance.ThroughaFouriertransformofthisstressrelation,thestressfrequencyresponseis

wherethefundamentalresonantfrequencyisf 0= /(2d) istheacousticvelocitybetweentheelectrodes,

theangularfrequencyis 0=2 f 0andn=
0,1,2,...Bothequations(5.2)and(5.3)aredemonstratedbyfigure5.1.Notethatonlyoddharmonicfrequenciesaregenerated.
Theelectricalinputimpedance,ZT( )ofapiezoelectrictransducercanberepresentedbyacapacitivereactanceinserieswitharadiationresistance,RA,anda
radiationreactance,XA

Tofirstorder,wecandeterminetheradiationresistancefromthefrequencyresponseofthestressfoundearlier.Therealelectricalpower,WE,intothetransducerfor
anappliedvoltageVandcurrentIis

wherethecurrentisI=i Q=i C0V.Thetotalacousticpowerintothemediumonbothsidesoftheceramicdeliveredintothesurroundingmediumofspecific

impedanceZA= Ais

Page93

Figure5.1.
Simplifiedmodelofpiezoelectricelementofthicknessd
andareaAwithvoltageinducedstressesatelectroded
sidesandcorrespondingstressfrequencyresponse.

Byequatingthepowersabovefromequations(5.5)and(5.6),RAcanbefoundas

inwhichsinc(x)=sin( x)/( x).Since

isacouplingcoefficient),RAOcanbeshowntobe

TheradiationreactancecanbedeterminedbycausalityastheHilberttransformofRA(NalamwarandEpstein1972)

Infigure5.2,thetransducerimpedanceisdissectedintoitsparts,RA,XA,XCandXA+XC.LetXC=1/( 0C0)andX=XA+XC.Atthecentrefrequencyof5MHzthe
radiationresistanceisRAOandXA=0,andX=1/( 0C0).
5.1.2
TransducerElementsasAcousticResonators
Thethreedimensionalnatureofthepiezoelectricelementresultsintheinevitablecouplingofthemainvibrationalmodealongthepolingaxistothoseintheothertwo
perpendiculardirections.Asthepiezoelectricmaterialissqueezedbetweentheelectrodes,itbulgesoutatthesidestherefore,theverticalextensionalmodeiscoupled
tolateraldilationalmodes.

Page94

Figure5.2.
Transducerelectricalimpedancefora5MHzresonant
frequencyPZT5Hbeammodetransducerwithan
impedanceof30X106kgm2s1forbackingand
waterloading.

Figure5.3.
Diagramshowingapiezoelectricelementasamultimode
acousticresonatorwiththreefundamentalresonantfrequencies
whichareintercoupled.

Thepiezoelectricelementcanbeconsideredtobeathreedimensionalacousticresonatorwitheachdirectioncapableofsupportingfundamentalandharmonic
resonantfrequenciesasillustratedinfigure5.3.Furthermore,thesemodesarecoupledmoretightlytogetherasthethreedimensionsbecomecloserinsize.
Fortunately,formostarrayelements,theelevationdimension,L,ismuchgreaterthantheothers,sothatitsresonantfrequencyisverylowandfarbelowtheimaging
frequencyband.Thepropertiesofatypicalarrayelementresonatordependmainlyonthewidthtothicknessratio, /d(Satoetal1979,KinoandDeSilets1980).
Twoextremegeometriesaregivenbyfigure5.4.Thethicknessmodeinwhich >>dandL>>d,applicabletolargemechanicaltransducers(withalargearea
normaltothepolingaxis),andthebeammodeforplankshapedelementswhereListhegreatestdimension, >>dandL>>d.Boththeelectromechanicalcoupling
constantandtheacousticvelocityareslowlyvaryingfunctionsoftheratio /d.Casesofinterestfortheseextremegeometriesarelistedintable5.1forawidelyused
piezoelectricceramic,PZT5H.Inpractice,the /dratiosaresmallsothatcouplingconstantsand

Page95

Figure5.4.
Piezoelectricelementsoftwoextremegeometries:
thebeamandthicknessmodes.
Table5.1.ConstantsforVernitronPZT5Hforthicknessandbeammodes.

Mode

Electromechanical
couplingcoefficientk

Thickness

k T=0.5

Beam

=29.7

Wavespeed (ms1X
103)
= 4.56

AcousticimpedanceZ
(kgm2s1X106)
Z=34.7

Relativedielectric
constant S/ 0
T

/ 0=1470

/ 0=1508

33

acousticvelocitiesareclosertothebeamvaluestherefore,smallelementsbenefitfromahighercouplingconstantcomparedtolargethicknessmodetransducers
(Souquetetal1979,Fukumotoetal1981).Theactualvaluesforthepiezoelectricceramicaredeterminedeitherbyexperimentalmethods(Szabo1982)orbythe
moreaccuratemodelsdescribedlater.
5.1.3
TransducerArrayStructures
Becauseapiezoelectricelementisbidirectional,effortshavebeenmadetooptimisetheconversionefficiencyandbandwidthintheforwarddirectiontowardsthe
tissue.Ontherearface,anabsorbingbackingmaterialisusedtoreflectenergyintotheforwarddirectionandtobroadenbandwidth.Thedisparitybetweenthe
acousticcrystalimpedance

Page96

Figure5.5.
Thegeometryofamultilayerstructurebeingdiced
intoarrayelementsbyasaw.

whereZcisnormalisedcrystalimpedanceandZwisnormalisedwaterimpedance.
Atypicalarraystructurebeginsasthesandwichoflayersshowninfigure5.5.Duringconstruction,thesandwichisdicedintoindividualelementsandfinallayersanda
mechanicallens(notshown)areaddedastoppings.Hereacousticport1ofthemodelcorrespondstothetopdirectioninthisillustration.Inordertobetterdescribe
theperformanceofthisstructure,morecomprehensivetransducermodelsarerequired.
5.1.4
TransducerModels
Byconvention,aonedimensionaltransducerequivalentcircuitmodelforapiezoelectricelementisviewedasathreeportdevicelikethatoffigure5.6.This
representationprovideselectricalanaloguesofvoltagesandcurrentsforacousticforceandparticlevelocity.Asinthesimplermodeldescribedearlier,the
piezoelectricelementhasanelectricalportwherevoltageisappliedandtwoacousticportsoneitherelectrodedface.Byreciprocity,thisthreeportmodelisequally
validforeithertransmitorreceiveoperation.Inordertorepresentoneelementofthedicedtransducerarraystructure,anacousticportisloadedbytransmissionline
sectionsrepresentingeachmatchingorbondinglayerandtheelectricalportisconnectedtoelectricalmatchingnetworksandterminationsasdemonstratedinfigure
5.7.Inputvariablesfortheoveralltransducermodeltypically

Page97

Figure5.6.
Onedimensionalequivalentcircuitmodelofa
piezoelectricelementasathreeportdevice.

Figure5.7.
Onewayonedimensionalequivalentcircuitmodel
ofwholetransducerincludingbacking,electrical
matchingandmatchinglayersandlens.

consistofthefollowing:forthepiezoelectricelement,theareaA,thicknessd,effectivevelocity e,couplingconstantk eandimpedanceZc,clampeddielectricconstant

S ,acousticloss,anddielectriclosstangentandforeachlayer,theacousticcharacteristicimpedance,velocity,layerthicknessandloss.Typicaloutputparametersof
interestaretheoverallelectricalinputimpedance,frequencyresponseorinsertionloss,animpulseresponse,andthepulse/spectrumresultingfromdifferentexcitation
functionswhichareobtainedbyaFourierapproachusingfastFouriertransforms(Mequioetal1983).
Whatarethespecificequivalentcircuitmodelsthatliewithintheboxoffigure5.6?Manymodelshavebeenproposed,butthetwousedmostfrequentlyarethe
Mason(Berlincourtetal1964,Mason1948)andKLM

Page98

Figure5.8.
Twofiniteelementsimulationsof2Darrays
theoneontheleftiscappedbyalensandtheone
ontherightiswithoutalens.Simulationsgeneratedby
PZFLEXprogram,courtesyofWeidlingerAssociates.

(Leedometal1971)thicknessmodemodels.Whilethestructuresofthesemodelsdiffer,theywerederivedfromthesameelasticwaveequationsandthereforegive
exactlythesamenumericalresults.TheKLMmodelusesthecentreofthecrystalasthepointofacousticexcitationwhichsomefindanalyticallymoreappealing,even
thoughphysicsshowsthatstressesarecreatedatthecrystalboundaries.Bothonedimensionalmodelsworkreasonablywellforfirstorderdesignpurposes,with
modificationsmadeforarrayelementswhereeffectiveparametersappropriatefortheelementgeometryaresubstitutedforthicknessmodevalues.Athirdmodelhas
thecapabilitytolinkthetransducertononlinearandactiveelectronicdriversandreceivers.Thismodel(HutchensandMorris1984)usesanapproximateMason
modelwrittenasaninputfiletotheSPICEprogram,softwarewrittenforelectricalcircuitandelectronicsimulationanddesign(Vladimerescu1984).
Finiteelementmodelling(FEM)(Wojciketal1993,1996)isbeingusedtosimulatetransducerarrayperformancemorerealistically,includingcomplexmodal
interactions.Thistypeofmodellingisusefuleitherforpreviewingarraybehaviourpriortoconstructionorforanalysingspuriousmodes.Fortwodimensionalarrays,
spacedonhalfwavelengthcentres,the /Lratiosapproachunity,sothatacousticresonantmodesarecoupledstrongly.Asimulationofa2Darraywithandwithout
alensisillustratedinfigure5.8.Realisationofmoreaccuratemodellingforhigherarray

Page99

Figure5.9.
Diagramshowingtransducerlossastheproduct
ofelectricalandacousticlossfactors.

performancedependsonthedevelopmentandfullcharacterisationofnewandexistingmaterials.Inaddition,simplifieddesignmethodsaccountingforcomplexarray
modalinteractionsareneeded.
5.1.5
TransducerDesign
Thestartingpointofdesignisusuallyfromaonedimensionalmodelwitheffectiveparametersappropriateforthegeometryselected.Thedesignprocessismademore
challengingbyfixedconstraintssuchasthesizeoftheelement,therequiredbandwidth,animpulseresponseofcertainminimumlength,theneedforalenswithlosses,
andelectricalrequirementssuchasacableandelectronicinterfaces.Theoverallcombinationofrequirementsforonewaytransducerlossisrepresentedschematically
infigure5.9forthetransmitcase.ThechallengeofdesignishowmostefficientlytocoupleenergyfromthesourceVgtothetissuerepresentedbyloadZwwhile
simultaneouslymeetingallgivenconstraints.Theproblemcanbeviewedinthefollowingtwoparts:maximisingtheelectricallossfactorELwhichistheratioofpower
deliveredtoRAtothatavailablefromthesourceandmaximisingtheacousticlossfactorAL,thepowertransferfromRAtoZw.
FromtheKLMmodel,theradiationresistanceatresonancecanbeexpressedinasimpleformwhichisageneralisationofequation(5.8)(DeSiletsetal1978),

whereZcistheacousticcrystalimpedanceZL,theimpedanceatacousticport2andZR,theimpedanceloadseenatacousticport1.Thisrelationis

Page100

Figure5.10.
Oneway3dBbandwidthsgeneratedby
maximallyflatcriteriaandanimpedance
mismatchratioof30/1.5=20.

usefulinexplainingrelationshipsamongessentialparameters.UsuallytherightportiscloselymatchedtoZcthroughquarterwavelengthmatchinglayers.Ifboth
acousticportloadimpedancesaremadeequaltoZc,broadbandwidthisobtainedattheexpenseofhalfthepowerlostinthebackingatport2.Attheotherextreme,
airbackingputs100%oftheacousticpowerinport1,butwithnarrowerbandwidth.Asthesizeoftheelementdecreases,C0decreases,andRAincreases,making
electricalmatchingtotheelementmoredifficult.Acousticlossatresonanceactslikeapowersplitter,

Thisrelationcanbeusedtoestimatetheimpactofquarterwavematchingandbackingimpedancecombinations.ForthebasicmodelwhenZL=ZR=Zc,AL=1/2.
Formultiplematchinglayers,severalschemeshavebeenproposedforselectinglayerimpedances(DeSiletsetal1978,Matthaeietal1980),includingbinomial(Pace
1979),maximallyflat,Tchebycheff,andothers(Souquetetal1979).Themaximumfractionalbandwidthforthemaximallyflatapproach(Matthaeietal1980)is
showninfigure5.10asafunctionofthenumberofmatchinglayersinpractice,somewhatlessisachieved,dependingondesignconstraints.Oncematchinglayer
impedancesareselected,findingtheappropriatelowlossmaterialsofthedesiredimpedanceisdifficultspecialcompositemixturesareoftenrequired.
MostarraysaremadewithferroelectricceramicssuchasPZT(leadzirconatetitanate).Otherpiezoelectricceramicssuchasmodifiedlead

Page101

Figure5.11.
3dBbandwidthandrelativedielectricconstantsfor
piezoelectricmaterialswiththeupperrightcorner
beingbestforarrays.

titanate(PbTiO3)(Takeuchietal1982)havebeenformulatedtohavelowercouplingtolateralmodes.Compositematerialshavebeendevelopedtocombinethehigh
piezoelectriccouplingofceramicswithmaterialsofloweracousticimpedance(Smithetal1984).Oneofthemostsuccessfulofthesecombinationsisthe13
composite(Gururajaetal1985),inwhichrodsofPZT,embeddedinanepoxymatrix,providethehighcouplingconstantoftherodmode(closetothatofthebeam
mode)withloweroverallacousticimpedance.ArecentresearchareaisthedevelopmentofhighercouplingsinglecrystalssuchasPZTPN(Lopathetal1997,
Saitohetal1997).
PiezoelectricmaterialscanbecomparedbytheirelectricalQ(Qe)andrelativedielectricconstants.Largedielectricconstantsincreaseclampedcapacitanceand
improvetheelectricalimpedancematchingofsmallelements.ForaninductivelytunedtransducerwithacousticloadingequaltoZconbothsidesandRAO=Rg,

Fractionalbandwidthfromthisequationand areplottedinfigure5.11forseveralmaterialsofinterest(Fukumotoetal1981,Lopathetal1997,Saitohetal1997).
Forbestarrayperformance,materialswiththehighestcombinationoffractionalbandwidthandrelativedielectricconstant,intheupperrightcorneroffigure5.11,are
preferred.
Imagingarraysaremorethanacollectionofindividualelementswhichhappentobeneighbours.Becauseofarrayconstruction,elementsaremechanicallyconnected
andinteractionsoccur(Larson1981).Crosscouplingcanaffectelementdirectivityandcontributeunwantedspurious

Page102

Figure5.12.
Blockdiagramforadiagnosticultrasoundimagingsystem.

signalsthatendupintheimageasclutter.Constructiveanddestructiveinterferenceofspuriousmodescanalterthemainpulsewidthandtail,narrowthe
correspondingspectrumandaddunwantedspectralpeaksandvalleys.Thesecondphaseoftransducerdesignistheminimisationofunwantedeffectsbyaccounting
forthethreedimensionalnatureofthearrayelementsandtheirconstructionaswellassafetyconsiderations(ZiskinandSzabo1993Weetal1995).Becauseof
multipleconstraints,nonresonantdesignmethodsareemployed(Szabo1984).
Thebasictypesofarrayarephased,linearandcurvedlinear,withmanyvariationsfordifferentclinicalapplications.Oneexampleisthetransoesophagealarray(Bom
etal1993)whichissmallenoughtoputdownathroatwithremoterotationalandflexuralmovements.Somearraysareshapedtofitotherorificessuchasthe
transrectalandendovaginalarrays,whileothersareforsurgicalenvironmentsandforintravascularimaging.
5.2
Imaging
Moderndiagnosticultrasoundimagingsystemsemploydigitalarchitecturestoachievemoreflexibilityandcontroloverbeamformingandsignalandimageprocessing,
calculations,andsysteminput/outputrequirements.Ablockdiagramofatypicalultrasoundimagingsystemwithelectronicfocusingisgiveninfigure5.12.Oneor
morecomputercontrollersorchestratetheinternalprocessing,beamformingandimagemanipulationinahighlyinteractivemannerresponsivetothesystemuser.The
formationofanimagebeginswiththeapplicationofexcitationsignalstothearrayfromthetransmitbeamformerinthefrontend.Afterabeamislaunched,pulseecho
signalsreturnfromtissueandenterthearrayelementsafterwhichtheyarebeamformedandsignalprocessedaccordingtolinepositionand

Page103

Figure5.13.
Twobasicimagingformats:linearandsector.

Figure5.14.
Illustrationofsingletransmitfocusandthe
useofzonesformultiplefocussplicing.

depth.Thebeampositionisthensequencedthroughapatternrequiredbytheselectedimageformat.Theselinesareconvertedintogreyscaleorcolourlinedata
whichareprocessedandinterpolatedtoformanimageframefordisplay.MoredetailsonhowimagingsystemsworkcanbefoundinthespecialissuesofHewlett
PackardJournal(1983)listedintheReferences.
Thetwomajorimageformatsarelinearandsector,asshowninfigure5.13.Forlineararraysanelectronicallyswitchedslidingconfigurationofactiveelements(an
apertureorwindow)formseachacousticimageline.Inasectorformat,all,orasubsetof,elementscentredatthemiddleofthearraycreateasequenceofimagelines
atdifferentscanangles.
5.3
BeamForming.
Electronicfocusingandsteeringoccurintheazimuthorimagingplane.Transmitandreceivefunctionsareillustrateddiagramaticallyinfigure5.14.Atransmitbeamis
launchedalongaselecteddirectionwithasinglefocaldepthasshownbythenarrowingofthe6dBbeamcontour(size

Page104

Figure5.15.
Parallelprocessingconsistsofawidetransmit
beamwithtworeceivebeamssteeredattwodifferent
angleswithinthetransmitbeamtoenhanceframerate.

Figure5.16.
Wideangledirectivityofasingleelementwhich
affectstheshapeofasteeredbeamatawide
steeringangle.

exaggeratedfromillustration)inthefocalregion.Additionaltransmitfocicanbeboughtattheexpenseofslowerframeratebydividingthetotalscandepthintoa
numberofzones,transmittingineachone,andbysplicingthefocalregionstogether.Onreceptionofthepulseechosignalsfromeachtransmitdirection,dynamic
receivefocusingisappliedateachdepth.
Electronictransmitbeamformingisachievedbydelayingtransmitexcitationwaveformsinacylindricalorsphericalprofilesothattheresultingpressurewaveforms
fromeachelementwilladdconstructivelyatthefocalpoint(Macovski1983).Alineardelayshiftprovidessteeringcapability.Onreception,returningechoesundergo
similarfocusingandsteeringdelaystofocusthebeamateachtime(depth)alonganacousticline.Bywideningthetransmitbeamandbyoffsettingthereceiveline
positionfromthe

Page105

Figure5.17.
Ontheleftisanunapodisedflatfunctionwithitscorresponding
beamshapeatafocus.OntherightisshownatruncatedGaussian
apodisationwhichhasabeamplotwithawidermainbeamand
lowersidelobesfora32wavelength,64elementlongarray.

transmitdirection,multiplereceivebeamscanbegeneratedsimultaneously,asdepictedinfigure5.15.Thisprocess,called'parallelprocessing',increasestheimage
framerate.
Eachelementhasitsowndirectivity(Macovski1983)whichhasabroadangularextentcomparedtoafocusedbeam.Becausetheelementsinanarrayarenearly
identical,theeffectofelementdirectivityisto'rolloff'ortapertheamplitudeofthefocusedbeamatwidesteeringanglesasillustratedinfigure5.16.
Apodisationisameansofalteringthesurfacedisplacementofatransducerthroughamplitudeweightingorshading('tHoen1982).Apodisationfunctionsaretapered
graduallytowardstheendsoftheapertureasexemplifiedbyatruncatedGaussianfunction.Thisiscomparedtoanunapodisedflatamplitudefunctioninfigure5.17.
Atthefocallength,thebeamshapeistheFouriertransformofthetransducerapertureapodisationfunctionasillustratedbythebeamsoffigure5.17forasingle
frequencyexcitation.Thisfiguredemonstratesthatapodisation(Kino1987)involves

Page106

Figure5.18.
Focusedbeamtaperingtoafocalplaneellipsewith
azimuthandelevationplanesdepicted.

atradeoffbetweenmainlobedetailresolution(6dBbeamwidth,forexample)andsidelobesuppressionorcontrastresolution(40dBbeamwidth).
Theimagingorazimuthplaneisnotconsistentlythinbuthasanonuniformslicethicknessintheelevationdirection,asillustratedinfigure5.18.Focusingintheelevation
planeisaccomplishedmostoftenwithasinglefixedfocusmechanicallens.Roundtripmeasurementsofbeamsaremadebyreflectionsfromasmallpointtargetone
waybeamsareusuallymeasuredwithhydrophonesand,recently,bySchlierenimaging(ZanelliandKadri1994).
Electronicfocusingcanalsobeusedfortheelevationplane.Infigure5.19,anordinary1Darrayisshownatthetopofthefigure.Forexample,thisarraymighthave
64elementsspacedhalfawavelengthapart.Atthebottomrightofthefigureisa2Darray(Smithetal1995)withthesamespacing,butwith64rowsand64
columnsofelementssothenumberofelementsandsystemchannelinterconnectsare6464=3600.
Ifthecompletefocusingandsteeringflexibilityofa2Darraycanbesacrificedsomewhat,a1.5Darraycanprovideintermediateperformance,henceitsname,'1.5D'.
The1.5Darrayinthefigureisundersampledintheelevationdirection(typicallyatseveralwavelengthintervals).Foranexample,lettherebesixsamplesinelevation
and64inazimuth,resultingin664=384elements.Thisundersamplinggivesrisetomultiplemain

Page107

Figure5.19.
Majorconfigurationsofarrays:1D,1.5Dand2D.

Figure5.20.
Resolutioncellintheformofa6dB
ellipsoidcentredonacoincident
azimuthandelevationfocus.

beamscalledgratinglobeswhoseeffectisminimisedbynotsteeringthebeam.Noelevationsteeringmeansfocusingsymmetrywhichallowsforhardwiringpairsof
elementsreceivingthesamefocusingdelays.Inthisexamplethreegroupsofelementscanbeorganizedintothree'YGroups'thatreducebyhalfthenumberof
connectionsto192.
Threedimensionalultrasoundimagesaregeneratedusuallyfromasequenceofimagingplanesthataremechanicallyscannedincertainpatternssuchasrotation,
translationorangularscanningorfanning.Theimageplanesareassembledthroughinterpolationtoforma3Dimagematrix.Oncethe

Page108

Figure5.21.
Harmonicimagingismadepossiblebyaverywidebandwidth
transducerwhichallowsfundamentalexcitationandsecond
harmonicreception.

matrixiscomputed,arbitrarysliceplanes,orsurfacerenderedimagesorimageswithtransparentsurfacescanbecreated.Throughsynchronisationmethodsduring
acquisition,moving3Dimagescanbegenerated,framebyframe(MasottiandPini1993).
Ateachpointinimagingspace,thespatialimpulseresponseorpointspreadfunctionhasameasurableresolutioncellsize.Forexample,a6dBbeamcontour
ellipsoidcanbeusedasameasureofresolutionasillustratedbyfigure5.20foracoincidentelevationandazimuthfocaldepth.Ingeneral,awayfromthefocus,the
timeresolutionisthesmallestandtheelevationresolutionisthelargest.For3Dimaging,consistentlyfineresolutionisdesired.1.5Dand2Darraysarewaysof
providingelevationplaneresolutionwhichisimprovedoverfixedmechanicallensfocusingmethods.
5.4
OtherImagingModes
Untilnow,thediscussionhascentredon2D(Bmode)imaging.Othermodesincludecolourflowimaging,Doppler(pulsed,CWorpower),andacoustic
quantificationbutspacedoesnotallowfurtherdiscussion.(ForDopplerseeChapter6.)
Arelativelynewmodalityisharmonicimaginginwhichadvantageistakenofthefactthatwaterandthebodytissuearenonlinearelasticmediaevenundermodest
pressureamplitudes(Dunnetal1981).Therefore,asfocusedbeamspropagate,finiteamplitudedistortiongenerateshigherharmonicspectralcomponents.
Transducersofverywidebandwidthscancapturenotonlythefundamentalexcitationfrequencybandbutthesecondharmonicspectrumaswell,asdepictedinfigure
5.21.Notethatthesecondharmonicispurelyanonlinearpropagationeffect.Atransducer,excited

Page109

atitscentrefrequencyunderlinearconditions,maybeexpectedonlytogenerateoddharmonics.Imagescreatedfromthesecondharmonicareprovidingnewclinical
information,especiallyforassessingheartfunctionwithcontrastagents(Goldberg1993)andforprovidingimprovedviewsofpatientsotherwisedifficulttoimage.
5.5
Conclusion
Transducerarraydesigniscomplicatedbecauseoftheincreasingnumberofconstraintsandrequirementsaswellasmechanicalinteractionswithinarraystructures.
Thegrowinguseoffiniteelementmodellingindesignisrevealingthatmostmaterialsarenotadequatelycharacterisedforaccuratesimulations.Newmaterialsincluding
compositescanextendtransducerperformance.Despitethesechallenges,arraysarecontinuingtoimprovewithtrendstowardswiderbandwidthsandhighercentre
frequencies.Thedevelopmentof1.5Dand2Darraysprovidesnewchallenges.Inaddition,newclinicalapplicationsfortransducerscontinuetoemerge.
Anothertrendisthecombiningofimagingwithquantitativemeasurementcapabilities.Newdevelopmentsareintheareasofcontrastandharmonicimagingwhich
requireverywidetransducerbandwidths.Afurtherareaofpotentialimprovementisimagingsystemmethodsforminimisingorcorrectingforunwantedelasticimaging
bodyeffects.
References
AuldBA1990AcousticFieldsandWavesinSolidsvol1,2ndedn(Malabar,FL:Krieger)ch8
BerlincourtDA,CurranDRandJaffeH1964PiezoelectricandpiezomagneticmaterialsandtheirfunctionintransducersPhysicalAcousticsvol1,partA,edWP
Mason(NewYork:AcademicPress)pp170270
BomN,BrommersmaPDandLance'eCT1993ProbesasusedincardiologywithemphasisontransesophagealandintravascularapplicationsAdvancesin
UltrasoundTechniquesandInstrumentationedPNTWells(NewYork:ChurchillLivingstone)pp1933
DeSiletsCS,FraserJDandKinoGS1978ThedesignofefficientbroadbandpiezoelectrictransducersIEEETrans.SonicsUltrasonicsSU2511525
DunnF,LawWKandFrizzellLA1981Nonlinearultrasonicwavepropagationinbiologicalmaterials1981IEEEUltrasonicsSymp.Proc.pp52732
FukumotoA,KawabuchiMandSatoJ1981DesignofultrasoundtransducersusingnewpiezoelectricceramicmaterialsUltrasoundMed.Biol.727584
GoldbergBB1993UltrasoundcontrastagentsAdvancesinUltrasoundTechniquesandInstrumentationedPNTWells(NewYork:ChruchillLivingstone)pp
3545
GururajaTR,SchulzeWAa,CrossLE,NewnhamRE,AuldBAandWangY1985Piezoelectriccompositematerialsforultrasonictransducerapplications,part
1:

Page110

ResonantmodesofvibrationofPZTrodpolymercompositesIEEETrans.SonicsUltrasonicsSU32481
HewlettPackardJournal198334specialissuesOctober1983andDecember1983
HuntJW,ArditiAandFosterFS1983UltrasoundtransducersforpulseechomedicalimagingIEEETrans.Biomed.Eng.BME3045381
HutchensCGandMorrisSA1984AthreeportmodelforthicknessmodetransducersusingSPICEII1984IEEEUltrasonicsSymp.Proc.pp897902
KinoGS1987AcousticWaves:Devices,Imaging,andAnalogSignalProcessing(EnglewoodCliffs,NJ:PrenticeHall)
KinoGSandDeSiletsCS1980DesignofslottedtransducerarrayswithmatchedbackingsUltrasonicImaging1189
LarsonJD1981Nonidealradiatorsinphasedarraytransducers1981IEEEUltrasonicsSymp.Proc.pp67383
LeedomD,KrimholtzRandMatthaeiG1971EquivalentcircuitsfortransducershavingarbitraryevenoroddsymmetryIEEETrans.SonicsUltrasonicsSU18
12841
LopathPD,ParkSE,ShungKKandShroutTR1997Pb(Zn1/3Nb2/3)O3/PbTiO3singlecrystalpiezoelectricsforultrasonictransducersProc.SPIE30371704
MacovskiA1983MedicalImagingSystems(EnglewoodCliffs,NJ:PrenticeHall)
MasonWP1948ElectromechanicalTransducersandWaveFilters2ndedn(NewYork:Wiley)pp20910,399404
MasottiLandPiniR1993ThreedimensionalimagingAdvancesinUltrasoundTechniquesandInstrumentationedPNTWells(NewYork:Churchill
Livingstone)pp6977
MatthaeiGL,YoungLandJonesEMT1980MicrowaveFilters,ImpedancematchingNetworks,andCouplingStructures(Dedham,MA:ArtechHouse)ch
6pp255354
MequioC,CoursantRHandPesqueP1983SimulationoftheacoustoelectricresponseofpiezoelectricstructuresbymeansoftheFastFourierTransform
algorithmActaElectron.2531123
NalamwarALandEpsteinM1972ImmitancecharacterizationofacousticsurfacewavetransducersProc.IEEE603367
PaceNG1979ImpulseresponseofwaterloadedairbackedpiezoelectricdisksIEEETrans.SonicsUltrasonicsSU263741
SaitohS,KobayashiT,ShimanukiSandYamashitaY1997SingleelementultrasonicprobeusingPZNPTsinglecrystalProc.SPIE3037229
SatoJ,KawabuchiMandFukumotoA1979Dependenceoftheelectromechanicalcouplingcoefficientonthewidthtothicknessratioofplankshapedpiezoelectric
transducersusedforelectronicallyscannedultrasounddiagnosticsystemJ.Acoust.Soc.Am.67160911
SmithSW,DavidsenRE,EmeryCD,GoldbergRLandLightED1995Updateon2Darraytransducersformedicalultrasound1995IEEEUltrasonicsSymp.
Proc.pp12738
SmithWA,ShaulovAAandSingerBM1984Propertiesofcompositepiezoelectricmaterialsforultrasonictransducers1984IEEEUltrasonicsSymp.Proc.pp
53944
SouquetJ,DefranouldPandDesboisJ1979DesignoflowlosswidebandultrasonictransducersfornoninvasivemedicalapplicationIEEETrans.Sonics.
UltrasonicsSU267581
SzaboTL1982Miniaturephasedarraytransducermodellinganddesign1982IEEEUltrasonicsSymp.Proc.pp8104
1984Principlesofnonresonantdesign1984IEEEUltrasonicsSymp.Proc.pp8048
'tHoenPJ1982ApertureapodizationtoreduceoffaxisintensityofthepulsedmodedirectivityfunctionoflineararraysUltrasonics2316

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TakeuchiH,JyomuraS,YamamotoEandItoY1982Electromechanicalpropertiesof(Pb,Ln)(Ti,Mn)O3ceramicsJ.Acoust.Soc.Am.721114
VladimerescuA1984SpiceVersion2F.1User'sGuide(Berkeley,CA:DepartmentofElectricalEngineeringandComputerScience,UniversityofCalifornia)
WojcikGL,DeSiletsC,NikodymL,VaughanD,AbboudNandMouldJJr1996Computermodelingofdicedmatchinglayers1996IEEEUltrasonicsSymp.
Proc.pp15038
WojcikGL,VaughanDK,AbboudNandMouldJrJ1993Electrochemicalmodelingusingexplicittimedomainfiniteelements1993UltrasonicsSymp.Proc.pp
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InstrumentationedPNTWells(NewYork:ChurchillLivingstone)pp15160

Page113

Chapter6
CurrentDopplerTechnologyandTechniques
PeterNTWells
Summary
TheDopplereffectisthechangeinthefrequencyofawaveperceivedbyanobserverwhenreceivedfromamovingsource.Scatteringofultrasoundbyflowingblood
canbecharacterisedasaGaussianrandomprocess.ThevelocityofbloodflowcanbeestimatedfromtheDopplershiftfrequency,whichgenerallyfallsintheaudible
rangeinmedicalapplications.Continuouswaveultrasoundcannotprovideinformationaboutthedistancetothetargetbypulsingtheultrasound,distancecanbe
estimatedfromtheechodelaytime.Dopplersignalscanbeprocessedtodeterminethedirectionofflow.Thefrequencyspectrumcanbeanalysedbynumerous
methods,themostusefulgenerallybeingthefastFouriertransform.CombiningpulsedDopplerandrealtimetwodimensionalscanningresultsinduplexscanning,
whichallowstheanatomicallocationoftheDopplersamplevolumetobeidentified.Incolourflowimaging,thewholeofthetwodimensionalscanissuperimposedby
acolourmapderivedfrommovingtargetswithinthescanplane.Frequencydomainandtimedomainprocessingarepossible.Thecolourcanbecodedeither
accordingtothevelocityoftargetmotion,oraccordingtothepowerofechoesfrommovingtargets.Theinformation,havingbeenacquiredincontiguoustwo
dimensionalscans,canbedisplayedinthreedimensions.Contrastagents,consistingofgasmicrobubbles,canbeusedtoenhancetheDopplersignalamplitude.
Contrastagentsalsoscatterultrasoundatthesecondharmonicoftheirradiatingfrequencyandthisprovidesatechniqueforclutterrejection.
6.1
TheDopplerEffect
ThepaperthatmadeChristianDopplerfamous,'Onthecolouredlightofdoublestarsandcertainotherstarsoftheheavens',wasreadbyhimbefore

Page114

theRoyalBohemianSocietyofSciencesinPragueon25May1842andpublishedinthefollowingyear(Doppler1843).Eden(1992)haswrittenafascinating
accountoftheseevents.SufficeittosayherethatDoppler'spaperbeginsbyrecapitulatingthewavetheoryoflightandintroducestheideathattheobserved
frequencyincreaseswhenmovingtowardsthesourceandviceversa.Usingaratherclumsymathematicalderivation,Dopplershowedthat

wheref oistheapparentfrequencyperceivedbytheobserver,f sisthefrequencyofthesource,cisthewavespeedand oand sarethevectorvelocitiesofthe

observerandthesourcerespectively.Dopplerwentonerroneouslytoconcludethatbluestarsowetheircolourtothefactthattheyareapproachingtheobserver
whilerecedingstarsarered.Thisargumentdependsonthefalseassumptionthatstarsonlyemitwhitelightandnotultravioletorinfraredlight.Onlylaterdiditbecome
establishedthatbluestarsappearsobecausetheyarehotterthanredones.
6.2
TheOriginoftheDopplerSignal
Thedetectabilityofultrasoundbackscatteredbybloodultimatelydependsonthesignaltonoiseratio.Thesuspendedultrasonicscatterersthatareoverwhelmingly
dominantaretheerythrocytes(theredcells).Anindividualerythrocyteisabiconcavedisk,about8mindiameterandwithamaximumthicknessof2m.Theratio
ofthetotalerythrocytevolumetothetotalbloodvolumeisknownasthehaematocrittypically,thisis0.45innormaladults,beingslightlyhigherinmenthaninwomen.
Atthetypicalultrasonicfrequencyof3MHz,thewavelengthinbloodisabout0.5mm.Thus,anindividualerythrocyteistwoordersofmagnitudesmallerthanthe
wavelengthitcanbeconsideredtobeaRayleighscatterer,forwhichthebackscatteredpowerincreasesasthefourthpowerofthefrequency(seeChapter4).Brody
andMeindl(1974)treatedbloodasasuspensionofpointscatterersinmodellingthescatteringprocess.Thisneglectsthefactthattheerythrocytesarequiteclosely
packed,sotheydonotbehaveasuncorrelatedscatterersbutactuallyarestronglyinteracting.Angelsen(1980)avoidedthisproblem,inhismodel,bytreatingblood
asacontinuousmediumcharacterisedbyfluctuationsinmassdensityandcompressibility.Thesituationisfurthercomplicatedbythetendencyoferythrocytesto
aggregate,formingrouleauxthatcansurviveevenundernormalflowconditions(Machietal1983).YuanandShung(1989)concludedthatscatteringbyporcine
blooddecreaseswithincreasingshearrate.Althoughbovineblooddoesnotexhibitthisshearratedependence,usingitasamodelforhumanbloodallowedMoand
Cobbold(1986)to

Page115

concludethatultrasoundbackscatteredbyflowingbloodcanbecharacterisedasaGaussianrandomprocess.
Ultrasonicbloodflowdetectionisonlypossiblebecauseultrasonicscatteringbybloodisastochasticprocess.Asflowingbloodinteractswithabeamofultrasound,it
behaveslikearandomarrayofdiscretetargets,albeitlimitedinextentbothtemporallyandspatially.Therearelimitations,however,intheassumptionthatthe
backscatteredpowerisproportionaltothenumberofredcellsinteractingwiththeultrasound(Shungetal1992).
Thechoiceoftheultrasonicfrequencythatgivesmaximumsignaltonoiseratioforechoesdetectedfrombloodisdeterminedbythecompromisebetweenthe
backscatteringefficiencyofblood(whichincreaseswithfrequency)andtheusefuldepthofpenetration(whichdecreaseswithfrequency).Inpractice,afrequencyof
around3.5MHzisgenerallyusedforapenetrationofabout150mm,butitcanbeincreasedto,say,10MHzwhenthepenetrationisreducedtoabout20mm.With
pulsedDopplersystems,asdescribedinsection6.3.2,itmaybeadvantageoustouseasomewhatlowerultrasonicfrequencybecausethisrelievestheconstraint
imposedbytheNyquistcriterion.
Happily,Doppler'sequationistrueforacousticwaves.TheDopplershiftinthefrequencyofultrasoundbackscatteredbybloodisaspecialcaseinwhichthesource
andtheobserverarestationaryandtheultrasonicbeamisfoldedbackbythemovingscatteringensemblessothatthetransmittingandreceivingbeamsareeffectively
coincident.Inthisway,motionofanensembleresultsinchangeinthedistancethattheultrasonicwavetravelsbetweenthetransmittingandthereceivingtransducers.
Describedinanotherway,amovingscatteringensembleoferythrocytesactsbothasareceiverofDopplershiftedultrasoundasthedistancebetweentheensemble
andthetransmittingtransducerchanges,andasatransmitterofthisalreadyDopplershiftedultrasoundwhichisDopplershiftedagainasthedistancebetweenthe
ensembleandthereceivingtransduceralsosimultaneouslychanges.
Itisactuallythedifferencef Dbetweenthefrequenciesoftheobservedandthetransmittedultrasound,knownastheDopplershiftfrequency,whichisimportant.In
general,fromequation(6.1),

Withultrasoundbackscatteredfromblood,thepathlengthchangesatarateequaltothevelocity2 i,where iisthevectorvelocityoftheensemble.Providedthatc

>> i,equation(6.2)canbesimplifiedto

usingthenotationthatmotiontowardstheeffectivelycoincidenttransmittingandreceivingtransducersispositive.

Page116

Thereisonefurtherpracticalconsideration.Often,thereisanangle betweentheeffectivedirectionoftheultrasonicbeamandtheflowofblood.Moreover,the
Dopplershiftfrequencyisthemeasuredquantityfromwhichtheabsoluteflowvelocityvofthebloodistobecalculated.Then,equation(6.3)becomes

ItisnowappropriatetocalculatetheDopplershiftfrequencyforsometypicalphysiologicalsituation.Consider,forexample,theDopplershiftfrequency
correspondingtobloodflowduringsystoleintheascendingaorta.Thepeakbloodflowvelocityisaround150cms1.Withanultrasonicfrequencyof3MHzand
coincidentflowandbeamdirections( =0),f D=6000Hz.Thus,althoughitisnomorethanaluckychance,theDopplershiftfrequenciesinthisandvirtuallyallother
practicalphysiologicalsituationshappentofallintheaudiblerange.
6.3
TheNarrowFrequencyBandTechnique.
6.3.1
TheContinuousWaveDopplerTechnique
AblockdiagramofacontinuouswaveDopplersystemisshowninfigure6.1.Uninterruptedultrasonicwavesofconstantfrequencyandamplitudeareemittedintothe
patientbythetransmittingtransducer.Theechoesdetectedbythereceivingtransducerhavethesamefrequencyasthatofthetransmitteriftheyarereflectedby
stationarystructures.Iftheyoriginatefromflowingblood,however,theyareshiftedinfrequencybytheDopplereffect.Thus,theoutputsignalsfromtheradio
frequency(RF)amplifierhaveastrongcomponentatthetransmittedfrequency.Inaddition,intheexampleshowninfigure6.1,wheretheultrasonicbeamintercepts
anarteryinwhichbloodflowsintheforwarddirectioninsystoleandinthereversedirectionduringdiastole,therearecomponentsintheupperandlowersidebands
correspondingrespectivelytoapproachingandrecedingflows.Thesesidebandscanbeseparatedbyphasequadraturedetection(Nippaetal1975),thecircuitfor
whichisidentifiedintheblockdiagraminfigure6.1.
Theoperatorcanlistentotheseseparatedsignalsonheadphones,asshowninfigure6.1,withtheforwardflowsignalsfedtooneearandthereverseflowsignalsto
theother.Althoughthisworkswell,oftenitisdesirabletohaveapermanentrecordingofthesignalsfordetailedexaminationandanalysis.Aconvenientwayinwhich
thiscanbeachievedinvolvestheuseofaheterodyneprocessorandfrequencyspectrumanalyser,alsoincludedintheblockdiagraminfigure6.1.Theforward(U)
andreverse(L)flowsignalsareseparatelymultipliedbyasignalatapilotfrequency,chosenatleastjust

Page117

Figure6.1
AblockdiagramofacontinuouswaveDopplersystemwithdirectionalphasequadrature
detectionprovidingaudibleforward(U)andreverse(L)flowsignals,andaheterodyneprocessor
andfrequencyspectrumanalyserforvisualdisplay.FromWells(1994).

Page118

toexceedthemaximumreverseflowfrequency.Theoutputfromtheforwardflowmultiplierconsistsofasignalatthepilotfrequencywiththeforwardflowsignals
arrangedsymmetricallyasupperandlowersidebandstothepilotfrequency.Ahighpassfilterisarrangedtoeliminatethelowersideband.Similarly,thereverseflow
signalsareobtainedasalowerfrequencysignalsidebandtothepilotfrequency.Addingthesetwofilteredsignalsresultsinaspectrumoffrequenciesinwhichthepilot
frequencycorrespondstozeroflowvelocity,frequenciesabovethepilotfrequencyarefromforwardflowandfrequenciesbelowarefromreverseflow.Figure6.1
showshowthisspectrumcanbedisplayedafterfrequencyspectrumanalysis,aprocessdescribedinsection6.4.
PhasequadraturedetectionisverywidelyusedtoseparateforwardandreverseflowsignalsinultrasonicDopplerinstruments.Forthecircuitdesigner,successlies
principallyindesigningthesecondofthe /2phaseshiftnetworks(seefigure6.1)sothatitsaccuracyismaintainedovertheentirerangeofDopplershiftfrequencies.
6.3.2
ThePulsedDopplerTechnique
PulsedDopplersystemsusepulseechorangegatingtoselectDopplersignalsfrommovingtargetsaccordingtotheirdistancesfromtheultrasonicprobe(Wells
1969).Figure6.2showstheessentialcomponentsofthecircuit.Themasteroscillatorrunsatthefrequencyofthetransmittedultrasound.Clockpulsesareobtained
bydividingdownfromthemasteroscillatorfrequencyandtheseclockpulsestriggerthetransmitsamplelengthmonostableatthepulserepetitionfrequencyofthe
system.Thismonostablegeneratesapulsethatopensthetransmitpulsegateforthelengthoftimethatultrasoundneedstobeemittedbythetransmittingtransducerto
producethedesiredsamplelength(about0.67smm1).EchosignalsfromthereceivingtransduceraresubjectedtoRFamplificationbeforebeingfedtothephase
quadraturedetectorandheterodyneprocessor,whichfunctionasexplainedinsection6.3.1.(Notethatthepilotfrequencycanbechosentomaximisethefrequency
spectrumthatcanbeaccommodatedwithintheNyquistlimit,whichisexplainedlaterinthissection.)Thus,followingthetransmissionofeachultrasonicpulse,the
outputfromtheheterodyneprocessorconsistsofawavetraininwhichlatertimecorrespondstoincreasingdepth.Thesampledepthmonostable,whichisalso
triggeredbytheclockpulse,introducesatimedelaychosenbytheoperatortocorrespondtotheechodelaytime(about1.33smm1)fromthebeginningofthe
samplevolumefromwhichitisdesiredtocollecttheDopplersignals.Thereceivesamplelengthmonostablethenopensthereceivepulsegateforaperiodequalto
thetransmittedpulselength,sothattheoutputfromthereceivepulsegateistheDopplersignalsample.Theamplitudeofthissignalsampleisheldinthesampleand
hold

Page119

Figure6.2.
AblockdiagramofapulsedDopplersystemproviding
depthandlengthadjustmentsforthesamplevolumeandphase
quadraturedirectionaldetection.FromWells(1994).

circuituntilitisupdatedbythesamplederivedfromthenexttransmittedultrasonicpulse.
Allthatisthennecessaryisfortheoutputfromthesampleandholdcircuittobefiltered(toeliminatebothlowfrequencyhighamplitudesignalsfromslowlymoving
stronglyreflectingstructuressuchasthewallsofbloodvessels,andhighfrequencysignalsassociatedwiththesamplingtransients)andamplifiedbeforefrequency
spectrumanalysis.

Page120

AccordingtotheNyquistcriterion,thereisnoaliasingintheDopplershiftsignalsattheoutputfromthesampleandholdcircuitprovidedthatthepulserepetition
frequencyismorethantwicethehighestDopplershiftfrequency.
6.4
FrequencySpectrumAnalysis
Acontinuousfrequencyspectrumisproducedbybothcontinuouswaveand,withintheconstraintsimposedbysamplingandtheNyquistcriterion,pulsedDoppler
methods.Therearenumeroustechniquesbywhichfrequencyspectrumanalysismaybeperformed.Althoughnowadaysoftendealtwithdismissively,thezero
crossingcounter(Lunt1975)isinfactquiteagoodestimatoroftherootmeansquarefrequency.Otheranaloguemethodsforfrequencyspectrumanalysis,suchas
bandpassfilterbanks(Light1970)andtimecompressionsystems(Coghlanetal1974)havelargelyfallenintodisuseforDopplerapplications.
Currently,Dopplersignalsofreasonabledurationthatdonotslewtoorapidly(examplesofsatisfactoryDopplerbloodflowsignalsarethoseobtainedwithstationary
continuouswaveorpulsedbeams)areusuallyanalysedbydigitalcalculationofthefastFouriertransform(FFT).Anexcellentreviewofthemethodispresentedina
tutorialpaperbyChallisandKitney(1991).Assumingthatthe'classical'Fouriertransformcanprovideadequateresolution,itisgenerallythebestoption.(Inthe
temporaldomain,resolutioninthiscontextrelatestotheminimumdurationofthesignalsegmentthatallowsitsfrequencytobeestimatedwiththerequiredaccuracy.)
Whenthisisnotthecase,oneofthetechniquesof'modern'spectralanalysisshouldbeused.Althoughthesecanbeeitherparametricornonparametric,itisthe
parametricapproachusing,forexample,theautoregressivealgorithmthathasturnedouttobethemostpromisingwithultrasonicDopplersignals(D'Alessioetal
1984,SchlindweinandEvans1990).
6.5
DuplexScanning
AduplexscanningsystemisonethatenablestwodimensionalultrasonicpulseechoimagingtoguidetheplacementofanultrasonicDopplerbeamandthustoallow
theanatomicallocationoftheoriginoftheDopplersignalstobeidentified.SinceitsinceptionbyBarberetal(1974),thecommonusageoftheterm'duplex'has
changedwhatmostpeoplenowconsidertobeaduplexscannerisonethathasrealtimeimagingcapabilitywitheithertheimagingtransduceroraseparate
transducerusedtocollectCWorpulsedDopplersignals,eithersimultaneouslywithimagingorsequentially.

Page121

Duplexscannerscanbebasedoneithermechanicalorelectronicarrayrealtimeimaging.Theimageframerateislimitedbythedepthofthescannedfieldandthe
numberoflinesperframe.Ifthedepthis,say100mm,thegoandreturnpulseechodelaytimeisabout130sperline.Thecorrespondingmaximumpulserepetition
rate(equaltothenumberofimagelinescollectedpersecond)isabout7700Hz.Thismeansthatimagesmadeupof,say,77linesperframecanbecollectedat100
framespersecond,andsoon.
ForthecollectionofDopplersignals,theultrasonicbeamhaseffectivelytobestationaryandtodwellinthedesiredpositionsufficientlyfrequentlyandforasufficiently
longtimeduringeachacquisitionperiodtoallowadequatesamplingofthemovingtargets.Inertiapreventstheaccelerationanddecelerationofthemovingpartsof
mechanicalsectorscannersthatwouldbenecessaryforsimultaneouscollectionofimagingandDopplerdata,sothe'frozen'imageframeapproachisnecessaryunless
aseparatetransducerisusedforDopplersignalacquisition.Movementofthebeamofanarrayscannercanbestartedandstoppedinstantaneously,sosimultaneous
operationispossiblewiththistypeofsystem.
6.6
ColourFlowImaging
6.6.1
BasicPrinciples
ThebasicprinciplesofcombiningpulseechoandDopplertwodimensionalimagesareillustratedinfigure6.3.BrandestiniandForster(1978)werethefirstto
demonstratethefeasibilityofthisapproach.Theyusedaduplexscanner:twodimensionalgreyscaleimagingwasachievedinrealtimeandthescanlineofa128
pointpulsedDopplersystemwassweptrelativelyslowlythroughtheimagedplaneto'paint'theflowsignalsintothevessellumenusingshadesofredandblue.Thus,
thecolourflowimagingitselfwasnotperformedinrealtimeinpractice,itwaseventuallypossibletooperateatfourframespersecond(Eyersetal1981).
Fundamentally,however,themultigatedpulsedDopplersystemusedbyBrandestiniandForster(1978)waslimitedintemporalresolutionbytheprocessoffrequency
estimationthatitemployed.SimilarconstraintsappliedtotheinstrumentsdevelopedbyHoeksetal(1981)andCastyandGiddens(1984)forthestudyofflow
velocityprofiles.
Itistheconstraintonthemaximumframeratethatisgenerallyofmostpracticalimportanceincolourflowimaging.Withasimplescanningstrategyinwhichthe
ultrasonicbeamsweepslinebylineinsequencethroughthescanplane,thebeamhastodwellineachpositionforlongenoughtoallowthelowestDopplershift
frequencythatitisdesiredtodetecttobedetermined.Simplistically,itisreasonabletoassumethatdeterminingthe

Page122

Figure6.3.
Ablockdiagramofarealtimetwodimensionalcolourflowimagingsystem.
Inthisexample,aphasedorcurvedarraytransducerisusedtoproduce
asectorscan.Alternatively,alineararraytransducercanbeused
toproduceascaninparallelogramformat.Theimageformatter
andscanconverteracceptthecolourandgreyscalesignals
togetherwithscanpositiondatafromtheultrasonicbeamsteeringcircuit.
Thescanconvertermayincorporateserialimagememoriestoprovide
acinreviewfacility.Theoperationoftheentiresystemissynchronised
byaclockpulsegeneratorwhich,forsimplicity,isnotshown
inthisdiagram.FromWells(1994).

frequencyofasignalrequiresameasurementtimeatleastequaltothedurationofonecompletecycleofthesignal.(Duringthistime,ofcourse,therearelikelytobe
numeroussamplesatthepulserepetitionfrequency,sosamplingquantisationisnotaproblem.)Asanexample,assumethatitisdesiredtodetectflowatvelocities
downto10cms1,thattheultrasonicfrequencyis3MHzand =0.ThisresultsinaDopplershiftfrequencyof400Hzthecorrespondingperiodofonecomplete
cycleis2.5ms.Thus,theultrasonicbeamhastodwellfor2.5msineachdiscretepositioninthescanplane.Evenifthereareonly100linesofcolourinformationin
theimage,thetimeperframeisthen250ms,correspondingtoaframerateofonly4s1.Thisishardly'realtime',anditisforthisreasonthatmoreadvanced
frequencyestimationandscanningstrategiesareusedtoincreasetheframeratetoproduceimageswithclinicallyusefultemporalresolutions.
Thespatialresolutionofcolourflowimagingiscontrolledbythesamebeamandpulsepropertiesasingreyscalepulseechoimaging.Generally,however,thebeamis
designedtobewiderthanforimaging(ifonlybecausealowerultrasonicfrequencyisused)and,withDopplerdetectionatleast,thepulseismadesomewhatlonger
(tominimisespectralbroadening).

Page123

Figure6.4.
Ablockdiagramofanautocorrelationdetectorandassociatedgating,
scanconvertingandcolourprocessingcircuits.Thepulseperioddelay
lineinsertsatimedelayequaltotheintervalbetweenconsecutively
transmittedultrasonicpulses.Themultiplierperformstheprocess
ofautocorrelation.Noticethesimilaritybetweenthisfrequencydomain
(Doppler)processingapproachandtimedomainprocessing
(seesection6.6.4)inwhichthemultiplyingautocorrelatoris
replacedinthecircuitbyatimeshiftingcrosscorrelator.
FromWells(1994).

6.6.2
AutocorrelationDetection
Thebasisoftheautocorrelationdetector(Kasaietal1985)isthattheechowavetrainfromstationarytargetsdoesnotchangewithtime,whereassequentialecho
wavetrainsfrommovingtargetshavecorrespondingchangesinrelativephase.Theautocorrelationdetector,illustratedinfigure6.4,producesanoutputsignalthatis
derivedfromtherelativephasesofconsecutivepairsofreceivedechowavetrains.Thus,theechowavetrainsthemselvesserveasreferencesforphasecomparison,
ratherthanmakingphasecomparisonwithafixedfrequencyreferencesignal.TheRFechowavetrainsfromthereceiveraresplitintotwocircuitpaths.Onepath
leadsdirectlytooneinputtoamultiplier.Theotherpathleadstotheotherinputtothemultiplierbutthroughadelayline,whichintroducesatimeshiftexactlyequalto
theintervalbetweenthetransmissionofsuccessiveultrasonicpulses.Hence,theoutputfromthemultiplieristheautocorrelationfunctionofconsecutivewavetrainsit
hasaconstantamplitudeunlesspairsofconsecutivewavetrainsdifferinphase.Forthisreason,theprocessissometimescalled'pulsepaircovariance'detection.
6.6.3
OtherDopplerFrequencyEstimators.
SincethedemonstrationofthefeasibilityofrealtimeDopplercolourflowimagingwithautocorrelationdetection(seesection6.6.2),therehasbeenincreasinginterest
inothermethodsoffrequencyestimationinthesearchforenhancedperformance.
TheidealestimatorwouldbeableaccuratelyandconsistentlytodeterminethemeanDopplershiftfrequency,irrespectiveofitsspectraldistributionandthelevelsof
thenoiseandstationaryechosignals.Allthesefactors,togetherwiththedurationofthetimewindow,affectthebiasandvarianceoftheestimate.Itisreasonableto
expectthatthevarianceincreaseswithlowersignaltonoiseratiosandshortertimewindows.BrandsandHoeks(1992)

Page124

havecomparedtheperformancesoffirstandsecondorderautoregressiveestimatorsandacomplexlinearregressionestimatorincombinationwithastationaryecho
cancellertoeliminatehighamplitudesignalsfrommajortissueinterfaces.Asecondorderautoregressivefilterisablesimultaneouslytoestimatethepositionsoftwo
peaksinthespectrum,oneofwhichcanbeassumedtocorrespondtotheDopplersignalsandtheothertohighamplitudeechoesfromsolidtissues.Bothafirstorder
autoregressivefilterandacomplexlinearestimator(whichdeterminestheslopeoftheregressionlinefittedthroughtheunwrappedphase)canonlyestimatethe
positionofasinglepeakinthespectrum.Withrealisticallychosenconditions,themeanfrequencyestimatorbasedontheregressionlinethroughtheunwrappedphase
oftheDopplersignal,togetherwithanappropriatestationaryechocanceller,givesthebestperformancewithshortobservationwindows.Forlongerwindows,
however,thefirstorderautoregressiveestimatorisbest.Theperformanceofthesecondorderautoregressivefilterisalwayspoorincomparisonwiththeothertwo.
6.6.4
TimeDomainProcessing
EmbreeandO'Brien(1985)andBonnefousandPesque(1986)independentlydescribedhowtargetvelocityinformationcanbeextractedfrombroadbandultrasonic
echoesbymeansoftimedomainprocessing.Themethoddependsontemporaltrackingofthespatialpositionofindividualcoherentbloodtargetensembles.In
principle,itcanbeappliedeithertotheRFortothevideosignals,althoughthetwoapproachesrequireverydifferentinstrumentdesigns.
6.6.4.1
CrossCorrelationDetection
BloodflowvelocitycanbedeterminedbyaonedimensionalcorrelationbetweenRFechowavetrainscollectedfromconsecutivelytransmittedultrasonicpulses.The
timetrequiredforanultrasonicpulsetocompletetheroundtripbetweenatransducerandascatteringensembleofbloodcellssituatedadistancezfromthe
transducerisgivenby

Ifthepulseperiod(thereciprocalofthepulserepetitionfrequency)isequaltot pand iisthevectorvelocityoftheensemble,thetimeshift oftheechoesfrom

consecutivepulsesisgivenby

Thistimedomainformulationisclearlysimilartothefrequencydomain(Doppler)formulationgiveninequation(6.3).Moreover,thesamecosinedependence
betweentheangulardirectionofflowandthatoftheultrasonic

Page125

beamappliestobothDopplerandtimedomainprocessing.Thecrosscorrelationcanbeachievedbyshiftingtherelativetimepositionsoftheconsecutivewavetrains
andmultiplyingthemtogether.
6.6.4.2
SpeckleTracking
Perhapsthemostobviousultrasonictechniqueforstudyingstructuremotionisthatwhichdependsontrackingastrongquasispecularechoisolatedfromwithin
sequentialAscansbyanappropriatelypositionedgate.ThisisthebasisofMmodeechocardiography(WellsandRoss1969).Anaturalextensionofthisapproachis
totrackthespecklestructurewithinasequenceofone,twooreventhreedimensionalimagesofbloodflow.Inthiscontext,itisthedemodulated(video)ultrasonic
signalthatgivesrisetotheimagespeckle,asdistinctfromtheRFechoesfromensemblestrackedbythecrosscorrelationtechniquediscussedinsection6.6.4.1.The
methodwasfirstdemonstratedbyTraheyetal(1987),usingtwosequential10MHzimagesofbloodinapoplitealvein.Ifthesensitivityissufficienttodisplaythe
coherentspecklefromtheblood,thedisplacementsoftheindividualbloodensemblescanbetrackedbyalocalisedtwodimensionalcorrelationsearch.Lines
representingthevelocityvectorscanbesuperimposedontheimage,sothatvelocityestimatesareangleindependentforinplaneflow.
6.6.5
ColourCodingSchemes
Besidespossessingluminosity(brightnessorshade),coloursareregardedaspossessingtheattributesofhueandsaturation.Hueisdeterminedbythewavelengthof
thelight.Saturationisthedegreetowhichacolourdepartsfromwhiteandapproachesapurespectralcolour.Whenahueisdesaturatedwithwhitelight,itis
classifiedasatint.Thewavelengthsofthevisiblespectrumextendfromabout740nm(red)to390nm(violet).Whensuitablypresented,theeyecandiscriminate
betweenhuesinthemiddlepartofthespectrumwithwavelengthdifferencesof1.2nmabout130stepsofhuedifferencecanbeperceivedacrossthevisible
spectrum.Asahueisdilutedwithwhite,about20tintscanbeidentified.
Variousschemesofcolourcodingareadoptedindifferentcolourflowimaginginstrumentsandindividualpreferencesvary.Ingeneral,however,increasingflow
velocitytowardstheprobeiscolourcodedredorangeyellowwhiteincreasingreverseflowvelocityisdisplayedindarkbluebluelightbluewhite.Thesecolour
scalescanbeinterpretedwithouttheneedtorefertoacodingkey.
Inadditiontocolourcodingaccordingtovelocity,informationconcerningflowdisturbance,whichisrelatedtothevarianceoftheestimateofvelocity,canbe
simultaneouslydisplayedbyappropriatecolourcoding.Thiscanbedone,forexample,byrestrictingthelimitsofthevelocitymaptotheredsandbluesandinjecting
anincreasingamountofyellowasflowdisturbance

Page126

increases.Theyellowconvertstheredstoorangeswithforwardflowandthebluestogreenswithreverseflow.Anotheruseforgreenistoidentifyareasofequal
velocity(orequalrangeofvelocity)ontheflowmap.Thisissometimescalled'greentagging'.
Inanotherkindofcolourcodeddisplay,theredorblueluminosity(dependingonpersonalpreference)isusedtoindicatethepowerofthebloodflowsignal.By
appropriatelyselectingthegainofthesystem,stationarystructuresaredisplayedwithlowluminosity,whilebloodflowappearsproportionallybrighterdependingon
thesignalpower.Althoughthiskindoffacilitywasavailableonsomeoftheearliestcommercialscanners(Jainetal1991),itfellintodisuseandhasonlyrecentlybeen
reintroduced(Rubinetal1994).Moderncolourflowpowerimagesdonotdistinguishbetweenforwardandreverseflowthecolourluminosityis,presumably,
relatedtothecorrespondingperfusionvolume.
6.6.6
ThreeDimensionalDisplay
Usingtherealtimeimagingprobeofacommerciallyavailablecolourflowscanner,Pretoriusetal(1992)describedhowtheytranslatedthescanplaneat5mm
intervalsthroughtheregionofthecarotidarterybifurcationandthejugularveintocollectathreedimensionaldatasetconsistingof33images.Thepresenceofcolour
wasusedtoseparateandthustosegmentthegreyscaleandbloodflowdata.Bythismeans,renderedsurfaceimagesofthebloodvesselscouldbedisplayed,with
theviewpointunderthecontroloftheoperator.
SimilartechniquesforimageacquisitionwereusedbyMiyagietal(1993)andPicotetal(1993).LikePretoriusetal(1992),Miyagietal(1993)suppressedthe
greyscaleimagetobeleftwithathreedimensionalsurfacerenderingofthebloodvesselimage,whichcouldbeexaminedfromanyviewpointselectedbythe
operator.ThethreedimensionalimagedisplayedbyPicotetal(1993),however,retainedthegreyscaleinformationtheviewpointcouldbechangedandtheimage
blockcouldbecutinanydesiredplane.
6.7
ContrastAgentsandSecondHarmonicImaging
Theuseofcontrastagentstoenhancetheechogenicityofblood(MelanyandGrant1997)hasobviousapplicationsinimprovingthesensitivityofcolourflowimaging.
Thereisscopeforthedevelopmentoffunctionalinvestigationsbasedonthetransittimeofcontrastagentboluses.Receptionofthesecondharmonicsignal
backscatteredfromresonancebubblecontrastagents(whichhavebubblediametersoftheorderofafewmicrometresatlowmegahertzfrequencies)provides
significantclutterrejectionandmayalsobeagood

Page127

approachtothemeasurementofperfusion(SchropeandNewhouse1993).TheuseofcontrastagentsisdiscussedmorefullyinChapter12.
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Page129

Chapter7
ThePurposeandTechniquesofAcousticOutputMeasurement.
TAWhittingham
7.1
WhyMeasureAcousticOutputs?
Overthethreedecadesorsoinwhichdiagnosticultrasoundhasbeeninuse,themagnitudesoftemporalaverageintensityandotheracousticoutputquantitieshave
increasedconsiderably.Thelackofanyconfirmedharmfuleffectsfromtheearliermachinesprovidesnoguaranteethattoday'smorepowerfulmachinesarefreefrom
potentialhazard.Indeed,weshallseethatfromthermalconsiderationsalonetherearegroundsforconcernoverthehighoutputsofwhichsomemodernmachinesare
capable.Itisimportantthatcliniciansandusershaveaccesstoaccuratedataabouttheacousticoutputoftheirmachinesiftheyaretomakeinformedriskbenefit
judgements.
7.2
UltrasoundDamageMechanismsandtheirBiologicalSignificance
Thetwomaindamagemechanismsaregenerallyconsideredtobeheatingandcavitation.Thereareotherpotentialmechanismsinvolvingmechanicalforces,suchas
bulkacousticstreamingandstandingwaveradiationforces,butthesearenotgenerallyconsideredtobeasimportantandthereforewillnotbediscussedfurtherinthis
briefsummary.Onlytheprincipalbiologicalconsequencesofheatingandcavitationarementionedbelowmuchmoreextensivereviewsareavailableintheliterature
(Whittingham1994,BarnettandKossoff1998).Inaddition,themechanismsofheatingandcavitationaredescribedfullyinChapters8and11ofthisbook,and
streamingandradiationforcemechanismsarediscussedinChapter3.

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7.2.1
Heating
Heatingoccursduetoabsorptionofultrasoundenergybytissueandtoselfheatingoftheprobe.Thetoleranceoftissuestotemperatureelevationdependsonthetype
oftissueandthedurationofthetemperaturerise.Tissuesundergoingorganogenesisareparticularlyatriskthisappliestotheembryointhefirst8weeksfollowing
conceptionandtothebrainandspinalcordevenafterbirth.TheWorldFederationofUltrasoundinMedicineandBiology(Barnett1998)hasconcludedthata
temperatureincreasetothefetusinexcessof1.5Cmaybehazardousifprolonged,while4Cishazardousifmaintainedfor5minutes.
Ignoringforthemomenttheacousticandthermalpropertiesofthetissues,thegreatestpotentialforheatingexistsatthepointintheinsonatedfieldwherethetemporal
averageintensityItaisgreatest.ThevalueofItaatthispointisknownasthespatialpeaktimeaveragedintensity,Ispta,andthisquantityfeaturesinseveralregulations
andstandards.Forconvenience,Itaisusuallymeasuredinwater,butinsomestandardsanattemptismadetoallowfortissueattenuation.The'derated'ItaistheIspta
value,asmeasuredinwater,butreducedbyafactortosimulatetheeffectofamediumwithastatedattenuationcoefficient,usually0.3dBcm1MHz1.Notethatthe
deratedIsptaisthelargestvalueofderatedItaintheultrasoundfield,andthisisnotthesameasthe'inwater'Isptawithaderatingfactorapplied.
Theactuallocalrateofheatenergyproduction(Wcm3)isequalto0.23 Ita,whereIta(Wcm2)isthetemporalaverageintensityinthetissue,and (dBcm1)isthe
localultrasonicabsorptioncoefficient.Bonehasamuchhigherabsorptioncoefficientthananysofttissue,andisthereforeanimportantpotentialtargetforheating
effects.FromtheaboveitmightbeassumedthatIsptaisareliablepredictorofworstcaseheating,undertheassumptionthatthemoststronglyabsorbingtargetcouldlie
atthepointofIspta.Althoughthisissometimestrue,itisnottrueingeneral.
Theactualtemperaturerisewillofcoursedependonthelocalspecificheatcapacityandthetimeofexposure,butitwillalsodependontherateanddistributionof
heatproductioninneighbouringtissues,andtheeasewithwhichthisheatcanbetransferredthroughthetissues.Thelattercanbedescribedbyaparameterknownas
theperfusionlength(Swindell1984),givenby

wherekisthethermalconductivityofthetissue,wisthebloodperfusionflowrateandsbisthespecificheatcapacityofblood.Theperfusionlengthisafew
centimetresinrelativelypoorlyperfused,orhighlyconductingtissuessuchasfat,boneormuscle,butonlyafewmillimetresinwellperfusedorpoorlyconducting
tissuessuchasheart,liver,kidneyorbrain.Wherethe

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perfusionlengthissmallerthananydimensionoftheinsonatedvolume,heattransferfromsurroundingtissueissmallandthelocalItaisareasonableindicatorofheating
potential.Whereitislargerthananyofthedimensionsoftheinsonatedvolume,heattransferwithintheinsonatedvolumebecomesimportantandthetotaltemporal
averageacousticpower,W,transmittedbytheprobemaythenbeabetterindicatorofheatingpotential.Amorecompletediscussionofthepredictionoftemperature
risesintissuesperfusedwithvesselsofmorecomplexgeometrymaybefoundinChapter8.
Ingeneralthen,neitherthetemporalaverageacousticpowernorthetemporalaverageintensitycansolelybeusedtocomparetheheatingpotentialofdifferent
machinesorcontrolsettings.Atheoreticallypredictedtemperatureriseforagivenacousticfieldandclinicalapplicationisthereforeabetterguideinassessingthermal
hazardthanarebasicacousticfieldparameterssuchasWorIspta.Calculations(Jagoetal1994)basedonmeasuredthreedimensionaldistributionsoftemporal
averageintensityfromclinicallyusedscannersandsimpletheoreticalmodelsoftissuelayers,indicatethatsomediagnosticultrasoundmachinesarecapableof
generatingworstcasetemperaturerisesinexcessof1.5Cinsofttissue,inallmodes,includingBmode.InpulsedDopplermode,temperaturerisesashighas2.5C
werepredictedforsofttissueand6Cforbone.Thesetemperatureriseswouldbeinadditiontoanypreexistingtemperatureelevation,forexampleduetofever.
Afurthercauseofheatingtoconsideristheprobeitself,particularlyintransvaginalapplications.Examplesofprobefacetemperaturesofmorethan10Cabovethe
ambientairtemperaturewerereportedseveralyearsago(Ducketal1989).Manufacturershaveaddressedtheproblem,butthispotentiallyimportantformofheating
shouldalwaysbechecked.
7.2.2
Cavitation
Thisreferstotheproductionandgrowthofbubblesbynegativepressureexcursionsandtotheirsubsequentbehaviour,andisdescribedingreaterdetailinChapter
11.Inthepresenceofanultrasoundwave,gasbubblescanformandgrowinthehalfcyclesforwhichthepressureisnegative.Twoformsofcavitationcanbe
distinguished.Incollapse(inertial)cavitation,pulseswithverylargevariationsinpressurecancausebubblestoformandcollapsewithinoneortwocycles,converting
relativelylargeamountsofsoundenergyintoheatandshockwaves,andcancreatehazardousfreeradicalssuchasOH.Collapsecavitationcanleadtotissue
damageandcelldestruction.Asevidenceofthis,itmaybenotedthatitisthemodeofactionofultrasoniccleaningtanks.Stablecavitationisalessviolent
phenomenonrequiringcontinuouswaves,orverylongpulses,ofmoremoderateamplitude.Here,bubblesofacriticalresonantsizeundergolargeamplituderadial
oscillationsatthefrequencyoftheappliedultrasound.

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Smallerbubblescangrowuntiltheyreachtheresonantsizebyaprocessknownasrectifieddiffusion,wherebymoregasistransferredintothebubbleinnegative
pressurehalfcycles,whenthebubblesurfaceareaisincreased,thanistransferredoutagaininthepositivepressurehalfcycles,whenthesurfaceareaisreduced.The
resonantoscillationsproducesuchvigorousswirling(microstreaming)oftheliquidintheimmediatevicinityofthebubblethatfreecellscanbecaughtupinitand
stressed.Ithasbeenpostulated(Dyson1991)thattheaccelerationofwoundrepairbyphysiotherapyultrasoundisduetoanincreaseinthepermeabilityofmastcell
andTcellwallsbroughtaboutbysuchmicrostreaming.
Bothformsofcavitationaremorelikelytohappenifthepeaknegativepressureamplitude,pr,islargeandthefrequency,f,islow.Infact,givenaliquidenvironment
withaplentifulsupplyofsmall'nuclei'(tinybubblescapableofgrowthintolargerbubbles),ApfelandHolland(1991)haveshownthatthepotentialfortheonsetof
collapsecavitationisproportionaltoa'mechanicalindex'(MI)givenby

AnaccountofthebackgroundandrationaleforMIisgiveninChapter11.
Anotherquantitythatissometimesusedasanindicatorofthelikelihoodofcavitationisthespatialpeakpulseaveragedintensity,Isppa,whichisthelargestvalueof
pulseaverageintensity(i.e.theintensityaveragedoverthedurationofapulse)tobefoundanywherewithinthesoundfield.Notethatalthough,atfirstsight,MImay
appeartobeapressureparameter,andIsppaapowerorenergyparameter,infactMI2isproportionaltotheenergyinthepeaknegativehalfcycleofthepulseand
isproportionaltothermspressureinthepulse.
Otherfactorswhichencouragecavitationincludetheavailabilityofnuclei,agitationtoencouragerenewaloffreshnucleianddissolvedgas,alowviscosityliquid
environment,ahighpulserepetitionfrequency(prf),longpulselengthsandtemperatureelevation.
Damagefromdiagnosticlevelsofultrasoundhasbeendemonstratedinvivoinanimaltissuescontaininggascavities,suchasthelungandintestine(Childetal1990,
Daleckietal1995).Thereisnoevidenceofahazardduetocavitationfromdiagnosticexposuresinvivoinothertissues,butthereisampleevidenceofbiological
effectsinvitro(see,forexample,AIUM1993orWhittingham1994).Therearenumerousliquidcollectionswithinandbetweentissuesinwhichcavitationcould
occurprovidedsuitablenucleiexist,includinginoraroundcriticaltargetssuchastheembryoorfetus,andtheneonatalcentralnervoussystem.Inviewoftheevidence
ofinvivocavitationfromphysiotherapyandlithotripsyexposure,thedemonstratedabilityofdiagnosticultrasoundtoproducebubblesingel(terHaaretal1989),
andthedifficultyofdetectingisolatedcavitational

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effectsintissue,thereisapossibility,evenalikelihood,thatcavitationaleventsdooccurinvivo.
7.3
TrendsinAcousticOutputs
Acousticoutputmeasurementsintheearlyyearsofdiagnosticultrasound(Hill1969,Ziskin1972,Carsonetal1978,FarmeryandWhittingham1978)reported
valuesofintensitiesthatwereoftheorderofafewmWcm2ortensofmWcm2forBmode,anduptoafewhundredmWcm2forDopplerdevices.Reported
valuesofacousticpowersweretypically20mWorless,althoughthoseforCWDopplerdevicessometimesexceeded100mW.Reportedvaluesofacousticoutputs
increasedduringthe1980s(Duck1989).Peaknegativepressuresofupto4MPaweremeasured,andIsptalevelsinDopplermodewerecommonlyintherange12
Wcm2.Acousticpowersreached360mWinBmodeand500mWinpulsedDopplermode(DuckandMartin1991,AIUM1993).
AlargersurveybyHendersonetal(1994a)showedacontinuingupwardtrendinreportedacousticoutput,particularlyinworstcasevaluesofIspta(i.e.thehighest
valueofIsptathatcouldbeobtainedunderanycombinationofscannercontrolsettings).Asshowninfigure7.1,reportedmedianvaluesofworstcaseIsptaincreasedby
afactorofsixforBmodeandtwoforcolourDoppler(CD)mode,betweensurveyspublishedin1991and1994.InpulsedDoppler(PD)mode,thegreatest
reportedIsptavaluedoubledto9Wcm2.Someofthisincreaseinreportedoutputlevelswasprobablyduetoimprovementsinmeasurementtechniquesandprotocols
forfindingworstcaseoutputs(Hendersonetal1993,1994b),aboutwhichmorewillbesaidlater.However,mostoftheincreaseislikelytobearealincrease
broughtaboutbydevelopmentsinscannermachinedesign.
Forexample,largeractiveapertures(moreactiveelements)havebeenusedinsomescannerdesignstoformnarrowerbeams,sometimesresultinginanincreasein
acousticoutputpower.Multipletransmissionsdowneachscanline(eachfocusedtoadifferentdepthzone)havereducedeffectivebeamwidths,andcorrespondingly
higherlinedensitieshavealsobeenintroduced.Thesedevelopmentshaveimprovedlateralresolution,buttheyhavealsoincreasedthenumberandfrequencyofpulses
experiencedbyeachfieldpoint.TheprovisionofaBmode'writezoom'facilityinmorescannershasalsobeenafactor.Unlike'readzoom',whichsimplymagnifies
partofthestoredimage,writezoominvolvestheselectedareabeingrescannedatahigherframerateandlinedensity,againleadingtoanincreaseinthenumberand
frequencyofpulsesinthescannedregion.Anotherfactorhasbeentheuseofhigherultrasonicfrequenciesforagivenclinicalapplication,againtoimprovespatial
resolution,requiringincreasedtransmissionenergiestocompensatefortheincreasedattenuationofthetissues.Thishasalso

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Figure7.1.
WorstcaseIsptalevelsreportedbyDuckand
Martin(1991)(black)andHendersonetal(1994a)(open).
Horizontalbarsindicatemedianvalues.

ledtoanincreaseinthepulserepetitionfrequency(prf),sincethesteeperrateofdecreaseofintensitywithrangeathigherfrequenciesmeanslesstimeisneeded
betweentransmissionstoallowforunwantedweakreturnsfrombeyondtheselectedmaximumdepth.Thesignificanceofultrasonicfrequencyandprfisindicatedby
thefactthatthehighestmeasuredoutputsforbothIsptaandprinthe1994surveywerefor7.5MHztransducers.
BmodeproducesthelowestIsptavaluesbecausethebeamisscannedacrossaregionoftissue.ThehighestIsptavaluesareproducedinpulsedDopplermode,
principallybecausethebeamisheldstationaryratherthanbeingscanned,andbecauseveryhighprfsareemployedinanefforttoincreasetheNyquistlimit,i.e.the
frequencyatwhichaliasingoftheDopplershiftedfrequencyoccurs.ColourDopplermodestendtohaveIsptavaluesintermediatebetweenthoseofpulsedDoppler
andBmodesince,althoughthebeamisscannedacrossthe'colourbox',asequenceofseveralpulsesistransmitteddowneachDopplerlineatahighprf.
7.4
RegulationsandStandards
IntheUK,therearenomandatorylimitsonanyacousticoutputparametersfromdiagnosticultrasoundequipment.However,beforeanultrasoundscannercanbe
soldintheUSAapprovalmustbesoughtfromtheFoodandDrugAdministration(FDA),anditsregulations(FDA1997)imposesomelimits.Theimportanceofthe
USAmarketmeanstheselimitsgenerally

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Table7.1.LimitssetbyFDA510(k),Track1.Deratinginvolvesreducingtheinwatervaluebyafactorwhichsimulates
theeffectof0.3dBcm1MHz1attenuationinthemedium.

DeratedIsptamWcm2

MI=(deratedp r)/ f(p rin

MPa,finMHz)

DeratedIsppaWcm2

Peripheralvessel

720

190

1.9

Cardiac

430

190

1.9

Fetalandother

94

190

1.9

Ophthalmic

17

28

0.23

applytomachinessoldintheUKandelsewhere.Someothercountries,forexampleJapan,alsohavemandatorylimits.ThereisalsoanInternationalElectrotechnical
CommissionstandardIEC61157(IEC1992)withwhichmanufacturersgenerallycomply,whichrequirescertainacousticoutputparameterstobedeclared.
7.4.1
FDA510(k)Regulations
ManufacturersmaychoosetoapplyforFDAapprovalbyeither'Track1'or'Track3'.(TherewasanoptioncalledTrack2,butitisnolongeravailable.)
FDATrack1requiresthatderatedIsptaandeitherderatedIsppaorMIarebelowthelimitsshownintable7.1.Notethattheselimitsvaryaccordingtotheapplication.
ThemeasurementsofIsppaandMImustbemadeatthepositionatwhichthe'deratedpulsepressuresquaredintegral(deratedPPSI)'isamaximum.ThePPSIis
proportionaltothepulseenergyperunitarea,andisfoundbyintegratingthevalueofp2overthepulseduration.
FDATrack3relaxesthelimitsforfetal,cardiacandallnonophthalmicapplicationstothoserequiredbyTrack1forperipheralvascularapplications,provided
mechanicalindex(MI)andthermalindex(TI)valuesaredisplayed.TheseindicesaredefinedintheOutputDisplayStandardoftheAmericanInstituteofUltrasound
inMedicine/NationalElectricalManufacturersAssociation(AIUM/NEMA1998),andarediscussedbelow.ForophthalmicapplicationstheTImustbelessthan1.0,
thederatedIsptamustbelessthan50mWcm2(comparedto17mWcm2inTrack1)andtheMImustbelessthan0.23.
7.4.2
AIUM/NEMAOutputDisplayStandard.
Thisstandard,usuallycalledthe'ODS',requiresthat,ifthemachineiscapableofproducingavalueforeitherMIorTIthatisgreaterthan1.0,theindexvaluemustbe
displayedwheneveritexceeds0.4.ItisnotnecessarytodisplaytheTIwheninBmode.

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Thermalindex(TI)isdefinedastheratioofthetotalacousticpowertotheacousticpowerrequiredtoraisethetissuetemperatureby1Cunderdefinedassumptions.
Theseassumptionsincludeverysimpletissuemodelsandbeamshapes.OneofthreedifferentTIsisapplicable,accordingtowherethegreatestheatingisanticipated.
TISapplieswhereitislikelytooccurinsofttissue,TIBapplieswherebonenearthefocusofanunscannedbeamislikelytobeheatedmost,andTICwhereitislikely
tooccurinboneclosetotheprobe,e.g.asintranscranialscanning.Considerationofwhethertheoperatingmodeisscannedorunscannedleadstofourdifferent
formulae,shownbelow.Intheseformulae,WandW.3aretheinwaterandderated(0.3dBcm1MHz1)totalacousticpowersrespectively(mW)W1isthemaximum
inwateracousticpowertransmittedbya1cmwidesectionoftheprobeface(mW)I.3isthederatedIspta(mWcm2)fisthecentrefrequency(MHz)Aisthe
radiatingaperture(cm2).
Softtissueonly.(a)Forscannedmodes,orforunscannedmodesthatuseanapertureof<1cm2:TIS=W1f/210.(b)Forunscannedmodesthatuseanapertureof
>1cm2:TIS=themaximumvalueofXasafunctionofrange,whereXisthelowerofW.3.f/210andI.3.f/210atanyrange.
Boneatfocus.(a)Forunscannedmodes:TIB=lowerof (W.3I.3)/50andW.3/4.4measuredwhereIsptaderatedat0.6dBcm1MHz1isgreatest.(b)Forscanned
modes:useTIS.
Boneimmediatelynexttoprobe:TIC=W/40DwhereD= (4A/ ).
Mechanicalindex(MI)isdefinedthespatialpeakvalueofthederated(0.3dBcm1MHz1)peaknegativepressure(MPa)dividedbythesquarerootofthepulse
centrefrequency(MHz0.5).Notethat,apartfrominsituationswhereboneisimmediatelynexttotheprobe,theODSspecifiesthatTISbeusedforscannedmodes
(e.g.BmodeorCDmode),irrespectiveofwhetherboneispresentornot.Thus,foracolourDopplerscanofasecondorthirdtrimesterfetus(inwhichbonewillbe
present),TISandnotTIBisconsideredappropriate.
7.4.3
IEC61157
IEC61157isaninternationalstandardthatrequiresmanufacturerstodeclareanumberofacousticoutputparametersifpr,Ispta,orIobexceedcertainthresholdvalues.
Iobisthe'outputbeamintensity',definedasthetotalacousticpowerdividedbythe6dBbeamcrosssectionalareaatthetransducer.Thethresholdforpr(measuredat
thepositionofgreatestPPSI)is1MPathatforIsptais100mWcm2thatforIobis20mWcm2.Thesethresholdsareexceededbyvirtuallyallcommercialscanners.
Parametersthatmustbedeclaredincludethethreementioned,plustotalacousticpower,frequency,6dBbeamwidthwherethePPSIisgreatest,andthemodes
andcontrolsettingsthatgivemaximumacousticoutputvalues.

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7.5
IsThereaNeedforIndependentMeasurements?
Itmightbearguedthatthedeclarationofoutputparametersbythemanufacturers,perhapssupportedbythetestingofrepresentativemachinesatjustoneortwo
independenttesthouses,shouldbesufficient.Ourexperienceisthatmanufacturers'reporteddataarenotalwaysreliable,andthatconsiderabledifferencescan
sometimesexistbetweentheoutputsofdifferentmachinesofthesamemakeandmodel.
Findingworstcasevaluesofacousticoutputparametersfrommoderncomplexscannerscanbeadifficultandelusiveprocess.Measurementequipmentissometimes
lessthanideal,particularlyinregardtohydrophoneaperturesize.Inaddition,recordkeepinglapsesarealwaysapossibility,resultinginsoftwareorhardwarechanges
beingmadetoindividualmachineswithoutanaccuraterecordbeingmadeinthescannerhandbooks.Itisperhapsnotsurprising,therefore,thattherehavebeenmany
instanceswhenourownmeasurementshaveexceededthosedeclaredbythemanufacturer,oftenbyalargefactor.Inanefforttohighlighttheproblem,wepublished
detailsofjustthreeexamplesofIsptameasurements,chosenbecausetheyhadbeensubjecttoclosescrutinybythemanufacturersconcerned(Jagoetal1995).Twoof
thethreemanufacturersacceptedourhigherfigures(whichwerefivetimesthedeclaredvalues),whilethethirdacknowledgedthattheiroutputswereprobablyhigher
thanquotedintheequipmentmanual.Onediscrepancywasduetothemanufacturernottakingsufficientaccountofmultiplefocalzoneswhenusingwritezoom,as
describedabovethesecondwasduetoanobsoletehighoutputsoftwareversionmistakenlybeingsuppliedwiththemachine.Thesecases,andthescoresofother
unpublishedexampleswehaveonrecord,demonstratethatthereisaneedforindependentacousticoutputmeasurementstobemadeoneverymachine.
7.6
WhichOutputParametersShouldBeMeasured?
Ifitisintendedtocheckthatequipmentcomplieswithaparticularregulationorstandard,itisclearlynecessarytomeasuretheworstcasevaluesofthespecified
parameters.InthecaseoftheODS,thisinvolvesmeasuringthepowerradiatedbya1cmwidelengthoftheprobe,thecentrefrequencyandderatedvaluesofpr,Ita
andPPSI.ParametersspecifiedinIEC61157includethe6dBdimensionsoftheproberadiatingarea,therangeandvalueofthegreatestinwaterPPSI,the6dB
beamcrosssectiondimensionsandthevalueofinwaterpratthatrange,aswellasWandinwaterIspta.
Thedifficultyofmakingthesemeasurementsathospitalsitesforallprobesandmodes,underawiderangeofcontrolsettings,meansthatwecurrentlyrestrictonsite
measurementstoinwatervaluesofpr,Ispta,W,andthe

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6dBbeamcrosssectiondimensionsattherangeofIspta.Wealsorecordthepulsewaveforms,correspondingtoworstcaseprandIsptathisallowsotherpulse
parameterssuchascentrefrequency,pulseaverageintensity,pulseenergyperunitarea,pcandpulsedurationtobederivedlater.Althoughweonlymeasureinwater
values,thesestillprovidesomedegreeofacheckonmanufacturers'declaredderatedvalues,sincederatingthespatialpeakinwatervalueshouldgiveaderatedvalue
whichisnomorethanthedeclaredderatedvalue.
Ifareportistobeissuedtothemachineuser,itisdesirabletokeepitbriefandeasytounderstand.Itisalsodesirabletogivetherecipientsomecriteriabywhichthey
cangaugethereportedoutputvalues.Currently,ourreportstouserssimplygiveworstcasevaluesofIsptaandprforallprobesandallmodes,andwehavechosento
comparethesewiththelimitsrecommendedbytheBritishMedicalUltrasoundSociety(BMUS1988).Ultimately,itislikelythatweshallcalculateandreportsome
formofthermalandmechanicalindicesaswell.ThesemaybethosespecifiedintheODSorotherfuturestandards,ormodifiedversionsthataremoreamenabletoa
portablemeasurementsystem.
7.7
TheNewcastlePortableSystemforAcousticOutputMeasurementsatHospitalSites
Accesstomostscanningsystemsislimitedbytheneedtocauseminimaldisruptiontothenormalclinicalworkload.Thiscanbebestachievedifmeasurementscanbe
madeatthesiteatwhichthescannerisinstalled.Themeasurementsystemmustthereforebeeasilyportable.Itshouldbeeasyandquicktoassembleatthe
measurementsiteaswellasbeinglightweightandcompact.ThesystemdescribedhereisbasedonthatofMartin(1986),andhasbeenusedsuccessfullyovera
numberofyearstomakemanyhundredsofmeasurementsonalmostthewholeavailablerangeofdiagnosticultrasoundscanners.Ablockdiagramofthesystemis
showninfigure7.2.Atthepresenttimeitisnotcapableofgivingrealtimereadoutsofderatedpressuresandintensities,butworkisinhandtomakethispossibleby
automaticallymonitoringthehydrophonedepthandpulsecentrefrequency.
7.7.1
TheHydrophoneandPreAmplifier
Twotypesofhydrophonearecandidatesforpressuremeasurementsondiagnosticultrasoundequipment:PVDFmembranehydrophonesandneedlehydrophones.
Theformerconsistofathinfilmofpolyvinylidenefluoride(PVDF)stretchedacrossa10cmdiametersupportingring.Onlyasmall(1mmor0.5mmdiameter)areain
thecentreispolarised,formingthe

Page139

Figure7.2.
BlockdiagramoftheNewcastleportablesystem.
Anoscilloscopecamera,digitisingtabletandpersonal
computerarealsousefulifananalogueoscilloscopeisused.

pressuresensingpiezoelectricelement.Printedcircuitleadsonthefilmconnectelectrodesoneachsideofthistotheinnerandouterconductorsrespectivelyofa
coaxiallead,viaterminalsonthesupportring.Thesupportringiswideenoughtobewelloutsidethebeaminmostapplications.A'bilaminar'versionhasthenon
earthedelectrodeandleadprotectivelysandwichedbetweentwoPVDFfilmsbondedtogether.Althoughhavingagreaterthickness,andhencealowerresonance
frequencyandbandwidthandahigherreflectioncoefficient,bilaminarhydrophonesaremoresuitableforuseinnondeionisedwaterandhavebetterelectrical
shielding.NeedlehydrophonesconsistofasmallPZTorPVDFpiezoelectricelementmountedonthetipofaneedlelikesupport.Theyareusedwiththeneedle
pointingtowardsthesourceinordertominimisetheeffectofreflectionsfromthesupportor,inthecaseofpulsedwaves,toallowsuchreflectionstobegatedout.
TheNewcastlesystemusesa50mthickbilaminarPVDFmembranehydrophone.
Nonlinearpropagationeffectscanresultinthegenerationofhighfrequencyharmonicsinthepulsewaveform(Chapter2).Theinternationalstandardonmeasurement
ofultrasonicfieldsIEC61220(IEC1993)recommendsthatthesensitivityofthehydrophoneandhydrophoneamplifiershouldvarybylessthan6dBovera
frequencyrangeextendingto3octavesabovetheacousticworkingfrequency,orto40MHz,whicheveristhesmaller.
Theresonancefrequencyfora50mbilaminarhydrophoneoccursatapproximately23MHz.Consequentlyatfrequenciesbelowresonancethehydrophone
sensitivityincreaseswithfrequency,byapproximately50%between2MHzand20MHz.Itispossibletocompensateforthisbyusingaspecialhydrophonepre
amplifierwithacomplementaryfrequencyresponse.ThefrequencyresponseofthecombinationofaGECMarconiY359724hydrophonepreamplifierwiththe50
mbilaminarhydrophoneisflatto

Page140

within10%between1and20MHzandvariesbylessthanafactoroftwouptoapproximately30MHz.Thiscombination,therefore,onlymeetstheIECbandwidth
criterionforprobesoperatingatfrequenciesbelowabout4MHz.Hydrophoneswithhigherresonancefrequencieswillbeusedwhentheybecomeavailable.Cable
resonancesinthe70cmcableusedintheNewcastlesystemoccuratapproximately65MHz,andthereforedonotcauseaproblem.Althoughthefrequencyresponse
isreasonablyflat,thecalibrationfactorfortheprecisemeasuredfrequencyisalwaysused.
Ideally,thehydrophoneelementshouldbemuchsmallerthanthebeamwidth.IEC61102(IEC1991)andAIUM/NEMAUD2(AIUM/NEMA1992)standards
specifythattheeffectivediameterofthehydrophoneelementshouldbecomparabletoorsmallerthan /2.Thiscorrespondstoadiameterof<0.15mmfora5MHz
probeand<0.075mmfora10MHzprobe.Needlehydrophonesdownto0.075mmdiameterareavailable,buttheyaredifficulttomountinthesmallmeasurement
tankoftheportablesystemandhaveanunevenresponseatlowfrequencies.Morerelaxedcriteriaarespecifiedformeasurementswherewavefrontscanbe
consideredtobereasonablyplanar.Thisappliestomostpracticalsituations.However,eventhesecriteriastillrequirehydrophonediametersbelow0.5mm.Atthe
presenttime,membranehydrophoneswithactiveelementdiametersoflessthan0.5mmaredifficulttoobtain.Algorithmsareavailabletocorrectforspatialaveraging
effectswhenusinghydrophoneelementsthatarelargerthanideal(IEC1993,Smith1989),althoughtheiraccuracyispoorifthe6dBbeamwidthislessthanthe
hydrophonediameterandtheyarenotroutinelyapplied.
Itisimportanttoreduceanyerrorduetointegratingnoiseassociatedwiththehydrophonesignal.Acousticnoiseisreducedbyliningthewallsandbaseofthetank
withacousticabsorber.Electricalnoiseandelectricalinterferencefromtheprobearereducedbyusingalownoisepreamplifier,connectedtothebilaminar
membranehydrophonebycoaxialcable.
7.7.2
VariableAttenuator,PowerAmplifierandPowerMeter
Thesecomponentsallowthetemporalaverageintensity,Ita,tobemeasuredanddisplayedinrealtimeasananaloguequantity,allowingrapidlocalisationofthepoint
atwhichItaisamaximumandhencemeasurementofIspta.Avariableattenuator(Hatfield2105)isusedtokeeptheinputvoltagetothepoweramplifier(Minicircuits
ZHL32A)withinthe600mVpeaktopeaklimitatwhichsaturationoccurs.TheoutputfromthepoweramplifiergoestoaMarconi6912powersensor.Thisconsists
ofa50 resistor,andasemiconductorthermocouplewhichproducesavoltageproportionaltothetemporalaverageelectricalpowerconvertedtoheatinthe
resistor.Thisvoltageisamplifiedanddisplayedbythemeter(Marconi6950).Thesensorhasathermaltimeconstantofapproximately30ms.Themetertime
constantisvariableupto15sandissettoavaluegreaterthanthescanrepetition

Page141

period,whichcanreachseveralhundredmillisecondsatthelowestframerates.Themeterreadingisthereforeproportionaltothetemporalaverageofthesquareof
thehydrophoneoutputvoltage,andhencetoIta.Thesensorandmetercombinationhasabandwidthfrom30kHzto4.2GHzandcanmeasureelectricalpowerlevels
from1Wto100mW.Theelectricalpowerofsignalsleavingthepoweramplifieristypicallybetween50WforalowoutputBmodesystemand60mWfora
highoutputpulsedDopplersystem.Electricalnoiseatthisstageistypicallylessthan1W.
7.7.3
Oscilloscope
Theoscilloscopedisplaysthesignalfromthehydrophoneamplifiersothatprcanbemeasured,andpositionsofpeakpulseamplitudemaybefound.Italsopermits
monitoringofanydistortionoftheultrasoundpulse.AdelayedtriggerfacilityisvaluableforisolatingindividualpulsesfromBmodeandcolourDopplersequences.A
Tektronix221560MHzanalogueoscilloscopewasusedinthefirstsystem,butoursecondsystemusesaLeCroy9350AM500MHzdigitaloscilloscope.Thedigital
oscilloscopehasafacilityforcalculatingcentrefrequencyandshowingPPSIvaluesinrealtime,aswellashavingmuchsuperiortriggeringfacilities.Itcanalsostore
digitisedpulsewaveformsforsubsequentanalysisifrequired.
7.7.4
OscilloscopeCamera,PCandDigitisationTablet.
Ifananalogueoscilloscopeisused,anoscilloscopecameraforrecordingpulsewaveformsisuseful.Thepulsewaveformmaythenbehanddigitisedonreturntothe
laboratory,usingapersonalcomputerandadigitisingtablet.Thisallowsthecentrefrequencyandotherpulseparameterstobecomputed,andfrequencydependent
calibrationfactorstobeappliedautomatically.
7.7.5
TheMeasurementTank
Theportablemeasurementtankisabucket,measuring30cmmaximuminternaldiameterby24cmdeep.Itislargerthanthedimensionsofthelargestultrasoundfield
tobemeasuredandthebottomiscoveredwithanacousticabsorber(carpetorastroturf)toreduceacousticnoiseintheformofreflectedultrasound.Analuminium
mountingplatearoundthetopofthebucketprovidesameansofattachingtheprobesupportandhydrophonepositioningsystem.Themainrestrictiononthesizeof
thetankisthevolumeofdistilledwaterneededtofillit.Whentransportingtheequipment,1012litresofwaterarecarriedinseparateclosedcontainers.
Althoughtheconductivityoftapwaterhaslittleeffectonbilaminarshieldedhydrophones,distilledwaterisusedinthemeasurementtank.Onereasonisthatitallows
thewelldocumentedacousticimpedancevalues,Z,forpurewatertobeusedinthecalculationofintensity(I)frompressure

Page142
2

(p)measurements,usingI=p /Z.Anotherreasonisthatdistillingalsoachievessomedegreeofdegassing,helpingtoreducefieldperturbationscausedbybubbles
adheringtothehydrophoneorprobe.
7.7.6
TheHydrophonePositioningSystem
Movementofthehydrophoneisachievedinthetwohorizontaldirectionsperpendiculartotheverticalbeamaxisbyamicromanipulatorwithareductiondriveanda
verniermillimetrescale.Movementintheverticalaxialdirectioniscontrolledbyathirdmicromanipulator,butwithoutareductiondrive.Thehydrophoneisattachedto
themicromanipulatorsystemviaaclampmadeinhousewhichsupportsitinahorizontalplane.ThestandardIEC61220statesthatthepositioningofthehydrophone
shouldbereproducibleto0.1mm.
7.7.7
TheProbeMountingSystem
Thishastoaccommodateandfirmlysupportmanydifferentsizesandshapesofultrasoundprobe.Theuseofretortstandclamps,attachedtobarsonthemounting
plate,isaflexibleandsatisfactorymethod.
7.7.8
CalibrationandAccuracy
ThehydrophoneiscalibratedbytheNationalPhysicalLaboratory(NPL),Teddington,every1218months.Thepowermeteriscalibratedatsimilarintervalsbythe
manufacturer.Theamplifiersaresuppliedcalibrated,andthegainsarecheckedinhouseannually.Accuracydependsonthecharacteristicsoftheultrasonicfieldbut
overallthe95%confidencelimitforprisapproximately12%,whilethatforIsptaisapproximately30%.
7.8
TheNPLUltrasoundBeamCalibrator
TheNPLUltrasoundBeamCalibratorisacomprehensivemeasurementsystem(Preston1988)whichhasbeendevelopedattheNPLtoenabletherapid
determinationoftheacousticoutputofmosttypesofmedicaldiagnosticultrasonicequipment.Itconsistsofa21element,50mPVDFmembranehydrophonearray
mountedinatesttankandconnectedtoafastdatacaptureandpresentationsystem.Elementsare0.4mmindiameterandspaced0.6mmbetweencentres(0.5mm
at1.0mmspacinginearlierversions).Thepressureprofileacrossthebeamandtheacousticpressurewaveformforanyselectedhydrophoneelementarepresentedin
realtime,togetherwiththepeakacousticpressures(positiveandnegative),PPSIandpulserepetitionrate.Otherimportantacousticalparameters,including

Page143

theacousticworkingfrequencyandFDAderatedvalues,arecalculated.Measurementuncertaintydependsontheparticularapplicationbutitistypically11%for
acousticpressureparameters,and22%forintensityparameters(95%confidencelevel).
Thesystemispowerful,butitisnotasconvenientastheNewcastlesystemforroutinemeasurementsathospitalsites.Itisbulkier,andrequirestriggersignalsthatare
oftendifficulttoobtainfromcommercialscanners.TheanaloguemethodusedintheNewcastlesystemisaneasierwayofmeasuringtemporalaverageintensities,and
itmaybenotedthattheNPLproposestousetheanaloguemethodinfutureversionsoftheirUltrasoundBeamCalibrator.
7.9
MeasurementofAcousticPower
Unfortunately,atthepresenttimethereisnocommerciallyavailableformofpowermeasuringdevicethatisbothsufficientlysensitiveandportableformeasurementsat
hospitalsites.However,thetwodesignsshowninfigures7.3and7.4havebeenfoundtobesatisfactory,andsuitableforinhouseconstruction.Theyareboth
examplesofradiationforcebalances,whichusetherelationshipthat,foranabsorbingtarget,

wherecisthespeedofsoundinthefluidaroundthetarget.
Thebalance(Perkins1989)showninfigure7.3isadevelopmentofadesignbyFarmeryandWhittingham(1978).Itusesanairfilled,45conicalreflectorasa
target,mountedwithinacylindricalabsorbertopreventreflections.Theforceonsuchatargetisthesameasthatonanabsorberperpendiculartothebeam(see
Chapter3).Radiationforcepushesthetargetback,generatingasignalfromanopticaldisplacementdetector.Thissignalisamplifiedandusedtogenerateacurrentin
anelectromagnetcoil,whichinturngeneratesacounterbalancingforceuponapermanentmagnet,attachedtotherearofthetarget.Ameterreadingofthecoilcurrent
givesadirectmeasureofthemagneticrestoringforce,andhenceoftheradiationforce.AmodificationofthisdesignbyWhittingham(unpublished)isthereplacement
oftheconicalreflectingtargetandsurroundingabsorbingcylinderbyaflatabsorbingtarget(figure7.4).Thisissufficientlywidetoallowthedirectmeasurementof
powerfromlineararraysinscanningmode,notpossiblepreviously.Theuseofaflattargetalsoallowsthedistancebetweentheprobeandthetargettobereduced.
Bothhavesensitivitiesofaround1mW,butatsettingsbelowabout100mWfullscaledeflection,vibrationtransmittedfromthesurroundingscanbeaproblem.Ten
minutesorsoshouldbeallowedforanydisturbanceof

Page144

Figure7.3.
PrincipleofthePerkinsbalance.

Figure7.4.
Modification(Whittingham)toaccommodate
widetransducers,e.g.lineararrays.

thewater,duetotransportationforexample,tosettledown.Iftheultrasonicfieldisstronglyconvergent(e.g.somestronglyfocusedstationarybeams),divergent(e.g.
sectorscannersinscanningmode),orobliquelyincidentonthetarget(e.g.angledDopplerorsectorscanbeams),thenanappropriate'cos 'correctionfactorshould
beestimatedandapplied.Withcare,anaccuracyofabout15%shouldbeachievable.Thebalancesmaybecalibratedeitherwithachecksource(atransducerand
driveunitthatdeliversabeamofknownacousticpower,availablefromtheNPL)orbymakingprovisionforadetachablearmtowhichweightsmaybeattached.The
equationforradiationforcegivenabovemeansthat,forcalibrationpurposes,1Wofacousticpowerproducesaforceof68mgweightonanabsorbingtarget.
Othermethodsofpowermeasurementincludecalorimetryandintegration

Page145

ofintensityacrossaplaneperpendiculartothebeam(planarintegration).Sofar,calorimetricmethodshavelackedsufficientsensitivity.Theplanarintegrationmethod
hasexcellentsensitivitybutisreallyonlysuitableasalaboratorybasedmethod.
7.10
FindingWorstCaseValues
Astheremaybemillionsofdifferentpossiblecombinationsofcontrolsettingsonamodernscanningsystem,asystematicapproachisclearlynecessary.Unfortunately
therearenofoolproofrules,ascontrolsandtheireffectsvarybetweenmachines,ofteninunexpectedways.Animportantstepistospendsometimeidentifyingwhich
controlsaffectthepositionofthespatialpeakofthequantity,andwhichaffectonlyitsmagnitude.Thisismucheasierwhenthemeasurerhasgainedexperience,but
protocolshavebeenpublished(Hendersonetal1993,1994b)whichcaneitherbeuseddirectly,orformausefulstartingpoint.Someguidanceforfindingworstcase
Isptavalues,basedontheseprotocolsisgivenbelow.Findingworstcasevaluesofprandacousticpowerisgenerallymorestraightforward.
Inthefollowingsummarisedprotocols,smallcapitalsdenoteamachinecontrol.
7.10.1
WorstCaseIsptaofStationaryBeams,e.g.PulsedDopplerMode.
Theprotocolmaybesummarisedas:
(i)SettheOUTPUTPOWERcontroltomaximumandsetthebeaminthe'straightahead'position,sincethisgivesthegreatestaperture,andhenceislikelytogivethe
greatestoutput.StartwiththeminimumpossiblesettingsofDEPTHOFFIELDandDOPPLERFOCUSdepth.
(ii)ExplorethefieldwiththehydrophonetofindthepositionofIspta.ThentryallcombinationsofGATEWIDTH,VELOCITYSCALE(prf)andDOPPLERFREQUENCYtofindthat
whichmaximisesthevalueofIsptaatthispoint.Makeanoteofthisvalue.
(iii)IncreaseDOPPLERFOCUSdepthuntilachangeintheamplitudeofthepulsecanbeseenontheoscilloscope.IftheGATEisatthebottomoftheimage,increasethe
IMAGEDEPTH.

(iv)MovethehydrophoneuntilthenewpositionofIsptaisfoundand,leavingitthere,againtryallcombinationsofthecontrolsmentionedin(ii)tomaximiseItaatthis
position.Makeanoteofthemaximumvalue.
(v)Repeatsteps(iii)and(iv)untilallDOPPLERFOCUSdepthssettingshavebeenselected.ThelargestIsptavaluefoundistheworstcaseIspta.Recordthisandthecontrol
settingsthatproducedit.

Page146

7.10.2
WorstCaseIsptaforScannedBeamModes,e.g.BMode
Incontrasttostationarybeams,thepositionofIsptavariesonlyslightlywithFOCUSdepth.Thisisduetothefactthatthebeamsoverlapinthescanplanesothat,asfaras
temporalaverageintensityisconcerned,thereisawiderelativelyuniformeffectivebeam.Withinthis,theshapeandfocalpositionofanyindividualbeamisrelatively
unimportant.Intheelevationplane,ofcourse,thereisnobeamoverlap,sotherangeatwhichtotalpowerisconcentratedmost,andthereforewheretheIsptais
located,isclosetothatoftheelevationplanefocus.Forsectorprobesandcurvilineararrays,thedivergenceoftheeffectivebeammeanstheIsptaisgenerallylocated
betweentheelevationfocusandtheprobe.
TheprotocolforBmodeismorecomplexandsubjecttomorevariationsbetweenmachinesthanisthatforpulsedDoppler.Consequentlyonlyafewgeneral
guidelineswillbegivenhere.SelectingtheminimumWIDTHOFFIELDgenerallygiveslargerIsptavalues,duetoahigherframerateand/orahigherlinedensity.Generally,
deepFOCUSsettingsgivegreaterIsptavalues,principallybecauseofthelargeraperturesthatareoftenemployed.However,theeffectofthiscanbeoffsetbythefactthat
adeepFOCUSsettingrequiresalargeDEPTHOFFIELD,whichmeansareducedpulserepetitionfrequency.TheeffectofincreasingtheNUMBEROFFOCIcanalsobedifficult
topredict.
StartwiththeOUTPUTPOWERcontroltomaximumandselectasinglefocusatthefurthestrangeinthedeepestDEPTHOFFIELDprogressivelyreducetheDEPTHOFFIELD
(leavetheFOCUScontrolalone,causingthefocustofollowautomaticallyatthefurthestrangeintheimage).OncetheIsptavaluesstarttofall,itisnotnecessaryto
continueinvestigatingnearerFOCUSsettings.IfnomaximumhasbeenfoundbeforethesmallestDEPTHOFFIELDhasbeenselected,tryallFOCUSsettingswithinthisfield.
NotethelargestIsptavalueobtainedsofar,advancetheNUMBEROFFOCIbyoneandstartagainwiththedeepestDEPTHOFFIELD.
mayincreaseIsptavaluesconsiderably,theincreasebeinggreatestforthegreaterZOOMBOXDEPTHsettings,sincegreaterrangesusuallyinvolvethegreater
apertures,andtheminimumZOOMBOXWIDTHsetting,sincethisinvolvesthegreatestframerateand/orlinedensity.TheeffectofchangesinZOOMBOXHEIGHTthatalso
changethenumberoffociwithintheboxshouldbeexplored.
WRITEZOOM

7.11
Conclusions
Itispossibleforamedicalphysicsdepartmenttomeasuretheprincipalacousticoutputcharacteristicsoftheclinicalscannersinitsarea.Thereareseveralreasonsfor
doingso.Therehasbeenalongtermtrendtowardshigheroutputs,andthisshouldbemonitored.Someclinicalmachinesarecapableofharmfuleffectsifnotused
prudently,withproperawareness

Page147

ofthemodesandcontrolsettingsthatleadtohighoutputs.Reportingtheresultstoclinicalusersallowsthemtobecomeawareofhowtoreduceexposure,tomake
informedriskbenefitjudgementsbasedontheirownmachine,andtodefendthemselvesintheeventofanyaccusationsrelatingtoultrasonicexposure.Manufacturers'
effortstomoderateorreduceacousticoutputswillbegivenaddedimpetusbyincreasedcustomerawarenessof,andinterestin,actualvalues.Biomedicalresearch
willhavethebenefitofaccurateknowledgeaboutrealclinicalexposures.
References
AIUM/NEMA1992UD2:AcousticOutputMeasurementStandardforDiagnosticEquipment(Rockville,MD:AmericanInstituteofUltrasoundinMedicine)
AIUM/NEMA1998StandardforRealTimeDisplayofThermalandMechanicalAcousticOutputIndicesonDiagnosticUltrasoundEquipment2ndedn
(Rockville,MD:AmericanInstituteofUltrasoundinMedicine)
AIUM1993BioeffectsandSafetyofUltrasound(Rockville,MD:AmericanInstituteofUltrasoundinMedicine)
ApfelREandHollandCK1991Gaugingthelikelihoodofcavitationfromshortpulse,lowdutycyclediagnosticultrasoundUltrasoundMed.Biol.1717985
BarnettSB(ed)1998WFUMBSymposiumonSafetyandStandardisationinMedicalUltrasound1997UltrasoundMed.Biol.inpress
BarnettSBandKossoffG(eds)1998SafetyofDiagnosticUltrasound(London:Parthenon)
BMUS1988Br.Med.UltrasoundSoc.Bull.no50,August
CarsonPL,FischellaPSandOughtonTV1978UltrasonicpowersandintensitiesproducedbydiagnosticultrasoundequipmentUltrasoundMed.Biol.3341
ChildSZetal1990AcousticcavitationproducedbymicrosecondpulsesofultrasoundUltrasoundMed.Biol.1681725
DaleckiD,RaemanCH,ChildSZandCarstensenEL1995IntestinalhaemorrhagefromexposuretopulsedultrasoundUltrasoundMed.Biol.21106772
DuckFA1989OutputdatafromEuropeanstudiesUltrasoundMed.Biol.15(Suppl.1)614
DuckFAandMartinK1991TrendsindiagnosticultrasoundexposurePhys.Med.Biol.36142332
DuckFA,StarritHC,terHaarGRandLuntMJ1989SurfaceheatingofdiagnosticultrasoundtransducersBr.J.Radiol.62100513
DysonM1991ThesusceptibilityoftissuestoultrasoundTheSafeUseofDiagnosticUltrasoundedMFDockerandFADuck(London:BritishInstituteof
Radiology)pp249
FarmeryMJandWhittinghamTA1978AportableradiationforcebalanceforusewithdiagnosticultrasonicequipmentUltrasoundMed.Biol.33739
FDA1997FDA510(k):InformationforManufacturersSeekingMarketClearanceofDiagnosticUltrasoundSystemsandTransducers(FoodandDrug
Administration,DepartmentofHealthandHumanServices,1390PiccardDrive,Rockville,MD20850,USA)
HendersonJ,JagoJ,WillsonKandWhittinghamTA1993Towardsaprotocolformeasurementofmaximumspatialpeaktemporalaverageintensityfromdiagnostic
BmodeultrasoundscannersinthefieldPhys.Med.Biol.38161121

Page148

1994aAsurveyoftheacousticoutputsofdiagnosticultrasoundequipmentincurrentclinicaluseintheNorthernRegionUltrasoundMed.Biol.21699705
1994bDevelopmentofprotocolsformeasurementofmaximumspatialpeaktemporalaverageintensityfromscannersoperatinginpulsedDopplerandcolour
DopplermodesBr.J.Radiol.67716
HillCR1969AcousticintensitymeasurementonultrasounddiagnosticdevicesUltrasonographiaMedica,Vol2,Proc.1stWorldCongressonUltrasonic
DiagnosticsinMedicineandSIDUOIIIedJBockandKOssoining(ViennaAcademyofMedicine)p21
IEC1991IEC61102:MeasurementandCharacterisationofUltrasonicFieldsUsingHydrophonesintheFrequencyRange0.5MHzto15MHz(Geneva:
InternationalElectrotechnicalCommission)
IEC1992IEC61157:RequirementsfortheDeclarationoftheAcousticOutputofDiagnosticUltrasoundEquipment(Geneva:InternationalElectrotechnical
Commission)
IEC1993IEC61220:GuidancefortheMeasurementandCharacterisationofUltrasonicFieldsGeneratedbyMedicalUltrasonicEquipmentUsing
HydrophonesintheFrequencyRange0.5MHzto15MHz(Geneva:InternationalElectrotechnicalCommission)
JagoJ,HendersonJ,WhittinghamTAandWillsonK1995Howreliablearemanufacturers'reportedacousticoutputdata?UltrasoundMed.Biol.211356
JagoJR,MitchellG,WhittinghamTA,HendersonJandWillsonK1994Experimentalmeasurementofthespatialdistributionoftemporalaverageintensityfor
complexbeamshapesandscanningmodesBritishMedicalUltrasoundSocietyAnnualScientificMeeting,Eastbourne,79December1993Abstract:Br.J.
Radiol.67716
MartinK1986PortableequipmentandtechniquesforacousticpoweroutputandintensitymeasurementPhysicsinMedicalUltrasoundedJAEvans(London:
IPEM)
PerkinsMA1989AversatileforcebalanceforultrasoundpowermeasurementPhys.Med.Biol.34164551
PrestonRC1988TheNPLultrasoundbeamcalibratorIEEETrans.Ultrasonics,Ferroelectr.Freq.Contr.3512238
SmithRA1989Arehydrophonesofdiameter0.5mmsmallenoughtocharacterisediagnosticultrasoundequipment?Phys.Med.Biol.341593607
SwindellW1984ThetemperaturefieldscausedbyacousticstandingwavesinbiologicaltissuesBr.J.Radiol.571678
terHaarG,DuckF,StarritHandDanielsS1989BiophysicalcharacterisationofdiagnosticultrasoundequipmentpreliminaryresultsPhys.Med.Biol.34153342
WhittinghamTA1994ThesafetyofultrasoundImaging63351
ZiskinMC1972SurveyofpatientexposuretodiagnosticultrasoundInteractionofUltrasoundandBiologicalTissuesedsJMReidandMRSikov(US
GovernmentPrintingOffice,WashingtonDC:DHEWPublication(FDA)738008)

Page149

PART3
ULTRASOUNDHYPERTHERMIAANDSURGERY

Page151

Chapter8
UltrasoundHyperthermiaandthePredictionofHeating
JeffreyWHand
Introduction
Themainpurposesofthischapterare(i)tosummarisethekeyfeaturesofultrasoundinducedhyperthermiaandassociatedtherapiesand(ii)todiscussthermal
transportmechanismsintissuesandtheirmodelling,atopicnotonlyofrelevancetothermaltherapiesbutalsotosafetyissuesrelatedtoultrasoundinduced
temperaturechangeswithintissues.
8.1
UltrasoundHyperthermia
8.1.1
Introduction.
Thebenefitofaddinghyperthermaltreatmenttoradiotherapyinthetreatmentoftumourslocatedeithersuperficiallyordeepinthebodyhasbeendemonstratedinthe
resultsofseveralrandomisedcontrolledclinicaltrials(Vernonetal1996,Overgaardetal1995,vanderZeeandvanRhoon1993).Ultrasoundisanagent
commonlyusedtoinducehyperthermiaandofferssomemarkedadvantagesovermicrowaveandradiofrequencytechniques.Theseinclude:
relativelylargevaluesfortheratiosourcedimensions/wavelengthfortransducersofpracticalsize,enablingcollimatedandfocusedbeamstobeproduced
relativelylowattenuationinsofttissues(upto1dBcm1MHz1)forfrequenciesofinterest(between0.5and5MHz).

Page152

Theabilityofultrasoundtoproducesmallfociofhighenergydensityopensupthepossibilityofhightemperature,shortdurationhyperthermiaandtissueablation
(sometimescalledultrasoundsurgery).Thesetechniquesforthermaltherapiesareattractingconsiderableresearch,clinicalandcommercialinterestwhicharedealt
withfurtherinChapter9.
Thefundamentalsofultrasoundarediscussedatlengthinotherchaptersinthisbookandinseveralexcellentreviews.Thosewrittenspecificallywithhyperthermiain
mindincludeHunt(1990),Hynynen(1990)andSwindell(1986).
8.1.2
UltrasoundIntensity,AttenuationandAbsorption
TheacousticintensityIistherateofenergyflowthroughunitareanormaltothedirectionofwavepropagation.Foraplanecontinuouswave,thetemporalaverage
intensityis

wherep0istheamplitudeoftheacousticpressureandZ(= 0c)istheacousticimpedance.cisthespeedofsoundinthetissuewhichhasequilibriumdensity 0.The

SIunitofintensityisWm2.AusefulpracticalunitforhyperthermiaisWcm2.
Whenpropagatingthroughamediumsuchastissue,ultrasoundenergyisattenuated.Foraplanewave,therelationshipbetweenI0,theintensityatthesurfaceandIz,
theintensityatadepthzis

where istheamplitudeattenuationcoefficient.Theattenuationcoefficientconsistsoftwoparts,one( a)duetoabsorptionandtheother( s)duetoscattering:

Thevariationofintensitywithdepthforfrequenciesbetween0.5and3MHz,assumingattenuationiseither0.5or1dBcm1MHz1,isshowninfigure8.1.These
valuesfortheattenuationcoefficientrepresentthelowerandupperendsoftherangeofvaluesforsofttissues(foradeeperdiscussionoftherelevantphysical
propertiesoftissueseeChapter4).
Energyabsorptionleadstolocalheating.Thescatteredenergyalsocontributestoheatingcausedbytheultrasoundfield.Althoughtherelativecontributionsof aand
saredependentupontissuetypeandfrequency(Gossetal1978,1979,1980andChapter4),whenconsideringmosthyperthermiaapplicationsitisoftenassumed
thatalmostalloftheenergylostfromthebeamisabsorbed(Hynynen1990).Formanytissues,

Page153

Figure8.1.
Attenuationofplanewaveultrasoundat0.5,1,
2and3MHzintissuewithattenuationassumedto
beeither0.5or1dBcm1MHz1.Thedottedline
indicatesthe50%relativeintensitylevel.

attenuationandabsorptionexhibitanapproximatelylinearrelationshipwithfrequencyovertherangeoffrequenciesusedforhyperthermia(seeChapter4).
Thelocalheatingcapabilityassociatedwiththepropagationofplanewaveultrasoundintissuedependsuponthedepthintothetissueandtheattenuationand
absorptionpropertiesofthetissue.Theabsorbedpowerperunitvolume,Wv,(equaltothespecificabsorptionrate*(SAR) density, 0)is

and,ifforsimplicitywetake = aand a=

f(

a0

istheabsorptioncoefficientat1MHzandfisthefrequencyinMHz),thenitfollowsthat

a0

*Specificabsorptionrate(SAR)isthetimederivativeoftheincrementalenergy(dE)absorbedbyanincrementalmass(dm)inavolumeelement(dV)ofagiven
density( 0):

Page154

Figure8.2.
Relativepowerdepositionversusfrequency
atdepthsfrom1cmto6cminsofttissue.
W/I0isnormalisedtothemaximumvalue
calculatedatadepthof1cm.Theabsorption
coefficientat1MHz, a0,istakentobe
1dBcm1.Thefrequencydependenceof
isassumedtobelinear.

leadingtoanoptimalfrequency,f opt,fromthepointofviewoflocaldepositionofpoweratdepthzgivenby

ThedependenceofWv/I0onfrequencyatvariousdepthsintissueisshowninfigure8.2.Theoptimumfrequencyforfocusedultrasoundsurgery,takingintoaccount
thefrequencydependentattenuationoftissue,hasbeendiscussedbyHill(1995).
8.1.3
TransducersforHyperthermia
8.1.3.1
PlanarTransducerSystems
Thesimplesttypeofultrasounddeviceforhyperthermiaconsistsofaplanecirculardisktransducerthatisairbackedandmountedinsuchawaythatitsfrontfaceisin
contactwithanintegralbolusofdegassed,andusuallytemperaturecontrolled,water.Theacousticfieldassociatedwithsuchasourcehasbeendiscussedbyseveral
authors(e.g.Zemanek1971,Harris1981)andisdescribedinChapter1.
Inpractice,thewatercolumnshouldbesufficientlylongtocontaintheintensitymaximaofthenearfieldandisusuallyclosedbyalatexmembrane.Evenwiththewater
bolus,tissuesareusuallyexposedtopartofthenearfieldandsothedriveisoftenfrequencymodulatedtoreducelocalhotspots.Thistypeofapplicator,depicted
schematicallyinfigure8.3,wasusedinearlyclinicalinvestigationsofhyperthermia,combinedwithradiotherapyor

Page155

Figure8.3.
Aschematicdiagramofaplanewaveultrasound
hyperthermiaapplicator.

chemotherapy,inthetreatmentofpatientswithsuperficialtumours(Marmoretal1979,Marchaletal1982).Frequenciesusedweretypicallyintherange13MHz,
forthereasonshighlightedinfigure8.2andtransducerdiameterswereusuallybetween3and10cm.Withthistypeofdevice,amonotonicallydecreasingtemperature
versusdepthprofileisgenerallyobtainedtheonlymeansofsignificantlychangingthenatureofthisprofileisbyloweringthetemperatureofthemostsuperficialtissues
throughaggressivecoolingwithacoldwaterbolus.Suchsimplesystemsprobablyapproachaworstcasescenarioasfarasultrasoundinducedhyperthermiais
concerned.AusefulappraisaloftheirclinicalutilityforsuperficialtumoursinarangeofanatomicalsitesistobefoundinCorryetal(1987).Theabilitytodynamically
adjustthespecificabsorptionratedistributionbeneathaplanewaveultrasounddeviceoffersgreaterflexibilityinclinicaluse.Suchfeaturesaretobefoundindevices
describedbyBenkeseretal(1989)inwhichsubsectionsoftheapplicator'saperturemaybedrivenindependently,offeringspatialcontrolofenergydeliveredtothe
tissues,andateitherthefundamental(around1MHz)oraharmonicfrequency(around3MHz),offeringsomecontroloverenergydepositionversusdepth.
Theadvantagesthatmaybegainedbyusingalargearrayofplanetransducersarethebasesunderlyingasystemdesignedfortreatingtheintactbreast(Luetal
1996).Acylindricalapplicatorconsistingofastackofeightringswithaninnerdiameterof25cmisused.Thereare48transducers,each1.5cm 1.5cmwith0.24
cminterelementspacing,inthefourupperringsand24inthelowerrings.Ineachring,alternatetransducersaredrivenathigh(4.34.8MHz)andlow(1.82.8
MHz)frequency.Transducers

Page156

Figure8.4.
Parametersdescribingaconcavebowltransducer.

withoverlappingfieldsaredrivenincoherentlytoavoidinterferenceeffects.Thepatientliesinapronepositionwiththebreastpositionedwithinthewaterfilled
cylindricalapplicator.Theuseofbothhighandlowfrequencytransducersenablespowerdepositionattheboundariesofthebreast(breastsurfaceandchestwall)
andwithinthebreasttobeadjustedindependentlyofeachother,whichisadvantageouswhenattemptingtoproduceuniformtemperaturedistributionsinregionswith
differingheatlosses.
MontesandHynynen(1995)describetheuseofanarrayofplanarcirculartransducers(1cmdiameter,operatingfrequency2or4MHz)incorporatedintoan
applicatorusedfordeliveringintraoperativeradiotherapy.Areflectingsurfaceformedattheinterfaceofdegassedwaterandstyrofoamisusedtoreflecttheultrasound
beamthrough90sothatthebeampropagatesinthedirectionparalleltotheincidentionisingradiation.Usingthisdevice,hyperthermiaandradiotherapymaybe
deliveredsimultaneously,offeringthepossibilityofanenhancedtherapeuticeffect.
8.1.3.2
FocusedTransducerSystems
Thegreatestadvantagethatultrasoundoffersoverothermeansofinducinghyperthermia,suchasmicrowaves,istheabilitytoproducefocusedfields.Thesimplest
methodofachievingafocusedultrasoundfieldistouseasphericallycurvedshell(orconcavebowl)transducersimilartothatdepictedinfigure8.4.Thefocusofsuch
atransducerliesonthecentralaxis,nearthecentreofcurvatureofthebowl(Kossoff1979).Theaxialintensitydistribution,I(z),excludingtheeffectofattenuation,is
givenby

Page157

Figure8.5.
Axialintensitydistributionforthree1MHzconcave
bowltransducersofdiameter60mmandradius
ofcurvature60,80and100mm.Theattenuation
coefficientofthemediumistakentobe1dBcm1.

whereI0istheaverageintensityatthesurfaceofthetransducerofdiameterra.Atthecentreofcurvature,theintensityis

TheratioIR/I0isknownastheintensitygainfactor.Figure8.5showstheaxialintensityvariationforthree1MHztransducerswithR=60,80and100mm,
respectively.Thediameterofeachtransduceris60mmandtheattenuationcoefficientistakentobe1dBcm1.Theshapeofthefocalregiontendstobelongand
narrow,theactualdimensionsbeingdependentuponthetransducer'sfrequency,diameterandradiusofcurvature,R.TheratioR/raisoftenusedtodescribea
transducer'sgeometricalfocusingproperties.Thefullwidthathalfmaximumoftheintensitydistributioninthefocalplane(3dBlevel)is

whileonaxis,thedepthrangeoverwhichtheintensityremainswithin3dBofthemaximumis

wherehisthedepthofthesphericalsurfaceofthetransducer,showninfigure8.4.(Thedimensionsd3andl3aremarkedasWandLonthisfigure.)Theratiod3/l3is
1.72ra/h(Clineetal1994).Thefocalvolumeofafocusedultrasoundtransducerisusuallymuchsmallerthanthevolumeofthetumourtobetreated.Several
approachestoovercomethisdifficultyhavebeen

Page158

considered.MuchpioneeringworkintheuseofscannedfocusedultrasoundhyperthermiawascarriedoutbyLele(e.g.Lele1983).Theintensitygainassociatedwith
focusedtransducersisduetotheenergyinthebeampassingthroughasmallerareainthefocalregioncomparedwiththatneartothetransducersurface,andsoa
mechanicallyscannedtransducershouldbemovedoveralargeareaatthesurface(window)whilebeingcontinuouslydirectedatthetarget.
Inothersystems,severalfocusedtransducersareorientatedsothattheirfocalvolumesareclosebutoffsetfromeachother.Nussbaumetal(1991)andLindsleyetal
(1993)describealargeaperturearrayof30transducerswithpolystyrenelensesarrangedinfourconcentricringsonacylindricalsurface.Thetransducersweredriven
atafrequencywithintherange0.5to1MHzandcouldbeadjustedtoformaringfocusofvariablediameter(upto11cm)atadistanceofapproximately32cmfrom
thearray.Furthercontrolallowedforthecompletearraytobetranslatedinthreeorthogonaldirectionsandrotatedaboutitscentralaxis.Thecompletearraywas
immersedinawaterbathwhichwaspositionedbelowthepatient.Preclinicalstudiesusingthissystemsuggestedthatselectiveheatingcouldbeachievedinvolumes
withlateraldimensionsbetween4and8cmatdepthsof11cminsofttissue.
Inanotherdesign,anoncoherentarrayoffocusedtransducers,eachpositionedsothattheirfocalvolumesarecoincident,ismountedonagantrywhichprovides
translationinthreeorthogonaldirections,rotatedandtilted.Thetrajectoryofthecommonfocalvolumemaybemovedthroughthetargetvolumebycontrollingthe
movementofthegantry(Hynynenetal1987,1990,Handetal1992).Thesesystemshaveshownthatbulkytumoursinthebreastandsomepelvictumourscanbe
treatedwhenanadequateacousticwindowisavailable.Anhaltetal(1992)addedhigherfrequencytransducerstothearrayandextendedtheapplicationofthe
techniquetothetreatmentofchestwalltumoursoflargearea.
8.1.3.3
PhasedArraySystems
Anultrasoundphasedarrayconsistsofrelativelysmalltransducerswhicharedrivencoherently.Thedistributionofphasesandamplitudesofthesignalsappliedtothe
elementscanbechosentoproduceeitherafocusedbeamwhichmaybescannedthroughthetreatmentvolume(atagreaterratethancanbeachievedusing
mechanicalsystems)oracustomisedpowerdepositionpatternwithspecifiedlocalmaximaandminima.Thefirstapproach,referredtoas'spotscanning'isthe
electronicanalogueofthemechanicalsystemsdiscussedinsection8.1.3.2.Electronicspotscanningmayobviatetheneedforlargescalemovementofthearraywith
respecttothepatient,thussimplifyingthecouplingbetweentheultrasoundtransducersandthepatient.Inthesecondapproach,SARdistributionsconsistingof
multiplefociaresynthesiseddirectlyandcomplexheatingpatternscanbeproducedbyswitchingbetweentwoormorepredeterminedmultifocipatterns(mode
scanning)(McGoughetal1994).

Page159

Anadvantageofferedbythisapproachisthatthetimeaveragedintensitiesthatarenecessarytoinducetherequiredincreaseintemperatureoveravolumeoftissue
canbeproducedwithoutunacceptablyhighspatialpeakintensitiesthatmaybeneededinthecaseofspotscanning.
Althoughphasedarraysofferseveraladvantagesoversinglefocusedtransducers(variablefocaldistance,rateofscanning,multifocipatterns),theyalsohavesome
disadvantageswhencomparedtothesimplertransducers.Singletransducersmaygeneratesoundbeamswithveryhighintensitiesinthefocalregionandmuchsmaller
intensitieswithintheinterveningtissues.Thisisespeciallyvaluableforultrasoundsurgerywhenitisnecessarytoablateatargetwithintissuelocallywithoutdamaging
thesurroundingtissues(seeChapter9).
Anotherdisadvantageoflinearphasedarraysarisesfromthepresenceofgratinglobesandsecondarylocalmaxima.Toavoidproblemswithgratinglobes,the
distancebetweencentresofarrayelementsideallyshouldbelessthan /2(Steinberg1976)butsatisfyingthisconditionwhilemaintainingasufficientlylargeaperture
canresultinalargenumberofelementsandhighcosts.Thecommonneedtosuppressgratinglobesassociatedwithpracticalphasedarraytherapeuticsystemshas
beeninvestigatedbyseveralauthors.Theuseofnonuniforminterelementspacingtosuppressgratinglobesinapplicatorsfordeeplocalisedultrasoundhyperthermia
wassuggestedbyEbbiniandCain(1991b).Hutchinsonetal(1996)andHutchinsonandHynynen(1996)adoptedasimilarapproachforalinearphasedarrayfor
transrectaluseandproducedanaperiodicarrayof57planeelements.Dupenloupetal(1996),usingannulararrays,demonstratedamethodforreducinggrating
lobesusingawidebandCWsource.DeactivationofalargesubsetofelementswasreportedbyHutchinsonetal(1995)asbeingusefulinreducinggratinglobes
whengeneratingfocilocatedatrelativelylargedistancesoffanarray'scentralaxis,whileGavrilovetal(1997)investigatedtheefficacyofsuppressinggratinglobes
usingelementdeactivationtooptimisethenumberofactiveelementsinthreelineararrayswithdifferentgeometricalandacousticalcharacteristicsandforvarious
focusingconditions.
IbbiniandCain(1990)investigatedthefocusingpropertiesofaconcentricringarrayandshowedthat,inadditiontosinglespotfocusingonthecentralaxis,both
singleandmultipleconcentricfocalringsofvariablewidthmaybeproduced.However,unwantedsecondaryfociproducedinfrontofandbeyondthefocalplaneare
alsoproduced.Afurtherlimitationofthisarrayisthatonlyannularpatternsmaybeproducedduetoitscircularsymmetry.Thesectorvortexarray(Umemuraand
Cain,1989)comprisesadisctransducercutintoMtracks,eachofwhichisdividedintoNsectorsofequalsize.Thistwodimensionalarrayhasadditionalgeometric
focusingprovidedbyalens.Aprototypedevice,drivenat0.5MHzandconsistingoftwotrackswith16sectorspertrack,isdescribedbyUmemuraetal(1992).

Page160

Therehavebeenseveraldesignsreportedthatattempttoreducethenumberofelementsand/orcomplexityassociatedwithtwodimensionalphasedarraysystems.
Ocheltreeetal(1984)describeastackoflinearphasedarraysinwhichelectronicsteeringofasetofneighbouringarrays(e.g.the(n1)th,nthand(n+1)th)is
achievedinoneplanewhileadjustmentofthepowerdepositionpatternintheorthogonalplaneisachievedbyswitchingtoanothersetofarrays(e.g.thenth,(n+1)th
and(n+2)th).Inthisway,theneedtoprovidecontrolandpowercircuitryisrequiredonlyfortheelementswithinasmallnumberoflineararrays,ratherthanforall
elementswithinthecompletetwodimensionalarray.AnotherapproachisthatofBenkeseretal(1987)whodescribearraysinwhichtheelementshavetapered
thickness.Theregionalongtheelementatwhichthethicknessisresonantatthedrivingfrequencywillproducethegreatestacousticaloutput.Thefocalregionofsuch
anarraycanbemovedintwodimensionsbycontrollingthephasesofthesignalsappliedtotheelementswhilemovementinthethirddirectioncanbeachievedthrough
appropriateshiftsinfrequency.ThisstructurerequiresNelementscomparedtoN2elementsforanN Ntwodimensionalarraywiththesamecentrecentrespacing.
FulltwodimensionalarraysthathavebeeninvestigatedincludeN Nsquareelementarrayswithplane,cylindricalorsphericalgeometry(IbbiniandCain1990,
Ibbinietal1990,EbbiniandCain1991a,McGoughetal1996).Sincethereare(2N1N21)valuestobeallocatedtothephasesandamplitudesofdrivingsignals
foranarrayofN1 N2elements,useofanoptimisationalgorithmisanimportantaidinachievingadesiredacousticfield.EbbiniandCain(1989)describeamethod
fordirectsynthesisofmultiplefocusfieldpatterns.Themethoddeterminesthephaseandamplitudeofdrivingsignalstoproducespecifiedfieldlevelsatasetof
'controlpoints'withinthetreatmentvolume.Thesecontrolpointscanbethedesiredfociorpointsatwhichreducedfieldlevelsarerequired.Therelationshipbetween
thecomplexpressureattheMcontrolpoints(locatedatr1,r2,...,rm ,...,rM)andthecomplexvelocityatthesurfaceoftheNarrayelementscanbewritten
Hu=p
whereu=[u1,u2,...,un,...,uN]tisthecomplexvelocityatthesurfaceoftheelements([]tdenotestranspose),p=[p(r1),p(r2),...,p(rm),...,p(rM)]tisthe
complexpressureatthecontrolpointsandHistheforwardpropagationoperatorwithelementshm,ngivenby

where representspointsonthatelement.Givenp,weneedtodetermineu.Inpractice,M<N,i.e.the

Page161

numberoffociorpointsatwhichthefieldisforcedtosomereducedlevelislessthanthenumberofelementsinthearray.EbbiniandCain(1989)showthatasolution
isgivenby

whereH*tistheconjugatetransposeofHandrepresentsthebackwardoperator(relatingthecontrolpointspacetothesourcespace).Inthissolutionforu,the
amplitudesofthedrivingsignalstoeachelementaredependentuponthecontributionmadebythatelementtothepressureatthecontrolpoint.Consequentlythereisa
widerangeofamplitudesleadingtoadecreaseintotalpowerradiatedbythearraywithrespecttothecasewhenallelementsaredrivenatfullpowerandfocusingis
achievedbyapplyingasuitablephasedistribution.Insomesituations,forexampleforarrayswithasmallaperture,thelattermaybethemethodofchoicesince
deliveryofadequatepowerwillbetheoverridingrequirement.
8.1.3.4
UltrasoundHyperthermiaDevicesforSpecificApplications
Inadditiontothegeneraltypesofhyperthermiadevicepreviouslydescribed,therehasbeendevelopmentofdevicesfortreatmentofparticularanatomicalsites,such
astheeye,andforendocavitaryandinterstitialapplications.
EndocavitaryDevices
Mostendocavitarydeviceshavebeendesignedfortransrectalapplicationfordeliveringvariousformsofthermaltherapytotheprostate,eitherfortreatmentofbenign
prostatichyperplasiaorprostaticcarcinoma.Earlytransrectalmultielementdevicesforhyperthermiaconsistedofnonfocusedsegmentedtransducers,withvarying
transducergeometry(cylindrical,semicylindricalandplanar),operatingataround11.6MHz(DiederichandHynynen1987,1989,1990,1991,Prieuretal1988).
Subsequently,electricallyfocusedarraysforendocavitaryuseweredeveloped.DiederichandHynynen(1991)usedanarrayof16halfcylindricalelements,each
2.25mmlongandcutfromalarger0.5MHzcylindricaltransducerwithouterdiameter15mm,andBuchananandHynynen(1994)improvedthedesigntoinclude64
elements(1.5mmwideand15mmOD)inanarray110.5mmlongwith1.73mmcentretocentrespacing.Theuseofcylindricalelementstendedtoincreasethe
volumeoverwhichenergywasdepositedandwasusefulforinducinghyperthermiaintumourmassessurroundingabodycavity.Handetal(1993)investigated
designsforalineararrayofplanarelementsthatwouldreducedivergenceoftheultrasoundfieldandsoachievegreaterlocalheating.Oneoftheaimsofthatapproach
wastoinvestigatetheuseofplanararraysnotonlyforhyperthermiabutalsoformorehighlylocalisedablationofprostatetissues.Practicallinearphasedarrayswere
laterfabricated(figure8.6)andinvestigatedindependentlyinseveralgroupsdesignsincorporatedeither

Page162

Figure8.6.
Aschematicdiagramofanendocavitarydevicecontaining
a35elementlinearphasedarray(GavrilovandHand,unpublisheddata).

planarelements(Hutchinsonetal1995,1996,HutchinsonandHynynen1996,GavrilovandHand1997,Gavrilovetal1997)orconcaveelements(Sheljaskovetal
1997).
InterstitialDevices.
Thecombinationofhyperthermiaandbrachytherapyisoftenusedinthetreatmentofbulkyorunresectabletumours.Althoughthisformoftherapyhasbeenused
duringthelasttwodecades(employingradiofrequencyelectrodes,microwaveantennas,inductivelyheatedferromagneticseeds,hotwatersources,etc),theuseof
ultrasoundinterstitialdevicesisrelativelynew(Hynynen1992,Jarosz1991).Twoapproachestoultrasoundinterstitialdeviceshavebeenreported.Inone(Jarosz
1991)an18to24Gstainlesssteelneedleiscoupledtoa1MHzplanardisctransducerbyavariabletaperedconicalvelocitytransformer.Aplasticsleeveisplaced
overtheproximalpartoftheneedlesuchthattheairgapencapsulatedpreventstransmissionofultrasoundtothetissueexceptoverthedistalunclad'active'length.
Themethodpermitstheuseofarelativelylowfrequencybutdoesnotoffercontrolovertheaxialpowerdepositionpattern.Thesecondapproachisbasedon
cylindricalpiezoceramictubes,typically12mmouterdiameterwithwallthickness0.25mmandlength25mm,whichformtransducersthataredrivenatafrequency
intherange412MHz.Thesetransducersareresonantacrossthewallthicknessanddeliver23Wofacousticpowerandinducetherapeutictemperatures(4245
C)overaradialdistanceof1517mm,althoughsomeasymmetryoftheradialpenetrationaroundthesetransducers,attributedtovariationsinwallthickness,is
observed.Thetransducersareplacedwithinabrachytherapyimplantcatheterandsurroundedbywater.Asaconsequenceoftheirfavourableradialpenetration
characteristicsrelativetomostotherinterstitialhyperthermiatechniques,ultrasoundinterstitialdevicescanbeusedinarrayswithspacingsofupto25mmbetween
implants(HynynenandDavis1993).

Page163

Figure8.7.
Aschematicdiagramofaninterstitialultrasoundapplicatorwith
anintegratedcoolingfacility(afterDiederich1996).

Diederich(1996)developedandevaluatedmultipleelementapplicatorscombinedwithcirculatingtemperaturecontrolleddegassedwatertocontrolthetemperature
ofthecatheter/tissueinterfaceandtoprovidecoolingofthetransducers(figure8.7).Thetransducersintheseapplicatorswere1.51.6mmouterdiameterandcould
beinsertedinto13Gbrachytherapycatheters.Thedrivingfrequency,intherange59MHzhadonlyasmallinfluenceontheradialpenetration.Acousticpowerofup
to56wattspercentimetrelengthoftransducerwerereported.InasubsequentreportDiederichetal(1996)describedmultielementdeviceswhicharecompatible
withtheinsertionofradiationsourcestoprovidesimultaneous,ratherthansequential,thermobrachytherapy.Theapplicatorscanbeimplanteddirectlywithinthe
targetregion,withtheplasticcoatedtransducersformingtheouterwallofthe'implantcatheter'.Twoormoretransducers,each2.5mmouterdiameter,0.33mmwall
thicknessand10mmlongandmadefromPZTpiezoceramicformedtheapplicator.125Iseedsor192Irsourcesfromremoteafterloadersoriridiumwireimplantsare
placedinthelumenofthepiezoceramictube.Since,unlikeapplicatorsdesignedforsequentialthermobrachytherapy,thereisnowatercooling,thesedeviceshavethe
characteristicsofbothhotsourceandacousticheatingdevices.
8.1.4
HighIntensityShortDurationHyperthermia
Theeffectofhyperthermiaisdependentuponboththeelevatedtemperatureandthetimeduringwhichtheelevatedtemperatureismaintained.Forhyperthermiato
haveanisoeffectonatissueatdifferenttemperaturesanddurations,thefollowingrelationshipmustbesatisfied
t 2=t 1B( T1T2)

Page164

wheret 1,t 2arethedurationsattemperaturesT1,T2,respectively.Fortemperaturesgreaterthanatransitiontemperature(anduptoabout57C),B=2,thatisthe

durationofheatingmustbedecreasedbyafactoroftwowhenthetemperatureisincreasedby1C.BelowthistransitiontemperaturethevalueofBhasbeen
observedinvivotobebetween4and8.Formosttissues,thetransitiontemperatureisintherange4243C(Dewey1994).Thisdependenceisoftendescribedin
termsofathermal(isoeffect)dosewhichinpracticehasbeencalculatedusing

where t eq(T)=2(T43) tifT 42.5Cor t eq(T)=20.56(T42.5) tifT<42.5Cand tisthetime(inminutes)betweentemperaturemeasurements(Handetal

1989).Theunitsofthermaldoseare'equivalentminutesat43C'.Thusanalternativetoconventionalhyperthermiaistoinducehighertemperatures(upto
approximately5560C)forperiodsoftheorderof10seconds.
Asalludedtoearlier,scannedfocusedultrasoundisuniqueamongnoninvasivemethodsofinducinghyperthermiainthatthespatialdistributionofSARmaybe
controlledonascaleoftheorderof1cmorbetterduetothesmallfocalvolumesachievable.Thishighdegreeofcontrolimpliesthatdifferencesinlocaltissuecooling
duetoheterogeneityinperfusion,variationsinthedensityofdiscretethermallysignificantvesselsandevenlocalcoolingaroundsinglelargevesselsmaybe
compensatedfor.
Hightemperatureshortdurationultrasoundtherapyreducesthedependenceofthethermaldosedeliveredonbloodflow(Huntetal1991,DorrandHynynen1992)
andsoarelativelyuniformthermaldosemightbegivenwithoutknowledgeofperfusionorflowwithinlargevessels.Lagendijketal(1994)simulatedthermaldose
distributionsinthepresenceofsinglevesselsorasimulatedvesselnetworkduetosonicatingthevolumeofinterestwithaseriesof5secondpulsesproducing17.5W
cm3inthefocalvolume.Whilethetechniqueresultedinasignificantlymoreuniformthermaldosedistributionthanwasachievablewhenthevolumewassubjecttoa
uniformSAR,thefocusneededtobeaccuratelypositionedandsteppedslowlyandinarandommannerthroughthetargetvolume.Inarapidheatingprotocol,alarge
fractionofthethermaldosedeliveredisaccruedaftertheultrasoundfieldisturnedoffandwhilethetissueiscooling.Koliosetal(1996)simulatedlesionformation
usingthermalmodels(seesections8.2.2and8.2.3)andshowedthatbloodflowcaninfluencetheshapeandsizeofthethermaldosedistribution,evenforexposures
asshortasapproximately8s.
Thereareseveralpracticalproblemstobeovercomebeforethisformofhyperthermiabecomesclinicallyviable.Theseincludeaccuratetargetingof

Page165

thefocalvolume,accountingforpatientmovementandlimitationsintermsofpatientpain.
8.2
PredictionofHeating
Wheneverthereisaspatialdependenceoftemperaturewithinamedium,energyintheformofheatflowsfromtheregionofhighertothatoflowertemperaturethisis
knownasheattransfer.Threemajortypesofheattransfermaybeconsidered:conduction,convectionandradiation.Heattransferbyconvectionresultsfroma
combinationofconductioninafluidandenergytransportduetothemotionofthefluidinthedirectionofenergyflow.Convectiveeffectsmaybeencounteredwhen
determiningboundarytemperatures,suchasthetemperatureoftheskinincontactwithawaterbolus,andthethermalsignificanceofbloodvessels,asdiscussedlater.
Everybodyemitselectromagneticradiationinproportiontothefourthpoweroftheabsolutetemperatureofitssurface.Thebalancebetweenthisenergylossandthat
gainedbyradiationfromitsenvironmentmaybeanetlossorgainandinpracticeisdependentupontheemissivityandabsorptanceofthebody'ssurface.Theeffects
ofconductionarediscussedbelow.ReviewsofheattransportwithintissuesaretobefoundinChato(1990),Lagendijk(1990)andArkinetal(1994).
8.2.1
ThermalConduction
AccordingtoFourier'slaw,theconductiveheattransferinaparticulardirectionisproportionaltothecrosssectionalareaoftheflowandtothetemperaturegradient.
Thus

whereQxisthe'heatflux'(inthexdirection)andhasunitsWm2.Theinclusionoftheminussignleadstoheatflowinthedirectionofdecreasingtemperature.kisthe
coefficientofthermalconductivityandhasunitsWm1K1.Ingeneralthermalconductivityisatensor,asshownintheaboveexpressionforQx.However,inmost
cases,theheatfluxinx,yandzcanbeconsideredtobedecoupled(onlyk x x,k y yandk zz 0),eachbeingdrivenbyasingletemperaturegradient.Ifthematerialis
isotropic,k x x=k y y=k zzandthethermalconductivitybecomesascalarconstant.
Accordingtothefirstlawofthermodynamics,energymustbeconserved.Thusenergybalancecanbeappliedtoanelementalvolume(dx.dy.dz)ofthemedium(figure
8.8)and,consideringonlyconduction,thethreedimensionalheatbalanceequation

Page166

Figure8.8.
Energybalanceforanelementalvolume.

maybederived.Here, 0andsarethedensityandspecificheatofthemediumandanyeffectsduetovolumetricexpansionhavebeenneglected.Inthecaseoftissues
subjectedtohyperthermia,thetermQicontainsdistinctcontributions,includingthevolumetricrateofmetabolismQm ,thepowerperunitvolumeabsorbedfromthe
ultrasounddeviceQusandatermaccountingfortheeffectsofbloodperfusion,QBF.TheformadoptedforQBFisdependentupontheparticularrequirementsforthe
descriptionoftheresultingtemperaturefieldT(x,y,z).
8.2.2
Pennes'BioheatTransferEquation
SeminalworkinthedevelopmentofmodelsdescribingheattransferwithintissueswasthatofPennes(1948)whomadeaquantitativeanalysisoftherelationship
betweenarterialbloodandtissuetemperatures.Temperaturesofhumanforearmtissuesandbrachialarterialbloodweremeasuredusingthermocoupleprobes
implantedradiallytodepthsof34cmtoevaluatetheapplicabilityofaheatflowtheorytotheforearmintermsofthelocalrateoftissueheatproductionand
volumetricflowofblood.Theeffectsofcirculatoryocclusionontheradialtemperaturedistributionwerealsoinvestigated.Pennesusedtheexpression
QBF=wbsbK(TTart)
torepresentthecoolingeffectofperfusion,wherewbisthevolumetricperfusionrate(kgm3s1),sbisthespecificheatofblood,Tartisthelocalarterialtemperature
(takentobeequaltobodycoretemperature),TisthelocaltissuetemperatureandKisaconstant(0 K 1)related

Page167

Figure8.9.
DatafromPennes(1948).Left:Meanexperimentaldata
(solidline)andtheoreticalpredictionsbasedonequations
(9)and(11)oftheoriginalpaperfor(dottedlinesfromtop
tobottom)volumetricbloodflowthroughthetissue,V=3.0
104,2.5 104and2.0 104gcm3s1,andrateoftissue
heatproductionhm =104gcalcm3s1.Arterialblood
temperaturewas36.25C(adaptedfromPennes'figure16).
Right:Experimentaltemperatureversusdepthcurves.
Pennesattributedtheformofthebiphasiccurveencircled
tobeing'undoubtedlycausedbysomelocalvariationin
vascularpattern'(adaptedfromPennes'figure15).

tothermalequilibriumbetweencapillarybloodandlocaltissue.Figure8.9showssomeofPennes'originaldata.Hismodelwasinverygoodqualitativeagreementand
reasonable(towithinabout0.5C)quantitativeagreementwithmeasurementswhenconsideredoveralengthscaleofafewcentimetresormore.Pennesnotonly
pointedtotheassumeduniformityofhismodelascontributingtodiscrepanciesbetweenpredictionsandmeasurementsbutalsostressedthatitwas'possiblethatthe
venousreturnfromthedistalportionoftheextremitymodifiedthedeeptissuetemperatureconsiderably'.Figure8.9alsoshowsthatPennesobservedtemperature
depthprofilesthatexhibitedlocalminimaandheattributedthesetolocaleffectsofthevasculature.
Consideringtheunderlyingassumptions,Pennes'formulationofthebioheattransferhasbeensuccessfulinfittingexperimentaltemperaturedistributions,althoughthe
valuesofotherparametersunderlyingthesefitswerenotverified(SekinsandEmery1982).Inanothercase(Schreieretal1990),agreementbetweenpredictionsand
inmeasurementsinvivooftemperatureswithinaregionoftissue(pigandrabbitthigh)implantedbyhotwatertubeswasreasonableifperfusionwasassumednotto
exceedavalueassociatedwithrestingmuscle,whichmaybequestionableinthepresenceofhyperthermia.However,somesimulationsinthisstudypredicted
temperaturesthatdifferedfromthosemeasuredbyupto2C.Inastudyoftemperatureandthermaldosechangesassociatedwithheatingbyfocused

Page168

ultrasound,Lagendijketal(1994)highlightedtheimportanteffectslargevesselsandahighdensityofvesselshaveonlocalheattransferwithintissues.
Theshortcomingsofthisapproachhavealsobeendiscussedwidelyintheliteratureandinclude:
theassumptionthatbloodentersthelocaltissuevolumeatarterialtemperatureandleavesatlocaltissuetemperature.Anticipatingadiscussionregardingthethermal
equilibriumlength(Xeq)ofvessels,thisimpliesthatXeqisinfiniteforallvesselsexceptcapillariesforwhichXeq=0
heattransportrelatedtomasstransportofbloodisneglected
theactualtemperatureofthebloodenteringthelocaltissuevolumeisneglected
individualcoolingorheatingbylargevesselsisneglected
theeffectsofthecompletevenousvesselnetworkareneglected.
Forthesereasonsandtheneedtodescribethedetailedtemperaturefieldwithfinerspatialresolution,otherdescriptionsofheattransferwithintissueshavebeen
developed.
Nevertheless,theuseofPennes'bioheattransferequationiswidespreadintheassessmentofpotentialthermalhazardsofultrasoundfieldsfordiagnosticpurposes
(NCRP1992,AIUM/NEMA1992,Shaw1994,Shawetal1996).Whilethismaybeadequateforsemiquantitativepredictionsoftheresultingtemperature
increase(e.g.'reasonableworstcase'or'typical'scenarios),amoredetailedpredictionofthelocaltemperaturefieldmayrequireuseofotherdescriptionsofheat
transport.
8.2.3
OtherApproachestoThermalModelling
Animportantquestiontobeansweredwhenconsideringheattransferbetweenbloodflowwithinavesselandthevesselwallisatwhatdistancefromtheentrancewill
thebloodtemperatureequilibratewiththatofthelocaltissue?AccordingtoChenandHolmes(1980)thevessellengthoverwhichthetemperaturedifferenceis
reducedbyafactoreis

whereristhevesselradiusandpb, ,k barethedensity,flowvelocityandthermalconductivityofblood,respectively. isdependentupontheinteractionofthevessel

withthesurroundingtissue.Assumingthermalconductivitiesofbloodandtissuearesimilarandthatthevesselthermallyinfluencesacylindricalvolumeoftissuewith
radiusapproximately10r,then 1.5.SomeexamplesofthevalueofXeqrelatedtovasculardataobtainedfromadogaregivenintable8.1.

Page169
Table8.1.Propertiesofvascularcompartments(afterChenandHolmes(1980)andCrezee(1993)).

Diameter
(mm)

Flow
(mms1)

Lengthl v
(mm)

Xeq
(mm)

Xeq/l v

Aorta

10

400

500

125000

310

Largearteries

200

130

2900

15

Mainbranches

100

80

200

72

Secondarybranches

0.6

40

40

Tertiarybranches

0.14

14

34

1.7

0.1

Terminalbranches

0.05

20

0.13

0.1

Terminalarteries

0.03

1.5

0.009

0.006

Arterioles

0.02

2.2

0.003

0.002

Capillaries

0.008

1.1

0.7

0.0001

0.0001

Venules

0.03

2.2

0.7

0.0016

0.001

Terminalbranches

0.07

1.5

0.7

0.009

0.006

Terminalveins

0.13

0.13

0.1

Tertiaryveins

0.28

14

1.6

0.1

Secondaryveins

1.5

40

13

Mainveins

2.4

100

Largeveins

200
400

Venacava

12.5

1.8

73

1.8

15

220

2.2

36

3200

16

330

129000

320

AusefulratiointhermalmodellingisthatoftheequilibriumlengthXeqtothetypicalphysicallengthofthevessellv.Thisisameasureofthedegreetowhichthe
temperatureofbloodinthevesselhasequilibratedwiththelocaltissuetemperature.ForexampleifXeq/lv>>1thenthebloodtemperaturewillneverreachthatofthe
localtissue,whileifXeq/lv<<1thenthebloodtemperaturewillequilibratewiththatofthelocaltissuewellwithinthelengthofthatparticularvessel.Fromtable8.1it
canbeseenthatforsinglevesselsthermalequilibriumtakesplace(Xeq/lv 1)somewherebetweenthesecondaryandtertiarybranchesandnotinthecapillariesas
assumedinthePennesformofthebioheattransferequation.However,mostarteriesandveinsarearrangedincountercurrentpairsandthisstructureleadstofaster
thermalequilibrationthansuggestedintable8.1.Weinbaumetal(1984)investigatedseveralvesselconfigurations,includingacountercurrentpair,andsuggestedthat
thevalueofXeqisreducedbyuptoafactoroftwoduetocountercurrentheatexchangeandsoequilibrationwilloccuratalargergenerationofvessels.Followingthis
newinsightintothemajorheatexchangebetweenvesselsandtissue,severalnewmodelsevolved.
ChenandHolmes(1980)consideredthatvesselsweregroupedintotwocategories:largevessels,eachtobetreatedseparately,andsmallvessels,tobetreatedas
partofthetissuecontinuum,andthattheboundarybetweenthesetwogroupsoccurredwhenXeq lv.Forthesmallvessels,threecontributionstoheattransferwere
suggested(CHmodel).Thesewere(i)aheatsinktermsimilartoPennes'perfusiontermforthe

Page170

largest,thermallynonequilibratedvesselsQp=w*pbsb(Ta*T)wherew*andTa*referonlytobloodflow,andthetemperatureofthebloodinthelargestvessels,
respectively,withinalocalelementalvolume(ii)aunidirectionalflowtermtoaccountforconvectiveheattransportassociatedwiththeequilibratedsmallvessels(iii)a
perfusionenhancedconductivityor'effectiveconductivity'todescribesmalltemperaturefluctuationsofnearlyequilibratedbloodalongthetemperaturegradient.
Weinbaumetal(1984)concludedfromanatomicalobservationsinperipheraltissuethatthemaincontributiontoheattransferfromlocalbloodperfusionisnotatthe
levelofthecapillariesbutisassociatedwiththeincompletecountercurrentheatexchangebetweenpairsofarteriesandveins.Amodel(WJL)basedonapairof
thermallysignificantvesselsconnectedbycapillarieswasproposedbutinpracticewasdifficulttoapplytomosttissues,otherthanperipheraltissue,becauseofthe
detailofthevascularstructurerequired.WeinbaumandJiji(1985)subsequentlyproposedasimplifiedmodel(WJ)inwhichthemeantissuetemperatureis
approximatedbyanaveragetemperatureoftheadjacentcountercurrentpairofnearlyequilibratedvesselsandthatmostoftheheatconductedthroughthewallofan
arterioleentersthewallofitspairedvein.Theseassumptionsleadtoaneffectiveconductivitythatrepresentsboththecapillarybleedoffandtheheatexchange
betweentissueandadjacentvessels.CriticismsoftheunderlyingassumptionsintheWJmodelweresubsequentlyraisedandalternateformulationssuggestedbyBaish
etal(1986a,b),Wissler(1987a,b)andCharnyetal(1989,1990).
Intheirreviewofthetopic,Arkinetal(1994)summarisethePennes,CH,WJandWJLmodelsandfindingsfromexperimentalverificationsofthemodels.Local
temperaturefluctuationsexistingclosetolargevesselsshouldbeaccountedforbyaconvectivetermsimilartothatsuggestedintheCHmodel.TheCHmodelcanbe
viewedasamodificationofPennes'modelbyusingamoreprecisedescriptionofperfusionandbyincludingaconvectiontermthatissignificantonlyclosetolarge
vessels.TheCHandPennes'modelsareapplicableinthesametissueregions(vesseldiameters<0.3mmXeq/lv<0.6).Inaddition,Charnyetal(1990)claimthat
Pennes'modeldescribesthebleedofffromlargevesselstothetissue(forvessels0.51.0mmindiameterandwithXeq/lv>>1).TheWJmodelappearstobevalid
onlyforsmallervessels(diameters<0.150.3mmXeq/lv<0.20.3).ThePennes',CHandWJmodelsdescribeacontinuumbyasingleequationinwhichperfusion
effectsareincorporatedimplicitlyintheheattransferequation.Incontrast,theWJLmodelandvariantsthereof(Baishetal1986b,Wissler1987a,Charnyetal
1989)consistofthreeequationscouplingheattransferofthevenousblood,arterialbloodandtissueandareapplicablewheremostofthevesselsarepaired.Although
theWJLmodelappearstobevalidonlyinregionswherevesselsaresmall(diameters<0.3mmXeq/lv<0.3),thevariantsworkforvessels>0.01mm

Page171

diameter.However,theirpracticaluserequiresdetailoftissueandorganvascularitythatiscurrentlyunavailableingeneral.Althoughnoneofthesingleequation
modelscanbeappliedtoalltissues,combinationsmaybevalid.Forexample,PennescanbeusedforlargevesselsandWJforsmallvesselsinregionssuchasmuscle
wheremostvesselsarepaired.However,thevalidapplicationofthevariousmodelstoregionsofthehumanbodyremainstobeverified.
Crezeeetal(1994)consideredpredictionsassociatedwithfourmodels:aheatsinkmodel(Pennes'),amodelusingeffectivethermalconductivity(k eff)(forvessels
0.5mmdiameter),amixedheatsink/k effmodelandadiscretevesselmodelandcomparedthesewithexperimentalfindingsinperfusedbovinetongues.Both
conductionandvenousheattransfermechanismswerefoundtobeimportant,aspredictedbythemixedmodels(k effforsmallvesselsanddiscretevessel/heatsinkfor
largervessels).Intheirefforttodevelopmodelsforhyperthermiatreatmentplanning,MooibroekandLagendijk(1991)describedamodelinwhichbendingand
branchingofdiscretevesselswasaccommodatedandmorerecentlyKotteetal(1996)usedaparametricdescriptionofvesselsinthreedimensions.An
analytical/numericaltechniqueincorporatingvasculartreeshasbeenusedbyBaish(1994)todeterminesteadystatetemperaturedistributionsintissue.
8.3
Summary
Fromaphysicalpointofview,theuseofultrasoundtoinducehyperthermiahassomemarkedadvantagesovercommonlyusedelectromagnetictechniques,including
relativelylowattenuationinsofttissues(upto1dBcm1MHz1)andshortwavelength(30.3mm)insofttissuesforfrequenciesofinterest( 0.55MHz).Thus
collimatedand,moreimportantly,focusedbeamsmaybeproducedfromtransducersofconvenientsize.Thesecharacteristicsenablearangeofpracticalsystemsto
bedesignedwhichoffercontrolovertheSARdistributionwithintissuesonascaleoftheorderof1cm,whichisimportantforeffectiveandsafetreatment.
Clinicalexperienceofultrasoundhyperthermiahasbeengainedinthetreatmentofbothsuperficialanddeepseatedtumours.Inmanycases,thesystemsusedwere
eitherprimitiveorprototypefocuseddevicesandassuchweresuboptimal.Insomecases,patienttolerancetoultrasoundtreatmentshasbeenlow,particularlywhen
relativelylowfrequencynonfocuseddeviceswereused.Theseproblemsarelikelytobeovercomeasnewsystemsinvolvingelectronicallysteeredphasedarrays
becomeavailable.Therecentsuccessesofclinicalhyperthermiacombinedwithradiotherapyprovideanincentivetoinvestigatethefullclinicalpotentialofultrasound
hyperthermia.

Page172

Therehasbeenprogressinunderstandingandmodellingheattransportprocesseswithintissuesinrecentyears.AlthoughPennes'bioheattransferequationcontinues
tobeusedformanypurposes,thestrengthsandweaknessofothermodelsbasedonmorerealisticdescriptionsofvasculareffectsonheattransportarenow
understood.Numericalalgorithmsforthepracticalapplicationofsuchmodelstothepredictionofspatiallyaccuratetemperatureandthermaldosedistributionsare
nowavailableandwillhavesignificantimpactonhyperthermiatreatmentplanning.
Acknowledgments
IamgratefultoDrLRGavrilovandDrJJWLagendijkfortheirconstructivecomments.
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Page177

Chapter9
FocusedUltrasoundSurgery
GailRTerHaar
Introduction
Mostmedicalultrasoundoperatesatfrequenciesintherange0.510MHz,withassociatedwavelengthsof0.153mmintissue.Theseshortwavelengthsmeanthat
anultrasonicbeammayinprinciplebebroughttoatightfocusoftheorderofamillimetre,afewcentimetresawayfromitssource.Wethushavethepossibilitythata
focusedbeammaybeusedtoproduceheatingsolelywithinthefocalregion,andnotelsewhereinthebeamprovidedhighfocalgainsareused.Thispropertyisused
infocusedultrasoundsurgerywherefocalintensitiesof14kWcm2areusedtoproducetemperaturesinexcessof60Cwiththeaimofablatingtissueinthewell
circumscribedfocalregion,whilesparingtissueelsewhere[1].Thevolumeofablatedtissueistermeda'lesion'.Ithasbeenshownthatthedemarcationbetweendead
cellsandlivecellsisverysharp,theboundarybeingonlyaboutsixcellswide.
Theprincipleofthetechniqueisshownschematicallyinfigure9.1.Asourceofultrasoundisplacedatadistancefromthetargettissuevolume.Thesourcemaybe
extracorporeal,orintracavitary(situated,forexample,intherectum).Thefocusofthebeamissettoliewithinthetissuevolumetobetreated.Thesource,whichmay
lieseveralcentimetresfromtheskin,iscoupledtothepatientbyanenclosedvolumeofdegassedwater.Exposuretimesof12secondsareusedtoensurethatheat
deliverymaybeindependentofperfusion.Byusinghighacousticpowersforshorttimes,ablativetemperaturesareachievedrapidly,andheatdissipationbyblood
perfusionandthermalconductionbecomeinsignificant,thusovercomingoneofthedisadvantagesofconventionalhyperthermiatechniques.Atypicallesioninexvivo
liverisshowninplate1(top).Plate1(bottom)showsthesharpboundarybetweentheinsideofthelesionandtheviablecellsoutside.

Page178

Figure9.1
Schematicdiagramshowingtheprincipleinvolved
infocusedultrasoundsurgery.Thefieldfroma
highpowerultrasoundsourceisbroughttoafocusat
depthwithinthetissue,thusproducinga'trackless'lesion.

9.1
MechanismsofLesionProduction
Therearetwomainmechanismsbywhichablativedamageisachieved.Firstlyabsorptionoftheultrasonicenergyleadstotissueheatingandsecondlyinteraction
betweentheultrasonicfieldandgascontainedinthetissuemayleadtoacousticcavitation.Thesetwomechanismswillbedealtwithseparatelyhere,butinreality
cannotalwaysbeseparated.
9.1.1
ThermalEffects
AfulldiscussionoftheheatingoftissuebyultrasoundisgiveninChapter8.Forthepurposesofthischapter,anapproximateestimateoftherateoftemperaturerise
thatmaybeexperiencedwhenabeamofintensity,I,passesthroughatissuewithintensityabsorptioncoefficient,a,maybemade.Theamountofheatproduced,Q,
isgivenby

Intheabsenceofcoolingbyblood,foratissueofdensity t,andspecificheatcapacityst,therateoftemperaturerisedT/dtisthereforegivenby

Fortypicalsofttissuesat1.7MHz,a=0.5dBcm1(seeChapter4), t=103kgm3,st=4.18103Jkg1K1.Infocusedultrasoundsurgery,spatialpeak
intensitiesofaround1000Wcm2areused,andthisleadstoa

Plate1.
(Top)Singlefocusedultrasoundlesionformedina
pieceofbovineliver.Thefocalpeakwas
placed1cmbelowthelivercapsule.
(Bottom)Histologicalsectionshowing(left)undamaged
'normal'cellsinratliver,and(right)deadcells
insidethelesion.

Plate2.
Photographshowingavolumeoftissue'painted'
outusingamovingtransducer.

Page179
1

rateoftemperatureriseof49Cs .Itisknownthatthetemperaturerequiredtoproducealesionisabout56C.Thus,exposuretimesaretypically12s.Ithasbeen
shown[2,3]thatifexposuretimesoflessthan3sareused,thetemperatureriseachievedintissueisessentiallyindependentofperfusion,andtheellipsoidalshapeof
theablativelesionfollowscloselythatofthe6dBcontouroftheultrasoundfield.
9.1.2
Cavitation
Thehighspatialpeakintensitiesusedinfocusedultrasoundsurgerylieclosetothecavitationthreshold.Bothinertialandnoninertialcavitationmayoccur(seeChapter
11).Whilecavitationbubblesaidvisualisationofalesionedvolume,thereisevidencethattheoccurrenceofcavitationrendersthelesionshapeandposition
unpredictable,althoughsomeauthorssuggestthatitisanessentialrequirementforsuccessfullesioning[4].
9.2
LesionShapeandPosition
Inordertocapitaliseonthesharpdefinitionoftissuedamagethatisproducedinafocallesion,itisimportantthatboththepositionandshapeofalesioncanbe
accuratelypredicted.
Itisexpectedfromalinearconsiderationoflesionformationthatthedamageshouldformmoreorlesssymmetricallyacrossthefocalplane.Figure9.2showsa
contourplotforafocusedtherapybeam.Underlinearconditions,theshapeandsizeofthelesionfollowsthe6dBcontourclosely.Ithasbeendemonstrated[5]that
astheintensityisincreased,thelesionmigratesforwardstowardsthetransducer.Inaddition,thelesionsmaybecomeasymmetric,witha'bulbous'endfacingthe
transducer.Anumberoffactorsmaybeinstrumentalinproducingtheseeffects.Firstly,cavitationbubblesformedatthe'front'ofthelesioncanactasscatterers,
enhancinglocallyabsorbedenergy,andscreeningtherearofthefocalregion.Secondly,theincreaseofattenuationcoefficientwithtemperaturewillleadtomore
absorptionatthefrontofthelesion,andareductionintheamountofenergyreachingtherear.Thethirdfactorthatmayplayarleisnonlinearpropagation(see
Chapter2).Thehighharmonicswillbeabsorbedmorerapidly(aheadofthefocus)thanthefundamental,thusalsoenhancingtheenergydepositionatthelesionfront.
9.3
SourcesofUltrasound
Theoptimumsourceforfocusedultrasoundsurgeryexhibitsahighpeakinthefocalregion,whilehavinglowprefocalpeaksonaxis,andnoside

Page180

Figure9.2
Beamplotshowingthepressuredistributionin6dBsteps.
Thelesioncloselyfollowsthe6dBcontour.

lobes.Theimportanceoftheprefocalintensitypeaksderivesfromthehighacousticabsorptionofskin.At1.7MHz,theabsorptioncoefficientofskinhasbeen
measuredasuptosixtimesthatofsofttissuessuchasliver.Thus,thereisthepossibilityofproducingaskinburnifahighprefocalintensitypeakoccursattheskin.
Thisproblemmaybecompoundedbythefactthatwhentheultrasonicbeamisscannedto'paint'outclinicallyrelevanttissuevolumes,thereisoverlappingofthe
ultrasonicbeamsattheskinsurface.

Page181

Themajorityoftransducersusedforfocusedultrasoundsurgeryareformedfromairbacked,highpowerpiezoelectricceramicsuchasPZT4.Intheearlydaysof
focusedultrasoundsurgeryquartzwasused[6],butpiezoelectricmaterialshavenowreplacedit.Piezoelectriccompositematerialsarenowbeingdeveloped.These
havetheadvantagethattheycanreadilybeshaped,andcanbedrivenasphasedarraystogiveelectronicbeamsteering(seeChapter5).
Twotypesoffocusedultrasoundsurgerydevicearecurrentlyavailablecommercially:transrectaldevicesdesignedprimarilyforurologicaltreatments(especiallyofthe
prostate),andextracorporealsystemsdesignedprimarilyfortreatmentofpathologyintheabdomenandbreast.Thetransrectaldevicesincorporateanimaginganda
therapytransducerintoonehead.Oneapplicatorusesa4MHzcrystalalternatelyforimagingandablation[7],andhasafocallengthof25mm.Whenafocal
intensityof1680Wcm2isused,thelesionis7mminlengthand0.6mmindiameter.Aseconddeviceusesaretractable7.5MHzimagingtransducer,anda2.25
MHztherapytransducer(focallength35mm,focalintensities7001000Wcm2)[8].Thisgiveslesionsthatare8mmlong,and1.5mmindiameter.
Therearecurrentlythreeextracorporealdevicesbeingusedforclinicaltreatments.ThemodifiedlithotripterofVallancienetal[9]usesmultiple,confocal1MHz
transducerelements.Ithasafocallengthof320mmandgiveslesionsthatare10mmlongand2mmindiameter.Intensitiesinexcessof10000Wcm2arequoted.
Imagingisachievedwithacentral3.5MHztransducer.Thepatientliesonawaterproofmembranethatisincorporatedintoabed.Theultrasoundsourceispositioned
belowthepatient.Asimilardevicehasbeenincorporatedintoamagneticresonancescanner[10].Inthiscase,asingle10cmdiameter1.5MHztransducerwith
radiusofcurvature8cmisusedasthesource[11].
AthirdextracorporealdeviceisthatusedattheRoyalMarsdenHospital.Thisusesa1.7MHz,10cmdiametersphericalbowltransducer,withafocallengthof14
cm[12].Itismountedabovethepatient,andiscapableofbeingpositionedwithfivedegreesoffreedom.Acousticcontactwiththeskinisachievedthroughasmall
bagofdegassedwater.Aninsitufocalpeakintensityof1490Wcm2givesanellipsoidallesionthatisapproximately1.5cmalongthebeamaxis,and1.5mmin
diameterina1sexposure.
Clearly,formanyapplications,thetissuevolumeablatedbyasinglefocusedultrasoundlesionisnotclinicallyuseful.Largervolumesare'paintedout'bymechanical
translationofthetransducer,orbyelectronicsteeringoftheultrasonicbeam,orbyacombinationofthesemethods.Sincetheacousticpropertiesoftissueare
changedupon'lesioning',ablationisstartedatthepointinthetargetvolumethatliesfurthestfromtheultrasoundsource.Plate2showstissueablationachievedby
movingthetransducerwhileexcited.

Page182

9.4
ImagingofFocusedUltrasoundSurgeryTreatments.
9.4.1
UltrasoundTechniques
Theinitialhopeoffocusedultrasoundsurgery(FUS)wasthatdiagnosticultrasoundcouldbeusedtoimagethetargetvolume,focusedultrasoundusedtotreatit,and
thenultrasoundimagingusedagaintomonitortheextentofdamage.ItnowseemsapparentthatconventionalBmodeimagingonlydisplaysalesionifitcontainsgas.
Othermethodssuchasthosebasedonchangesintissueattenuationorelasticityaremorelikelytoyieldusefulvisualisationofdamagedtissue.Ultrasoundtemperature
monitoringtechniquesmayproveusefulforplacingthefocalpeak[13].
9.4.2
MagneticResonanceImaging
Magneticresonance(MR)imagingisbeingusedincombinationwithMRthermometrytodeterminethetreatmentvolume,andtotargetthefocusedultrasoundbeam.
AlowpowerpulsemaybeusedtositethefocusunderMRguidance,andthenhighpowertreatmentscanbecarriedout[14].Damagedtissue,whichhasalower
watercontentthannormaltissue,canbevisualisedonaT1weightedMRscan[11].
9.5
ClinicalApplications
WhilefocusedultrasoundsurgerywasfirstproposedbyLynnetalin1942[15]asatoolforneurosurgery,ithastodateonlyfoundsignificantapplicationin
ophthalmologyandurology.Currentdevelopmentsareexpandingpossibleusesintooncologyandvascularocclusion.
9.5.1
Neurology
ThefirststudiesoftheuseoffocusedultrasoundinthebrainwerethosepublishedbyLynnetal[15]andLynnandPutnam[16].Theyattemptedtoputlesionsinthe
brainthroughtheskull.Acousticabsorptionandmodeconversionintheboneresultedinprofounddamagetothescalpwithonlysmalllesionsbeingseeninthebrain,
mostlyatthebeamentrysite.
Severalstudieshavebeenconcernedwithplacinglesionsincatbrain.Fryetal[17]showedthatthewhitematterwasmoresusceptibletodamagethangreymatter
whichhasalowerabsorptioncoefficient.
SubsequentlyFrytreated50patientswithParkinson'sdiseasewithfocusedultrasoundsurgery[18,19].Followingcraniotomy,thebeamwasdirected,underlocal
anaesthetic,throughtheexposedduratothesubstantianegra

Page183

andansalenticilaris.Thetreatmenttookupto14hours.ItwasclaimedthatsymptomsofParkinsonismwereeliminated.Despitethesegoodresults,thetreatment
wasnottakenupmorewidely,probablybecauseoftheintroductionofLdopatherapyatthistime.
Ballantineetal[20]usedfocusedultrasoundsurgeryforthetreatmentofpainfulneuromataintensitesinsevenpatients.Despitereportedsuccessinsevenoutofthe
tensites,nofurtherreportsofthistreatmenthavebeenpublished.
9.5.2
Ophthalmology
Lavineetal[21]reportedtheformationofcataractswhenultrasoundisfocusedintheeye.Hethereforeclaimedthistobeamethodforselectivedestructionof
ophthalmologicaltargets.Purnelletal[22]wereabletodemonstratechoroidalbleaching,chorioretinaladhesionsandlocaliseddestructionoftheciliarybody.
RosenbergandPurnell[23]showedthathighintensityultrasoundcouldbeusedtodecreaseintraocularpressure.
Focusedultrasoundsurgeryhasbeenusedsuccessfullyforthetreatmentofglaucoma.Thetechniquewasfirstdemonstratedinrabbits[24]andinpigs[25]andwas
thencarriedintohumans[26].Inatrialof1117treatments(880patients)79.3%hadasustainedloweringofintraocularpressureafteroneyear.Thistechniquehas
alsobeenusedforsealingtraumaticcapsulartears[27],fortreatingintraoculartumours[28,29],forretinaldetachment[30]andforthetreatmentofretinal
haemorrhage[31].Thetechniquehasnotbeenwidelytakenupinophthalmology,probablybecauseoftheintroductionoflasersurgery.
9.5.3
Urology
Transrectalultrasoundisusuallytheimagingmodalityofchoiceforurologistswhowishtoinvestigatetheprostate.Itisthereforeanobvioussteptoincorporatehigh
intensityfocusedultrasoundtherapyintosuchanexamination.Intheurologicalfield,therefore,FUShasbeenmostwidelyusedforthetreatmentofbenignprostate
hyperplasia(BPH).Themostpopularcurrenttreatment,transurethralresection(TURP),requiresgeneralanaesthesia,andcarrieswithitsignificantmorbidityand
mortalityrates.Thereisthereforeconsiderableinterestinthermaltherapiesoftheprostate,ofwhichFUSisanobviousfavouredcontender.Humantrialshaveshown
thattransrectalFUScanleadtonecrosisofprostatictissueinthetargetvolume[8,32,33],andanimprovementinsymptomsandurineflowrateshavebeen
demonstratedayearaftertreatment[34,35].Extensivelongtermfollowupstudiesarerequiredbeforethiswillbecomethetreatmentofchoice,butearlyresultsare
encouraging.
IthasbeenshownthatextracorporealFUScanbeusedtoproduceselectivedamageinbladderandkidney,inlargeanimalmodels,andinman[3640].

Page184

Vallancienetal[39]showedthat33%ofpatientswithsuperficialprimarybladdertumourshadnorecurrenceoftheirdisease.
9.5.4
Oncology
Ultrasoundwasfirstusedtotreattumoursin1933whenSzentGyorgi[41]usedplanewaveultrasoundtotreatneoplastictissue.FUShasasignificantadvantage
overconventionalhyperthermiatreatments(seeChapter8)inthattheenergyisdepositedsufficientlyquicklythatthefinaltemperatureachievedisindependentof
bloodperfusioninthetargetvolume.Inaddition,thetemperaturesused(inexcessof60C)arecytotoxic,andsonoadjuvanttherapyisrequired.
Goodlocalcontrolhasbeenachievedin50%ofprostatecancerpatientsinonestudy[42]andin30%inanother[43].APhase1trialofsofttissuetumoursofthe
abdomenhasshownthatFUStreatmentofprostate,kidneyandlivercanbetoleratedonanoutpatientbasiswithouttheneedforanaesthesiaorotherformof
sedation[44].
9.5.5
OtherApplications.
Anintriguingpossibleapplicationliesinitsabilitytooccludebloodflowwhenlesionsareplacedacrossbloodvessels.Thishasbeendemonstratedintumours[45]
andinnormaltissue[4648].Potentialapplicationsofthisfacilitylieinfetalmedicinefortheocclusionofshuntvesselsinvolvedinfetofetaltransfusionsyndrome[48]
andinoncologyinthetreatmentofrenaltumours.ThepossibilityofusingFUSforthetreatmentofcardiacarrhythmiashasbeendiscussed[49].
9.6
Conclusion
Focusedultrasoundsurgeryprovidesanalternativenoninvasivemethodoftheselectivedestructionoftissueatdepth.Regionsofablatedtissuecanbeimagedusing
ultrasound,magneticresonanceandXrayCTimaging.Thistechniqueislikelytofindapplicationwhereprecisetissuedestructionisrequired,andwheretoleranceto
othertherapies(suchasradioorchemotherapy)hasalreadybeenreached.Thereisnoevidenceforabuildupoftoxicitywiththistechnique,andthusrepeat
exposuresinadjacenttissuevolumesareapossibility.However,FUShasnoroletoplayinorgansthatareoverlainbygasorbone.
References
[1]terHaarGR1995UltrasoundfocalbeamsurgeryUltrasoundMed.Biol.211089100

Page185

[2]BillardBE,HynynenKandRoemerRB1990EffectsofphysicalparametersonhightemperatureultrasoundhyperthermiaUltrasoundMed.Biol.1640920
[3]ChenL,terHaarGR,HillCR,DworkinM,CarnochanP,YoungHandBenstedJPM1993Effectofbloodperfusionontheablationofliverparenchymawith
highintensityfocusedultrasoundPhys.Med.Biol.38166173
[4]ChapelonJY,PratF,SibilleA,AbouElFadilF,HenryL,TheilliereYandCathignolD1992Extracorporeal,selectivefocuseddestructionofhepatictumoursby
highintensityultrasoundinrabbitsbearingVX2carcinomaMin.Inv.Ther.128793
[5]WatkinNA,RivensIandterHaarGR1996TheintensitydependenceofthesiteofmaximalenergydepositioninfocusedultrasoundsurgeryUltrasoundMed.
Biol.22(4)48391
[6]FryWJ1958PrecisionhighintensityfocusedultrasonicmachinesforsurgeryAm.J.Phys.Med.371526
[7]FosterRS,BihrleR,SanghviNT,FryFJandDonohueJP1993HighintensityfocusedultrasoundinthetreatmentofprostaticdiseaseEur.Urol.23Suppl.1
2933
[8]GeletA,ChapelonJY,MargonariJ,TheilliereY,GorryF,SouchonRandBouvierR1993Highintensityfocusedultrasoundexperimentationonhumanbenign
prostatichypertrophyEur.Urol.23Suppl.1447
[9]VallancienG,ChartierKastlerE,BatailleN,ChopinD,HarouniMandBougaranJ1993FocusedextracorporealpyrotherapyEur.Urol.23Suppl.14852
[10]ClineHE,SchenckJF,HynynenK,WatkinsRD,SouzaSPandJoleszFA1992MRguidedfocusedultrasoundsurgeryJ.Comput.Assist.Tomogr.16
95665
[11]HynynenK,FreundWR,ClineHE,ChungAH,WatkinsRD,VetroJPandJoleszFA1996Aclinical,noninvasive,MRimagingmonitoredultrasound
surgerymethodRadiographics1618595
[12]terHaarGR,RivensI,ChenLandRiddlerS1991HighintensityfocusedultrasoundinthetreatmentofrattumoursPhys.Med.Biol.361495501
[13]SeipR,VanBarenP,CainCandEbbiniE1996NoninvasiverealtimemultipointtemperaturecontrolforultrasoundphasedarraytreatmentsIEEETrans.
UltrasonicsFerroelectr.Freq.Control43106373
[14]HynynenK,DamianouCA,ColucciV,UngerE,ClineHEandJoleszFA1995MRmonitoringoffocusedultrasonicsurgeryofrenalcortexexperimental
andsimulationsstudiesJ.Magn.Res.Imag.525966
[15]LynnJG,ZwemerRL,ChickAJandMillerAE1942AnewmethodforthegenerationanduseoffocusedultrasoundinexperimentalbiologyJ.Gen.
Physiol.2617992
[16]LynnJGandPutnamTJ1944HistologicalandcerebrallesionsproducedbyfocusedultrasoundAm.J.Pathol.2063749
[17]FryWJ,BarnardJW,FryFJ,KruminsRFandBrennanJF1955UltrasoniclesionsinthemammaliancentralnervoussystemScience1225178
[18]FryWJandFryFJ1960FundamentalneurologicalresearchandhumanneurosurgeryusingintenseultrasoundIRETrans.Med.Electron.ME716681
[19]MeyersR,FryFJ,FryWJ,EggletonRCandSchultzDF1960Determinationoftopologicalhumanbrainrepresentationsandmodificationsofsignsand
symptomsofsomeneurologicaldisordersbytheuseofhighlevelultrasoundNeurology102717
[20]BallantineHT,BellEandManlapazJ1960ProgressandproblemsintheneurologicalapplicationsoffocusedultrasoundJ.Neurosurg.1785876

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[21]LavineO,LangenstrassK,BowyerC,FoxF,GriffingVandThalerW1952EffectsofultrasonicwavesontherefractivemediaoftheeyeArch.Ophthalmol.
472049
[22]PurnellE,SokolluA,TorchiaRandTanerN1964FocalchorioretinitisproducedbyultrasoundInvest.Ophthal.365764
[23]RosenbergRSandPurnellE1967EffectsofultrasonicradiationontheciliarybodyAm.J.Ophthalmol.634039
[24]ColemanDJ,LizziFL,DrillerJ,RosadoAL,BurgessSEP,TorpeyJH,SmithME,SilvermanRH,YablonskiME,ChangSandRondeauMJ1985
TherapeuticultrasoundinthetreatmentofglaucomaIIclinicalapplicationsOphthalmology9234753
[25]ColemanDJ,LizziFL,DrillerJ,RosadoAL,ChangS,IwamotoTandRosenthalD1985TherapeuticultrasoundinthetreatmentofglaucomaI
experimentalmodelOphthalmology9233946
[26]SilvermanRH,VogelsangB,RondeauMJandColemanDJ1991TherapeuticultrasoundforthetreatmentofglaucomaAm.J.Ophthalmol.11132737
[27]ColemanDJ,LizziFL,TorpeyJH,BurgessSEP,DrillerJ,RosadoALandNguyenHT1985Treatmentofexperimentallenscapsulartearswithintense
focusedultrasoundBr.J.Ophthalmol.696459
[28]BurgessSEP,SilvermanRH,ColemanDJ,YablonskiME,LizziFL,DrillerJ,RosadoALandDennisPH1986Treatmentofglaucomawithhighintensity
focusedultrasoundOphthalmol.938318
[29]LizziFL,ColemanDJ,DrillerJ,OstromogilskyM,ChangSandGrenallP1984UltrasonichyperthermiaforophthalmictherapyIEEETrans.Sonics
UltrasonicsSU3147381
[30]RosecanLR,IwamotoT,RosadoAL,LizziFLandColemanDJ1985Therapeuticultrasoundinthetreatmentofretinaldetachment:clinicalobservationand
lightandelectronmicroscopyRetina511522
[31]ColemanDJ,LizziFL,ElMoftyAAM,DrillerJandFranzenLA1980UltrasonicallyacceleratedabsorptionofvitreousmembranesAm.J.Ophthalmol.89
4909
[32]SusaniM,MadersbacherS,KratzikC,VingersLandMarbergerM1993MorphologyoftissuedestructioninducedbyfocusedultrasoundEur.Urol.23
Suppl.1348
[33]MadersbacherS,KratzikC,SzaboN,SusaniM,VingersLandMarbergerM1993Tissueablationinbenignprostatichyperplasiawithhighintensityfocused
ultrasoundEur.Urol.23Suppl.13943
[34]MulliganED,LynchTH,MulvinD,GreeneD,SmithJMandFitzpatrickJM1997Highintensityfocusedultrasoundinthetreatmentofbenignprostatic
hyperplasiaBr.J.Urol.7917780
[35]MadersbacherS,KratzikC,SusaniMandMarbergerM1994TissueablationinbenignprostatichyperplasiawithhighintensityfocusedultrasoundJ.Urol.
152195661
[36]VaughanMG,terHaarGR,HillCR,ClarkeRLandHopewellJW1994Minimallyinvasivecancersurgeryusingfocusedultrasound:apreclinical,normal
tissuestudyBr.J.Radiol.6726774
[37]WatkinNA,MorrisSB,RivensI,WoodhouseCRJandterHaarGR1996Afeasibilitystudyofthenoninvasivetreatementofsuperficialbladdertumours
withfocusedultrasoundBr.J.Urol.7871521
[38]WatkinNA,MorrisSB,RivensIHandterHaarGR1997HighintensityfocusedultrasoundablationofthekidneyinalargeanimalmodelJ.Endourol.11
1916

Page187

[39]VallancienG,HarouniM,GuillonneauB,VeillonBandBougaranJ1996Ablationofsuperficialbladdertumourswithfocusedextracorporealpyrotherapy
Urology472047
[40]ChapelonJY,GeletA,MargonariJ,LebarsEandCathignolD1991Tissueablationwithfocusedultrasound(TAFU)J.Endourol.5Suppl.1S50
[41]SzentGyorgiA1933ChemicalandbiologicaleffectsofultrasonicradiationNature13127880
[42]GeletA,ChapelonJY,BouvierR,SouchonR,PangaudC,AbdelrahimAF,CathignolDandDubernardJM1996Treatmentofprostatecancerwith
transrectalfocusedultrasound:earlyclinicalexperienceEur.Urol.2917483
[43]MadersbacherS,PedevillaM,VingersL,SusaniMandMarbergerM1995Effectofhighintensityfocusedultrasoundonhumanprostatecancerinvivo
CancerRes.55334651
[44]terHaarGR,RivensIH,MoskovicE,HuddartRandVisioliA1998Phase1clinicaltrialoftheuseoffocusedultrasoundsurgeryforthetreatmentofsoft
tissuetumoursSurgicalApplicationsofEnergyedTPRyanProc.SPIE32492706
[45]RivensI1992QuantitativestudiesofbiologicaldamageinducedusinghighintensityfocusedultrasoundPhDThesisUniversityofLondon
[46]DelonMartinC,VogtC,ChignierE,GuersC,ChapelonJYandCathignolD1995Venousthrombosisgenerationbymeansofhighintensityfocused
ultrasoundUltrasoundMed.Biol.211139
[47]HynynenK,ChungAH,ColucciVandJoleszFA1996Potentialadverseeffectsofhighintensityfocusedultrasoundexposureonbloodvesselsinvivo
UltrasoundMed.Biol.22193201
[48]RivensIH,RowlandIJ,DenbowM,FiskN,LeachMOandterHaarGR1998Focusedultrasoundsurgeryinducedvascularocclusioninfetalmedicine
SurgicalApplicationsofEnergyedTPRyanProc.SPIE32492706
[49]ZimmerJE,HynynenK,HeDSandMarcusF1995ThefeasibiltyofusingultrasoundforcardiacablationIEEETrans.Biomed.Eng.428917

Page189

Chapter10
AcousticWaveLithotripsy
MichaelHalliwell
Introduction
RenalanduretericstonesareverycommoninmanycountriesandinWesternEuropetheincidenceisestimatedat3%to4%ofthepopulation.Tothisfiguremust
alsobeaddedthefrequentproblemofgallstones.Conventionalremovalofrenal,mosturetericandgallbladderstonesinvolvesatraumaticsurgicalincision,whichis
associatedwithahospitalstayofonetothreeweeksandaprolongedconvalescentperiod.
Sinceabout1978twonewmethods,percutaneousultrasoniclithotresisandextracorporeallithotripsy,havegrowninimportanceandalargenumberofoperations
nowinvolveoneortheotherofthesemethods.Bothreduceoreliminateinvasivesurgeryandgreatlyreducehospitalisationandpostoperationalconvalescence.Both
proceduresemployhighintensityacousticwavestoproducedisintegrationofthestones.
Earlyultrasonicequipmentforthisapplicationwasbasedoncontinuouswavesourcesanddirectcontactapplicators.Bycontrast,stonedestructionusing
extracorporealmethodsisusuallycarriedoutusingtheapplicationofaseriesofpressurepulses.Theuseoflasertechniquesforpercutaneouslithotripsyhasbecome
importantasanotherexampleofminimallyinvasivesurgery.
10.1
PercutaneousContinuousWaveSystems
Theconceptoftheuseofcontinuouswaveultrasoundforstonedisintegrationwasreportedasearlyas1953andpracticalworkwascarriedoutintheearly1970s.
However,theslownessofstoneerosionhaspreventedwideadoptionofthemethod,althoughequipmentisstillproduced.Itisnot

Page190

proposedtodiscusspercutaneousorsemiinvasivesystems,includinglaserlithotripsy,althoughthelattermayactthroughacombinationoflocalisedplasmaandshock
waveaction.Onlyextracorporeallyinducedpressurepulsemethodsandinstrumentswillbeconsidered.
10.2
ExtracorporeallyInducedLithotripsy
Extracorporeallithotripsyisrapidlygrowingasaprimarymethodforkidneystonedestructiondespitethehighcapitalcostofequipment.PioneeredinGermanythe
processhasbecomepopularbothwithpatientsandhospitalsduetothenoninvasivenatureoftheprocedureandtheshorttreatmentandrecoverytime.Several
differentformsoftheequipmentarenowavailablefromanumberofmanufacturers.
Animportantfactorintheprocedureistheaccuratedeterminationofthestonelocationandtheorientationofthetransducertopositionthefocalvolumeatthestone.
ThisiscarriedoutusingXrayordiagnosticultrasoundscanninginthreedimensions.Withanultrasonicscanningsystemanestimationoftreatmentprogresscanbe
undertakeninrealtime.
Thetreatmenttimeisveryvariableanddependscriticallyonthelithotriptersystemaswellasontheform,locationandsizeofthestone.Withkidneystonesthe
disintegratedfragmentsarepassedthroughtheureter,bladderandurethrabynormalexcretoryprocessesduringthenextfewdays.Gallstonesaresomewhatmore
difficulttodealwithbecauseoftheiranatomicallocationandinsomecasestheirrelativesoftness.
10.2.1
TypesofPressureWaveTransducer
Fourtechniquesareatpresentemployedforthegenerationoftherequiredpressurepulse,theoperatingprinciplesbeing:sparkdischargepiezoelectricexcitation
electromagneticinductionchemicalexplosion.Futureequipmentmayusemagnetostrictiveelements,basedonthenewmassivemagnetostrictionmaterials.Inthethree
electricalsystems,theshortdurationhighpeakenergyissuppliedbytheelectricaldischargeofabankofcapacitorsintoanelectromechanicaltransducer.The
chemicalsystememployssmallexplosivechargesdetonatedwithinafocusingreflector.
10.2.1.1
SparkDischarge.
Anellipsoidalreflectorisusedwithasparkgapmountedatoneofthetwofoci.Duringusetheotherfocusshouldcoincidewiththelocationofthestone.Thespark
gapmaybeaselfcontainedunitthatiseasilydemountableforservicingorreplacement.Inmostcasesthelifeofthedischargetipsisrelativelyshortandeaseof
replacementformsanimportantpartofthedesign.Thegapcanbeintheformofacartridgeorfittedastwoseparateelectrodes.Thereflectormaybeclosed

Page191

byaflexiblediaphragmandfilledwithdegassedwaterorotheracousticallyefficientliquidwithlowtransmissionloss.Applicationtothepatientmaybefromaboveor
belowandmanydifferentversionsareavailable.
10.2.1.2
Piezoelectric
Thetransducerdesigncanbeoneofthreetypes.Themostcommonformiscomposedofmultiplepiezoelectricceramicelementsmountedinamosaicpatternona
sphericaldish.Eachelementissynchronisedtoensuresimultaneouspulsetransmissionandthelargeapertureenergysourceprovidesaccuratefocusingofthepressure
wave.Unlikeasparkgap,eachindividualelementhasarelativelylowemissionenergy,andhighintensityoccursonlyatthefocus.Thelowstresslengthensthe
maintenancefreeperiodandensureshighreliability.Malfunctionofafewisolatedelementswillnotmateriallyaffecttheoverallperformanceandtheconstruction
enablesthesetobereplaced.Anotherformusesaringortubularpiezoceramictransducermountedatthefocusofaparabolicreflector.Alternatively,planewave
sourcescanalsobeusedandfocusedusingacousticlensesmanufacturedfromplasticsormetals.
10.2.1.3
Electromagnetic
Onetypeofelectromagnetictransduceremploysaspirallywound'pancake'coiltomoveametaldiaphragminaliquidfilledcylinder.Theplanewavefrontisfocused
withanacousticlenstoprovideaconvenientfocalpointwithinthepatient.Thefrontofthecylinderisincontactwiththepatientandisclosedbyaflexiblediaphragm.
Anothertypeusesanellipsoidalreflectorwiththeelectromagnetictransducermountedattheinternalfocus.
10.2.1.4
Magnetostrictive
Thedevelopmentofhighefficiencymagnetostrictivematerialshasstimulateddevelopmentofsinglepulsetransducersoperatingwithlowvoltagedrives,focusingbeing
achievedwitheitherparabolicmirrorsorplasticlenses.Commercialexploitationhasnotyetcommenced.
10.2.1.5
Chemical
Smallexplosivechargesmountedonan'ammunitionbelt'arelocatedoneatatimeattheinternalfocusofanellipsoidalbowl.Thedischargeproducesarapidly
expandinggasbubblewhichgeneratestheacousticpressurepulse.
10.2.2
PositioningSystems
Theaccurateexternalpositioningofthepressurepulsetransmitterisofgreatimportanceifdamagetothesurroundingtissueistobeavoided.Asthepositionisdefined
withinthreedimensionalspace,thedetectionmethodmustbecapableofdefiningallaxes.Insomeequipmentahighresolutionultrasonicscannerisusedwiththe
probepositionedwithinthetreatmentheadormountedonalocationarm.Thepositionofthefocusrelativeto

Page192

theprobeisfixedandacontinuousimageofthestonecanbedisplayedduringtheoperatingprocedure.Microprocessorcontrolofthemovementofthetransmitter
relativetothepatientcanbeusedtoensureaccuratesettingirrespectiveofpatientmovement.
ThealternativesystemisXrayfluoroscopy.However,incontrasttoultrasoundimaging,Xrayuseislimitedbyconsiderationsofradiationdose,andtherefore
fluoroscopicscreeningcannotbeusedcontinuouslytomonitortheprogressoftreatment.Furthermore,whenlithotripsytreatmentofgallstonesisbeingcarriedout,
theremaybepoorXraycontrastbetweenthestonematerialandthesurroundingsofttissue,makingitdifficulttoevaluatethestonedestruction.
10.2.3
FieldMeasurement
10.2.3.1.Measurementprobesandhydrophones.Anumberofmeasuringdeviceshavebeenusedfordeterminingthecharacteristicsofpulsedlithotripterfields.
Conventionalhydrophonesandpressuretransducersaregenerallyinadequateforthesemeasurementsduetothetransientnatureofthepulse,theshortrisetime(tens
ofnanoseconds)andtherelativelyshorttimeoftheoccurrence.Thehighpressuresatthefocus(upto100MPaforthepeakpositivepressure)enforcerequirements
onthetypeofdetectorwhicharenotnormallyfoundinotherapplications.Thebroadfrequencyresponserequired,from0.5to100MHzalsoimposeslimitsonthe
designofrobustelements(Colemanetal1989).
Detectorsarerequiredtoperformtwofunctions:theamplitudeoftheshockwaveatthefocusmustbemeasuredtheshapeofthepressureenvelopemustbetraced.
Piezoelectricpolymer(PVDF)membranehydrophonesarewidelyemployedbuthavethedisadvantagesofhighcostandshortoperatinglife(DeReggieetal1981,
Prestonetal1983,Harris1988).Miniaturepiezoelectricceramictubularelementsofferanalternativewithsomeadvantagesofrobustness,lowercostandminimal
disturbanceoftheacousticfield(LewinandSchafer1991).Someneedlehydrophoneswitharigidbackingtothepolymerelementdonotreproducetherarefactional
portionofshockwavesdemonstratedwithmembranetypehydrophones(Granz1989,IdeandOhdaira1981,Platte1985).Furtherassociateddiscussiononthe
performanceanduseofmembranehydrophonesindiagnosticultrasoundfields,whenthewaveformshaveundergonesignificantdistortionfromnonlinearpropagation
effects,maybefoundinChapters2and7.Whichevertypeisusedcaremustbetakentoensurethattheimpedanceofthemeasuringdevicedoesnotsignificantlyload
thehydrophone,andthatthecalibrationtakesaccountofanysmallloadingwhichmayexist.Oftenthehydrophoneissuppliedwithaheadamplifiertomatchthe
impedancesappropriately.

Page193
Table10.1.Possiblehydrophonesforfocusandfieldmeasurements.
Description

Remarks

Literature(examples)

PVDFsinglesheetspot
Focushydrophone
poledmembrane,lessthan
25mthick

Use

Liferestrictedtofewshocks

DeReggieetal1981

PVDFneedletype

Widelyusedforlithotripter
measurements

Prestonetal1983
Harris1988

Fieldhydrophone

Granz1989
IdeandOhdaira1981
Platte1985

Laseropticfibre

Focusandfieldtype

Easyrepairandrecalibration
followingstressfailure(not
commerciallyavailablebutwell
described)

StaudenrausandEisenmenger
1993
Kochetal1997
Chanetal1989

Table10.2.Measurementtechniquesandprobesforqualityassurancepurposes.
Probe

Features

Parameter
measured

Literature
(examples)

Capacitivecoupling:PVDF
spotpoledmembrane

Largesensitivearea

Pressurewaveform

FilipczynskiandEtienne1990

Steelballelectromechanical

Veryrobust

Energyperpulse

Pyeetal1991

Modelstones

Mimicsclinicalapplication

Destructiveforceperpulse

Deliusetal1994

Pressuresensitivepaper

Robust,qualitativefield
parameters

Spatialpressuredistribution, Oyanagietal1994
semiquantitativepeak
pressuremeasurement

Capacitancehydrophonesandopticaltechniquesinvolvinginterferometryareavailablebutrequirerelativelycomplicatedanddifficulthandlingprocedures(Filipczynski
andEtienne1990).Acoustoopticfibrehydrophoneshavebeendeveloped.Quartzglassfibresseemcapableofreproducingtherarefactionalacousticpressuremore
faithfullythanmembranehydrophones(StaudenrausandEisenmenger1993,Kochetal1997,Chanetal1989).Theyarereportedtobemoresensitivetothe
presenceofcavitationbubblesandthefibretiphasalimitedlifetime.Theirrepairandrecalibrationisdescribedasuncomplicated.Anelectromagneticprobehasbeen
developedwhichisbasedonthepressurewavestimulatedmovementofametalball

Page194

Figure10.1.
Typicalpressurepulsewaveformatthefocus.

Figure10.2.
Typicalspatialpressure
distributionatthefocus.The
pulseintensityintegral
(energydensity)isshownasa
dashedline.

coupledtoacoilheldwithinamagneticfield.Thisextremelyrobustdeviceismoreusefulfortheindicationofthetotalenergyofthepressurepulseratherthanits
shape(Pyeetal1991).Pressuresensitivepaperisalsoavailableforuseatthepressuresfoundinthefocusofalithotripteralthoughitsvalueforquantitative
measurementsisnotclear(Oyanagietal1994).
Modelstonesmaybeusedasatestofoverallsystemefficacy.Stonesareavailablewithsufficientlywellcontrolledconstructionthatthismethodisvaluableforroutine
checking(Deliusetal1994).
Thelimitationsoflithotripterdetectorspreventcontinuousdaytodaymonitoringofperformanceintheoperatingtheatre,restrictingmeasurementstomaintenance
periods.Thisisadisadvantageandimprovedequipmentisrequired.
10.2.3.2
TestChamber
Themeasurementofthepressurewave(figure10.1)andthemappingofthefocalzone(figure10.2)canbecarried

Page195

outinachamberfilledwithdegassedwater.Inonetypeoftestchamberatransducerpositioningsystemismountedatthetopofthechamberwithremotelycontrolled
steppingmotorsusedtodrivethehydrophonecarrierinthreeseparateaxes.Thepressurewavegeneratorisplacedbeneaththeacousticdiaphragmandpressed
firmlyagainstit,afterhavingbeencoatedwithacouplinggeltoassistinenergytransfer.Insomelithotriptersthepressurewaveunitmaybeinclinedanditisnecessary
toconstructthechamberbaseatamatchingangle.Formeasurementsofpressurepulsewaveformandpeakcompressionalacousticpressure,itisessentialthatthe
hydrophoneisaccuratelypositionedatthefocus.
10.2.3.3
AcousticPulseEnergy.
Theenergyperpulsecanbecalculatedbyintegratingthefieldoverthe6dBsurfacearoundthefocus.Theenergyinalithotripsypulseatthefocuscanbe
approximatedbytheexpression

wherep(x,y,z,t)istheacousticpressurefunctionSisthefocalsurface,inthexyplanecontainingthefocusatdepthztistimeandZisthecharacteristicacoustic
impedanceofwater(=1.5 106kgm2s1).
Forabeamwithcircularsymmetry

wherePII(r)isthepulseintensityintegral(energydensity)attheradiusrz,atadepthz,givenby
onameasurementofthepeakpositiveacousticpressureprofile.Ateachradialposition,

,andtheintegrationextendstoX6,the6dBradiusbased

Onenumericalsolutionofequation(10.2)is

Here,itisassumedthatameasurementofthebeamhasbeenmaderadiallyatNpointsfromr=0tor=Randthatthepulseintensityintegralatpointr=RiisPIIi.
AlsoR0=0andRN=R.

Page196

References
ChanHWL,ChiangKS,PriceDC,GardnerJLandBrinchJ1989Useofafibreoptichydrophoneinmeasuringacousticparametersofhighpowerhyperthermia
transducersPhys.Med.Biol.34160922
ColemanA,SaundersJ,PrestonRCetal1989AsurveyoftheacousticoutputofcommercialextracorporealshockwavelithotriptersUltrasoundMed.Biol.15
21337
DeReggieAS,RothSC,KenneyJMandEdelmanS1981PiezoelectricpolymerprobeforultrasonicapplicationsJ.Acoust.Soc.Am.698539
DeliusM,UeberleFandGambihlerS1994DestructionofgallstonesandmodelstonesbyextracorporealshockwavesUltrasoundMed.Biol.202518
FilipczynskiLandEtienneJ1990CapacitancehydrophonesforpressuredeterminationinlithotripsyUltrasoundMed.Biol.1615765
GranzB1989PVDFhydrophoneforthemeasurementofshockwavesIEEETrans.Electr.Instrum.24499502
HarrisGR1988HydrophonemeasurementsindiagnosticultrasoundfieldsIEEETrans.Ultrasonics,Ferroelectr.Freq.Contr.3587106
IdeMandOhdairaE1981WidefrequencyrangeminiaturehydrophoneforthemeasurementofpulseultrasonicfieldJapan.J.Appl.Phys.20Suppl.2032058
KochC,MolkenstruckWandReiboldR1997ShockwavemeasurementusingacalibratedinterferometricfibertipsensorUltrasoundMed.Biol.23125966
LewinPAandSchaferME1991Shockwavesensors:I.RequirementsanddesignJ.Litho.StoneDisease3317
OyanagiM,KudoN,YanagidaY,IwamaNandOkazakiK1994Measurementofshockwavepressuredistributionofextracorporealshockwavelithotripterusing
pressuresensitivepaper:practicalusefulnessandlimitationsJapan.J.Appl.Phys.3331558
PlatteM1985ApolyvinylidenefluorideneedlehydrophoneforultrasonicapplicationsUltrasonics241138
PrestonRC,BaconDR,LivettAJandRajendramK1983PVDFmembranehydrophoneperformancepropertiesandtheirrelevancetothemeasurementofthe
acousticoutputofmedicalultrasonicequipmentJ.Phys.E:Sci.Instrum.1678696
PyeSD,ParrNJ,MonroEG,AndersonTandMcDickenWN1991RobustelectromagneticprobeforthemonitoringoflithotripteroutputUltrasoundMed.
Biol.179319
StaudenrausJandEisenmengerW1993FibreopticprobeforultrasonicandshockwavemeasurementsinwaterUltrasonics3126773

Page197

PART4
ULTRASOUNDANDBUBBLES

Page199

Chapter11
AnIntroductiontoAcousticCavitation
TimothyGLeighton
11.1
TheAcousticPropertiesoftheBubble
Perhapsthesimplestoftheinteractionsbetweenagaspocketinaliquid,andanacousticwaveinthatliquid,isthatofgeometricalscattering.Thisoccurswhenthe
wavelengthoftheacousticwaveismuchlessthanthebubbleradius.Soundisscatteredbecauseofthestrongacousticimpedancemismatchbetweenthegasandthe
liquid,andthebubblecastsanacousticshadow.Inpracticethehighestfrequenciesemployedinliquidstendtobe30MHz(givingawavelengthinwaterofaround50
m),andthewavelengthevenat1MHzis1.5mm.Assuch,truegeometricalscatteringwouldoccuronlyforbubbleswhicharesolargeastohaveanimportant
implication:bubblesofasmallersizearelikelytobemorecommoninthepopulation.Whilethescatteringofsoundfrombodieswhicharenotmuchlargerthanthe
wavelengthdiffersfromthatdescribedabove(MorseandIngard1986),anevenmoreimportantfactoristhis:thatsmallerbubblestendtobehavelessliketheinert
bodiesdescribedabove,whosewallsactassimplereflectiveboundariesforthesound,andmoreasoscillatorswhichcanbedrivenbythesoundfieldtopulsate.Such
pulsationenhancesthecouplingbetweenthesoundfieldandthebubbles.Thisnotonlydramaticallychangesthescatteringofsoundbutalsocausesarangeofother
effectswhichbroadlycharacteriseacousticcavitation.
11.1.1
StiffnessandInertia
Anoscillatorrequirestwokeyelements:stiffnessandinertia.Inthebubblesystem,thefirstoftheseisprovidedbythegas.Ifcompressed,itexerts

Page200

aforcewhichresiststhatcompressionandwouldtendtomakethebubbleexpandandviceversa.Potentialenergyisstoredinthegasasthebubblevolumechanges.
Whenthebubblewallmoves,thesurroundingliquidmustalsomove.Ifthesystemhassphericalsymmetry,thenthevelocityofanincompressibleliquidfallsoffasan
inversesquarelawawayfromthebubblewall(Minnaert1933).Thereforethereisakineticenergyassociatedwithbubblepulsationswhichisinvestedinthemoving
matter.Sincetheliquidissomuchdenserthanthegas,thisisprimarilyinvestedintheliquid(thoughmotionofthegascontributestoamuchsmallerextentLeightonet
al1995a).Comparisonofthepotentialandkineticenergies(whichisacomparisonofthegasstiffnesswiththeliquidinertia)allowstheformulationofthenatural
frequencyf roftheoscillator.Asimplecalculation,basedonthelinearpulsationsofasphericalairbubbleofradiusR0inwaterwhichisassumedtobeincompressible
andinviscid,gives

anapproximationwhichneglectssurfacetension,makingthisformulationlessvalidforsmallerbubbles.
11.1.2
Resonance
Whenabubblepulsatesinasoundfield,itlosesenergythroughviscousandthermalmechanisms,andthroughtheradiationofacousticwavesintotheliquid(Devin
1959).Theexistenceofanaturalfrequencyanddampingsuchasthismeansthatwhendrivenbyasoundfield,thebubblecanexhibitaresonanceatafrequency
similartothatgiveninequation(11.1).Thisresonancepossessespropertiesincommonwithothers.Bubblesjustlargerthanthesizewhichisresonantwiththesound
fieldwillpulsateinantiphasetothosejustsmallerthanresonancesizetheamplitudeofpulsationtendstobelargestclosetotheresonancecondition(Leighton1994a,
4.1).Howeverthebubblepossessesacomplexrangeofotherpropertiesassociatedwiththeresonance,whichwillbedetailedinsections11.2and11.3.Inbrief,as
thewallpulsationamplitudeincreasesnearresonance,thenonlinearcharacteroftheoscillationbecomesmorepronounced,andtheresultantbubbleactivitycanbe
dividedintotwoclasses.Inthefirstcategoryarethoseeffects,suchastheemissionofharmonicsofthedrivingfrequency,whichincreasecontinuouslywithincreasing
pulsationamplitude.Thereforeifthebubbleisresonantatadriving(or'pump')acousticfrequencyoff p,thentheemissionofsignalsat2f p,3f p,etcmaybetakento
indicatethatthebubblesareclosetoresonancesize(Milleretal1984,Leighton1994b).Thiscanbeusedasamethodofsizingbubbles.Howeverithasdrawbacks
inthatphenomenaotherthanresonantbubblescangiverisetoharmonicemissions,andforsuchsizingpurposes,atwofrequencytechniquemaybesuperior
(Leighton

Page201

etal1997,Phelpsetal1997).Asecondclassofphenomenonoccursasathresholdwiththeincreasingpulsationamplitude,suchasthestimulationofsurfacewaves
onthebubblewall*(PhelpsandLeighton1996,1997).Whilethetwoexamples(harmonicemissionandsurfacewaveactivity)reflectthedynamicsofsinglebubbles,
phenomenawhichhavestrongimplicationsforthebubblepopulationasawholecanbefoundinthesetwoclasses(respectiveexamplesofradiationforcesand
rectifieddiffusionarediscussedinsection11.3).Themostimportantofthethresholdphenomena,historicallystudiedinpopulationsbutwithrecentimportantfindings
throughobservationofsinglebubbles,isinertialcavitation,describedinthefollowingsection.
11.1.3
InertialCavitation
In1917LordRayleighprovidedatheoreticalanalysisforthephenomenonwenowcallinertialcavitation.Theimpetusforthisstudyhadcomefromtheproblemofthe
erosionofshippropellers,andconsiderationwasgiventothepossibilitythatgasbubbles,excitedbythepressurefluctuationsgeneratedclosetothepropeller,were
responsibleforthe'pitting'seenontheblades.Inertialcollapseofasphericalgasbubbleinaliquidischaracterisedbyarelativelyslow(i.e.timescalesoftheorderof
halfanacousticcycle),approximatelyisothermalgrowthofaninitialbubblenucleustomanytimesitsoriginalsize.Thisisfollowedbyarapidcollapse,theinitialstages
ofwhicharedominatedbytheinertiaofthesphericallyconvergingliquid.Duringthecollapse,thegastemperaturerisesasitiscompressed,andshockscanpropagate
withinthegas.Bothhightemperatures(Neppiras1980)andshocks(Bradley1968)canpotentiallygeneratefreeradicals,thesubsequentradiativerecombinationof
whichcanemitlight.Lightemissionfromcollapsingbubbleshasbeenobserved,andiscalled'sonoluminescence'.Theproductionofthisemissionissometimestaken
asindicativeof(butnotnecessarilyrequisitefor)theoccurrenceofinertialcavitation,anditisperhapsinthisthatthemainpracticalexploitationofthephenomenonof
sonoluminescenceiscurrentlyrealised.Thisisbecausemany,butbynomeansall,ofthephysicalandbiologicalchangeswhichultrasoniccavitationcaninduceoccur
asaresultofinertialcavitation(section11.4).
However,asecond,andsomewouldsaymoreimportant,reasonforconsideringsonoluminescenceisitsabilitytoprovideexperimentalevidenceagainstwhichtotest
theoriesofbubbledynamics.Inrecentyearstherehasbeenasignificantincreaseinthenumberofpublicationssupportingonemechanismoranotherforthegeneration
ofsonoluminescence,andthetopicremainscontroversial(Leighton1994a,4.2.1).Throughoutthe60yearsofinvestigationtodateintosonoluminescence,the
proposedmechanismsby
*

Withassociatedimplicationsfornucleationandmicrostreaming,whichwillbediscussedinsection11.3.

Page202

whichtheemissionisproducedhavebeendebated.Arangeofmechanismshasbeenproposed,andalthoughtherehavebeenseveralperiodswherethebroad
consensusofopinionfavoursone,thesehavenotlasted.Manypeopleinthe1980sfavouredathermochemicalmechanism(WaltonandReynolds1984),proposed
byGriffing(1950,1952).Inthis,oxidisingagentssuchashydrogenperoxideareformedbythehightemperatures(~5000KSuslicketal1986)withinthe
compressedgas,andgiverisetochemiluminescentreaction.However,therehasbeensupportforover50yearsformechanismsbasedonelectricaldischarge
(FrenzelandSchultes1934,Frenkel1940,Bresler1940),thoughdetailsofthemechanismhavechanged(Margulis1985,Lepointetal1994).Jarman(1960)
proposedgasshocksasthesourceoftheemission,andvariationsofthistheorytoohavesurvivedtopresent(VaughanandLeeman1989,WuandRoberts1993,
Mossetal1994).Howeverothermechanismsproposedintheearlydayscurrentlyhaveveryfewsupporters(Chambers1936,WeylandMarboe1949,Guntheret
al1959).ReplacingtheseinrecentyearshavebeenpublicationsintroducingintothegenerationofsonoluminescencethephenomenaofCasimirenergies(Schwinger
1992)rectifieddiffusion(CrumandCordry1994)molecularcollisions(FrommholdandAtchley1994)quantumradiation(Eberlein1996)andjetting(Prosperetti
1997).
Perhapsthemainreasonfortheincreaseinrecentyearsinpublicationsontheproposedmechanismsfortheemissionwasthediscoverythatitwaspossibleto
produceasonoluminescingbubblewhichbehavedquitedifferentlytothoseenvisagedpreviouslybymostpeople.Afterreachingminimumsize,thebubblerebounds,
emittingapressurepulseintoaliquid.Untilrecently,thebubblewasthenthoughttofragment,andassuchthephenomenonwenowcall'inertialcavitation'wasuntil
recentlytermed'transientcavitation'.However,GaitanandCrum(1990)discoveredsonoluminescenceovermeasurementintervalsofthousandsofacousticcycles
fromrepeatedcollapsesofasinglebubblewhichapparently*didnotbreakup.Thediscoverythatthesonoluminescentflashinsuchcircumstancesisoflessthan50ps
duration(Barberetal1992)throwsintoquestionthemechanismbywhichlightisgeneratedinthis'singlebubblesonoluminescence'(SBSL).Howeverinpractical
applicationsinvolvingthecavitationofmanybubbles,thebreakdownofspatialsymmetrymightsuggestthateachbubbleperformssuchinertialcollapsesonceoronly
afewtimesandthenfragmentsonrebound.Insuch'cavitationfieldsonoluminescence'(CFSL)or'multibubblesonoluminescence'(MBSL)itmaybethatthesameor
anotherofthevariousmechanismsforgeneratinglightfrombubblecollapsedominates,dependingonthedetailsofthecollapse.Currentlythemostwidelyaccepted
theoryforCFSLisbasedon
*

Barberetal(1992)didnotobservefragmentationandrecoalescenceoccurringduringeachacousticcycle,thoughitispossiblethatthismightoccurovertimescalestoorapid
tomeasure.

Page203

therecombinationofthermallygeneratedfreeradicals(Kamathetal1993).Thereare,however,differencesbetweenthepredictionsofthistheoryandrecent
measurementsofCFSLemissions(Matulaetal1997).TheauthorssuggestanupperlimitonthepulsewidthduringCFSLof1.1ns.
Asmentionedatthecloseofsection11.1.2,theoccurrenceofinertialcavitationisathresholdphenomenon.Whetheritoccursornot,forafreefloatingspherical
bubblenucleusofknowngascontentinagivenliquid,dependsprimarilyontheacousticpressureamplitude,theacousticfrequency,andthesizeofthenucleus.Ifthe
nucleusistoosmall,thensurfacetensionforcespreventtheinitialsuddengrowth,andinertialcavitationdoesnotoccur.Ifitistoolarge,thenthebubblemaygrow,but
betoo'sluggish'toconcentratetheenergysufficientlyoncollapsetogeneratefreeradicalsetc*.Thereisthereforeacriticalsizerangeinwhich,foragivensoundfield,
theinitialsizeofthebubblemustfallifitistonucleateinertialcavitation(Flynn1964,FlynnandChurch1984,HollandandApfel1989,Leighton1994a).Thelower
thefrequency,thewiderthisrange.
Thisisclearlyshowninfigure11.1,wherethetransitionthresholdbetweeninertialandnoninertialcavitationisplotted,baseduponcalculationsbyApfelandHolland
(1991).Theyassumedthat,inresponsetoasinglecycleofultrasound,abubblewhichissphericalatalltimes,wouldgrowanduponsubsequentadiabaticcollapse,
thegaswithinthebubbleshouldattainatemperatureofatleast5000Kifthecollapseistobe'inertial'(Apfel1981a,b,ApfelandHolland1991).Thoughthereare
clearapproximationsandthechoiceofsuchacriterionfordefininginertialcavitationisnotfundamental,thisisneverthelessanextremelyusefulcalculation.Itillustrates
thattheacousticpressureamplituderequiredtocauseabubbletoundergoinertialcavitationisdependentupontheinitialradiusofthatbubble.Sinceinmost
applicationsthefrequencyistheeasiesttocontrolofthethreeparametersshowninfigure11.1,followedbytheacousticpressureamplitudeatthebubble,withthe
radiiofthenucleipresentbeingtheleastaccessible,thenthegraphcanbeinterpretedinanothermanner.Atafixedfrequency,say10MHz,anultrasoniccyclewitha
peaknegativepressureof1.5MPa(assumedtobeconstantthroughoutthefield)willonlygenerateinertialcavitationwithinawatersampleif,accordingtothismodel,
itcontainsbubbleshavingradiibetween0.03and0.77m.Asthepressureamplitudedecreases,sodoestherangeofbubblesizeswhichcannucleateinertial
*

Asimplecatapultanalogyisinformative.Bubblesundergoinginertialcavitationtendtogrow,priortocollapse,toaroughlysimilarsize(Leighton1994a,4.2.3,4.3.1b(iii)).This
isliketryingtoachievethesamelengthofdraw(i.eaboutonearm'slength)onanumberofcatapults.Iftheelasticonthecatapultistooshort,thenitisnotpossibletodrawafull
arm'slength(ifthefulldrawwereonlyafewcentimetres,thethrowofthecatapultwouldbeveryshort).Thisissimilartothecaseoftheverysmallbubble,wheresurfacetension
preventsbubblegrowth.Iftheelasticinthecatapultwere,atequilibrium,verylong,itwouldbeeasytodrawafullarm'slength,buttheelasticwouldnotbetaut,andagainthe
throwwouldbeshort.Thisisakintothecaseofthelargebubble.

Page204

Figure11.1.
Thethresholdforinertialcavitation,aspredictedbythetheoryof
ApfelandHolland.Foreachfrequencyalinecanbeplotted:ifthe
conditionsofpeaknegativepressureandoftheinitialbubbleradius
aresuchthatthepointofinterestonthegraphliesbelowtheline,
noninertialcavitationwilloccur.Ifthepointofinterestisabove
theline,inertialcavitationwilloccur.Reprintedbypermissionof
ElsevierSciencefrom'Gaugingthelikelihoodofcavitation
fromshortpulse,lowdutycyclediagnosticultrasound'byRE
ApfelandCKHolland,UltrasoundinMedicineandBiology,vol18,
pp26781,copyright1991byWorldFederationof
UltrasoundinMedicineandBiology.

cavitation.Theverylowestpeaknegativepressurewhichcouldgiverisetoinertialcavitation,accordingtothismodel,isPopt(around0.84MPaat10MHz),andat
thispressureonlybubblesofaradiusRopt(0.2mat10MHz)couldpossiblynucleateinertialcavitation.
ThetheoryofApfelandHollandhasgivenrisetoameasurecalledthe'mechanicalindex',whichmaybeusedtoindicatethelikelihoodofexceedingthethreshold
requiredtonucleatecavitation.Asdescribedforfigure11.1,themodeldemonstratesthatforagivenacousticfrequencythereisaminimuminthecurve.Ifthewhole
rangeofbubblesizeclassesarepresent,thenthereisaspecificinitialbubblesizeforwhichthethresholdacousticpressurerequiredtonucleateinertialcavitationisa
minimum.Astheinsonationfrequencyincreases,thebubbleradiuswhichrequiresminimumpressuretonucleateinertialcavitationdecreases.Thisisbecauseinertial
andviscousforcesincreasewithincreasingfrequency,andthereisinsufficienttimetobringabouttherequiredamountofbubblegrowth.Forthesamereasonthe
acousticpressurerequiredtonucleateinertialcavitationinallbut

Page205

thesmallestbubblesincreaseswithincreasingfrequency.Surfacetensiondominatestheresponseofthesmallestbubbles.
Ifoneisinterestedinaworstcaseassessmentofthelikelihoodthatinertialcavitationwilloccurwhenaliquidisinsonated,clearlyonemustassumethatthebubble
populationcontainsbubblesattheradiuscorrespondingtotheminimuminthethresholdcurve.Atagivenfrequency,itisbubblesoftheradius,Ropt,whichtheanalysis
predictswillrequirethesmallestpeaknegativepressure,popt,toundergopromptinertialcavitationinresponsetoasingleacousticcycle.ApfelandHolland(1991)
generatedaplotofPoptagainstfrequencyforwaterandwholeblood,usingpurefluidbulkpropertyvaluesforthesurfacetension,densityandviscosityrelevanttothe
twofluids.TheliquidsareassumedtocontaintherelevantnucleiatsizeRopt.ApfelandHollandemployedatwoparameterleastsquaresfittotheseplotsinorderto
obtainarelationshipbetweenPoptandinsonationfrequencyf= /2 .Theyfoundaleastsquaresfitof:

whereifPoptismeasuredinMPaandfinMHz,theconstantatakesvaluesof2.10forwaterand1.67forblood,andbhasvalues0.06forwaterand0.13forblood.
ForagivensoundfieldwithamaximumnegativepressureofPrthenbytakingavalueofa 2toapproximatetheappropriatephysiologicallyrelevantliquid,a
mechanicalindexMIcanbedefinedforthesoundinthatliquid:

ThemechanicalindexMIforpromptcavitationrepresentsanapproximatemeasureoftheworstcaselikelihoodofnucleatinginertialcavitation.Assuchitcanbeused
toestimatethepotentialfornucleatinginertialcavitationresultingfrominsonationbydiagnosticultrasound.Clearlyitwouldbelessappropriatetoapplythisindexto
toneburstorcontinuouswaveinsonations,duringwhicharangeofcomplicatedprocesses,includingrectifieddiffusionandenhancementofthecavitationbyultrasonic
pulsing,canoccur(section11.3Leighton1994a,4.4.3,5.3).HollandandApfelrecommendthatthepulselengthshouldnotexceed10cycles,northedutycycle
1:100.Thepeaknegativepressureoutputfromthedevice,asmeasuredinwater,mustbederatedtogivetheappropriatepeaknegativepressurethatwouldbe
attainedinvivoatthelocationofthemaximumpulseintensityintegral(AIUM/NEMA1998).Thecentrefrequencyisusedforfwhich,foraccuracy,isexpectedto
beoftheorderofMHz.ApfelandHolland(1991)suggestthatamechanicalindexvaluebelow 0.5 0.7wouldindicatethat,eveninthepresenceofabroadsize
distributionofnuclei,theconditionsarenotsufficienttoallowsignificantbubbleexpansion.IfMI 0.5,Apfel

Page206

andHollandsuggestthat'theusershouldbeadvisedofthepotentialforbubbleactivity'.TheAIUM,NEMAandFDAhaveadoptedthemechanicalindexasareal
timeoutputdisplaytoestimatethepotentialforcavitationinvivoduringdiagnosticultrasoundscanning(AIUM/NEMA1998).TheuseofMIrelatedtopractical
exposuremeasurementproceduresisdiscussedinChapter7.
Keypointsshouldbenoted.First,themodelfortheindexisbasedontheassumptionofafreefloatingsphericalnucleusofoptimumsize.Incertaincircumstancesit
maybethatthenucleusisofadifferenttype(section11.3.3).Second,themechanicalindexgaugesthelikelihoodofpromptcavitation,andnothingmore:theeffectof
interest(e.g.abioeffect)mayberelatedtosomeothermechanism(section11.4).Third,theeffectsofnonlinearpropagation(Leighton1994a,1.2.3)arenot
included,andhencetheindexmightunderestimateconditionsinsitu.Fourth,whenappliedtodiagnosticultrasoundinstruments,themechanicalindexdescribes
conditionsonlyatthefocus,whichisnotnecessarilythepointofinterest.Fifth,themechanicalindexhasarisenfromatheorywhichgivessmoothcurvesoftheform
showninfigure11.1suchcurvesmayinfactshowpeakswhenothereffectsareincorporated(Roy1996,Allenetal1997).
Lastly,theunderlyingtheoryisappliedtoderivethemechanicalindexinawayintendedtoelucidatetheconditionswhichattainthethresholdfornucleatinginertial
cavitation.Theamountbywhichthemechanicalindexisexceededisthereforeonlyaguidetothedegreeofcavitationalactivity,andbynomeansanexactpredictor.
ConsidertheMHzrangeillustratedinfigure11.1,wheretherangeofnucleisizewhichcanseedinertialcavitationisrelativelynarrow.Insuchasoundfieldoffixed
frequencyandincreasingacousticpressure,asoneexceedsthethresholdinfigure11.1,therangeofnucleiwhichmaynucleateinertialcavitationincreases.Inafield
containingabroadrangeofbubblesizes,withauniformnumberofbubblesineachsizeclass,thetotalnumberofnucleatedeventswouldbeexpectedtoincrease.
Howeverifthereisonlyanarrowdistributionofbubblesizes,exceedingthethresholdbyincreasingamountsinthismannerwould,tofirstorder,havelittleeffecton
thenumberofinertialeventswhicharenucleated.Whatmightbeexpectedtoincreaseistheenergyassociatedwitheachcollapse.Similarly,astheacousticfrequency
changes,itisnosimplemattertopredicthowthemechanicalindexmightcorrelatewiththeamountofcavitational'activity'observed(Leighton1997).
11.2
TypesofCavitation.
Insection11.1anisolatedsphericalbubblewasdiscussed.Suchabubblecancastageometricacousticshadowinanultrasonicfieldofsufficientlyhighfrequency.
Thiscould,forexample,monitortheslowdissolutiononemightexpectofsuchabubble(figure11.2(a))ortheslowgrowthwhich

Page207

mightoccurunderdecompressionorheating(figure11.2(b)).Sincethebubbleundergoesnooscillationinthesetwocases,ithasnoacousticeffectbeyondthatofan
impedancemismatch.However,asamechanicaloscillatorpossessingstiffnessandinertia,thebubblehasanaturalfrequency(figure11.2(c)),whichcorrespondsto
thenoteemittedwhensuchabubbleisentrained(forexampleinawaterfallLeightonandWalton1987).Furthercouplingwithanoscillatorypressurefieldoccurs
whenabubbleisdrivenintopulsationbyanincidentsoundfield.Thebubblemightbedrivensuchthattheamplitudeofoscillationofthebubblewallislow(for
example,theincidentsoundfieldhasalowacousticpressureamplitude,orthebubblehasasizewhichdiffersgreatlyfromthatrequiredforresonancewiththedriving
frequency).Insuchacase,energyislostfromthebeamthroughacousticreradiationand,asdiscussedinsection11.2,throughconversiontoheatbyviscousand
thermaldampingmechanismsassociatedwiththebubblemotion(Devin1959,Eller1970).Figure11.2(c)showsjustsuchanoscillation.Despitedamping,the
illustratedbubblepulsationsareshownnottodecreaseinamplitude,suggestingacontinuouswaveortoneburstinsonation,ratherthanashortpulse(whichisthe
caseillustratedinfigure11.2(d)).
Inertialcavitation,typifiedbythesuddenexpansionandthenrapidcollapseofthebubble,isshowninfigure11.2(e).Thebubblemayfragment,orrepeatthe
growth/collapsecycleanumberoftimes(Apfel1981a,b)or,inspecialisedconditions,canpulsateforthousandsofcycles,emittingasonoluminescentflashateach
collapse,asdiscussedinsection11.1.3.Thegenericoscillationshowninfigure11.2(f)isahighamplitudepulsationofasphericalbubble.Dependingonthe
amplitude,suchoscillationmaybeinertial,ornoninertialbutofhighamplitude.Ifnoninertial,thereareanumberofinterpretationsofhowthissituation,whichdiffers
inwalloscillationamplitudefromthatshowninfigure11.2(c),arises.Itmight,forexample,occuriffigures11.2(c)and(f)showthesamebubble,butinfigure11.2
(f)theacousticpressureamplitudeofthedrivingfieldisgreater.Alternativelythebubblesinfigures11.2(c)and(f)mightbeinthesamesoundfield,butwiththe
bubblesinfigure11.2(f)beingclosertoresonance.Howeverasthebubbleismorecloselydriventoresonance,othereffectsbegintooccur.Mostnotableofthese
aresurfacewaves,whichvisuallycausea'shimmer'toappearonthesurfaceofthebubble(Neppiras1980),andacousticallymaybedetectedwithacombination
frequencytechnique(PhelpsandLeighton1997).Suchsurfacewavesareillustratedinfigure11.2(g).Surfacewaveswillbestimulatediftheamplitudeofthebubble
walldisplacementexceedsacertainvalue,whichitwilltendtodoastheamplitudeofthesoundfieldincreases(providingnoothereffect,suchasinertialcavitationor
fragmentation,occurs)or,morecommonly,thecloserthebubbleistotheresonancecondition.Ingeneral,thegreaterthedegreebywhichtheamplitudeofthedriving
fieldexceedsthethresholdconditiontoexcitesurfacewavesonresonantbubbles,thebroadertherange

Page208

Figure11.2.
Aschematicillustrationoftherangeofbubblebehaviour.
Thebehavioursaredescribedinthetext.Theexpansion
ratiosdrawnforthesebubblesareexaggeratedtoillustrate
thepulsationsmoreclearly.

ofbubblesizes,centredabouttheresonance,onwhichsurfacewaveswillbestimulated(PhelpsandLeighton1996).Surfacewavescanbeassociatedwithanerratic
'dancing'translationalmotion(CrumandEller1969)and,athighamplitudes,microbubblesmightbreakofffromthetipsofthesurfacewaves(figure11.2(h)Leighton
1995).Surfacewaveactivityisalsoassociatedwithmicrostreaming,localcirculationcurrentsaroundavibratingbodywhichcaninfluencemasstransportintheliquid
(section11.3.1)andgenerateshearforces(section11.4)closetoabubble.

Page209

Otherdeparturesfromsphericalsymmetryincludeshapeoscillations(figure11.2(i)),foundparticularlyinlargerbubbles,wherethetendencyofsurfacetensionto
promotesphericityisweaker(Strasberg1956,LonguetHiggins1992a,Leighton1994a,3.6).Ifextreme,suchshapeoscillationscanbreakabubbleup,usually
generatingasmallnumberoffragmentsofroughlysimilarsize,incontrasttothesheddingofmanymicrobubblesfromalargerparentbubble,showninfigure11.2(h)
(LonguetHiggins1992b,Leighton1995,Leightonetal1995a,1998).Shapeoscillationsareencouragedbyanisotropiesinthelocalenvironment.Commoncauses
forthesearethepresenceofotherbubbles,particlesorwalls.Ifsucharepresent,thenduringthesubsequentcollapsethebubblemayinvolute,onewallpassing
throughthebubbletoformahighspeedliquidjet(LauterbornandBolle1975,PlessetandProsperetti1977).Thisisshowninfigure11.2(j).Thoughthejettingofa
bubblemaybequitecomplicated,withforexampletheformationofcounterjets,theneteffectisthatthebubblewillusuallyfragment(Neppiras1980).
Suchbehaviournecessitatestheadoptionofmodelshavingagreaterdegreeofsophisticationthanthatoftheisolatedsphericalbubbleinaninfinitefluidemployedat
theoutsetofthischapter.Departuresfromsphericalsymmetryinboththebubblewallandtheenvironmentmustbeincorporated.Theconceptofthe'stabilisedgas
body'goesfurtherthantheinteractionsdescribedabove,assimilatingsolidstructuresintothewallboundingthegaspocket.Thepocketispartiallyboundedbyliquid,
andpartiallybysolidstructures,whichcanstabilisethegasbodyagainstdissolution.Theymightcomprise,forexample,approximatelycylindricalpocketsofgas
containedwithintubularvessels,suchasarefoundinbiologicalstructures.Examplesincludestructuresinplants(Miller1979),insecttracheae(Childetal1981),and,
speculatively,mammalianbloodvesselsandearcanals(Leightonetal1995b)(figure11.2(k)).Thestructuresmayberigid,inwhichcasethecurvedinterfaces
betweenthesolidandgaswouldnotmove.Howeverthegas/liquidinterfaceswhichcomprisetheendwallsofthecylindermightoscillateinapistonlikeora
membranelikemanner(MillerandNyborg1983,Miller1984,MillerandNeppiras1985).Oscillationsofsuchgaspocketsmaycausethenucleationoffreefloating
bubblesintotheliquid(figure11.2(l)section11.5.2).
Figure11.2givesrisetothreequestions.Whatdetermineswhichofthetypesofbehaviouragivenbubblewillundergo?Whataretheimplicationsoftheoccurrenceof
onetypefortheoccurrenceofanother?Whataretheimplicationsoftheoccurrenceofonetypeofcavitationforcausingchangetothemedium?Thefirstofthese
threequestionshasalreadybeendiscussed,intermsoftheresonanceandthethresholdsforinertialcavitation,surfacewaveactivity,etc.Thesecondandthird
questionswillbeansweredinsections11.3and11.4respectively.

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11.3
TheImplicationsoftheOccurrenceofOneTypeofCavitationfortheOccurrenceofAnother
Givenafixedacousticfrequencyandintheabsenceofinhomogeneitiesinthemedium,thetypeofbubbleactivitypresentdependsontheresonancecondition(which
inturndependsonthebubblesize),andtheamplitudeandhomogeneityoftheacousticfieldatthebubble.Insections11.3.1and11.3.2,twoexamplesaregivento
showhowthesecanchange,andtoallowillustrationoftheirinterdependence.Inabubblepopulation,suchinterdependenceandfeedbackcanworkthrougha
complicatedseriesofrelationshipstosetupasteadystatecavitatingcondition(Leighton1995).
11.3.1
AlterationoftheBubbleSizebyRectifiedDiffusion
Byrectifieddiffusionabubblecan,inanappropriatesoundfield,increaseitsequilibriumradiusthroughanetfluxofpreviouslydissolvedgasoutofsolutionandinto
thebubble.Thisfluxisthereforecountertothedirectionthatwouldbetowardsequilibriumwerethesoundfieldnotpresent,sinceagasbubbleinaliquidwilltendto
dissolveowingtotheexcessinternalgaspressurerequiredtobalancethepressure2 /R0duetosurfacetension (EpsteinandPlesset1950).Thus,intheabsenceof
asoundfieldoranystabilisingmechanism*,bubblesgraduallydissolve(GuptaandKumar1983).Inthepresenceofasoundfield,thesituationisquitedifferent.
Duringnoninertialcavitation,sinceevaporationandcondensationtakeplacesomuchmorerapidlythanthebubbledynamics,itiscommonlyassumedthat,tofirst
order,thevapourpressurewithinthebubbleremainsconstantattheequilibriumvalue.Howeverthisisnotsoforthegascontentofthebubble,agaswhichwillalso
bedissolvedintheliquid.Harveyetal(1944),studyingtheformationofbubblesinanimals,suggestedamechanismbywhichbubblesundergoingstablecavitationina
soundfieldcanexperienceasteadyincreaseintheirequilibriumradius,R0.Thisinwardlydirected'rectifieddiffusion'comesaboutthroughtheactivepumpingofgas,
initiallydissolvedintheliquid,intothebubble,usingtheenergyofthesoundfield.Therearetwocontributoryelementstoafulldescriptionoftheprocesses,an'area
effect'anda'shelleffect'(Leighton1994a,4.4.3(a)).
Theareaeffectarisesthroughthecorrelationbetweenthedirectionofmassfluxandtheareaofthebubblewall.Whilethebubbleradiusislessthanequilibrium,the
gasinsideisatagreaterpressurethantheequilibriumvalue,andthusdiffusesoutintotheliquid.Conversely,whenthebubbleradiusissignificantlygreaterthanR0,the
internalgaspressureislessthantheequilibriumvalue,andsogasdiffusesfromtheliquidintothebubbleinterior.Thenetflowrateofthegas,however,isnotequal
duringthe
*

Seesection11.3.3.

Page211

compressedandexpandedphasesofthebubblemotion,becausetheareaofthebubblewall(thetransferinterface)isgreaterinthelattercasethanintheformer.
Therefore,overaperiodoftime,therewillbeanetinfluxofgastothebubbleinterior.
Theshelleffectoccursbecausethediffusionrateofagasinaliquidisproportionaltotheconcentrationgradientofthedissolvedgas.Asthebubblepulsates,a
sphericalshellofliquidsurroundingthebubblewillchangevolume,andsotheconcentrationgradientwillchange.Whenthebubbleisexpanded,eachliquidshell
contracts.Theconcentrationofdissolvedgasintheliquidadjacenttothebubblewallislessthantheequilibriumvalue(Henry'slaw),buttheshellisthinnerthanwhen
thebubbleisatequilibriumradius,sothatthegradientacrosstheshellishigher.Thereforetherateofdiffusionofgastowardsandintothebubbleishigh.Whenthe
bubbleiscontracted,theliquidshellssurroundingthebubbleareexpanded.Thoughtheconcentrationofgasnearthebubblewallishigherthanwhenthebubbleis
expanded(Henry'slaw),theincreasedthicknessoftheshellmeansthattheconcentrationgradientisnotasgreataswhenthebubbleisexpanded.Thetwofactors
(gasconcentrationatthebubblewall,andshellthickness)worktogetherwhenthebubbleisexpanded,butagainstoneanotherwhenthebubbleiscontracted.On
expansionthereisalargeconcentrationgradientdrivinggasashortdistance,andinthesecondcaseasmallergradientdrivesthegasalongerdistance.Theformer
effectisdominant.
Theresultisthatboththebubblewallsurfaceareaandthedissolvedgasdiffusionrateareasymmetricalwithrespecttoexpansionandcontraction:the'area'and'shell'
effectsreinforceoneanother.Thecombinedeffectmeansthatduringnonlinearcavitationinacousticfieldswhicharesufficientlyintense,theequilibriumradiusabout
whichthebubblepulsateswilltendtoincrease(EllerandFlynn1965,Eller1972,Crum1984,Church1988a,b).
Thethresholdacousticpressureforgrowthisdependentonthebubblesizeandtheacousticfrequency.Localminimaintheacousticpressurethresholdareseenat
harmonicsandsubharmonicsoftheresonance(Church1988a).Thegrowthrateoncethethresholdhasbeenexceededisstronglyinfluencedbythepresenceof
surfaceactiveagents,andbymicrostreaming(introducedin11.2),whicheffectsthetransportofdissolvedgasbeyondthebubblewall(Church1988b).
Microstreamingwasnotincorporatedintotheabovesimplediscussion,butitseffectsarequalitativelysimple.Asabubblegrowsbyrectifieddiffusion,thedissolved
gasistakenfromtheliquidnearthebubble.Ifthereisnoflow,thentherateatwhichthedeficitismetdependsontherateatwhichdissolvedgascandiffusefrom
regionsfurtheroutfromthebubble.Sincethisisingeneralaslowprocess,theliquidoutsidethebubblewallwillbecomedepletedofdissolvedgas.Theresulting
changeinconcentrationgradientreducestherateoffurthergrowth.However,microstreamingflowswilltendtobringliquidfromfurtheroutclosetothebubblewall.
Theconvectionofdissolvedgasreducesthedepletionandincreasesthegrowth

Page212

rate.Microstreamingwillcontinuallyrefreshtheliquidatthebubblewall,givingitadissolvedgasconcentrationclosetothatfoundfarfromthebubble.Theconverse
processisofcoursevalid:ifabubbleisdissolving,microstreamingwilltendtoremovefromtheregionoutsidethebubblewalltheexcessdissolvedgasconcentration,
soincreasingtherateofdissolution(Church1988b).
Rectifieddiffusionanddissolutionallowbubblestosteadilychangetheirequilibriumsize,andthereforemodifythecavitationalactivitytheyundertake.Amongthewide
rangeofpossibilitiesarethefollowing.Abubblemaygrowtobecomeclosertotheresonancecondition(where,forexample,surfacewavesandmicrostreaming
requireloweracousticpressureamplitudestobestimulated).Ifabubblefragmentsfollowinganinertialcollapse,andtheresultingsmallbubblesaresmallerthanthe
sizerequiredtonucleateinertialcavitation,butlargerthanthatrequiredtogrowbyrectifieddiffusion,suchgrowthcanmakeinertialcavitationaselfnucleating
process.Church(1988a)outlinessomeofthesepossiblescenarios,andassessestheirlikelihood.
11.3.2
AlterationoftheAcousticPressureFieldattheBubblebyRadiationForces
Inanacceleratingliquid,agasbubble,beinglessdensethanthesurroundingfluid,willaccelerateinthesamedirectionasthesurroundingliquid,buttoagreaterdegree
(Leighton1994a,3.3.2(d)).Thatdegreeisgovernedbythemagnitudeofthedifferenceindensitybetweengasandliquidor,equivalently*,theinstantaneousbubble
volume.Asanacousticfieldpassesthroughaliquid,theliquidparticleaccelerationoscillates,reversingdirectionperiodicallysuchthatitisalignedwiththedirectionof
propagationforhalftheacousticcycle,andcontrarytoitfortheremainder.Thebubble,beinglessdensethantheliquid,willfollowsuit,acceleratinginthesame
directionasthecontinuallyalternatingliquidparticleacceleration**.Howeverifthebubbleispulsatingwiththesameperiodicityasthedrivingfield(whichalinear
oscillatorwilldo),thenthephaserelationissuchthatthebubblewillbeintheexpansionphase(i.e.withitsradiusgreaterthanequilibrium)asittravelsinonedirection,
andinthecompressionphaseasittravelsintheotherdirection(Leightonetal1990).Thebubbleacceleratesmoreduringtheexpansionphasethanthecompression,
sincethenitsvolumeisclearlygreater,anditsdensityless.Thereforesuchabubbleinasoundfieldwillexperienceforceswhichreversedirectiontwiceeachacoustic
cycle.Howevertheneteffectwillbethatittravelsinthedirectiontakenbytheliquidaccelerationwhenthebubbleisintheexpansionhalfcycle.Ifthe
*

Assumingthebubblecontainsafixedmassofgas.

**

Assumingthatinertialeffectsontheresponsetimesaresmall.

Page213

bubbleisassumedtobeanoscillatorwithasingledegreeoffreedom,bubblesoflessthanresonancesizewillpulsateinantiphasetothoseofgreaterthanresonance
size.Thereforeifonetypeofbubbleisacceleratedinonedirectionbythesoundfield,theothertypewillbeforcedintheoppositedirection.
Thisbehaviourismostreadilyobservedinastandingwavefield,wheretheradiationforcesarecommonlycalled'primaryBjerknesforces'.Theycausebubblesofless
thanresonancesizetotraveluppressuregradientstocollectatacousticpressureantinodes,whilebubblesoflargerthanresonancesizemigratedownthegradientsto
thenodes.Similarcommentsapplyinfocusedacousticfields,wherebubblesoflessthanresonancesizemigrateuppressuregradientstowardsthefocus.Such
migrationschangetheacousticpressureamplitudeatthebubble,andthereforeaffectthetypeofcavitation.Howevertherecanbeimportantindirecteffects,suchas
theacousticshieldingwhichsuchaggregationsofbubblesproduce,whichalsoaffectthelocalacousticfield(Leighton1995).
Formulationsalsoexistfortheradiationforceonabubbleintravellingwaveconditions,wheretheforceisgreatestonresonantbubblesandfortheforceonaparticle
suspendedinaliquidclosetoabubble(CoakleyandNyborg1978),anexampleofthelatterbeingtheaggregationofplateletsinblood(Milleretal1979).Theso
called'secondary'or'mutual'Bjerknesforceisexertedbetweentwopulsatingbubbles(Bjerknes1906,1909,Prandtl1954,Batchelor1967,Leighton1994a,
4.4.1).Thereisageneralrulethattwobubbleswhicharebothlessthan,orbothgreaterthan,resonancesizeattractbutthatifonebubbleisgreaterthan,andthe
otherlessthan,resonancesize,theyrepel.Howeverthisisasimplification,andtheresultsmaybemorecomplicatedifthebubblepopulationdensityishighorthe
incidentsoundfieldisstrong.
Radiationforcesthereforecancausemutualrepulsionorattractionbetweenbubbles.Thelattercancausethenetbubblesizetoincreasebycausingcoalescenceor
decrease,becausetheproximityofonebubblecaninduceshapeoscillationsinanother(figure11.2(i)).Ifsufficientlypronounced,suchoscillationscanleadtobubble
fragmentation(Leighton1995,Leightonetal1995a,1998).Asdiscussedwithrespecttofigure11.2,theequilibriumsizeofabubble(alongwiththeacoustic
pressureandfrequency)stronglyinfluencesthetypeofcavitationitwillundergo.Inertialcavitationcanbenucleatedbybubblesofanappropriatesize(section11.1.3).
Detailsofthenucleationwillbediscussedinsection11.3.3andsection11.3.4willreturntothethemeofhowradiationforces,nucleationandtheacousticfield,as
wellasgasdiffusion,determinethecavitationtypeandeffectswhichwilloccurwhenultrasoundispassedthroughaliquid.
Theradiationforcesassociatedwithbubbleswhichhavebeendescribedinthissectioncanbeconsideredasparticularextensionsofthemoregeneralradiationforces
actingatinterfaceswhichhavebeendiscussedinChapter3.

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11.3.3
Nucleation
Atthestartofsection11.1.3,afreefloatingbubbleisconsideredtobeanappropriatenucleusforinertialcavitation.Thetheoryoutlinedthereassumesnucleationof
inertialcavitationwithinthefirstacousticcycle,socalled'promptcavitation',fromafreefloatingsphericalbubblenucleus.Clearlyeffectsrelatingtolongerinsonation
periods,suchasgrowthbyrectifieddiffusion,arenotcovered.Inpracticeofcourseitisnotarequirementthatsuchnucleibepresentbeforethestartofinsonation.
Notonlymaybubbleswhichareinitiallytoolargetonucleateinertialcavitationenterthecriticalrange(through,forexample,dissolution,orfragmentationthrougha
shapeoscillationormicrobubbleshedding,asdiscussedabove).Bubblestoosmalltonucleatecavitationmayalsoenteritthroughrectifieddiffusionorcoalescence.
Radiationforcescanaffectbothsizeincreasesandsizereductions,byrelocatingbubblestoregionsofgreaterorlesseracousticpressureamplitude,ortothepresence
ofneighbours.Radiationforcesinfocusedfieldscanevenconvectsuitablenucleiintothefocustonucleateinertialcavitationthere(Madanshettyetal1991,
Madanshetty1995).
Themodelemployedtoproducefigure11.1isbaseduponthedynamicsofisolated,sphericalbubbles,whichdefactomustbefreefloating.Suchbodiesarenot
stablewithrespecttolossfromtheliquidasaresultofbuoyantforces,andindeedwilltendtodissolve.Whythereforeanysuitablenucleicanbefoundinasampleof
liquidwhichhasbeenleftstandingforhoursisaninterestingquestion(Leighton1994a,2.1).Hydrophobicimpurities,ifpresent,cancollectonabubblewallover
time,andhinderfurtherreductioninsize(Akulichev1966,Sirotyuk1970,Yount1979,1982,Yountetal1984).Otherpossiblenucleicanbefoundnaturallyasgas
pockets,stabilisedagainstdissolutionincrevicesandcracksinthecontainerwallorwithinfreefloatingparticleswithintheliquid(Harveyetal1944,Trevena1987,
AtchleyandProsperetti1989Leighton1994a).Theprocessbywhichthesebringaboutnucleationisillustratedinfigure11.2(l).Highamplitudeultrasonicwaves
causethegaspocketstoeitherexpandoutoftheircrevice,orconceivablyshedmicrobubblesthroughsurfacewaves,togeneratefreefloatingnucleiforcavitation.If
inertialcavitationisundesirable,thensuchparticlescanberemovedbyfiltering.Howevereventhiswillnotcompletelyremoveallsuitablenucleiforinertialcavitation,
whichmaybegenerated,forexample,bythepassageofcosmicraysthroughthesample(GreenspanandTschiegg1967).
11.3.4
PopulationEffects
Foragivenliquid(includingitsgasandsolidcontent),itwasshowninsection11.1.3that,tofirstorder,whetherabubbleundergoesinertialornoninertialcavitation
dependsonthreeparameters:theacousticfrequency,theacousticpressureamplitudeatthebubble,andtheequilibriumbubblesize.In

Page215

section11.2thisideawasextendedtoshowthat,ofthewiderangeoftypesofcavitationthatexist,theonesthatoccurinagivensituationwilldependontheabove
parametersplusothers(suchastheproximityofthebubbletoinhomogeneitiessuchasotherbubbles,particlesorwalls).Section11.3hasoutlinedhowsuchkey
parametersasbubblelocationandsizecanbealteredduringinsonation(byradiationforces,rectifieddiffusion,coalescenceandfragmentationetc).Itisusuallysimple
tocontroltheacousticfrequencytowhichasampleissubjected.Itis,understandably,oftenmuchmoredifficulttocontrolthebubblesizeandlocation.
Thetypeofcavitationalbehaviourabubbleundertakesdependsontherelationbetweenitssizeandtheothercriticalsizes(figure11.2).Theseinclude:theradius
whichisresonantwiththesoundfield(governing,forexample,radiationforceeffects,surfacewaveactivityandmicrobubblesheddingetc)theupperandlowerlimits
oftheradiusrangeforthenucleationofinertialcavitationandthethresholdforrectifieddiffusion.Howsuchchangesaffectthebubblesizedistributionwithrespectto
thecriticalsizesmentionedabovedeterminesthebubbleactivityseen.Theissuesinvolvedmaybecomplex,asthefollowingscenariossuggest.Dissolutionand
fragmentationprovidemechanismsbywhichbubblesizereductionsinthepopulationcanoccur.Coalescenceandrectifieddiffusionprovidethewaystoproduce
largerbubbles.Toproduceabubblewhichislargerthanresonance,itmusteitherpreexist(andcontinuetopersistduringinsonationdespitebuoyancyandpossible
fragmentation)formthroughcoalescenceorgrowtoasizelargerthanresonancebyrectifieddiffusion.Actingagainstthelatterscenarioisthefactthatitison
reachingresonancesizethatthebubbleismostlikelytolosegasthroughmicrobubbleemissionfromsurfacewaves(figure11.2(h)).Also,ifthebubbledoespass
throughresonanceintact,thenrectifieddiffusionbecomesfarlessefficientonceabubbleexceedsresonancesize,thepressurethresholdincreasingandthegrowthrate
decreasing.Thereisalsothegeneraltrendthatthelargerthebubble,themoreeasilyitisfragmented.Thereforeinmanyfields,itistheaggregationofthesmaller
bubblesatpressureantinodesorthefocuswhichismorecommonlyobserved(figure11.3).Bubbleaggregationssuchastheonementionedaboveareacoustically
active.Theymayshield,channel,orscattertheacousticfield.Thisleadstothesurprisingobservationthat,ofthethreeparametersmentionedatthestartofthis
section,theacousticpressureamplitudeatthebubblemayalsosometimesbedifficulttocontrol.
Thetypesofcavitation(andtheremaybemany)whichoccurwhenaliquidisinsonatedthereforedependonalargenumberofinteractingparameters,introduced
aboveandsummarisedinfigure11.4(Leighton1995).Itispossibletocontrolsuchinteractionstoproducesurprisingeffects,suchas'pulseenhancement'.Thisoccurs
whenthemagnitudeofaneffectproducedwhenultrasoundisusedinpulsedmodeexceedsthatobservedwhenthesameamountofultrasonicenergyisdeliveredin
continuouswave.

Page216

Figure11.3.
Twophotographsofaeratedwatercavitatinginacylindrically
focused10kHzcontinuouswavesoundfield,takenapproximately
3sapart.Theviewisalongthelineoftheaxialfocus,wherethe
acousticpressureamplitudeis0.24MPa.Exposuretime,1/30th
second.Streamersareclearlyvisible,comprisingbubblesmoving
rapidlytowardsthefocus,drivenbyradiationforces.Comparison
of(a)with(b)illustratesthat,althoughthegeneralform
isconstant,thedetailschange.

Thereareanumberofmechanismsbywhichthiscanbebroughtabout,involvingcomplexinteractionsoftheparametersdescribedabove.Detailed

Page217

Figure11.4.
Aschematicillustrationofhowthevariousfactorsinteracttodeterminethe
typesofcavitationwhichoccur,andhencetheeffectobserved.Thelatter
maybechemical,physicalorbiological.Itdependsbothonthetype
ofcavitation(e.g.inertial,noninertial,jetting,fragmentaryetc)andits
location.Boththesefactorsdependstronglyonthelocalsoundfield
atthebubble,andonthesizesofbubblepresentinthepopulation.
Thesetwotogether,forexample,characterisetheinertialcavitation
threshold,andalsowherebubbleswillmigrateandaccumulateunder
radiationforces.Suchaccumulationwillinturnaffectthelocalsoundfield,
throughtheprocessesofchannelling,scattering,andshieldingandwill
affectthebubblesizedistributionthroughitsinfluenceontheprocesses
ofcoalescence,fragmentation,andrectifieddiffusion.Insummarytherefore,
theobservedeffectdependsonthecharacteristicsofthecavitation,
whichisdeterminedbythelocalsoundfieldandthebubblesizedistribution.
Howeverthereisfeedbackfromthecavitationwhichinfluences
thesetwokeyparameters.

discussionofsuchmechanisms(Leighton1994a,5.3)isbeyondthescopeofthischapter.Inthefinalsection,theobservableswhichcanbeproducedbycavitation,
the'endresult'infigure11.4,willbediscussed.
11.4
TheImplicationsoftheOccurrenceofOneTypeofCavitationforCausingChangetotheMedium
Asshowninfigure11.4,cavitationcanproducephysical,chemicalandbiologicaleffects.Giventhecomplexityofinteractionsshowninthatfigureand,further,the
rangeofbehaviourasinglebubblecanundergoinanacousticfield(figure11.2),itisnotsurprisingthattheproductionofagiveneffectmaynotbeuniquelytheresult
ofoneformofbubbleactivity.Theexploitationofthechemicalandmechanicaleffectsresultingfromthe

Page218

acousticallyinducedcavitationofacloudofbubblesinmanycommonapplications(suchascellkilling,ultrasoniccleaning,cavitationerosionandsonochemistry)relies
inactionuponthethermal,sonochemical,gasandliquidshock,andjettingprocessesdescribedabove.Thefollowingdiscussionillustratestheabilityofthetypesof
cavitationtoproduceaneffectonthemediumthroughtheexampleof,primarily,erosion,withspecialemphasisondamagetobiologicalmaterial.Forfurtherdetails
seeLeighton(1994a,5).
Thatbubbleactivitymaycauseerosionhasbeenknownsincethestartofthecentury(Rayleigh1917).Themostdramaticerosiveeffectsareproducedbytheimpact
ofaliquidjetwhenabubbleinvolutesoncollapse(figure11.2(j))andbythereboundpressurepulsesemittedwhenabubbleundergoesaninertialcollapse(figure
11.2(e))(NoltingkandNeppiras1950,NeppirasandNoltingk1951,PlessetandProsperetti1977).Whilethepressurepulsefromanindividualbubbleisrapidly
attenuatedwithdistancesuchthatonlysurfaceswithinaboutonebubbleradiusfromthecentreofcollapsemaybedamagedbythereboundpressureemissionofa
singlebubble,cloudsofbubblesmaycollapsecooperatively,enhancingthedamage(VyasandPreece1976).Itislikelythatcavitationerosionresultingfromjetting
andinertialcollapsesplaysapartinlithotripsy(Colemanetal1992,1993).
Ifnoninertialpulsationsareofsufficientamplitude,bubblesmaycausedamagebyanumberofmechanisms.Forexample,celldisruptionmaybebroughtabout
becausethebubblescantravelrapidlythroughtheliquidundertheinfluenceofacousticradiationforces,generatinghydrodynamicstresseswhichhavebeenshownto
producehaemolysis(MillerandWilliams1989).Iftheacousticfieldamplitudeexceedsacertainthreshold,whichislowerthecloserthebubblesaretoresonance
(PhelpsandLeighton1996),surfacewavesarestimulated(figure11.2(g)).Associatedwiththesearethemicrostreamingcurrentsdiscussedinsections11.2and
11.3.1,whichcancauseanerosiveeffect(forexample,withdentalultrasonicsAhmadetal1987).Noninertialcavitationmayindirectlyinfluenceerosionthrough
affectingthedamagewhichresultsfrominertialcavitation.Thismightoccurthroughshieldingofthesoundfield,orthroughtheproductionofnuclei,throughsurface
waveactivity(figure11.2(h))orrectifieddiffusion(section11.3.1).
Theabilityofnoninertialcavitationtodirectlybringaboutphysicaldamageisusuallyofgreatestimportanceintheabsenceofinertialcavitation(whichwould
otherwisedominatetheerosion,maskingthecontributionfromstablebubbles).Bioeffectfromnoninertialcavitationisthereforemorereadilyidentifiablewhenlow
intensityfieldsareappliedtosensitivechemicalorbiologicalsystems.Demonstrationsincludemicrostreaminginducedcelldeathassociatedwithgasbodyactivation
(Miller1985,Vivinoetal1985)andtheuseofphotometrytodetectATPreleasefrominvitrohuman

Page219

erythrocytes(WilliamsandMiller1980),atechniquewhichhasprobablyproducedeffectsatthelowestcontinuouswaveintensityrecordedforadetectablebio
effect,4mWcm2(Williams1983).Themechanismwasprobablyruptureorachangeinpermeabilityofthecellmembranebroughtaboutthroughmicrostreaming
stressesatthecellwall.
11.5
Conclusion
Therearemanytypesofbubbleactivitywhichcanoccurinanacousticfield.Thedetailsofhowanisolatedbubblewouldbehavewilldependonkeyparameters,
includingtheacousticfrequencytherelationshipbetweenthebubblesizeandthethresholdsforinertialcavitation,rectifieddiffusion,surfacewaveactivityandthe
acousticpressureamplitudeatthebubble.Howeverinmostpracticalsituationsthebubbleisnotisolated,andinhomogeneitiesinthefluidandsoundfieldmaybe
important.Thatsaiditisoftentheeffectsofcavitation,ratherthanthetypeofbubbleactivityperse,whichareimportant,andthesewilldependontheinteractions
betweenthebubblepopulation,thesoundfield,andthemedium.
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Page225

Chapter12
EchoEnhancing(UltrasoundContrast)Agents
DavidOCosgrove
Introduction
Unlikeallotherimagingtechnologies,ultrasoundhaslackedagentsthatcanbeadministeredtopatientstoimproveorenhancethediagnosticinformationavailable.The
naturalcontrastduetodifferencesinbackscatter(seeChapter4)isinsufficientinmanycircumstancestodifferentiateonetissuefromitsneighbour.Withtherecent
introductionofsafeandeffectiveagentsthatenhancetheultrasonicinformation,thishasnowchanged[13].Mostimportantbyfararemicrobubblesbutsomeother
attemptstoimproveimagingbyothermeansareofinterest.Commonlycalled'contrastagents',theimpliedanalogywithXrayandMRagentsmaybeunhelpful
becauseinmanysituationstheultrasoundagentsactuallyreducethetargettobackgroundcontrast(e.g.whenanintravenousmicrobubbleagentisusedinalarge
vascularspacesuchastheheartormajorbloodvessels)whilethepurposeofadministeringnonvascularagentsisoftentoimprovevisualisationofdeeperlying
structures(e.g.gastricagentstoaidimagingtheretroperitoneum)ratherthantooutlinethegutitself.Theneutralterm'echoenhancingagents'ispreferredhere.
12.1
NonBubbleApproaches
Thesimpleapproachestoimprovingimagequalityintheabdomenandpelvisbyfillingthegutandthebladderwithfluid,whichactedbydisplacingbowelgas,has
beenimproveduponwiththedevelopmentofachoppedcelluloseandsimethiconemix(SonoRx,ImaRxInc.,Tucson,Arizona)fororaluse

Page226

inamountsofupto500ml.Itisclaimednotonlytodisplacegasbutalsotoactasanadsorber.Reportsofitseffectiveness,includingcomparisonswithdegassed
water,haveshownittobeclinicallyusefulfortheupperretroperitoneum[4].
Instillationofsimplefluidsintobodyspacescanalsobeuseful.Anexampleissalinesonohysterographywhereanechofreefluidoutlinestheuterinecavityand
providesexcellentimagesofpolypsanddevelopmentalanomalies.Thesimilartechniqueofsonosalpingographyrequiresinstillationofanechogenicfluidandtwo
microbubbleagentshavebeenusedtogoodeffect(Echovist(ScheringAG,Berlin)[5]andAlbunex(Malinkrodt,StLouis,Missouri)).Themicrobubblestendto
obscureuterinedetailandsothesequentialcombination(salinefirstfortheuterus,microbubblesafterwardsforthetubes)providesthemostcompleteinformation.
Sonosalpingography,thoughnotprovidingasdetailedanatomicalinformationasaconventionalXraysalpingogram,issufficientforestablishingtubalpatencyand
thuscanbeusedasascreeningtesttoavoidunnecessaryionisingradiation.
Isotonicfluidinstilledintothecolonfollowingcolonoscopyimprovesdelineationofthebowelwallwithexquisitedetail.Theentirecoloncanbevisualisedinmost
patientsand,justasinotherpartsofthegut,theuseofhighresolutionprobesallowsthefivelayeredstructurewithinthe56mmwallthicknesstobediscerned.
Polypsformechogenicprojectionsintothelumen,thestructureofthewallatthepointofattachmentbeingpreserved.Carcinomasmayhavethesameappearancebut
invasionintothewallandsurroundingtissuesdestroysthelayers,replacingthemwithamassgeneratingechoofloweramplitude.Theadvantageovercolonoscopyof
revealingsubmucosalchangesisclear.Accuraciesof83to100%inthedetectionandstagingofcoloniccarcinomahavebeenreported[69]andthetechniqueseems
tobeusefulinchildrenwithbleedingfromfamilialpolyposis[10].ChangesinthewallallowCrohn'sdiseasetobedistinguishedfromulcerativecolitis,inwhich
thickeningrarelyextendsdeeperthantheinner(mucosal)layer[11].However,inpseudopolyposistheultrasonicdistinctionbecomesdifficultorimpossible.Inmost
casesofCrohn'scolitisthereiseffacementofsomeorallofthelayersofthewalltogetherwiththickeningofupto10mm:caseswherethelayersarenormalhaveonly
superficialulcersatcolposcopy.
Hydrostaticreductionofanintestinalintussusceptioncanbemonitoredbyultrasound[12].
12.2
MicrobubbleAgents
12.2.1
History
Thebehaviourofgasfilledbubblesinanacousticfieldhasbeenstudiedformanyyears,andisreviewedfullyinChapter11.Neverthelessitwasachanceobservation
byacardiologist,DrCharlesJoiner,aslongagoasthelate1960s

Page227

thatledtothedevelopmentofeffectivemicrobubbleechoenhancingagents:hewasperformingatransthoracicMmodeechocardiogramwhileinjectionsof
indocyaninegreenwerebeinggiventhroughaleftventricularcathetertomeasurecardiacoutputusingtheFickdyedilutionprinciple[13].Joinernoticedtransient
increasesinechostrengthintheoutflowtractoftheheartfollowingeachinjection.Muchfurtherresearchshowedthatthesesignalswerenotspecifictotheparticular
fluidinjectedandtheproposalthattheechoeswereduetomicrobubbleswassupportedbyinvitroobservationsthatanincreaseinambientpressureobliteratedthe
enhancement[14,15].Injectionofhandmadebubblesformedbysquirtingphysiologicalsalinebetweentwosyringesviaathreewaytapinhascontinuedtobe
widelyusedinechocardiography.
Thougheffectiveenhancers,thetransienceandpoorreproducibilityofthesebubbleslimitstheirclinicaluseandsowaystoimprovethemwerestudied.Itturnedout
thatmixingsomeofthepatient'sownbloodwiththesalineimprovedthestabilityofthebubbles.Feinsteinpursuedthislineandfoundthatserumalbuminwasthe
criticalbloodcomponentandthatsonicationproducedmorereliablemicrobubblesofcontrolledsize[16].EventuallythisapproachledtotheproductionofAlbunex,
thefirstpharmaceuticalechoenhancer(MolecularBiosystemsInc.,SanDiego,California)[17].
Subsequentlymanypharmaceuticalhousessetupdevelopmentprojectsusingavarietyoftechniquestoformstablemicrobubblesoftherightsizerange.Ofthese,
Levovist(ScheringAG,Berlin)isthemostwidelystudiedandisnowcommerciallyavailableinmanypartsoftheworld,includingEurope[18].Itisamodificationof
Echovistandbotharemadeofgalactose,structuredasmicrocrystalsthatactasnucleationsitesforairintheampoule.Whenmixedforinjection,asolution
suspensionisformedwithmicrobubblesofairattachedtominuteirregularitiesonthesurfaceofthosemicrocrystalsthatremaininthesolidstate.Oninjection,the
remainingcrystalsdissolve,releasingthemicrobubblesintotheblood.Echovistwasoflimitedvaluefortheheartbecausethemicrobubblesdissolvedbeforeitcrossed
thelungbed,though,asmentioned,ithasfoundanimportantapplicationinsalpingography(HyCoSy,hysterocontrastsalpingography)[5].Inanimportant
development,thesurvivalofthemicrobubbleswasimprovedbyaddingasurfactant(palmiticacid)intraceamountsand,inthisform,abolusofLevovistlastsfor1to
4minintheblood(thiscanbeprolongedadlibiftheagentisinfusedratherthangivenasabolus[19]).Itprovidessome1020dBincreaseinechosignalsthatcan
bedetectedongreyscaleimaginginlargevesselsandintheheartbutrequiresthehighersensitivityofDopplerforitsdetectioninsmallervessels,especiallyinthe
microvascularcirculation[20].
EchoGen(developedbySonus,Bothel,Washington,licensedtoAbbott,Chicago,Illinois)isanotherexampleofanagentwherethemicrobubbles

Page228

areformedinvivo,butthemechanismofformationofitsmicrobubblesisentirelydifferent[21].Essentiallyitconsistsofaperfluorocompound(perfluoropentane)
whichisliquidatroomtemperaturebutisagasatbodytemperature.Itispreparedasanaqueousemulsionwithsurfactantsand,oninjection,thedropletschangeto
thegasphase,expandingtoformmicrobubblesinthe28mrange.Inpractice,thephasetransitionisgreatlyimprovedifthecolloidalsuspensionisactivatedby
subjectingittoavacuumbeforeinjection.Thisisachievedbywithdrawingtheplungeroftheclosedoffsyringeandthenquicklyreleasingthetension:this'hypobaric
activation'methodispopularlyreferredtoas'popping'.
Albunex,ontheotherhand,istypicalofthepreformedmicrobubbleor,moreprecisely,microcapsuletype,wheretheentirestructureispresentintheampoule,and
onlyneedssuspensionofthebubblesbeforeinjection.Mostnewermicrobubblesfallintothiscategorybutboththecapsulematerialandthegastheycontainvary
widely.Somealsousebiologicalmaterials,suchasthephospholipidsofSonovue(BR1,Bracco,Milan)[22]andAerosomes(DuPontJerk,NBillerica,
Massachusetts)[23],whileothersusebiodegradablesyntheticcapsules,anexamplebeingSonovist(ScheringAG,Berlin)[24].Inthisinterestingagenttheshellis
cyanoacrylate('tissueglue'),amaterialthatissostablethattheinjectedmicrocapsulesaretreatedasforeignparticlesanddisposedofbyphagocytosisintothe
macrophagesysteminthebody.Theyaretakenupbytheliver'sKupffercellswheretheypersistformanyhoursbeforeeventuallybeingdegraded.Thisproperty
underliestheuseofSonovisttodelineatenormallivertissue(see'sonoscintillation'below).
Whileairisthegasusedintheearlyagentsandalsoinsomeofthenewerones,thereareadvantagesinusinginertgasesofhighmolecularweight,chieflybecausethey
diffusemoreslowlyandsoconferalongerlifeintheblood.ApartfromtheiruseinEchoGen,perfluorogasesareusedinFS069[25](MBI),aderivativeofAlbunex
[16],aswellasinAerosomesandinImagent(AlliancePharmaceuticals,SanDiego,California)[26].SulphurhexafluorideisusedinSonovue(Bracco,Milan)this
inertgaswasformerlyusedtomeasuregastransferinthelungs[22]andsoisknowntobewelltolerated.Thechoiceofgasalsoaffectstheechogenicityoftheagent
incomplexwayswhicharenotyetwellunderstood.Whenthepartialpressureofthemicrobubble'sgasislowerthanthatofblood(effectivelywhenanygasotherthan
airisused)bloodnitrogenmaydiffuseintothebubbles.Thisaddstotherectifieddiffusionthatcancausethemtoenlargeatsomephasesoftheirlifeandsotheir
survivalbehaviourmaybequitecomplex.
Thusthedevelopmentofclinicallyusefulechoenhancingagentshasbeenalongtrailofexplorationduringwhichmanyingeniousmethodshavebeendevisedtomake
them.Theirphysicalstructureisatleastasimportantastheirchemicalconstituentsandthefieldisperhapsbestregardedasanexampleofengineeringnanotechnology
ratherthanasconventionalpharmacology.

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12.2.2
SafetyofContrastAgents
Animportantclinicalfeatureofmicrobubblesistheirexcellentsafetyprofile:nosignificantadverseeventsattributabletotheagentshavebeenreportedovermany
thousandinjectionsinseveralthousandpatientsandvolunteers.However,theirsafetyhastobeconsideredmorewidelythanthatofotherdiagnosticagentsbecause
theinteractionoftheinsonatingsoundbeamwiththebubblesisanadditionaltopicofpossibleconcernoverandabovetheusualissuesofthesafetyoftheconstituents
andofthemicrocapsulesthemselves.
Theconstituentshaveallbeenchosenfortheirknownsafety,biologicalandbiocompatiblematerialsbeingselectedforthecapsuleandforthesurfactants,together
withairorinertgasesforthecontents.Minorresidualconcernsregardingallergicresponses[27]andthedifficultyofsterilisingthemseemtobewithoutfoundation.
Turningtotheeffectsofinjectingparticles,themostobviousworryisthepossibilityofembolismbuttherearetheoreticalandpracticalreasonsforthistobeaminor
concern.Sincethemicrobubblesaredesignedtobesmallenoughtocrosscapillarybeds,theyshouldnotemboliseunlesstheyenlargeoraggregateintoafoam.Both
arepossiblebutunlikelytobeimportantconsiderations,especiallyinviewofthesmallamountsofgasinvolved.InLevovisteachclinicaldosecontainslessthan200l
ofair,muchlessthanisofteninjectedinadvertently,forexample,whenanintravenousinfusionissetup.Incomparisonwithembolifromothersources,e.g.platelet
embolifromanunstableatheromatousplaque,theshortlifeofmicrobubblesintheblood(some5minutes)actsasaprotectingfactorwhilemuchlargerparticles
deliberatelydesignedtoemboliseareusedinperfusionlungscanswithnountowardeffects.Extensiveanimalandhumantestslookingforbiochemicalproductsof
centralnervoussystemdamage,aswellasneurologicaltesting,havebeenconsistentlynegative[28].
Similarconsiderationsapplytootherpossibleeffectsofinjectingparticleswhiletriggeringthereleaseofvasoactiveandbronchoconstrictorcompoundsinthelungis
aknownproblemwithsomeagentsinsomespecies(especiallyinthepig),theseeffectsdonotseemtooccurinman.
Thepossibilityofcavitation(seeChapter11)producedbytheinteractionofthesoundbeamwithmicrobubbleshasbeengivenprominencebythedescriptionof
haemorrhagicdamagefollowinglithotripsysonificationinvivo,buttheseeffectsrequiremuchhigherpowerdepositionthanisachievedwithdiagnosticscanners.They
seemtohaveverysharplowerpowercutofflevelsandhavenotbeendemonstratedinsituationssimilartothosethatobtaininvivowithdiagnosticscanneroutput
levels[29].Nobiochemicalmarkersoffreeradicalproduction(e.g.peroxides)havebeenfoundinexperimentsdesignedtotestthispoint.
Thusfar,therefore,theseagentsseemtobeverysafe,muchmoreso,infact,thantheiodinatedagentsthatcontinuetobeusedforXrays.

Page230

Nevertheless,prudentuseandpreandpostmarketingsurveillanceforadverseeventsshouldbecontinued[30].
12.2.3
BasicPrinciples
Theessentialmechanismswherebymicrobubblesactasechoenhancersarethesameaspertaintoscatterersingeneral:theechointensityisproportionaltothechange
inacousticalimpedanceasthesoundbeamcrossesfromthebloodtothegasinthebubbles.Theimpedancemismatchatsuchaninterfaceisveryhighsothat
essentiallyalloftheincidentsoundisscattered(thoughnotallwilltravelbacktothetransducer).However,thoughthereflectionisnearcomplete,byitselfthiswould
notproduceaveryeffectiveenhancingagentbecausethemicrobubblesaresmallandsparsereflectivityisproportionaltothesixthpoweroftheparticlediameterand
directlytotheirconcentration[31].ThescatteringofsoundisdiscussedinChapter4.
Theextraordinaryechogenicityofmicrobubblesresultsfromthefactthattheyresonatewheninsonated(seeChapter11)andthismakesthembehaveasthoughthey
haveaverymuchlargercrosssectionthanarigidbubbleofthesamediameterbyafactorof1014[32](figure12.1).Designingmicrobubblestoexploitthisresonance
iscentraltopharmaceuticalresearchinthefield.Obviouslytheymustbemadesmallenoughtocrossthecapillarybeds( 8m)and,likeanymechanicalresonance
system,thecriticalfrequencydependsontheirdiameter.Thefortunatecoincidencethatmicrobubblesof17mdiameterhappentohavetheirresonancefrequencies
inthe215MHzrangeofultrasoundthatisusedforclinicaldiagnosisisthefortuitousbasisfortheentiresubject.
AnimportantdifferencefromtheionicagentsusedforXrayandMRIneedstobeborneinmind:sincemicrobubblesdonotdiffuseacrossthecapillaryendothelium,
thereisnointerstitialphaseofenhancement.Thustheyareessentiallymarkersforthebloodpool(orforanyotherbodyspaceintowhichtheyhavebeenplaced)and
theirdistributionissimilartoredcells.
12.2.4
ClinicalApplications.
Theenhancementofultrasoundechoamplitudegivenbymicrobubblescanbeexploitedinanumberofdifferentways,ofwhichthemostobviouslyusefulistoenable
studiesthatwereotherwisetechnicallydifficultorunreasonablyprotracted(table12.1)[33].This'rescue'roleofmicrobubblesiscurrentlythemostimportantclinical
advantagetheyprovideandisusedwidely,bothinBmodeandforDoppler.However,theeffectalsomakespossiblesomenewtypesofapplicationthatcannotbe
performedwithoutmicrobubbles,especiallydemonstratingflowinthemicrocirculation,e.g.inthemyocardiumandintumours,andprovidingtheuniqueopportunityto

Page231

Figure12.1.
Diagramofmicrobubbleresonancewith
transmittedpower.Simplereflectionoccurs
atlowinsonatingintensitiesbut,asthe
transmittedpowerisincreased,microbubbles
begintoresonate,atfirstinalinearmodeand
thennonlinearly.Harmonicandtransient
phenomenasuchasstimulatedemission
(sonoscintillation)resultathigherpowers.
Alltheseeffectsoccurwithin
thepermittedoutputlevels.

performfunctionalstudiesbytrackingthetransitofamicrobubblebolusthrougharegionofinterest.Inthefuturemanyotherapplicationsareexpectedtoemergewith
thedevelopmentofnewtypesofmicrobubbleagentandpromisingnewwaystousethem(seebelow).
Agentsthatarecurrentlylicensedgivesufficientenhancementonagreyscaletobeusefulintheheartandgreatvessels.Theyfill('opacify')thecardiacchambersand
thusimprovedelineationoftheleftventricularendocardialborder.Thisimprovesdetectionofwallmotionabnormalities(especiallyimportantduringstress
echocardiography)andmakesitpossibletoperformthesemeasurementsin'difficulttoimagepatients'(plate3)[34].Theyarealsousefulindemonstratingshuntsand
valvulardiseaseandhavebeenusedinuterotodemonstratetwintwintransfusion[35].
However,inthelowerconcentrationsobtainedinthemyocardium,special

Page232
Table12.1.Usesofmicrobubbles.
Use

Comments

1.Dopplerrescue

Ofpoorqualitystudybecauseofattenuationorweaksignals
(e.g.portalveinincirrhosis)Ofimpracticallyprotractedstudy
(e.g.renalarteriesforstenosis)

2.ExtendtheapplicationsofDoppler

Microvasculature(e.g.intumours)

3.Functionalstudies

TransittimingfordynamicinformationFunctionaldiagnostic
indicesFunctionalimages

4.Newfields

Targetedagents:diagnostic

drugdelivery

techniquessuchasintermittentimaginganduseoftheharmonicmodeareneededtorevealtheirpresence.DopplerismoresensitivethanBmode,butthetissue
motionofthemyocardiumswampstheDopplersignalsunlesstheyaresuppressedbyimagingintheharmonicmode.
Thisbulktissuemotionislesssevereoutsidetheheart,andthemicrobubbleenhancementisverywelldemonstratedonconventionalDoppler.Mostlytheyareused
for'Dopplerrescue',e.g.enablingtranscranialDopplertobeperformedreliably,differentiatingbetweenatightinternalcarotidarterystenosiswithtrickleflowanda
totalocclusion,andenablingotherwisedifficultportalveinandrenalarterystudies(plate4).Fortherenalarteries,reducingtheexaminationtimeisasimportant
clinicallyasthereductioninfailedstudies[36].Similarconsiderationsunderlietheiruseinperipheralarterialdiseaseandtheymayalsobeusefulfordemonstrating
deepveinthrombosis[37].
Sincetheeffectofthemicrobubblesistoincreasethesignalintensitywithoutalteringbloodflow,theintensityorloudnessofthespectralsignalsistheaspectthat
changes.ForcolourDoppler,theequivalentistheincreaseinintensityinpowerDoppler,andgenerallythisisthebestmodetochoose.Indeeditmaybeaskedwhy
anythingisdisplayedinvelocitycolourDoppler:theveryobviousincreasesinboththenumberofcolourpixelsandthefrequencyshiftsthatareobservedarelikelyto
beeffectsofthesensitivityfiltersweaksignalsthatwerenotDopplerdetectedriseabovethisthresholdafterenhancementandarenowregistered.Thisphenomenon
alsoexplainsthefindingofanincreasedspectralbroadeningafterenhancement:bothhighermaximumandlowerminimumvelocitiesareregistered,correspondingwith
flowstreamsthatwerenotdetectedbeforeenhancement.Thismaynecessitateareevaluationofcriteriafordiseasedetection,especiallywherepeakvelocityvalues
areused,forexample,toestimatethedegreeofastenosis.Presumablyratiosof,forexample,the

Plate3.
Leftventricularenhancement.Thenormally
echofreeheartchambers(top)areenhanced
(opacified)followingintravenousinjectionofa
microbubbleagent.Inthispatient,Albunexhas
improveddelineationoftheleftventricularendocardial
borderinalongaxisview(bottom).(ImagescourtesyofDr
PetrosNihoyannopoulos,HammersmithHospital,London.)

Plate4.
EnhancementofDopplersignalsfromtheportalvein.
Inthispatientwithcirrhosis,noDopplersignalscouldbe
obtainedfromtheportalvein(top)becauseofthehighly
attenuatingoverlyingliver.Afterenhancementwiththe
microbubbleagentLevovist,usefulsignalswereobtained
(arrowed,bottom),andtheredcolourcodingindicatedthat
theflowwasintheoppositedirectiontonormal,animportant
signofportalhypertension.

Plate5.
Ischaemictestis.Nocoloursignalscouldbeobtained
fromthetestisitselfeitherbefore(top)orafter(bottom)
enhancementwithLevovistinthismanwhopresented
withacutetesticularpain,thoughtherewereabundant
signalsfromthesurroundingtissuelayers.Thissuggestedthe
diagnosisoftesticulartorsionthatwasconfirmedat
subsequentsurgery.

Plate6.
Carcinomaofthebreast.Asmallamountofvascularisation
isdemonstratedinthispowerDopplerscan(top)butmuchmore
oftheneovascularisationisseenafterenhancement
withtheperfluoroagentEchoGen(bottom).

Page233

peakvelocityintheinternaltothecommoncarotidartery,willnotsufferfromthiseffect.
Inthemicrocirculation,Bmodewillbethepreferredformofultrasoundusewhensuitablyreflectiveagentsbecomeavailablebecauseofitsbetterresolution(both
spatialandtemporal)but,atpresent,Dopplerisessentialtodetecttheweaksignals.Flowinvesselsdowntoperhaps100mindiametercanbedemonstratedunder
idealsituations,thelimitbeingsetbytheoverwhelmingclutterfrombulkmovementofthesurroundingtissues,aswiththemyocardium.Thisallowsatleastarterioles
andvenulestobepickedupandshowsregionsofinfarctionorischaemiaascolourvoids(plate5).
Theimproveddisplayoftheneovascularisationoftumoursisanimportantclinicalarea:enhancedcolourDopplerimprovesdisplayofthetortuousandtangledpattern
andcanhelpdifferentiatebenignfrommalignantlesions,forexampleinthebreastandliver(plate6).Sincemalignantneovascularisationisapredictoroftumour
aggressivity,itsdirectandnoninvasivedisplaybyenhancedDopplermightbeuseful,forexample,inplanningadjuvantchemotherapy.Similarly,changesduring
treatmentmayformusefulindicesofresponseorthedevelopmentofchemoresistanceandhavebeenusedtodeterminewhethersufficientinterstitialtreatmentby
alcoholisationorRFheatinghasbeengiven[38].Withthedevelopmentofspecificblockerstoangiogenesisfactors,thisapplicationisexpectedtobecome
increasinglyimportant[39].
Tissuebloodflowisalsolikelytobeusefulininflammatoryconditionssuchasforassessingtheseverityofarthritisanditsresponsetotreatmentandsimilarlyin
inflammatoryboweldisease.Evaluationofregionsofreducedflowisalsointeresting:demonstratingmyocardialischaemiahasbeenmentionedasoneofthemost
importantgoalsofmicrobubbleresearchandsimilarconsiderationsapplytothespleenandthekidneys,especiallyrenaltransplants.Ahithertounexploredareathat
couldbecomeveryimportantistheplacenta.Placentaldysfunctionisamajorcauseoffetalgrowthretardationandofpreeclampsiaatpresentthediagnosisisclinical
andthereforelate.Ifearlychangesintheperfusionofthematernalvasculatureoftheplacentacouldbedemonstratedbystructuralchangesinthevasculatureorby
transittimeabnormalities,managementmightbecomemoreeffective.Sincemicrobubblesareunlikelytocrossintothefetus,safetyisnotaspecialconcern.
12.2.5
QuantificationandFunctionalStudies
ThefactthatmicrobubblescanbeinjectedasabolusopensupawholenewfieldforultrasoundbyquantifyingtheDopplersignalstrengthtogeneratetimereflectivity
curves.Videodensitometryhasbeenusedwidelyforgreyscalequantificationandhasprovedtobeausefultoolforthepharmaceuticalindustryandinclinical
echocardiography.Systemsformeasuringthesignal

Page234

intensityhavebeendevelopedforallformsofDoppler[40]and,despitethenonlinearityofDopplersignalprocessing,havebeenshowntocorrelateverycloselywith
relativemicrobubbleconcentrationbothinvitro[41,42]andinvivo[43].ThusthebasisformeasuringchangesinBmodeandDopplerreflectivityhasbeen
established.Quantificationsystemsarebeginningtobeincorporatedintocommercialscanners.
Fromthesemeasurements,transittimecurvesofthewashinandwashoutofthemicrobubblescanbegenerated,andimportantfunctionalindicescanbecalculated
fromthem,inthesamewayaswithMRIandCTcontrastagents.Becausemicrobubblesactasbloodpoolmarkers,theyarecomplementarytotheseagentswhich
diffuseintotheextracellularspace.Bothsimplemeasurementssuchasthetransittime,thepeakvalue,theareaunderthecurveandthefractionalvascularvolume,and
complexfeaturessuchasthoserequiringdeconvolution,canbeperformedandpromisetoyieldusefuldiagnosticcriteria.Forexample,thetransitseemstobelonger
andperhapsmorecomplexinmalignanttumoursthaninbenignmasses.Thereiseverylikelihoodthatphysiologicalindicessuchasthemeantransittimeandtruetissue
perfusioncanbecalculated.
Theseindicescouldbepresentedasdataforaregionorpointofinterestorcouldbedisplayedasfunctionalimages[44].Initiallyonlytwodimensionalcalculations
andrepresentationsarelikelytobeachievedbutthepossibilityofextendingthistothreespatialdimensionsisrealisticinviewofthefastframeratethatultrasound
allows.Sincethefasterwashinphaseofthetransitneedsonlybesampledapproximatelyoncepersecond,sweepingtheprobecontinuouslythroughavolumewould
seemfeasible.Thuseventuallyfourdimensionalanatomicofunctionaldatasetscouldbegenerated.
12.2.6
NewUses:AgentsandTechniques
Aseriesofnewagentsisbeingdeveloped,thegoalbeingtoimprovethemicrobubbles'echogenicityandpersistence.TheincreaseinechogenicityallowsBmodeto
beusedinthemicrovasculature,adesirablefeatureinviewofthesimplerequipmentrequired,thebetterspatialandtemporalresolutionandthelowerlevelof
artefacts.Thelongerdurationofenhancementwillsimplifysomeclinicalapplicationswherecurrentlyrepeatinjectionsareneeded.
Somemicrobubbleshaveinterestingnewpropertiessuchassonoscintillation(seebelow).Envisaged,butonlybeginningtobedeveloped,aretargetedagentssuchas
Aerosomestowhichligandsforactivatedplateletshavebeenattached:thispreparationstickstofreshthrombusandisexpectedtobeusefultohighlightitspresence
[45].Drugdelivery,wherebyanactivepharmaceuticalisattachedtoamicrobubbleandthenreleasedlocallybydisruptingthebubblesusingahighpowerultrasound
beam,couldeventuallybecomethemostimportantuseofmicrobubbles.Themicrobubblescan

Page235

berupturedultrasonicallyatthechosensitetoreleasethedruginahighconcentrationwhiletheremainderofthebodyreceivesonlyasmallamountofdilutedrugso
thatthetherapeuticratioisimproved.Localiseddeliveryofgeneticmaterialhasbeendemonstratedusingthisapproach[46]andattachmentofthrombolyticdrugsto
theplatelettargetedAerosomescouldprovidesaferthrombolysis.
Thedevelopmentofnewwaystoinsonatemicrobubblesinordertoimprovetheirreflectivityordurationincludetriggeredorintermittentinsonationtoreducebubble
destruction.ThisapproachhasprovedespeciallyusefulformyocardialimaginginBmode[47].Allowinganintervalbetweensequentialpulsesnotonlyminimises
bubbledestructionbutalsoallowsrefreshmentofthebubblesinthescannedplanebecauseofinflowoffreshbloodandthisimprovestheechointensity,sometimesto
asurprisingextent[48].Therateofthisinflowofmicrobubblesmayitselfcontainfunctionalinformationregardingtissueperfusionbecausethebubblesarecarriedby
themicrocirculation.Thegeometryofthisflow,however,islikelytobecomplexsincetheultrasonictomogramonlysamplesasliceoftissueanddoesnotcontain
completeinformationontheflowdirection.Nevertheless,averagetissueflowvaluescouldformausefulmeasureofthemicroperfusion.
Thebubbledestructionthatintermittentimagingseekstominimisecanitselfbeexploitedinadifferentway:ifahighintensitybeam,deployedtodestroyallthebubbles
atonelocationinavessel,isabruptlyswitchedtoalowintensitybeamforimaging,asharpflushofundamagedbubblesflowsintothevessel,thesocalled'negative
bolus'effect[49].Thisistheequivalentofadirectarterialinjectionoftheagent,asituationthatisidealfortransittimemeasurements.
Secondharmonicimagingisanintriguingandpromisingfieldwhichdependsonthenonlinearoscillationofmicrobubblesduringwhichtheyemitovertones(harmonics)
attwicetheinsonatingfrequency[50].Sincetissuehasonlyminornonlinearbehaviour,itemitslowerlevelsofsecondharmonicsignals.Thisapart,theharmonic
signalsareamicrobubblesignaturesothatintheharmonicmode,echoesfromtissue,bothstationaryandmoving,aresuppressed,thusincreasingthesignalto
noise/clutterratio.Theeffect(butnottheprocess)isanalogoustodigitalsubtractionXrayangiography.Intheharmonicmode,myocardialmicrobubblescanbe
detectedonBmodedespitethestrongechoesfromcardiacmuscle[51]and,inDoppler,harmonicsignalsfrombloodflowandthemovementsofsolidtissueare
suppressed.Thisallowssmallervesselswithevenslowerflowtobedetectedand,inanexperimentalsetup,vesselsdownto40mindiameterhavebeen
demonstratedinthekidneys[52].
Evenintheharmonicmode,stationarybubblesintheperipheryarehardtodetect,butanothernonlinearbubblemodeisabletoachievethis.Variouslyknownas
'sonoscintigraphy','stimulatedacousticemission(SAE)'and'lossofcorrelation(LOC)imaging',theseuniquemicrobubblesignalsseemto

Page236

resultfromabubblewithinacohortbeinginactivatedbytheinsonatingbeam.SincethecolourDopplerprocessoroperatesbycomparingsequentialechotrains,
inactivationofabubbleproducesadifferencebetweenpairsofsignalsthatthescannercircuitryinterpretsasaDopplershift.Thealternativeexplanation,thatthe
scintillationrepresentsthedirectDopplervisualisationofthecollapseofamicrobubble,seemslesslikely.Sonoscintillationisrecognisedasashimmering,multicoloured
mosaic,betterseeninvelocitycolourDopplerthaninpowerDoppler.Productionoftheeffectiscriticallydependentonthetransmittedultrasonicpowerandsofalls
offwithdepthandismorestronglyelicitedbylowultrasonicfrequencies.
SonovistisanexcellentsonoscintillatorandinthelivertheeffectpersistsformanyhoursbecausetheserobustmicrobubblesarephagocytosedbytheKupffercells
[24].Inanimalstudies,itrevealstumoursasstrikingcolourvoids.ThesameeffectcanbeproducedwithLevovistand,thoughitismuchmoretransient,issufficientto
highlightfocallesionsthataredifficulttodetectongreyscaleimaging[53].
Ageneralaspectoftheeffectsofmicrobubblesisthefactthattheimprovedsignaltonoiseratiothattheyproducecouldbeexploitedinanumberofwaysbeyond
merelyviewingormeasuringtheboosttotheechoes.Forexample,itshouldbepossibletoutilizesomeofthe20dBextrainformationtoimprovespatialresolutionor
framerateortoreducemotionartefacts.Novelwaystousethepresenceofthemicrobubblesincludeestimatesofthefrequencydependenceofattenuationintheliver
(basedonthedepthtowhichthescintillationeffectcanbeachievedforagiventransmitpower)andexploitationofindividualscintillationeventstocorrectfor
aberrationsintheultrasonicfield.
12.3
Conclusion
Thedevelopmentandintroductionofmicrobubblesassafeandeffectiveechoenhancershasextendedandopenedupnewopportunitiesforclinicalapplicationsand
forfundamentalresearch.Theyheraldaneweraforultrasound.
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Page241

Chapter13
SonochemistryandDrugDelivery
GarethJPrice
Introduction
Alongwithanimalnavigationandsonarmethods,themedicalusesareprobablythemostwidelyrecognisedapplicationsofultrasound.However,thereisgrowing
interestintheuseofhighpowerultrasoundtocausechemicalandphysicalchangesinsystems[13].Inadditiontothemorefamiliarmedicalapplicationsoflithotripsy
(Chapter10)andfocusedsurgery(Chapter9),andcleaningtanks,newindustrialtechniquesarebeingdevelopedwhichrangefromtheweldingofplasticstothe
synthesisofcomplexpharmaceuticalintermediatesandfromthecrushingofmetalorestotheextractionofplantflavourings.Thischapterwillreviewbrieflysomeof
theseapplicationswiththeemphasisonaphysicalexplanationofwhytheeffectshappen.Inordertonarrowthefieldtomanageableproportions,inthemain,
applicationswillbetakenfromwaterbased(aqueous)chemistry.Formorecompletediscussionofaspectsofsonochemistry,thereaderisreferredtoreferences[1]
to[3].Thechapterwillconcludebyreviewingsomerecentworkindrugdeliverywhichbridgesthestudyofchemistryandthemedicalapplicationswhicharethemain
focusofthisbook.
Chemistryisaboutmakingthingsandunderstandingwhyreactionsandprocessesactinthewaytheydo.The'buzzword'inchemistryatpresentiscontrol.Weneed
tocontrolthestructureofthemoleculeswemakesothatwecontrol,forexampletheirpharmaceuticalactionwemustcontrolthewaythatthemoleculesorganise
themselvessothatwecontrolthebulkpropertiesofourmaterialsweneedtocontroltheprogressofareactionintermsofrate,yieldandproductdistributionsothat
safetyandeconomicfactorsarekeptundercontrol.Finally,weneedtocontrolenergyusageandwasteproductstogiveenvironmentally'clean'chemistry.Ultrasound
hasallowedchemiststoexertthesetypesofcontroloverawiderangeofreactions.

Page242

Applicationsofsound,andparticularlyultrasound,inchemistryhavebecomeknownassonochemistry.Mostchemistsdivideultrasound(somewhatarbitrarily)into
twocategories.Thetypeusedinmedicaldiagnostics,sonarornondestructivetestingapplicationsnormallyuseshighfrequenciesinexcessof1MHzsoastoobtain
goodresolution.Relativelylowpowers(<1W)areusedinordernottochangethematerial.Thisiscommonlyreferredtoasdiagnosticultrasound.Whilethiscanbe
usedinchemistry,forinstanceinfollowingthecourseofreactionsorinstudyingconformationalchangesincompounds,diagnosticultrasoundhaslimitedapplicationin
influencingchemicalprocessesorreactions.Forsonochemistry,powerultrasoundisused,usuallyinthefrequencyrange20500kHz,andatpowersofuptoseveral
hundredwatts.Suchhighpowersleadtotheformationofmicrobubblesinaliquidanditisthegrowthandrapidcollapseofthesebubbles,orcavitation,which
providesthesourceofenergyforchemicalreactionsasoutlinedinthefollowingsection.
Twotypesofapparatusarecommonlyusedforperformingsonochemistryalthoughvariationsoftheseexist.Theseareillustratedinfigure13.1.Thesimplestandmost
commonisacleaningbathofthetypenormallyencounteredinlaboratories.Areactionvesselissimplyimmersedintothebathandtheultrasoundconductedintothe
reactionthroughthewallsofthevessel.Itseconomyandreadyavailabilityhaveledtoitswidespreaduseforsyntheticchemistryalthoughithasthedrawbacksofpoor
reproducibilityandtemperaturecontrol.Themajordisadvantageisthatoflimitedsoundintensitysincemuchoftheultrasonicenergyisdissipatedinthereactionvessel.
Ingeneral,betterresultsareobtainedusingahornorprobesystem.Thesecoupletheultrasoundfromthetransducerintothereactionusingametallicrodwhichalso,
dependingonitsshape,amplifiesthevibration.Veryhighintensitiesareavailablebutcaremustbetakentoensureadequatetemperaturecontrolasconsiderable
amountsofheatcanbegenerated.Also,thehornmustbeinerttothereactionbeingirradiated.Glasswarecanbecustomisedtoaccommodatethehorn,thatshownin
figure13.1havingathermostatjacketandportsforadmittinginertgasesandremovingsamplesduringthereaction.
OthercommerciallyavailablesystemsarelesscommonlyusedandhavebeenreviewedbyMason[4].Inadditiontolaboratoryapparatus,equipmentforoperatingat
muchlarger,commerciallyrealistic,scalesisbeingdeveloped[57]ofteninflowsystemswhichcanprocessvolumesupto1502001min1dependingonthe
requiredintensity.Unitscapableofdelivering10kWofacousticpowerareavailableandcanbeplacedinseriestoachievethedesiredeffects.Hence,theequipment
existstoexploitsonochemicaleffectsonatleastpilotplantandpossiblylowvolumeproductionscale.

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Figure13.1.
Experimentalapparatusforperforminglaboratorysonochemistry.
Left:ultrasoniccleaningbath.Right:'horn'typeapparatus.

Thegenerationoftheultrasoundreliesonthetransducer.Oftentheseareconstructedfrompiezoelectricelementsofthesametypeusedformedicalapplications
althoughformanyindustrialenvironmentsthegreaterrobustnessofmagnetostrictivemetalssuchasnickelorironcobaltalloyhasbeenusedtoadvantage.
13.1
CavitationanditsEffects
Inordertoappreciatethepotentialadvantagesofusingultrasound,weneedtounderstandtheoriginofsonochemicaleffects.Itmightbethoughtthatthesound
vibrationswouldcoupleintomolecularbondsandsoenhancetheirreactivity.However,thevibrationfrequenciesofchemicalbondsareinthegigahertzregionandso
atleast23ordersofmagnitudehigherthanultrasoundfrequencies.Itisnowacceptedthatvirtuallyallsonochemicaleffectsarisefromcavitation.
Amorecompletedescriptionofcavitationappearselsewhereinthisbook(Chapter11)andcanalsobefoundintheliterature[8].Inorder

Page244

Figure13.2.
Schematicrepresentationofbubbleeffectsduringcavitation.

tounderstandsonochemicalevents,asimplifiedmodelcanbeused.Mostchemistsessentiallyunderstandcavitationtobethenucleation,growthandimplosive
collapseofmicroscopicbubblescausedbypassageofasoundwavethroughaliquid.Thereremainsconsiderabledoubtanddiscussionastothepreciseeffectsof
cavitation.Ontheassumptionthatthebubblecollapseoccursadiabatically,NoltingkandNeppiras[9]showedthattemperaturesashighas5000Kandpressuresin
therangeof3040MPacanbegeneratedandthereisnowexperimentalevidencetosupportthissocalled'hotspot'theory[10,11].Otherexplanationsintermsof
theformationandrapiddischargeofelectricfields[12]orplasmadischarges[13]havebeensuggestedtoexplainsomephenomena.Whatiscertainthoughisthat
speciesexistinhighenergy,dissociated,vibrationallyexcitedformsinsidecollapsingcavitationbubbles.
Three'zones'inthereactionsystemcanthusbeidentifiedassuggestedbyfigure13.2.Theprimarysonochemicalactivitysuchastheproductionofradicalsand
reactiveintermediatestakesplaceasaresultoftheharshconditionsinsidethebubble.Secondly,thebulkliquidhasnoactivityapartfromreactionwithsonochemically
generatedspecieswhichdiffuseoutofthebubble.Finally,theinterfacialregionaroundthebubbleshasverylargetemperature,pressureandelectricfieldgradientsand
alsoverylargesheargradientscausedbyrapidmovementofsolventmolecules.Thislastfactorhasaspecialimportanceinsituationswheremacromoleculesare
presentinsolution.Thereisanextraeffectinheterogeneoussystemswherecavitationcanoccurintheregionofaninterface.Inimmiscibleliquidmixtures,theinterface
isdisruptedandefficientmixinganddispersionoccurs.Bubblecollapsenearasolidsurfaceisasymmetricandcanresultinjetsofliquidimpingingonthesurfaceat
highspeed.Additionally,masstransportofreactantstoandfromthesurfacecanbeenhanced,speedinguptherateofchemicalreactions.Alloftheseeffectshave
beenusedtoadvantageby

Page245

chemistsandsomeexamplesoftheutilityofeachwillbegiven.
Thethemeofthischapteriscontroloverchemicalreactions.Sincevirtuallyallthechemicaleffectscanbetracedbacktocavitation,itisimportanttounderstandwhich
factorsaffectthethresholdandintensityofcavitationinaliquid.Thesefactorshavebeendescribedindetail[8,14]butitisworthwhilesummarisingthoseofmost
importancetoaccountforthebehaviourdescribedinthefollowingsections.
Perhapstheleaststudiedfactoristheultrasoundfrequency.Itwasthoughtthattheamountofcavitationproducedforthesameintensitywouldfallasthefrequency
rose.However,therearesomerecentstudies[15,16]whichshowthatthereisanoptimumvaluebetween100kHzand1MHzwhichdependsonthesystemunder
investigation.Themostimportantultrasoundparameteristheintensitywhichdefinestheamountofenergyenteringthereactionorprocess.Asmightintuitivelybe
expected,theamountofcavitationalactivityriseswithincreasingintensitybutthereisanoptimumvalueabovewhichactivityfalls[17,18].
Sincealiquidisnecessaryforthetransmissionofsound,solventpropertiessuchasdensityandviscositywhichaffectthemobilityofthemoleculesareimportant,
particularlyindefiningthecavitationthreshold.However,ofmoreinfluenceonchemicalactivityisthesolventvolatility.Volatilesolventswillevaporateintothebubble
asitgrowsand'cushion'itscollapse.Thistypeofeffectalsoexplainsthetemperaturedependenceofsonochemicalreactions.Atlowertemperatures,lessvapour
entersthebubblessothatcollapseismoreintenseandchemicaleffectsareenhanced.Thus,anaccelerationatlowertemperaturesisoftenobservedincontrasttothe
normal'Arrhenius'behaviourwhereincreaseinratesisseenathighertemperatures.
Manychemicalsystemsareheterogeneousandmaycontaintwoliquidphasesorsolidparticlessuspendedintheliquidandthischangesboththesoundtransmission
andthecavitationthresholds.Thus,althoughcompletecharacterisationofasonochemicalsystemiscomplicatedbythelargenumberofparametersthatcanaffect
cavitation[19],theroleofmostofthemisatleastqualitativelyunderstoodandtheirmanipulationoffersthepossibilityofcontrollingareactionwithconsiderable
precision.
13.2
WhatcanUltrasounddoforChemists?
Wewillbeginwithadiscussionoftheusefulnessinchemistryofwhatmightbetermedthe'physical'effectsarisingfromcavitation.Thefirstoftheseistherapidmotion
ofliquidscausedbystreamingandparticularlytherapidmotionsaroundcavitationbubbles.Particlesofsolidssuspendedintheliquidarethereforesetintomotionand
undergointerparticlecollisions.Theshockwavescausedbycavitationcanalsoimpingeontheparticles,bothfactorsleadingtomodificationoftheaverageparticle
size.Inmetallic

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powders,particlescaneitherbefusedtogetherorfragmenteddependingonthephysicalpropertiessuchashardnessandmeltingpoint[20,21].Withinorganicsolids,
twoprocessescanbeidentified.Firstly,large(>10m)particlescanbefragmented.Alternatively,looselyboundaggregatesofsmall(<0.51m)particlescanbe
brokenuptogiveabetterdispersionoftheoriginalmaterial.Althoughthemechanismsmaybedifferent,thisprocesshasamedicalanalogueinthelithotripsyofsolid
depositsinvivo.Aparticularcommercialapplicationisintheproductionofsuspensionsoftitaniumdioxide,TiO2,whichisusedasafillerandwhitepigmentinmany
paints.Thequalityoftheproductdependsonthequalityofthedispersion.StofferandFahim[22]studiedsometypicalpaintformulationscontainingTiO2andfound
thatusingultrasoundforthedispersalandmixingphasesoftheprocessledtosmaller,moreevenparticlesizesinshortertimesthanconventionalmethods,with
consequentsavinginenergyconsumptionofupto70%.
Theefficientmixinganddispersionofliquidsusingultrasoundisacommoncommercialprocess,forexampleinthefoodindustry.Thelargedegreeofmotioninduced
byacousticstreamingefficientlydisruptstheinterfacebetweentheliquidswhiletheveryhighshearforcesaroundcavitationbubblesacttobreakupdropletsofliquid
andmaintainasmallandevendistributionofdropletsizes.Agoodexampleofthisistheproductionoforganicpolymersasemulsionsdispersedinwater,usedto
makepaintsandothersurfacecoatings.
Inadditiontowaterandtheorganiccomponents,stabilisersanddispersantsareusuallyaddedtoformastabledispersionaswellasinitiatorsbeingneededtobegin
thereaction.Ultrasoundwasfirstappliedtothistypeofreactioninthe1950sbutrecentwork[2325]hasshownthatultrasoundallowsloweramounts(andinsome
casesnone)oftheseadditivestobeused,improvingthepolymerproperties,andthatthereactionproceedsatafasterratereducingtheprocesstime.Thistypeof
technologyhasalsobeenappliedonalarger,pilotplantscale,forexample,toprepareTiO2encapsulatedinPVCwherethecoatingwasmuchmoreuniformwhen
carriedoutinthepresenceofultrasound.Scaleupstudieswereperformedandtheprocesscarriedoutonapilotplanttoproduce200kgofcoatedmaterial[26].
Thereareanumberofchemicalreactionswherepowerfuloxidisingagentsareneededinorganicsystems.However,theseareoftenverytoxic,dangerousand
environmentallyunfriendly.Theuseofaqueousagentswouldbebeneficialbutmanydonotmixwithorganicsolvents.Therapidmixingofthereactantsgivesan
obviousroleforultrasoundhere.Forexample,theoxidationoffattyacidestersisanimportantreactionandithasbeenshowntoproceedsmoothlyusingaqueous
solutionsofpotassiumpermanganate[27].OthersignificantphasetransferreactionshavebeenreviewedbyLuche[28].
Alargenumberofchemicalreactionsarecarriedoutusingsolidreagentsorcatalysts.Theratesofreactionherearelimitedbytherateatwhich

Page247
Table13.1.Thesonochemicalenhancementofreactionsusingmetalliclithiumasareagent(datatakenfrom[29]and
[30]).
Reactant

Solid

Product

Conventional
(%)

Sonochemical
(%)

C4H9Br

Lithium

C8H18

Noreactiona

55b

C6H5Cl

Lithium

(C6H5)2

<5a

70b

C6H5Br

Lithium

(C6H5)2

<5a

72b

Bromotoluene

LiAlH4

Toluene

98

98d

Iodotoluene

LiAlH4

Toluene

92c

95d

Bromonaphthalene

LiAlH4

Naphthalene

70c

99d

Iodonaphthalene

LiAlH4

Naphthalene

72c

99d

1224h,110C

1h,25C

624h,100C

56h,25C

reactantscometothesurfaceandproductsaredesorbedandalsobytheavailabilityofa'clean'surface.Activepartsofthesurfacecanbecomeblocked,preventing
thereaction.Aneverydayexampleisthatofaluminiumandmagnesiumwhicharehighlyreactivemetalsbuttheycanbecommonlyusedsincetheyrapidlyform
stronglyadheringoxidelayers.Ametalwithsimilarpropertiesmuchusedinorganicsynthesisislithiumandthiswasinvolvedinsomeoftheearliestreportedorganic
sonochemistrydatingfromtheearly1970s.Table13.1showssomeresultsfromHanandBoudjouk[29,30]whichclearlydemonstratethatreactionswhichdonot
takeplaceunder'silent'conditionsgiverespectableyieldswhenperformedunderultrasoundfromacleaningbath.Theseexamplesarenotverysignificantin
themselvesbutrepresentclassesofreactionwhicharecommonlyusedwhenbuildingupthestructuresofcomplexmolecules.Theresultscanbeexplainedbythe
continualcleaningactionremovingtheoxidelayersandexposingfreshmetalwhichcanreactfurther.Also,thereductioninparticlesizereferredtoearliergivesa
highersurfaceareaandhencemorereactionsites.Manyotherexamplesoftheseeffectshavebeenpublished[3134].Theeffectsarenotconfinedtometallic
surfacesandmodificationstothesurfacesofinorganicmaterialsandpolymershavebeenenhancedusingsonochemicalmethods.
Thefinalexampleofaphysicaleffectisrathermoresubtle.Whenmacromolecules(moleculesconsistingoflongchainswithbackbonescontaininguptoseveral
thousandatoms)arepresentinsolutionnearacavitationbubble,theyarecaughtinthemovementandsubjectedtostrongshearfields.Providedthatthe
macromoleculeissufficientlylong,itisstretchedoutandcanbreakunderthestrain.Thisis,infact,oneoftheearliestreportedeffectsofpowerultrasoundinchemistry
havingbeennotedinthe1920s.Itwasfirstattributedtothixotropiceffectsbutitwasthenrealised

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Figure13.3.
Ultrasonicdegradationoftoluenesolutions
ofpolystyreneswithdifferingchainlengths.
(Thelinesrefertodifferingstartingmolecular
weights.)

thatthepolymerchainswerebeingbrokenandhenceshortened.Thisledtoalargeamountofworkoverthesucceedingdecadestocharacterisetheprocessinterms
oftherateofbondcleavageforawiderangeofpolymersandtheeffectofthesolutionandultrasoundparameters.Furtherwork[35,36]hasbeencarriedoutmore
recentlywiththeadventofbetterapparatusforsonicatingchemicalreactionsand,inparticular,bettermethodsofpolymeranalysis.
Thebasiceffects[37]ofirradiatingapolymersolutionwithpowerultrasoundareshowninfigure13.3usingpolystyreneintolueneasanexample.Thedegradation
proceedsmorerapidlyathighermolecularweightsandapproachesalimitingvaluebelowwhichnofurtherdegradationtakesplace,inthiscase~30000.Polymers
withthis,orlowervalues,areunaffectedbyultrasoundundertheseconditions.Theseeffectsappeartobeuniversalinthattheyhavebeenseenforawiderangeof
organicandinorganicpolymersinorganicsolvents[35,36]andforaqueoussystemssuchaspolyethyleneoxide[38],cellulose[39],polypeptides,proteins[40]and
DNA[41].
Moststudieshaveshownthatthedegradationisrelativelyinsensitivetothenatureofthepolymer.However,thereisawiderangeofbehaviourdependingonthe
physicalpropertiesofthesolventandoftheultrasound.Insummary,thedegradationproceedsfasterandtolowermolecularweightsatlowertemperatures,inmore
dilutesolutionsandinsolventswithlowvolatilityaswouldbeexpectedfromthediscussionoftheeffectoftheseparametersoncavitation,above.Otherfactorswhich
havebeenquantifiedaretheultrasoundintensityandthenatureofdissolvedgases.Thereisnoevidencethattheextremeconditionsoftemperaturefoundincavitation

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Figure13.4.
Schematicdiagramofultrasonicpolymer
degradation.

bubblescontributetothedegradation.Anumberofworkershaveshownthatcleavageoccurspreferentiallynearthemiddleofthechain[42,43]andhavefoundthat
thebestfittoexperimentaldatawasgivenwhenthepointofbreakagewasdistributedinaGaussianmannerwithin~15%ofthecentreofthechain.Furthermore,it
hasbeenclearlyshownthatneitherarandommodelnoramodelwherebreakageoccurredexclusivelyatthechaincentrefittedtheexperimentalresultsaswellasthat
derivedfromtheGaussiandistribution.
Underconditionswhichsuppresscavitation,nodegradationhasbeenfound.Themechanismcanbrieflybebestdescribedasthepolymerchainbeingcaughtinthe
rapidflowofsolventmoleculescausedbythecollapseofcavitationbubblesandintheshockwavesgeneratedaftertheimplosionofthebubbles.Thechainsarethus
subjectedtoextremelylargeshearforcesresultinginthestretchingofthechainandeventualbreakageofabondinthechainasschematicallyshowninfigure13.4
(notethatthisisnotdrawntoscaleapolymerchainwillbe<1minlengthandsofullyextendedcomparedwiththe50200mofthebubble).Someworkershave
alsointerpretedtheeffectintermsoffrictionalforcesbetweenthesolventmoleculesandpolymerchains.The'centrecleavage'modelisalsoconsistentwiththe
stretchingandbreakagemechanismoutlinedabovesincethemaximumstresswillbegeneratedinthemiddleofthechain.Degradationofpolymersolutionsinshear
fieldsformedbyextensionalflowinnarrowcapillaries[44,45],inotherflowsystems[46]aswellasinhighshearstirrersalsoresultsinpreferentialbreakageatthe
chaincentres.
Clearly,macromoleculardegradationwouldbeunwelcomeinvivo.However,thephysicalpropertiesofsyntheticpolymersdependmarkedlyontheaveragechain
length.Theultrasonicdegradationisnowunderstoodwithsufficientdetailtomakeitcommerciallyapplicableinanumberofareasasamethodforcontrollingthechain
length.Thechainbreakageleaves

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averyreactiveradicalchainendandthiscanbeusedtoinitiatefurtherchemistry.Bysuitablemanipulationoftheexperimentalconditions,wecanexertagreatdealof
controlovertheprocess,exploitationofwhichallowsthemodificationofexistingpolymersintonewmaterials.
Alloftheaboveexamplesinvolveheterogeneoussystemswherethereismorethanonephasepresent.Whenultrasoundisappliedtoasingleliquidorsolution,
sonochemicaleffectsrelyonthegenerationofreactiveintermediates.Theextremeconditionsatthecentreofcavitationbubblesaresufficienttodecomposeall
moleculeswhicharevolatileenoughtoenterthebubbleinappreciableamountsandtoformhighlyreactiveintermediatesincludingfreeradicals:veryreactivespecies
withunpairedelectrons.Thetimescaleofcavitationalcollapseissuchthatasignificantproportionofthesecanescapefromthebubbleandreactwithother
intermediatesinthebubbleorwithcompoundsinsolution.
Inanearlyexample,Suslickandcoworkers[47]exposedlongchainalkanestohighintensityultrasoundfromahornandshowedthatshorterchaincompoundswere
formedinsignificantyields.Thedistributionofproductssuggestedthatthereactionwassimilartothoseoccurringinhightemperaturepyrolysisor'cracking'processes
suchasthoseusedtotreatoil.Other,syntheticallymoreusefulexampleswerestudiedbyHengleinandFischer[48]whousedthefragmentsformedwhenchloroform
isexposedtoultrasoundacarbenetointroducechlorinatedgroupsintomolecules.
AnoveluseofthecavitationaleffectswasdevelopedbySuslicketal[49]topreparemetalparticlesinunusualforms.Volatile,metalcontainingcompoundsenterthe
bubblesanddecomposetoformmetalatomsinthevapour.Thelifetimeofcavitationalcollapseissuchthatthetemperatureconditionsexperiencedbytheseatoms
changesfromseveralthousandkelvintoroomtemperatureinlessthanamicrosecondgivinghugeratesofcooling.Thismeansthatasthemetalatomscondense,they
havenotimetocrystalliseintoregularstructuresandsoformrandomaggregatesofatoms.Withmetalssuchasiron,theseaggregateshaveverydifferentmagnetic
propertiesfromironparticlesproducedbyconventionalmeans.Thesurfacechemistryisalsodifferentsothatthenewmetalshavedifferentcatalyticactions.
Oneofthemajoruses(althoughitistheauthor'sresearchareaandsotheremaybeanelementofbias!)offreeradicalsinorganicsystemsistoinitiatepolymerisation
reactionstogive,forexample,polystyreneandPMMA.Thesearenormallymadebyheatingthemonomerstoaround120Cwhereradicalsareformedby
decompositionorbyaddingacompoundtheinitiatorwhichbreaksdowntoformradicalsatlowertemperatures(~7080C).Bytrappingtheradicalsand
measuringtheirconcentration,wehaveshownthat,byusingultrasoundat25C,wecanproduceradicalsatthesamerateasusingaconventionalinitiatorathigh
temperature[50].Carryingoutthereactionatlowertemperatureshassomeadvantagesincontrollingthepolymerstructure.

Page251

Waterisparticularlysusceptibletocavitation.Aqueoussonochemistryisdominatedbyasinglereaction:thedecompositiontohydrogenandhydroxylradicals
H2O

H+OH

Thehydrogenradicalsarethoughttorapidlycombinetoformhydrogengasandarelostfromthesolution.However,theOHremainandformhydrogenperoxide,
H2O2,apowerfuloxidisingagentwhichcanbeusedtoperformmuchusefulchemistry.ThereisconsiderableevidenceforthepresenceofOHfrom
sonoluminescence[51],fromelectronspinresonancespectroscopies[52]andfromhydrogendeuteriumisotopeexchangeexperiments[53].
Incommonwiththeorganicsystemsdescribedabove,thehydroxylradicalscanbeusedtoinitiatepolymerisationtowatersolublepolymers[54].However,someof
themostinterestingaqueouschemistryhasinvolvedtheuseofOHandH2O2asoxidisingagentstodestroycontaminantsinwater.Inadditiontotheoxidation,volatile
componentscanvaporizeintothebubbleandareliterallypyrolysedtorelativelyharmlesscomponents.Thishasbeenanactiveareaofresearchoverthepastfew
yearsandhasnowreachedthepointwhereithasbeenconsideredasaviablemethodofcommercialwastetreatment.Petrierandcoworkers[55]haveshownthata
widerangeofpotentialcontaminantscanbedestroyedsimplybyapplicationofhighintensityultrasound.Forexample,thepesticideatrazineaswellasawiderangeof
otherorganiccompoundshavebeenconvertedtotallytowater,carbondioxideandnitratesinashortperiodoftreatment.Inourwork[56],wehavestudiedaromatic
compoundswhichcanbeconsideredasmodelsforpolycyclicaromatics(PAHs)andpolychlorinatedbiphenyls(PCBs).Hoffmannetal[57]havemodelled
sonochemicaldegradationofanumberofcontaminantsanddemonstratedthattheenergyconsumptionismoreefficientthanhighintensityultravioletlighttreatment.
Clearly,theproductionoflargeconcentrationsofOHinmedicalapplicationsofultrasoundwouldnotbedesirable.However,ithasbeendetectedinseveralsystems.
ThetechniquesfordetectingOHmentionedaboveareratherspecialisedsothatinourworkwehaveusedamorestraightforwardtechnique.Hydroxylradicalsreact
rapidlywithterephthalateionsinsolutiontoformahighlyfluorescentspecieswhichcaneasilybemonitoredasshowninfigure13.5.Wehaveusedthismethodto
extensivelycharacteriseOHproductioninsonochemicalsystemsbuthavealsoadaptedittoinvitrostudiesofmedicalsystems[58].Theapparatusinfigure13.6
wasdesignedtoallowthebeamfromanultrasoundsourceaTherasonic1032physiotherapyunitwhichwasoperatedatfrequenciesof1.1and3.3MHztopass
throughanacousticallytransparentchambercontainingterephthalate.
SimilartechniqueswereusedbyMillerandThomas[59]whofounditnecessarytoperiodicallyrotatethechambertoachieveconsistentresultsandHollandetal[60]
whowereable,usingthismethod,todemonstratecavitationactivityina2.5MHzdiagnosticpulsedbeam.Weadoptedthe

Page252

Figure13.5.
Reactionbetweenhydroxylradicalsandterephthalate
ionsinsolutiontoformahighlyfluorescentspecies.

Figure13.6.
Apparatusformonitoringhydroxylproduction
frommedicalultrasoundsources.

technique[58]of'seeding'thesolutionbyaddingasmallquantityofsolidparticlestoactascavitationnuclei.SignificantamountsofOHweredetectedwiththe
thresholdforOHproductionbeing0.50.15Wcm2at1.1MHz.Itwasnoticeablethatlowerconcentrations(bytwoordersofmagnitude)wereproducedatthe
higherfrequency.
Thishasbeenaveryrapidsurveyofalimitedrangeofchemicalapplicationsofultrasound.Itisimpossibletodojusticetoarapidlyrisingfieldofworkinsuchashort
reviewand,amongactiveresearchtopicswhichhavenotbeendescribedaredetailedorganicsynthesis,electrochemistry,colloidscienceandareasoffoodscience.
Theremainderofthispaperisdevotedtoadiscussionofpotentialbenefitstotherapeuticusesofultrasound.
13.3
BioeffectsandDrugDelivery
Adiscussionofthevariousinvivoeffectscausedbyultrasoundwouldbeoutofplacehere.Itissufficienttonotethatalloftheeffectsofcavitation

Page253

describedabovecouldpotentiallybeseeninvivoifultrasoundisappliedattherelevantcombinationoffrequencyandintensity.Possiblebioeffectshavebeen
reviewedbyBarnettetal[61]andbyMillerandcoworkers[62].Clearlyinmanyifnotmostmedicalsituations(withtheexceptionoflithotripsy)majorcavitational
eventswillhaveundesirableconsequences.However,theremainderofthischapterisgivenovertoapotentiallymoreprofitableapplicationofcavitationalultrasound
intherapy.
Therehasbeenconsiderableinterestoverrecentyearsinthetargeteddeliveryofpharmaceuticalagents[63].Theaimistoensurethatadrugispresentatappreciable
concentrationsonlyatthesiteofitsactionratherthanthroughoutthebody.Deliveryisthereforeviasometypeofimplanteddeviceandtheaimistodevelopamethod
ofcontrolledrelease.Inmostcases,thereisathresholdconcentrationbelowwhichthedrugisineffectivebutalsoamaximumconcentrationatwhichitbecomestoxic.
Ofparticularinterestforthisformoftherapyareapplicationsrequiringlongtermadministrationsuchascontraceptionorinsulintreatmentofdiabetes.
Oneformofdeliverysystemistoimplantapolymerimpregnatedwiththeactiveagentwhichisreleasedbydiffusionintosurroundingtissueorbodyfluids[64].
However,whilethisgivessteadyconcentrationsofdrugoverlongperiods,thedoseratecannotbechangedafterimplantation.Oneapproachtoovercomethis
deficiencywasadoptedbyKostetal[65,66]whousedultrasoundtopromotethereleaseofmodelcompoundsfromabiodegradablepolyanhydridematrix.The
ultrasound(1MHz,1.7Wcm2)actedbothbysurfaceerosionofthepolymerandalsobyacceleratingthenaturalhydrolysisreaction.Thisapproachhasalsobeen
adoptedmorerecentlybyAgrawalandcoworkers[67],whousedshortexposures(2minday1for30days)of1MHz,1.5Wcm2ultrasoundtopromotethe
releaseofproteinsfromamatrixofpolylacticandpolyglycollicacids,bothbiodegradableinthemselves.Inaninterestingtwisttothistechnique,Kostetal[68]used
ultrasoundtorapidlyremovealloftheagent,inthiscaseacontraceptive,fromimplantedmicrospheresoverseveraldaysratherthantheprojectedlifetimeofseveral
weeks.Thisenabledthetherapytobeterminatedwithouttheneedforsurgicalintervention.
Themajormethodtowhichultrasoundhasbeenappliedhasbeentransdermaldelivery.Thishastheadvantagethatapplicationcanbemadelocaltothedesiredsiteof
actionsothatlargeconcentrationsoftheactiveagentarenotpresentelsewhereinthebody.Also,theharshconditionsofthestomachandintestinesareavoidedso
thatcompoundswhichcannotbeadministeredorallycanbeused.
Theouterlayerofhumanskinthestratumcorneumisatough,relativelyimpenetrablebarriersothatpermeationofcompoundsintothebloodstreamistooslowto
providetherapeuticconcentrations.Therateofpermeationcanbeincreased[69]bytheuseofchemicalenhancerssuchaswater,ethanol,Nmethylpyrollidone
(NMP),polyethyleneglycolsor

Page254

dimethylsulphoxide(DMSO).Theseactbyhydratingorswellingthecellandlipidstructureoftheskintoincreasetherateofpermeation.However,thisapproachis
limitedbythepotentialtoxicityoflargeamountsofsomeofthesecompounds.
Externalmodificationofpermeabilityhasbeenachievedbytheapplicationofelectricfieldsfromelectrodesplacedontheskin(iontophoresis)butthewidespreaduse
ofultrasoundformedicaldiagnosisandtherapyledtoitsdevelopmentasatechniqueforregulatingtransdermalpermeation(sonophoresisorphonophoresis).
Thetechniquewasfirstreportedsome30yearsagobyGriffinetal[70,71].Alargenumberofstudiesofthisareahasbeenundertakensincebutthereremains
considerabledoubtovertheinterpretationoftheresults.Manyofthesepapershavesimplyreportedtheeffectwithnomechanisticinformationorinterpretation
provided.Thisreviewwillsummarisethefindingsofsomestudieswheresuchinterpretationwasattempted.Papersintheformercategoryarereferencedinthose
givenhere.
Therehasbeenaconsiderableresurgenceofinterestoverthepastfiveyearsorsoandinoneoftheearliestofthesestudies,HofmannandMoll[72]includedbenzyl
nicotinateinthecouplinggelusedontheskinandshowedthatthecompoundwasbothreleasedfromthegelatafasterrateandalsopermeatedthroughskinfaster
thanintheabsenceoftheultrasound.Theythereforesuggestedthatenhancedtransporttothesurfaceoftheskinwastheprimarymechanism.
Thereareanumberofpotentialeffectsofultrasoundwhichcouldberesponsiblefortheobservedresults.Forexample,diffusionandpermeationareacceleratedbyan
increaseintemperaturewhichcouldbegeneratedbythepassageofsound.Secondly,streamingeffectsandtheacousticpressurecouldenhancetransportthroughthe
gel,eliminatingboundaryandinterfacialeffectsandliterallyforcingthedrugthroughtheskin.Finally,cavitationeffectssuchasthosenotedabovecoulddisruptthe
structureofthestratumcorneumtoformchannelsthoughwhichthepermeantscouldrapidlymove.
Machetandcoworkers[73]foundthatthepermeationrateofdigoxinthroughmouseorhumanskinwasacceleratedslightlybytheuseof1.1or3.3MHzultrasound
at1Wcm2butmorethandoubledwhentheintensitywasincreasedto3Wcm2.Significantly,theymeasuredthetemperatureonthereceivingsideofthediffusion
cellandfoundanincreaseofover25Cfor10minsonicationatthehigherintensityandalsoreportedovertdamagetothemicrostructureoftheepidermis.
Yamashitaetal[74]madeaninvitrostudyofthepermeationofprednisolonefromagelspreadontohairlessmouseskin.Theuseofultrasound(1MHz)significantly
enhancedthepermeationandtheenhancementwasinproportiontothetimeoverwhichitwasapplied.However,theyalsoshowedthatanythermaleffectsonthe
skinwereinsufficienttoaccountfortheenhancement.

Page255
Table13.2.Combinedeffectofchemicalenhancersand1MHzultrasoundonthetransdermalpermeationofcorticostrone
(datatakenfromtables14.1and14.3of[76]).
Relativefluxenhancement
Compound

Noultrasound

Ultrasound

Control(phosphatebufferedsalineatpH
7.4)

Polyethyleneglycol200

1.9

3.5

Isopropylnyristate

4.5

Glyceroltrioleate

0.8

16
1.1

50%ethanol

40

Linoleicacidin50%ethanol

903

75
>13000

Uedaetal[75]studiedtheeffectofultrasound(150kHz,0.11Wcm2)inconjunctionwithaseriesofcommonchemicalenhancersontherateofpermeationof
aminopyrineandreportedasynergisticeffectasdidJohnsonandcoworkers[76].Intheirwork,illustratedintable13.2,arangeofchemicalenhancerswhich
operatebyavarietyofmechanismscouldbecombinedwiththerapeuticultrasound(1MHz,1.4Wcm2)togiveenhancedperfusionsinexcessofthoseachieved
usingonlyoneoftheapproaches.
Simonin[77]reviewedtheliteraturewhichhadbeenpublishedpriorto1995andcriticallyreevaluatedthedata.Insomecases,theeffectofultrasoundwasnot
positiveanddependedcriticallyonthenatureofthedrug,thegelusedandtheexactconditions.Heestimatedthat,inanumberofliteraturestudies,theeffectof
heatingwouldchangethepermeationbynomorethanaround20%andanadditionalincreaseof10%mightbeexpectedfromstreamingandradiationpressure
phenomena.Healsosuggestedthat,giventherelativesizesofcavitationbubbles,thewavelengthofthesound(~1.5mmat1MHz)andthethicknessofthestratum
corneum,cavitationwasunlikelytocauseappreciabledisruptiontoitsstructure.Speculationwasthereforemadethat,althoughthesweatductsmayplayanimportant
role,themajorfactorininfluencingthepermeationwasthedisruptionofthelipidlayersandintracellularspaces.
TheseconclusionsaresomewhatatoddswiththoseofMitragotietal[78]whoagreedthatcavitationaleffectsweredominantbutwhousedconfocalmicrosopyto
demonstratethattherapeuticultrasound(13MHz,02Wcm2)didcausecavitationinsidethestratumcorneumanddisruptedthestructuretoformchannelsthrough
whichthepermeantscouldflow.Atheoreticalmodelwasalsodevelopedtoquantitativelyexplaintheresults.Inanextensiontothiswork,lowerfrequency,20kHz
ultrasoundwasusedratherthanthe13MHz'therapeutic'frequenciesusedintheabovework.Theresultshereweredramatic.Inmostoftheworkathigh
frequencies,ultrasonicenhancementsinpermeationofupto1050werethemaximum

Page256

noted.Useof20kHzgaveenhancementsofupto3000.Theauthorsusedthisasfurtherevidenceoftheircavitationmodelsincetheeffectsofcavitationshouldbe
morepronouncedatthelowerfrequency[79].
Meidanetal[80]andByl[81]havealsoconsideredmuchoftheliteratureevidenceandreviewedmanyoftheinvitroandinvivostudies.Theysuggestthatmuchof
theworkissubjectivesincepropercontrolexperimentshavenotbeenperformedorthepreciseultrasoundparametersnotfullyreported.However,oftheproper
documentedtrialstheyconsider,theresultsconfirmthesuggestionthatthereisnosinglesonophoreticeffect.Inmanycases,heatingeffectsalonecanexplainthe
observedenhancementtopermeability.However,thereareothercaseswherethetemperaturechangescannotaccountfortheobservations.Theredoesappeartobe
evidenceinfavourofthestructuraldisruptionresultingfromcavitationdamage.
Thereisaneedforfurtherworkinthisareaanditseemstomethatitisanarearipeforcollaborationbetweenthemedicalphysicists,theanalyticalchemistsandthe
sonotherapists.
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Page261

PART5
RESEARCHTOPICSINMEDICALULTRASOUND

Page263

Chapter14
ImagingElasticPropertiesofTissue
JamesFGreenleaf,RichardLEhman,MostafaFatemiandRajaMuthupillai
14.1
Introduction
Palpationisroutinelyusedfortheevaluationofmechanicalpropertiesoftissueinregionsthatareaccessibletotouch.Detectingpathologyusingthe'stiffness'ofthe
tissueismorethan2000yearsold.Itiscommonforsurgeonstofindlesionsduringsurgerythathavebeenmissedbyadvancedimagingmethods.However,palpation
issubjectiveandlimitedtoindividualexperienceandtotheaccessibilityofthetissueregiontotouch.Ameansofnoninvasivelyimagingelasticmodulus(theratioof
appliedstresstostrain)anywhereinthebodymaybeusefultodistinguishtissuesandpathologicprocessesbasedonmechanicalpropertiessuchaselasticmodulus
(Sarvazyanetal1994).Manyapproachestoimagingmechanicalpropertieshavebeendevelopedovertheyears(Krouskopetal1987,Parkeretal1990,Lerneret
al1990,Bertrandetal1989,Ophiretal1991,Skovorodaetal1994,O'Donnelletal1994).Conventionalimagingmethodsaretypicallyusedtomeasure
mechanicalstrainoftissueinresponsetomechanicalstress.Static,quasistaticorcyclicstresseshavebeenapplied.Theresultingstrainshavebeenmeasuredusing
ultrasound(Sarvazyanetal1994,Krouskopetal1987,Parkeretal1990,Lerneretal1990,Bertrandetal1989,Ophiretal1991,Skovorodaetal1994)or
MRI(LewaanddeCertaines1995a,b,Plewesetal1994,Muthupillaietal1995a,b,Fowlkesetal1995)andtherelatedelasticmodulushasbeencomputedfrom
viscoelasticmodelsoftissuemechanics.
14.1.1
ExogenousTransverseWaves:ImagingwithMRE
RecentlyanewMRIphasecontrasttechniquehasbeenreportedinwhich

Page264

transversestrainwavespropagatingintissueareimaged(Muthupillaietal1995a,b,1996).Becausethewavelengthsofpropagatingwavesarerelatedtodensityand
theshearmodulus,thismethodpromisestohavegoodresolutionandtobesensitivetotheshearmodulus.Thewavelengthsoflowfrequencytransversewavesareof
theorderofmillimetres.Thispaperreviewsthetheoryofthemethod,presentssomeapplicationsanddiscussestheimplicationsofthemethod.
14.1.2
StimulatedAcousticEmission:ImagingwithUSAE
Othermethodscanbeusedtolookattheglobal(bulk)mechanicalparametersofobjects.Forexample,inResonantUltrasoundSpectroscopy(Maynard1996),an
ultrasoundsourceanddetectorareusedtomeasuretheresonancefrequenciesofasamplewithknownsizeandmass.Thesevaluesareusedtocalculatethebulk
mechanicalparameters,includingtheelasticconstants,ofthematerial.Inthischapter,wepresentamethodtointerrogate,orimagetheobjectathighspatial
resolution,andatthesametime,toobtainthelowfrequencyresponseoftheobjectateachpoint.Theimagingtechniqueusedhereisbasedontheradiationforce
(Torr1984,Westervelt1951)oftwoultrasoundbeamsreportedbytheauthorselsewhere(FatemiandGreenleaf1998).Briefly,twoultrasoundbeamsofslightly
differingfrequencyinterfereon,orwithin,anobjectandtheresultingdynamicradiationforceproducesanacousticfieldthatisdependentonmechanicalpropertiesof
theobject.Theacousticfieldisdetectedwithamicrophoneorhydrophone.
14.2
MagneticResonanceElastography(MRE)
BecauseoftheeffectofmotionofspinsinMRI,tissuedisplacementcanbemeasuredwithMRI.Whentheresultingimagesrepresenttheelasticityoftheobject,the
imagingmethodistermedMRE(magneticresonanceelastography).
14.2.1
Theory.
WewilltermthemicroscopicregionoftissuethatrespondstotheMRIsignalaspin.Thetransversemagnetizationphase ( ),ofaspinmovinginthepresenceofa
varyingmagneticfieldgradientG(t),isgivenby

wherer(t)isthepositionvectorofthemovingspin,and isthegyromagneticratiowhichischaracteristicofthespinunderinvestigation.

Page265

Inthecaseofapropagatingtransversewaveintheacousticfrequencyrange,thepositionvectorcanbedescribedby

wherer0isthemeanpositionofthespin, istheangularfrequencyofthemechanicalexcitationcausingthestrainwave, istheinitialphaseoffset,kisthewave

numberofthestrainwave,andx 0isthepeakdisplacementofthespinfromitsmeanposition.
IfthegradientG(t)isasquarewavewithmagnitudealternatingbetween+|G|and|G|forNcycleswithaperiodTequaltothestrainwaveperiod2 / ,thenthe
resultingphaseshiftinthereceivedsignalisgivenby

Equation(14.3)illustratesthatthephaseshiftisrelatedtothescalarproductofthedisplacementandgradientvectors,thusprojectionsofthemotioncanbeobtained
foreachofthethreecoordinateaxesifthreesetsofdataareobtainedwithmutuallyorthogonalgradients.ThephaseshiftisalsoproportionaltotheproductNTwhich
isthetotalontimeofthegradient.Byvarying ,thephaseoffsetbetweenthegradientsandthemechanicalexcitation,imagesfordifferentpointsintimecanbe
obtained,producingcineloopsthatdepictthewavepropagationthroughtime.
14.2.2
Methods
Testswereperformedinaseriesofexperimentsusinga1.5TSignaimager*,toprovideexamplesofapplicationsofthetheory.
Phantomswhichsimulatedtissueswithvaryingstiffnessweremadebymixingvaryingamountsofagarose**indistilledwaterataround70C.
Aschematicoftheexperimentalsetupforgeneratingstrainwavesisshowninfigure14.1.Weconstructedanelectromagneticelectromechanicalactuator,similartoa
speakermechanism,toproducetransversewavesintheacousticfrequencyrange.Awaveformgeneratorfedasinusoidalsignaltotheactuatorcoilthroughastereo
amplifier.ThesinusoidwassynchronizedwiththegradientcyclesprovidedbytheMRimager.
Aphasecontrastgradientechosequencewithcyclicgradientwaveformswasusedforimaging(figure14.2).Thenumberoftriggerpulseswas
*

GEMedicalSystems,Milwaukee,Wisconsin.

**

BactoAgar,DifcoLaboratories,Detroit,Michigan,1.03.0%w/w.

Page266

Figure14.1.
Schematicforproducinglowfrequency
transversewavesinphantomsortissues.The
actuatorcoilisonashaftthatishinged.When
currentispassedthroughthecoil,the
currentcausesthecoiltoalignwiththe
Bfieldofthemainmagnetforcingaplateonthe
phantomtoshiftbackandforth.Thisproduces
transversewavesinthephantom.Thewavegenerator
istriggeredfromtheMRimagerensuringthatthe
gradientswithintheimagerareswitchedinsynchrony
withtheexcitationwavefrequency.Reproduced
withpermissionofWilliamsandWilkinsfrom
Muthupillaietal(1996).

adjustableandcouldbeinitiatedpriortotheimagingcycle,producingimagesofwavesthathadpropagatedintothephantomforvariousdepths.
Eachrepetitionofimagingpulseswasdonetwice,alternatingpolarityofthemotionsensitisinggradients(figure14.2).Thisacquisitionschemereducedphasenoise
anddoubledthesensitivityofthephasemeasurements.IntheexamplesshownthegradientsG(t)werecollinearwiththedisplacementx 0tomeasuretransverse
waves.Rangesofdataacquisitionparameterswere:repetitiontime,50300msechotime,1560msacquisitionmatrix,128256acquisitiontime,20120sflip
angle,1060.Thefrequencyofmechanicalexcitationrangedfrom100to1100Hzandthenumberofgradientpulses(N)rangedfrom2to30cycles.Theimages
areofphasedisplacementcomputedfromequation(14.3),aftercorrectionforthebalancedacquisition.
14.2.3
MREResults
Transversestrainwavesinanagarosegelphantomareshowninfigure14.3.Themotionoftheactuatorwasorthogonaltotheplaneofthefigureand

Page267

Figure14.2.
Pulsestotriggerthewaveformgenerator,shown
infigure14.1,areproducedinsynchronywith
themotionsensitisinggradients.Thephase
relationshipbetweenthegradientsandthe
mechanicaldrive ,canbealtered.The
motionsensitisinggradientscanbeappliedalong
arbitraryaxesallowingmeasurement
ofdisplacementalonganyaxis.Tworepetitionsare
usedwithoppositemotionsensitisinggradientsto
subtractoutsystematicphaseerrorsandtodouble
sensitivity(NTinequation(14.3))tosynchronous
motion.ReproducedwithpermissionofWilliamsand
WilkinsfromMuthupillaietal(1996).

collinearwiththesensitisinggradients.Inonecase,contactonthephantomwasapointandintheotheraplane.Theresultsweresphericaltransversewavesandplane
transversewaves,respectively.Theimageswereproducedfrommotionsensitisinggradientsthatwereinitiatedafteranearsteadystateconditionwasachievedbythe
actuator.Thepointsourceimageillustratestheinverseradiusrelationshipofamplitudeandshowssomefaintreflectionsfromthewallsofthephantom.Theplane
sourceimageillustratesedgewavescausedbytheedgeofthe'aperture'andsomereflectionsfromthewalls.
Figure14.4illustratesthepropagationofatransversepulsethroughaheterogeneousphantomconsistingoftworegionshavingdifferenthardnesses.Thehardergel
(2%agar)isatthetopandthesoftergel(1.25%)ispouredinthecontaineratanangle.Refractionofwavepropagationisshownintheareamarkedbythearrow.
Theshearmodulusforinhomogeneousmaterialcanbecalculatedasshowninfigure14.5.Twoagarosegelcylindersofhighandlowstiffnesswereembeddedinan
agarosephantomofmediumstiffness.Adisplacementimagewasobtainedat250Hzusingplanewaveexcitation.Figure14.5(top)displaysthedisplacementimageof
transversewavespropagatingthroughthephantomandthetwocylinders.Thestiffercylinder,ontheleft,displays

Page268

Figure14.3.
Imagesoftransversewavesproducedat400Hzinagar
phantommaterialusingtheactuatoroffigure14.1.
Apointcontactproducedsphericaltransversewaves
(left)andaplanarcontactproducedplanewaves(right).
Thenumberofgradientcyclesusedforthemeasurementwas15.
Equation(14.3)wasusedforthecalibrationscale.Reproduced
withpermissionofWilliamsandWilkinsfromMuthupillaietal(1996).

Figure14.4.
Refractionofapropagatingtransverse
waveisexhibitedinthisdisplacement
imageformechanicalexcitationof250Hz.
Sixgradientsensitisingcycleswereused.
Thewhitearrowdepictswavepropagation
directionfortheagarosegelpouredintothe
phantomcontaineratanangle.Reproduced
withpermissionofWilliamsandWilkins
fromMuthupillaietal(1996).

Page269

Figure14.5.
Magneticresonanceelastographyimagesoftwo
cylindersofagarosewithhighandlowstiffness
embeddedinabackgroundmaterialwithaverage
stiffness.Planetransversewaveswereappliedatthe
topofthephantom.Thephaseimagetakenat250Hz
showslargewavelengthinthehardcylinderand
shortwavelengthinthesoftcylinder(top).Computation
ofthelocalwavelengthandtheassumptionof
densityof1gcm3resultsinaquantitativeimage
ofshearmodulus(bottom).Theindicatedhardnessofthe
cylinderontheleftisabout22kNm2compared
tostiffnessmeasurementsoflargesamplesofthe
samegelof23.8kNm2.Reprintedwithpermission
fromMuthupillaietal,Science,vol269,
18547,copyright1995AmericanAssociation
fortheAdvancementofScience.

largerwavelengthsandthesoftercylinderontheright,shorterwavelengthsthanthebackgroundmaterial.Thisimagewasprocessedwithalocalwavelengthestimation
filter(Manducaetal1996)tocomputethelocalshearmodulusassumingthedensityofthematerialtobeconstantat

Page270
3

1.0gcm .Theresultingquantitativeimageofshearmodulusisshowninfigure14.5(bottom).
14.3
UltrasoundStimulatedAcousticEmission(USAE)
14.3.1
TheoryofUSAE
Thegeneralprincipleisthatforceisgeneratedbyachangeintheenergydensityofanincidentacousticfield.Letusconsideracollimatedultrasoundbeaminteracting
withanobjectofarbitraryshapeandboundaryimpedancethatscattersandabsorbs.Theradiationforcearisingfromthisinteractionhasacomponent,F,inthebeam
direction.Thiscomponentisproportionaltothetimeaveragedenergydensityoftheincidentwave(E)andtheprojectedareaoftheobject,S,asshowninthe
followingrelationship(Westervelt1951):

whereDisthedragcoefficient,whichisafunctionofthescatteringandabsorbingpropertiesoftheobject(seeChapter3).
Applicationofthisforceforobjectinterrogationandimaging,aswillbedescribedlater,ideallyrequiresthestressfieldtobeconfinedtoapoint,whileitsamplitude
oscillatesatselectedfrequencies.Togeneratealocalisedoscillatoryfield,twointersectingcontinuouswave(CW)focusedultrasoundbeamsofdifferentfrequencies
areused.Itisonlyintheintersectionregionthattheultrasoundfieldenergydensityissinusoidallymodulated,andhencethefieldcangenerateanoscillatoryradiation
forcebyinteractionwiththeobject.Theultrasoundbeamscanbeshapedinavarietyofwaysforthispurpose.Aninterestingconfigurationisobtainedwhentwo
coaxial,confocaltransducersareused(figure14.6).Inthiscase,theelementsofatwoelementsphericallyfocusedannulararray(consistingofacentraldiscandan
outerring)areexcitedbytwoCWsignalsatfrequencies 1and 2.Letusassumethatthebeamsarepropagatinginthe+zdirectionwiththejointfocalpointatz=0.
Theresultantfieldonthez=0planemaybewrittenas:

whereg1(x,y)andg2(x,y)arethebeamprofileswith 1and 2beingtheassociatedphasefunctionsacrossthez=0plane.Forfocusedbeamsg1(x,y)andg2(x,y)

diminishquicklyawayfromtheorigin.Letthedifferencefrequency = 2 1<< 1, 2,thenitcanbeshownthattheshorttimeaverageoftheacousticenergy
densityintheintersectionregion

Page271

Figure14.6.
Experimentalsystemforultrasonicallystimulatedacousticemission.
Thesystememploysaconfocalultrasoundannulararraytransducer,
consistingofacentrediscandanouterring.Transducercentre
frequencyis3MHz,outerdiameter22.5mmanditisfocusedat70mm.
TheelementsaredrivenbytwoCWsources,atfrequenciesequal
to 1and 2= 1+ ,wherethesefrequenciesareveryclosetothe
centrefrequencyoftheelements,and ismuchsmallerthan
(<1%)thecentrefrequency.Thetransduceranditsbeampatternis
illustratedontheleft,showingthatbeamsinteractonlyata
smallregionaroundthejointfocalpoint,wheretheamplitude
ofthefieldoscillatesatthedifferencefrequency .Theobjectis
placedatthejointfocalpointvicinity,andinterrogatedpointbypoint
byscanning.Thesoundfieldresultingfromobjectvibrationsat
eachpositionisreceivedbyahydrophoneandrecordedafterdigitisation.
Therecordedsignalatoneormoredifferencefrequenciesisusedto
formanimageoftheobject.Theexperimentsareconductedinawatertank.

hasslowvariationsatfrequency

aboutitslongtimeaverage.DenotingthislowfrequencycomponentbyE1(t,x,y),wecanwrite

whereAisaconstantrelatingthefieldquantitytotheenergydensity.Now,consideraplanartargetonthez=0plane.Referringtoequation(14.4),andconsidering
thattheaverageenergydensityispositionandtimedependentinthiscase,thenormalcomponentofthetimevaryingforceonthistargetisfoundbythefollowing
integration:

whereCisaconstantand isaphaseconstant.SistheareaoverwhichE1(t,x,y)hassignificantvalues.Thisarea,definedastheinteractionregionofthebeams,
canbeverysmallforwellfocusedbeams.Hence,F1(t)canbethoughtofasanoscillatingpointforceappliedtotheobjectattheorigin.

Page272

Objectvibrationsresultinanemissionofacousticenergywhichcanbedetectedbyamicrophone(orhydrophoneinwater).Thecomplexamplitudeofthisfield,
( ),canbewrittenas(ignoring )

whereQ( )isacomplexfunctionrepresentingthemechanicalfrequencyresponseoftheobjectatthispoint,andH( )representsthecombinedfrequency

responseofthepropagationmediumandthemicrophone.H( )isassumedtobeunchangedforanytargetpointintheobject.Bykeepingthesourceintensity
constant,Cinequation(14.8)willremainfixedatagivenpointintheobject.Now,knowingH( ),bychanging andrecording ( ),wecanobtainQ( )for
thatpointwithinaconstantmultiplier.Repeatingthesameprocedureforotherpointsoftheobjectatagivenplane(e.g.thez=0plane),wecancollectasetof
responses.Thesedatacanbemappedintoapictorialformat.Forinstance,atafixedfrequency = 0,thevalueof| ( )|atvariouspointsrepresentsthe
spatialdistributionofD|Q( 0)|,whichcanbemappedintoamonochromaticimage,displayingobjectmorphology.Thespatialresolutionoftheresultingimageis
determinedbytheareaS,whereitssizeisoftheorderoftheultrasoundpowerbeamwidthatthefocalpoint.Todisplayfrequencydependencyinformationinaddition
toDdistribution,wecanusecolour.Forinstance,thefrequencyresponseateachpointcanbedividedintothreefrequencybandsusingthreebandpassfilters.The
averageamplitudeineachbandismappedintoamonochromeimage.Byassigningadifferentcolourforeachimage,amulticolourimage(spectrograph)isformedby
superimposingthethreecolourcomponents.Inthiscase,Dinfluencesthebrightness,whilethefrequencyvariationsof|Q( 0)|arerepresentedbythehueofeach
imagepixel.Inpractice,|H( )|maynotbeknown,butsinceitispositionindependent,variationsofimagehueversuspositionqualitativelyrepresent|Q( )|
variations.
14.3.2
USAEResults
Theexperimentalsetupusedtotestthemethodisshowninfigure14.6.Theexperimentwasconductedinawatertankbecausewaterisagoodacousticcoupling
mediumwhileprovidingfreedomofmovementfortheprototypescannermechanism.Atwoelementconfocalultrasoundtransducerarraywaspositionedsuchthatthe
beamsmeettheobjectattheirjointfocalpoint.Soundproducedbytheobjectvibrationswasdetectedbyasubmergedhydrophoneplacedwithinthewatertankor
ontheobject.Inasystemdesignedforinvivoimaging,onewouldusesofttissueasthecouplingmediuminsteadofwater.
Basicparametersofanimagingsystem,suchasthespatialresolution,canbeevaluatedusinganisolatedpointastheelementarytestobject.The

Page273

Figure14.7.
Experimentallymeasuredpointspreadfunction
ofthesystem.Anisolatedpointtargetwas
simulatedbya380mdiameterglassbead
placedonapieceofthinlatexsheet.Thelatex
surfacewasscannedat0.2mmincrementsin
eitherdirection.Thedifferencefrequencywasfixed
at7.3kHz.Theacousticspectrogramofthebeadis
showningreyscale.Thelatexsheetisalmost
transparenttotheimagingsystem.Theglassbead
presentsahighacousticimpedancediscontinuity
resultinginsignificantradiationforce,and
thusproducesasignificantacousticfieldwhen
exposedtothetwobeamsandstandsoutinthe
imagewithhighcontrast.Theimageshowsthatthe
systemresolutionisabout500m,similarto
thatoftheconfocaltransducer.

resultingimageiscalledthepointspreadfunction(PSF)ofthesystem.Forthispurpose,weuseda380mdiameterglassbeadasamodelforapointandplacedit
onapieceofthinlatexsheet.Thelatexsheetproducesonlyasmallchangeintheincidentenergy,andisalmosttransparenttotheultrasonicbeam.Theentireobject
wasplacedinawatertankandthelatexsheetsurfacewasscannedinarasterformat.Thedifferencefrequency,inthiscase,wasfixedat7.3kHz.TheresultingPSF
isshowninfigure14.7.Fundamentalimageresolution,definedasthewidthofthePSF,wasapproximately500mineitherdimension.Thisresultshowsthatthe
systemiscapableofdetectingobjectssmallerthanitsresolutioncell.
Toshowthecapabilityofthemethodindisplayingthefrequencyresponsesofanobjectversusposition,asetofthreetuningforkswaschosenasthetestobject.The
forksaremadefromidenticalmaterial,andhaveidenticalfingercrosssections(lengthsaredifferent).Resonancefrequenciesinwaterare:407Hz(right),809Hz
(middle)and1709Hz(left).Theforkswerescannedinawatertankusingthesystemshowninfigure14.6.Thescanningplanecoversthefrontfingersatthebottom
partoftheforks.Thedigitisedhydrophonesignalwasfilteredbythreeoverlappingbandpassfilterseachhaving6dBbandwidthof500Hz.Theoutputsofthefilters
withcentre

Page274

Figure14.8.
Spectrogramofthetuningforks.Thefilteredcomponentsareshownin
greyscale:(R)theredcomponent,(G)thegreencomponentand
(B)thebluecomponent.

frequencies500,1000and1500kHzwereusedtoproducethered,greenandblueimagecomponents,respectively.Thethreecomponentsareshowninfigure14.8
asthreegreyscaleimages.Toobtainacolourimagetheseimagescanbecodedinappropriatecoloursandsuperimposed(notshown).
Nextweinvestigatedthepossibilityofusingtheboththeamplitudeandphaseoftheacousticemissionsignaltoimagethedifferencesinthemechanicalpropertiesof
biologicaltissues.Forthis,weusedspecimensofcalcifiedandnoncalcifiedhumaniliacarteries.Thearterieswerescannedinaplaneperpendiculartothebeamaxis.
Theamplitudeandphaseoftheacousticemissionfieldwererecordedateachposition.Thedifferencefrequencywasfixedat6kHz.Resultingimagesareshownin
figure14.9.Calcificationsareclearlyidentifiedastheyexhibitdistinctiveamplitudeandphasevalueswhencomparedtothearterialwalls.

Page275

Figure14.9.
Acousticspectrographyofhumaniliacarteries.Top:
Xrayimageofnormal(N)andcalcified(C)excised
humaniliacarteriesobtainedfroma35yearold
womananda67yearoldman,respectively.Bright
areasindicatecalcifications.Bottomleft:Acoustic
spectrogramamplitudeimageatthedifferencefrequencyof6.
0kHz.Calcificationdetailsappeardistinctivelybright,
whilethearterialwallsaredim.Bottomright:
Correspondingphaseimage,indicatingthatthe
calcifiedregionsvibrateoutofphasewithrespect
tothesofttissues.

14.4
Conclusions
BothMREandUSAEcanobtainimagesofmechanicalpropertiesoftissues.Eachhasitsplaceinimaging,perhapsincomplementaryapplications.
14.4.1
MRE
Usingsynchronousmotionsensitisinggradients,magneticresonanceelastography(MRE)iscapableofproducingeithersnapshotsorcineloopsofcyclicdisplacement
causedbyexternallyappliedtransversewavesintheacousticrange.Thedisplacementcanbemeasuredinthethreeorthogonaldirectionsprovidingavectorvalued
function(x (r,t)inequation(14.3)).MREcanbeusedtostudypropagationeffectssuchasrefractionanddiffractionandcanprovidequantitativemeasuresofshear
modulus.

Page276

TheadvantagesofMREarethatitcanprovideimagesvirtuallyanywhereinthebodyandinanyorientation.Forqualitativestudiesofwavepropagation,suchas
refractionanddiffraction(figures14.3and14.4),MREhasthesameresolutionasastandardMRimagingsystemofabout0.5mm.Forshearmodulusorwavelength
measurements(figure14.5),MREisquantitativewithaspatialresolutionoftheorderofthewavelengthofthetransverseelasticwavesandacontrastresolutionof
severalpercent(Smithetal1997)forstiffnessorattenuation.
AdisadvantageofMREisthateachtwodimensionaldisplacementimagerequiresseparaterepetitionsofthemechanicalexcitationoveratimespanofaboutone
minutetoacquiredatafortheimage.Thisacquisitiontimeismultipliedbythenumberofphaseoffsets, ,acquiredforthecineloopandisstilllongerformeasurements
ofthreedimensionaldisplacementvectors.
MREcertainlyprovidesapracticalnewexperimentaltoolformeasuringpropagatingtransversewavesintissuesandtissuelikemedia.MREmayalsoprovideanew
clinicalimagingtool,extendingtheclassicalpalpationmethodstoanywhereinthebodyandtofullthreedimensionalquantitativelevels.
14.4.2
USAE
MeasurementofthePSFofUSAE,showninfigure14.7,indicatesthatthesystemresolutionisabout0.5mm,whichisaboutthebeamwidthoftheultrasound
system.Thisisinagreementwiththeexperimentalimagesofthetuningforks.Thissystemcanbeusedasanimagingtool.HoweveronemustnotethatthePSFofthe
systemisanglesensitive.
Themethoddescribedinthischapterprovidesacombinationofhighresolutionmeasurementoflocalandbulkphysicalparametersoftheobject.Applicationsofthis
methodincludenondestructiveevaluationofmaterialsandcharacterisationofbiologicaltissues.
Acknowledgments.
TheauthorsthankElaineQuarveforsecretarialassistanceandRandyKinnick,UltrasoundLaboratory,andTCHulshizer,MRIResearchLaboratory,fortechnical
assistance.
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FowlkesJB,EmelianovSY,PipeJP,SkovorodaSR,CarsonPL,AdlerRSandSarvazyanAP1995Magneticresonanceimagingtechniquesfordetectionof
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AcousticalImagingvol21,edJPJones(NewYork:Plenum)
SkovorodaAR,EmelianovSY,LubinskiMA,SarvazyanAPandO'DonnellM1994Theoreticalanalysisandverificationofultrasounddisplacementandstrain
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TorrGR1984TheacousticradiationforceAm.J.Phys.524028
WesterveltPJ1951ThetheoryofsteadyforcecausedbysoundwavesJ.Acoust.Soc.Am.2331215
YamakoshiY,SatoJandSatoT1990UltrasonicimagingofinternalvibrationofsofttissueunderforcedvibrationIEEETrans.UltrasonicFerroelectr.Freq.
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Page279

Chapter15
TheSignalToNoiseRelationshipforInvestigativeUltrasound
ChristopherRHill
Ultrasoundoffersthepotentialbasisforasubstantialsetofclinicalinvestigativetechniques,onlyafewofwhichareatpresentinwidespreaduse.Atthesametime,
ultrasoundisitselfasubsetofthefullrangeofphysicaltechniquesthatareavailableforinvestigationofparticularclinicalproblems.Thischapteranalysesqualityof
investigativeperformanceinthiscontext,intermsoftherelationshipbetweentissueinformativesignalsand'noise'(inthebroadsenseoftheterm),anddiscussesthe
derivationofaquantitativefigureofmeritforinvestigativeperformance.Thisapproachhasmoregeneralapplicationthansimplytoultrasoundbutindicates,in
particular,thatsomehithertounderdevelopedultrasoundbasedtechniquescouldshowconsiderablepromiseintheclinicalinvestigationoftumoursandother
pathologies.
Thereisnowofcourseaconsiderablearmouryofphysicaltechniqueswhichare,orpotentiallymightbe,usedforclinicalinvestigation.Ultrasoundprovidesthebasis
foronesubsetofthesemethodsand,inspiteofitswidespreaduse,itisstillfarfrombeingexploitedtoitsfullpotential.Contemporaryinvestigativeultrasound*is
basedalmostentirelyontwotechniquesthathappenedtobetechnicallyfeasiblesome30ormoreyearsago:backscatteramplitudeimagingandbackscatterDoppler
processing.Withmoderntechnology,awholerangeofadditionalapproacheshasbecomepossible:speedofsoundreconstructionimaging,andmovementcorrelation
processing,tonamejusttwo.
*

Although'diagnosticultrasound'isconventionaljargon,theclinicalinvestigationstowhichultrasoundcancontributeencompassmuchmorethansimplydiagnosis.Hencethe
preferredusehereoftheterm'investigative'.

Page280

Weshouldthereforebeaskingourselvesanumberofquestions,suchas:
What,technically,arewetryingtodoininvestigativeultrasound?
Howwellarewedoingthisjob?
Howdowedefineandquantify'doingwell'inthiscontext?
Couldwe'dobetter'usingalternative,ultrasoundbasedmethods?
Howdoesultrasoundperformanceindoingaparticularjobcomparequantitativelywithotherinvestigativemodalities?
Thus,ingeneral,howgoodisultrasound?
Findinganswerstosuchquestionsmaytakealongtimebutthepurposeofthischapteris,first,tosuggestthatthequestionsareworthyofstudyand,second,to
indicatesomeapproachesthatmayhelptowardsfindingsolutions.
Physicalmethodsofmedicalinvestigation,whetherbasedonXrays,radioisotopes,NMR,ultrasoundoranyothermeansareallexercisestowhichthemethodsof
communicationssciencecanusefullybeapplied(see,e.g.ICRU1996).Whatevertheparticularmethod,theinvestigativeprocessessentiallyentailsretrievalofa
'signal'carryinginformationaboutsomeaspectofapatient'scondition,andconveyingtoan'observer'asmuchofthatinformationasisnotobscuredby'noise'.In
simplisticterms,wearethusconcernedwitha'signaltonoiseratio'fortheprocess.Beforethiscanbehelpful,however,weneedtoconsiderthenaturebothofthe
signalsandofthenoise,andwealsoneedtothinkaboutthecharacteristicsoftheobserver.
Particularlyinthepresentcontextofinvestigativeultrasound,thesearecomplexissuesonwhichnogeneralconsensuscanbefoundintheliterature.Theyhave
howeverbeendiscussedinsomedetailintwopapersbythepresentauthor(Hilletal1990,Hilletal1991),onlysomeofthecontentofwhichitwillbepossibleto
summarisehere.
Clinicalinvestigationsgenerallyrequireinformationsignalsthatwillhelpthemanswertwoseparatebutinterrelatedclassesofquestion:'Whatisit?'and'Whereisit?'
Thusthequalityofperformanceofaninvestigativeprocessneedstobecharacterisedcorrespondingly.First,howaccuratelyandpreciselycanagivenanatomical
structurebelocatedinspace(and/or,relatedtothis,withwhatspatialresolutioncantwoneighbouringstructuresbedistinguished)?And,second,howaccuratelyand
preciselycanthematerial/tissueofananatomicalregionbeidentified(and/or,relatedtothis,withwhatsensitivitycantwosuchmaterials/tissuesbedistinguished)?A
third,practicallyimportantconsiderationisthespeedwithwhichtheprocesscanprovidetheseanswers.
Thesituationis,however,complicatedbytheinterrelatednatureofthesethreeaspectsofperformance.Spatialresolutionis,forexample,generallybestforhigh
contraststructures,whilethesensitivitywithwhichatissuecanbeidentifiedwillgenerallyincreasewiththequantityoftissueavailableforstudy(thusinverselywith
spatialresolutionoftheidentificationprocess)andalsowiththetimeavailablefortheprocess.

Page281

Inallthistheconceptofcontrastresolutionturnsouttobecentral.Hilletal(1990)analysethisintermsthatanyindividualtissueexhibitsavalue,Pi,ofsomephysical
propertyandthatthisgivesrise,insomeultrasonicinvestigativeprocess,toasignalvalue,Si.Onecanthenconsidersystematicallytheprocessesthatgiveriseto
uncertainty('noise')inSiand,correspondingly,inthevalueofPi,whichiswhat,ideally,theobserverwishestoknow.
Formally,ifaninvestigativeprocessisrequiredtodifferentiatebetweentwodifferenttargets/tissuesonthebasisoftheirphysicalpropertyvaluesPiandPj ,the
criterionforsuccessis

whereUisthenumericaluncertainty(or'noise')ofthesystemandthescaleoftheinequalityconstitutesafigureofmeritforthesystem.Uncertainty,inthiscontext,
arisesfromanumberofdifferentsources,allofwhichcanaffecttheaccuracyofanobservationbutonlysomeofwhichmayaffectitsprecision*.Thesesources
includethefollowing:
Therelativepropertyseparation,Pi/Pj ,asbetweentwotissuetypes.
The'biological'variance,s2(P)b,inPcorrespondingtonominallyidenticaltissuetypes.Arelatedvariance,s2(S)b,willoccurforthecorrespondingsignals.
Thetechnicalprecision,s2(S)t,withwhichthetechniquetransformsthenumericalpropertymeasure,P,intoasignal,S.
TheforegoingistreatedinmoredetailinHilletal(1990),whereitisshownthatageneralexpressionforthefigureofmeritofaninvestigativesystemis

where istheeffectivestandarddeviation(noiselevel)ofthesystem(i.e.thesquarerootofthesumofthevariances)andNisthenumberofuncorrelated
measurementsemployed.
Itisinterestingtonoteherethatthisisessentiallyamoregeneralformoftheexpressionthathasbeenderivedindependentlyforcomparingthevirtueofvariouspulse
sequencesinobtainingprecisevaluesofNMRrelaxationtimes(Edelsteinetal1983).Aspecialconsiderationarises,however,whenthistreatmentisappliedto
investigativeultrasound.Thisrelatestothethirdoftheabovefactors,thePStransformationprecision,andarisesbecauseofthecoherentnatureoftheultrasound
sourcesemployed,whichgivesrisetoafundamentallyimportantsourceof'noise':coherentradiationspeckle.
*

'Accuracy'isanindexoftheextenttowhichanexperimentallymeasuredvalueofaquantityapproximatesitstruevalue'precision'isanindexoftheextenttowhichdifferent
measuredvaluesofsomeparticularquantityapproximatetoeachother.

Page282

Atthispointitwillbehelpfultodigressbrieflywithadiscussionofthevarioususesthatwehavebeenmakingoftheterm'noise'.Initsmostgeneralsense,theterm
'noise'mayconnoteanyartefactthatcanbemistakenforawantedsignalandcannotbedistinguishedfromit.Conventionally,however,andparticularlyinradio
engineering,'noise'hastherestrictedconnotationofarandom(andthusbroadfrequencyband)sourceofpseudosignal.Coherentspeckle,however,isanartefactthat
hasarelativelynarrowfrequencyspectrumsetbythedrivingsource(inourcasetheultrasonictransducer),andmaybemoreappropriatelytermed,asinradar
parlance,'clutter'.
Forinvestigativeultrasound,coherentradiationspeckleisdoublybadnews.Inthefirstplace,itsfrequencyspectrumpeaksexactlywiththatofthesystemmodulation
transferfunction(MTF),andthusspecificallydegradesperceptionofdetail.Ontopofthis,itmayalsointeractnegativelywiththeparticularnatureofthevisual
physiologyofahumanobserver.ThissituationisdiscussedinHilletal(1991)andillustratedhereinfigure15.1,whichisreproducedfromthatpaper.Theproblem
arisesbecausehumanvisionismaximallysensitivetoimagefeaturesexhibitingaparticularspatialfrequency,oftheorderof2cyclesdegree1.Presentingimagestoan
observeratsuchamagnificationthatthespatialresolutionoftheultrasonicimagingsystemappearsinthepresentedimageatthisspatialfrequencywouldthusseem,in
onesense,tooptimiseoverallmachineobserverperformance.Unfortunately,bysimultaneouslymaximisingtheperceptionofspeckle,thisarrangementisalsoaworst
caseforachievementofcontrastdiscrimination.
Twoapproacheshavebeenconsideredformitigationofthisproblem.Inthefirstplace,attemptshavebeenmadetousepartiallyincoherentsystemsbut,without
incurringunacceptabledegradationinsensitivityandspatialresolution,thishasprovedtobeofonlyverylimitedvalue.Secondly,however,theroleofhumanobserver
performancesuggestssubstitutionofamorenearlyideal,machineobserverand,incertaincircumstances,thishasbeenshowntoyieldsignificantimprovementin
overallperformance(Wagneretal1991).
Referringbacktothediscussiononequations(15.1)and(15.2),specklenoisecontributestotheuncertaintyinthePStransformation.Afurthercontributioncomes
fromelectronicnoiseandtherelationshipbetweenthetwoisillustratedinfigure15.2.ThisshowstheconditionunusualelsewhereofanS/Nratioconstantwith
depthuptoaboundarywhereelectronicnoisetakesoverfromspeckleasituationthatcanbeobservedonsuitablydisplayedscans.Itthereforeseemsthatwehave
tolivewithspeckle,andthusaccept,intermsofequation(15.2),thelimitationthatthisimposesonattemptstominimisethevalueof .Toachievegoodcontrast
discriminationwethereforehavetolookforwaystoobtainhighvaluesforthe(dS/dP)factor.Morespecifically,foranygivendifferentiationtask,

Page283

Figure15.1.
Illustrationofhowthecharacteristicsofhumanvision
caninfluencethesignaltonoiseratio(SNR)ofaninvestigative
procedurethatusescoherentradiation.(c)showstheformof
thelinespreadfunction(lsf)foranimagingsysteminwhich
theparameter'd'representsthefullwidthofthelsfat
halfmaximumamplitude(fwhm).(d)isthecorresponding
modulationtransferfunction(MTF)ofthesystem,
whichisidenticalinshapetotheMTFofthesystem
specklenoise.Curve(b),drawnheretohavethesamearea
as(a),isthespreadfunctionofalowcontrastobjectof
lineardimension10d(e.g.atumour)and(e,1)isitsMTF.
(e,2)isthecorrespondingspecklenoisespectrum,asin(d)
butdrawnheretohavethesamenumericalareaunderthe
curveas(e,1),takingintoaccountthelogarithmicscale.
Thedifferenceinareabetweentwosuchsignaland
noisespectra(the'modulationtransferfunctionarea'
orMTFA)isawellrecognisedmeasureofSNR.Introduction
ofthehumanobserverintothecalculationnowentails
appropriatelymultiplyingthedataof(e)bythespatial
angularfrequencysensitivityofthehumaneyebrain
system,i.e.takingintoaccounttheeffectofviewingdistance:
seee.g.Pearson(1975).(c)and(f)showtheresulting
spectraforviewingdistancesof0.5and2mrespectively
where,ineachcase,imageluminanceisoftheorder500
cdm2andtheparameter'd'hasthevalue1mmin
objectspace(e.g.onaviewingscreen).Fromsuchdata

SNRcanbecalculatedas10log10(As/An),whereAsandAn
aretheareasunderthesignalandnoisespectra
respectively.Intheaboveexamples,for(f)SNR
10dBwhile,for(c),SNRisnegative:'Nowyouseeit,
nowyoudon't'.

weneedtolookforaclassofsignalwhosevaluewilldiffersubstantiallybetweenthetwopropertyconditionstobedifferentiated.
Inonesense,thisisnotsayinganythingnew.Itiswellknown,forexample,thatthereasonwhyultrasoundisgenerallybetterthanCTfor

Page284

Figure15.2.
ApproximateformofthedependenceofSNR
ofanechographicsystemonpenetration
depth,forthecommonsituationwheresignal
arisesascontrastbetweendifferentregionsof
ascatteringmedium,suchasasofttissue
(fromHilletal1991).
Table15.1.Classesofsignalandcorrespondingphysicalproperties.
Classofsignal

Physicalproperty

Backscatterechoamplitude

Bulkbackscatteringcoefficient

Slopeofechoamplitudewithdepth

Attenuationcoefficient

Slopeofechoamplitudewithfrequency(and/orfeaturesof
imagetexture)

Characteristicspacingoftissuetexture

Speedofsound

Bulkmodulus/density

Nonlinearityparameter,B/A

Bulkmodulus/density

Tissuemovementcorrelation

Shearmodulus

solidcysticdifferentiationisthat,whiletheXrayattenuationcoefficientinthetwotissuesmaybeverysimilar,amplitudesofultrasonicbackscatterreceivedfromthem
areverydifferent.Whatthisdoessuggest,however,isthat,particularlywhenconventionalultrasonicbackscatterimagingisunsatisfactory,wemightlookfordifferent
classesofsignalforwhichthe(dS/dP)valuemaybemorefavourable.
Whatarethepossibleclassesofsignalthatwemightconsider?Thisisthesubjectofwhathascometobecalledultrasonictissuecharacterisation,or,more
descriptively,iflessconventionally,telehistology.Therehasbeenconsiderableinterestinthissubjectinrecentyearsandwhatisremarkableinthepresentcontextis
thelargenumberof'classesofsignal'thathavebeenconsideredandinvestigated.Anumberofthesearelistedhereintable15.1,togetherwiththecorresponding
principalphysicalpropertythatsuchasignalrepresents.
Someofthemeritsanddemeritsoftheemploymentofsuchsignalsare

Page285

Figure15.3.
Comparativespreadofmeasured
valuesofbulkandshearelasticmoduli
(pascal)forvariousmammaliantissues
(adaptedfromSarvazyanandHill(1999)).

discussedinHilletal(1990).Asanexample,wecanconsiderherethelastonthelistintable15.1:investigationoftissueshearmodulusviaobservationofmovement
correlation.Allthemoreconventionalsourcesofsignal,aslistedinthistable,correspondinsomewaytotissuepropertiesbasedonsomecombinationoftissue
densityandbulkelasticmodulus,andlocalvariationsofthesequantities.Whilethesecanoftenbeproductiveofusablesignals,theactualvariationofthesequantities
betweendifferentsofttissuesistypicallyrathersmall.Thisisillustratedinfigure15.3(takenfromSarvazyanandHill(1999)).Thisfigurecontrastsgraphicallythe
rangesofvariationthatoccurwithinvarioustissuegroupsforbulkandshearmoduli,anddemonstratestherelativelyverysmallspreadofbulkmodulus

Page286

values.Itisthemuchhighernumericalrangeofshearmodulusvaluesthatunderliesthepromisingresultsofthetechniquethathasbecomeknownas'elastography':
essentiallythequantitation,viaultrasonicimaging,oftherheologicalpropertiesoftissues(Tristametal1988).Anillustrativeexampleofthepotentialvalueofthis
approachisintheinvestigationofsomeneoplasms,whosestructuremayleadthemtoshowappreciableanomaliesinshearmodulus(andthus,ifsufficientlysuperficial,
maybemanuallypalpable),whilestillyieldingundetectablebulkmechanical,andevenXrayorNMR,contrast.
Inconclusion,partoftheanswertothequestion:'Howgoodisultrasound?'isthatitdependsonhowintelligentlyitisappliedtotheparticulartaskinhand.Thereare
systematicwaysofdeterminingafigureofmeritfortheapplicationofagiventechniquetoagiventask,althoughsuchaquantitativeapproachhasgenerallynotbeen
followedhitherto.Atthesametime,ultrasoundprovides,potentially,averyrichandvariedsetofapproachesforobtaininginformative'signals'relatingtohuman
tissues.Thereasonswhymanyofthesehavenotbeensubstantiallyexploitedhithertomayhavemoretodowiththemechanicsofcommercialmarketingthanwiththeir
inherentpotentialasinvestigativetools.Thuswemayeventuallyseesomeveryinterestingdevelopmentsfromideasthatarealreadycurrent.
References
EdelsteinWA,BottomleyPA,HartSRandSmithLS1983Signal,noiseandcontrastinnuclearmagneticresonance(NMR)imagingJ.Comput.Assist.Tomogr.
7391401
HillCR,BamberJCandCosgroveDO1990PerformancecriteriaforquantitativeultrasonologyandimageparameterisationClin.Phys.Physiol.Meas.11(Suppl.
A)5773
HillCR,BamberJC,CrawfordDC,LoweHJandWebbS1991Whatmightechographylearnfromimagescience?UltrasoundMed.Biol.1755975
ICRU1996MedicalImagingtheAssessmentofImageQualityICRUReportNo54(Bethesda,MD:InternationalCommissiononRadiationUnitsand
Measurements)
PearsonDE1975TransmissionandDisplayofPictorialInformation(London:Pentech)
SarvazyanAandHillCR1999PhysicalchemistryoftheultrasoundtissueinteractionPhysicalPrinciplesofMedicalUltrasonicsedCRHill,JCBamberandG
RterHaar(London:Wiley)2ndedn,ch7,inpress
TristamM,BarbosaDC,CosgroveDO,BamberJCandHillCR1988ApplicationofFourieranalysistoclinicalstudyofpatternsoftissuemovementUltrasound
Med.Biol.14695707
WagnerRF,InsanaMF,BrownDG,GarraBSandJenningsRJ1991Texturediscrimination:radiologist,machineandmanVision,CodingandEfficiencyedC
Blakemore(Cambridge:CambridgeUniversityPress)

Page287

Chapter16
ChallengesintheUltrasonicMeasurementofBone
JohnGTruscottandRolandStrelitzki
Introduction
In1994theUK'sAdvisoryGrouponOsteoporosisreportedthattheprevalenceoflowbonedensityis22%inwomenover50yearsofageandresultsin60000hip
fracturesayearintheUK.Themostfrequentosteoporoticfracturesareofhip,spineandwristandbythetimetheyare70yearsoldalmosthalfofallwomenwill
haveexperiencedsuchafracture[1].ThecosttotheUKNationalHealthServiceofsuchfracturesissome750000000peryear.
Currentmeasurementtechniquesusedtoidentifyosteoporosisinvolvetheuseofionisingradiation(e.g.dualenergyXrayabsorptiometry(DXA)),orsinglephoton
absorptiometry(SPA)tomeasurebonemineraldensity(BMD)orbonemineralcontent(BMC)inthelumbarspineandthehip.Overthelast5years,however,a
numberofultrasonicbonemeasurementdeviceshavecomeontothemarket.Thecalcaneushasbeenthemeasurementsiteofchoiceforseveralreasons.Vogeland
coworkersbroughtoutfivekeypointsinarecentreview[2]:
Thecalcaneusismorethan90%trabecular(seebelow)byvolume.
Inwomen,agerelatedbonelossinthecalcaneusandlumbarspinearesimilar,withbothcommencingbeforethemenopause.
CalcanealBMDreflectsspinalosteoporosisaseffectivelyasspinalBMD.
Fractureriskinbothspinalandnonspinalsitesmaybestbedeterminedfromcalcanealbonemineralcontentmeasurement.
Althoughbonemeasurementsatmanysitesarecorrelated,indicatingthesystemicnatureofosteoporosis,itisnotpossibletopredictabonevalueatonesitefroma
measuremadeelsewhereinthebody,suggesting

Page288

Figure16.1.
Photomicrographofcorticalbone.Concentriclamellae
surroundthecentralHaversiancanal.Reproducedwith
permissionofLippincottRavenfrom[16].

thatcorrelationofcalcanealultrasoundwithothertechniques(e.g.DXAofspine/femur)isofquestionablevalue.
ArecentEuropeanprospectivestudyofhipfracturein5662elderlywomen[3]demonstratedultrasonicmeasurementofthecalcaneumtobeasgoodapredictorof
futurehipfractureriskasDXAofthefemoralneck.ThisworkhassincebeenconfirmedbyanAmericanstudyof6189womenagedover65[4].Becauseofthese
factors,andtheaccessibilityoftheheel,themajorityofultrasoundsystemsmeasureparametersinthecalcaneusandweshallconcentrateonthatsiteinthischapter.
16.1
Bone
Bonemaybeclassifiedintotwobasictypes:corticalandtrabecular.Corticalboneishardandcompactandistypicallyfoundintheshaftsoflongbones.Figure16.1
showsaphotomicrographofthistypeofboneanditsdense,lamellarnaturecanbeseen.Inthebodysome80%ofboneisofthistype.Theother20%istrabecular
bonewhichcomprisesanopennetworkofstrutsandbarsofbonewiththeintersticescontainingbonemarrow.Thisnetworkcanbeseeninfigure16.2whichisa
scanningelectronmicrographofhealthytrabecularbone.Suchboneistypicallyfoundattheheadoflongbones(e.g.theheadofthefemur),inthevertebraeandalso
inthecalcaneus.

Page289

Figure16.2.
Scanningelectronmicrographofnormaltrabecularbone
showingthicktrabecularplatesallconnected.CourtesyofAlanBoyde.

Boneisnotaninertsubstancebutanorganwhichundergoescontinuousremodellingthroughoutlife.Cellsknownasosteoclastsresorbboneandarefollowedby
osteoblastswhichformanddepositbonematrixwhichisthenmineralised.Anyimbalanceinthisprocesscanleadtopathologicalbonebeingcreated.Theprocessof
majorinteresttousinosteoporosisaredueeithertooverresorbtionortoinadequateformationofbone.Boneremodellinginhealthandosteoporosisareshownin
figure16.3.Astrabecularbonehasastructurewhichgivesitalargesurfaceareaperunitvolumeitismetabolicallyveryactive,typicallyhavinganeighttimeshigher
turnoverratethancorticalbone,makingsitescontainingthistypeofboneidealsitesforobservingboneloss.Theeffectofosteoporosisontrabecularboneis
dramaticallyillustratedinthescanningelectronmicrographinfigure16.4wheremarkedthinninganddisconnectionofthetrabeculaecanbenoted.Thestrengthofthe
boneisseverelyunderminedbysuchchangesandcanleadtofracturesbeingcausedbyverysmallimpacts.Infactsomefracturesinveryosteoporoticboneappearto
occurspontaneously.Asmentionedintheintroduction,thecalcaneusisasiteofhightrabecularcontentmakingitidealforthemeasurementofbonecondition.
16.2
UltrasonicMeasurementsSuitableforBone
Currentcommercialbonemeasurementsystemsconcentrateontwomeasurementsoftheultrasonicwave:attenuationduetothecalcaneusand

Page290

Figure16.3.
Boneremodellinginhealthandinosteoporosis.CourtesyofMerck,
SharpeandDohme.

thespeedofsoundalongtheacousticpath.Becauseofthedensityofboneanditshighlyattenuativepropertiestheonlymodesuitableformakingsuchmeasurements
isbytransmission(insertiontechnique).Thisrulesoutsuchfrequentlyusedmethodsas'singaround'and'pulseechooverlap'(see

Page291

Figure16.4.
Scanningelectronmicrographofosteoporotictrabecularbone
showingmarkedthinninganddisconnectionoftrabeculae.
CourtesyofAlanBoyde.

Chapter4).Measurementsareoftenmadeinawaterbathtoaidtransducertosubjectcoupling.Drysystemsalsoexistandtheseassumethesameinsertiontechnique
aswetsystemsusingavirtualwaterpathtoallowforacomparisontracetoassesschangesinthesignalwhentheheelisplacedinthebeam.
16.2.1
SpeedofSound(SOS)
Usingawaterbathwithtwofixed,coaxialtransducers,oneactingasatransmitterandoneasareceiver,itispossibletomeasurethechangeofthetimeofflightof
anacousticpulsecausedbytheinsertionoftheheelintotheacousticpath.Becausethesoundtravelsfasterinbonethaninwater,theacousticpulsewillarriveearlier
byatime t,which,ifthespeedofsoundinwaterisknown,maybeusedtocalculatethespeedofsoundinthecalcaneus.Thismeasurementisshowninfigure16.5
fromwhichthevelocityinthesubject(cs)canbecalculatedas

wherecwisthevelocityinwateranddstheheelwidth.
Incurrentwaterbathsystemsthemanufacturers'assumptionsaboutheelwidtharenotknown.Insystemswhichusesurfacecontactthedistance

Page292

Figure16.5.
Schematicdiagramoftheprincipleusedfor
measurementsofthevelocitywithabroadbandsignal.
Thenumbersrepresentthezerocrossingpointsofthe
broadbandsignalinwaterandbone.

betweenthetransducersismeasuredandassumedtobetheheelwidth.Contactsystemsassumeaninsertiontechniqueanduseaneffectivebonefreesignalwhichis
basedonthetimeofpassageofthesignalthroughasofttissueequivalentmaterialofknowntransmissionspeed(e.g.water).Theassumptionofwaterasasofttissue
equivalentorofhomogeneityofsofttissueandfatcoverageoftheheelbonemayleadtoinaccuracyinthemeasurementofspeedofsound.Forexampleinpeople
withahighfatcontentinthesofttissueoftheheelthemeasuredspeedofsoundmaybereducedindependentofbonecondition.
16.2.2
Attenuation.
Manycommercialsystemsconfineattenuationmeasurementstoatechniqueknownasbroadbandultrasonicattenuation(BUA),ameasurementfirstdevelopedby
Langtonetalin1984[5].ThefollowingdescriptionofthemeasurementofBUAisagainbasedonasystemusingwaterasacouplingmediumbetweentransducers
andheel.Twotransducersarelocatedcoaxiallyinawaterbath,oneactingasatransmitterandtheotherasareceiver.Theheelispositionedbetweenthetwoas
showninfigure16.6.Abroadbandfrequencyrichpulseisgeneratedatthetransmitter(typicallyhavingfrequenciesintheband0.21MHz),passedthroughtheheel
andcollectedatthereceiver.Similarlyapulseistransmittedthroughthewaterbathwiththeheelremoved.Thetworeceivedsignalsareanalysedbetween200KHz
and1MHztoestablishthefrequencyrelatedamplitudeofthereceivedsignals.Twosuchsignalsareshowninfigure16.7.Thedifference

Page293

Figure16.6.
Thepositionofthefootinthewaterbathshown(top)
mediolaterallyand(bottom)inplantarview(i.
e.fromthesoleofthefoot).CourtesyofChristianLangton.

betweenthetworepresentstheattenuationduetotheheelboneandwhenexpressedasalogarithmicratiogivesusadiagnostictool.Agraphoffrequencydependent
attenuationisshowninfigure16.8andtheslopeofthisgraphdefinesBUAwhichisexpressedindBMHz1.Undertheassumptionthattherelationshipbetween
attenuationcoefficientandfrequencyislinear,ofwhichmorelater,BUAmaybedefinedintermsofthelogratioofamplitudesoftheFouriertransformsofthe
transmittedsignals:

wherefisthefrequency(200kHzto1MHz),Aw(f)istheamplitudeoftheFouriertransformwithouttheheelpresentandAH(f)istheamplitudeoftheFourier
transformwiththeheelinthebeam.
Figure16.9showstwographs:oneforayounghealthyfemaleandtheotherforafemalewithafracturedneckoffemur.ThehighervalueofBUA

Page294

Figure16.7.
Waterandheelamplitudetraces.
CourtesyofChristianLangton.

Figure16.8.
Attenuationtraceforthetwocurvesin
figure16.7.CourtesyofChristianLangton.

isassumedtobeindicativeofboneofbetter'quality'.Somenoiseandnonlinearityisobviousinthehigherfrequencypartsoftheuppergraphandforthisreasonthe
regionbetween200and600kHzhasbeenadoptedforclinicalusebymostmanufacturers.

Page295

Figure16.9.
Comparativetracesforatypicalyoung
femaleadultandtypicalfractured
neckoffemurpatient.CourtesyofChristian
Langton.

16.2.3
Problems
AnumberoffactorsleadtovariabilityinthemeasurementofBUAinbone.Forexample,transducercoupling,phasecancellationandthefittingofalinearmodelare
allsourcesofvariation.Mostimportant,however,isthestructuralanddirectionalarchitectureofthebonewhichhasaneffectonthesignals,whichwillbeconsidered
inthenextsection.Asthemeasurementhasbeenshowntobeagoodpredictoroffuturehipfracture[3,4]thisvariabilityhasbeentolerated.
Speedofsoundmeasurementisinherentlyamoreaccurateandprecisemeasurementtomake.Itis,however,notwithoutproblemsandweshallexploretheseand
somepotentialwaysofunderstandingthemlaterinthischapter.
16.3
EffectofStructureonBroadbandUltrasonicAttenuation
InordertoassesstheeffectsofstructureonmeasuredBUAwemeasuredarangeofphantomswithporositiesbetween46.5%and82.4%.Thereweretwosetsof
thesephantomswithuniformporesizesof0.6mmand1.3mmrespectively.ThesephantomsweremanufacturedusingatechniquedescribedbyClarkeetal[6].
Liquidepoxy(CW1302,CibaGeigy,Duxford,Cambridge,UK)andhardenerweredegassedat3Torrinavacuumchamberandthenmixedwithcubicgranulesof
gelatine.Thesievesizefortheproductionofthesegranuleswaseither0.8mmor1.5mmandthusporesizesinthetwophantomsetsdifferedbyafactorofabout
two.Thegelatine

Page296

Figure16.10.
Sizenormalisedattenuationcoefficientasafunction
ofporosityfortwodifferentporesizes.

andepoxyweremixedtogivevariousporositiesandlefttocureforfourweeks.Thephantomblockswere40mmlongby50mmwideby15mmthick.
Theseporositiesandporesizesarewellwithinthosefoundinvivo[7].Theattenuationcoefficient(dBcm1)ofeachphantomwasmeasuredat600kHz.Thedata
andfittedcurvesareshowninfigure16.10.Attenuationcoefficientsnormalisedforphantomsize(nBUA,dBMHz1cm1)werealsomeasuredintherange200600
kHzandthesedataandtheirfittedcurvesareshowninfigure16.11.Twostrikingfactorsemergefromthesedata:
bothattenuationcoefficientandBUAreducewithincreasingporosity
foragivenporosity,alargerporesizeproducesanincreaseinbothBUAandattenuationcoefficient.
Asporosityanddensityareinverselyrelated,themeasurementofBUAcanbeseentoreflectdensity.However,thechangesinporesizedemonstrateachangein
BUAorattenuationcoefficientwiththeinternalstructureofthematerial.ThiscouldgosomewaytoexplainingthedifferentvaluesofBUAfoundforsimilardensity
valuesinstudiesofexcisedbone[811].AsstructurehassuchamarkedeffectuponBUAatanydensityvalueitisnotsurprisingthatattemptstocorrelateBUAwith
DXAmeasuresofbonemineraldensity(whichofcoursehasnostructuralcomponentinitsmeasurement)havebeeninconclusivewhereasthosemeasuringsome
aspectsofstrength,albeitintermsoffuturefracturerisk[3,4],haveshownBUAtobeausefulparameter.

Page297

Figure16.11.
SizenormalisedBUAasafunctionofporosityfor
twodifferentporesizes.

16.4
ProblemsintheMeasurementofSpeedofSound
16.4.1
TimeDomain(ZeroCrossingPointMeasurement)
Asstatedabove,themajorityofcommercialsystemsusethepulseinsertiontechnique,eitherexplicitlyorimplicitly,tomakemeasurementsofspeedofsound.This
involvestheselectionofareferencepointoneachofthetwowaveformsbetweenwhich tcanbemeasured.Figure16.12showsabroadbandsignalpairandfive
referencepointswhichmaybeconsidered.Zerocrossingpointshavebeenselectedtomirrorthecriteriausedincommercialinstruments.Abroadbandsignalhasalso
beenusedagain,tobeequivalenttocommercialsystemsinwhichBUAismeasured,allowingbothmeasurementstobemadefromasingleacquisition.Themeasured
timedifferencebetweenthereferencepointsischangingfrompointtopointandthisisshowninfigure16.13.Thisfigurealsoindicatesthespeedmeasuredusinga750
kHzsinglefrequencytoneburst(centrefrequencyofthetransducers).Thissinglefrequencymeasurementofspeedisclosetothespeedofsoundmeasurement
associatedwiththeuseofthethirdzerocrossingpoints.Somesystemsusethefirstzerocrossingandothersthethirdwhichcouldleadtodifferencesinmeasured
speedofsoundofasmuchas100ms1inthesamesample.ThiseffectmaybeexplainedifwerememberthatBUAissuchthattheattenuationdependenceon
frequencyisapproximatelylinear.Thiswouldtendtoattenuatehigherfrequenciesmorethanlowerfrequenciesproducingashiftinthefrequencycontentofthe
attenuatedpulsetowardsthelowerendofthespectrumandleadingtoanincreaseinspacingbetweenzerocrossingpoints.Measured

Page298

Figure16.12.
Schematicdiagramoftheprincipleusedfor
measurementsofthevelocitywithabroadbandsignal.
Thenumber(15)representthezerocrossingpointsof
thebroadbandsignalmeasuredwithwaterandbone.

Figure16.13.
Measuredtimesandcalculatedvelocitieswitha
broadbandsignalonitszerocrossingpoints
ontheoscalcis.

BUAinarangeofbonesamplesiscomparedtothetimebetweensecondandthirdzerocrossingpoints,forthatsample,infigure16.14.Anobviouslinear
proportionalitycanbeseen.Thispromptedustomodelthesituationonacomputer.Wedigitisedabroadbandpulseafterpassagethroughwater,appliedfreqency
dependentattenuationat20,40and60dBMHz1intheFourierdomain,andinversetransformedtogivethewaveformsshowninfigure16.15.Forclarity,onlythe
water,20dBMHz1and60dBMHz1,simulatedwaveformsareshown.Noaccountwastakenofphaseinthis

Page299

Figure16.14.
Timebetweensecondandthirdzerocrossing
pointinthebroadbandsignal.

Figure16.15.
SimulatedBUAonascantakenthroughwater
(solidline)for20dBMHz1(dashedline)and60dB
Mhz1(dottedline).

analysis.Thetimedifferencesforeachzerocrossingpointcanbecalculatedandtheseareplottedinfigure16.16(cf.figure16.13)whichissimilartotheinvivocase.
Thetimedifferencesdifferleastamongthemselvesaroundthethirdzerocrossingpointand,rememberingthe750kHztoneburstmeasurement,oneistemptedto
concludethatthismayrepresentsomeformof'true'value.

Page300

Figure16.16.
Timedifferencestakenfromabroadbandsignal(water)to
thesimulatedsignalsofdifferentBUA(fittingcurves:20
dBMHz1,dashed40dBMHz1,solidand60dBMHz1,
dotted)onthezerocrossingpoints.

16.4.2
FrequencyDomainMeasurements
Becauseoftheproblemsidentifiedwithzerocrossingmethodsitmaybeworthwhileexaminingsomeothertechniqueswhicharecarriedoutinthefrequencydomain
ratherthanthetimedomain.Weare,insomeways,driventothesebythefactthattherearepracticaldifficultiesassociatedwithsinglefrequencymeasurementsin
commercialsystems.Wehaveconsideredthreemeasurementsmadeinfrequencyspace:phasevelocity,groupvelocityandmeanpulsevelocity.Exceptforgroup
velocity,avalueof tneedstobeobtainedinordertocalculatevelocityfromequation(16.1).Groupvelocityisobtainedfromphasevelocitydata.Allmeasurements
utilisedbroadbandpulsesanddidnotrestrictthemselvestotherange200600kHzcurrentlyinuseinclinicalpractice.
16.4.2.1
PhaseVelocity
Measurementswerecarriedouton10oscalcestakenfromhumancadavers.Detailsofageandsexwereunknown.Thesampleswerestoredin10%buffered
formaldehydesolutionat4Candweresubsequentlydegassedat3torrindistilledwaterforfourhourspriortomeasurementsbeingmade.Foreachbonesample
usedinthisinvestigationdigitisedwaveforms,at40nsresolution,wereobtainedwithandwithoutthesamplepresentinawaterbath.Bothwavesweresubjectedto
Fouriertransformationtoproducephasevaluessimilartothoseshowninfigure16.17(top)whichwerethen'unwrapped'togiveacontinuousangularscaleshownin
figure16.17(bottom).Thetimedifference( t)at

Page301

Figure16.17.
(Top)phaseofthesignaland(bottom)unwrapped
phaseofthesignal(solidline)anditslinearregression
(dottedline)withaboneinsertedinawatertank.

eachfrequency(f)couldthenbecalculatedfrom:

where wand barethephasesthroughwaterandbonerespectivelyatfrequencyf.Thesevaluesof t(f)canbeusedinequation(16.1)tocalculatethephase

velocity(cp)whichisfrequencydependent.Thisvelocityisplottedasafunctionoffrequencyfortwobonesinfigure16.18.Acuriousfeatureofthesecurvesisthe
negativechangeinvelocitywithfrequency(velocitydispersiondcp/df)whichcanbeseeninallthesamplestested

Page302

Figure16.18.
Velocityasafunctionoffrequencyfortwobonesof
differentdensity(bone6(solidline)andbone7
(dottedline)fromtable16.1).
Table16.1.Datafor10samplesofcalcaneum:cpphasevelocity(700kHz)dcp/dfslopeofphasevelocityversusfrequency
(velocitydispersion)cggroupvelocityat700kHzcc cmeanpulsevelocitycp(fcentre)phasevelocityattransducercentre
frequency(750kHz)nAttenattenuationcoefficientat700kHznormalisedforsamplesizenBUABUAfortherange600
800kHznormalisedforsize.
cp

dcp/df

cg

cc c

cp(fcentre)

nAtten

nBUA

ms1

ms1MHz1

ms1

ms1

ms1

dBcm1

dBMHz1cm
1

Sample
1

1544

35.3

1520

1547

1543

16.0 34.0

1511

4.1

1508

1511

1511

7.0

12.5

1528

39.2

1501

1528

1525

12.6

23.3

1552

63.4

1509

1553

1549

16.1

26.5

1508

12.4

1499

1507

1507

6.5

12.1

1561

79.6

1507

1562

1557

16.4

39.9

1503

11.0

1496

1504

1503

5.7

11.9

1511

6.6

1507

1510

1511

7.8

15.9

1517

12.0

1508

1515

1515

7.9

14.0

10

1540

51.9

1504

1542

1537

14.4

29.2

(table16.1).Suchnegativedispersionisrarelyfoundinnaturebuthasbeenreportedinthelung[12]whichisalsohighlyattenuatingandporous.Thepredominant
findinginthelungwasofslightpositivedispersionbutmuchofthelowerfrequencydatashowedapronounceddownwardtrendingroupvelocityvalueswith
increasingfrequency.MorerecentlyNicholson[13],inmeasurementson30oscalces,obtaineddatawhichdisplayednegativedispersionalthoughtheauthorsdidnot
commentonthisphenomenon.Anotherstudyinvolvingskullbone[14],however,demonstratespositivedispersionbutthiscouldbebecausebothdensityand
structurearesodifferentintheskullfromthecalcaneum.

Page303

16.4.2.2
GroupVelocity
Thegroupvelocity(cg)maybecalculatedfromthephasevelocityanditsdispersionusingtheequation

Asvelocitydispersionisnegativeinallcasesthisalwaysleadstogroupvelocitybeinglowerthanphasevelocity(seetable16.1).
16.4.2.3
MeanPulseVelocity
Themeanpulsevelocity(cc c)isobtained,indirectly,fromacrosscorrelationinFourierspaceofthewavesdigitisedforthecalculationofphasevelocity.Thecross
correlationfunction,s( t),asafunctionoftimeiscalculatedfromthefollowinginverseFouriertransform(IFT):

whereZb(f)*isthecomplexconjugateoftheFouriertransformedsignalinboneandZw(f)istheFouriertransformedsignalinwater.Thepeakvalueofthisfunctionis
takentobe tandusedtocalculateavelocityfromequation(16.1).Theresultsforeachbonearegivenintable16.1asisthephasevelocitycalculatedatthecentre
frequencyofthetransducers.
16.5
Discussion.
Themeasurementofspeedofsoundinthefrequencydomainmaybemorerobustthanmeasurementinthetimedomain.Inthetimedomainvariationsofupto7%can
occurduesolelytoselectionofazerocrossingpointformeasurementof t.Thisoccursasaresultoffrequencydependentattenuationandvelocitydispersion.Using
frequencydomainmeasurementsofcp,cgandcc c,correlationwascarriedoutwiththecorrectedattenuationandBUAvaluesgivenintable16.1.Forcpandcc c,the
valueofr2wasgreaterthan90%forbothattenuationterms,whereasforcgthesevalueswerelessthan30%.Thephasevelocitycorrelationwouldbeexpectedfrom
thewellknownKramersKronigequation[15],butnegativedispersionintheoscalciswouldnotbepredictedbythismodel.Sincethegroupvelocityiscalculated
fromthedispersionofthephasevelocitythismaygosomewaytowardsexplainingthelackofcorrelation.
Acomputermodelwasusedtoinvestigatethedifferencesbetweencpandcc c.ThismodelusedaGaussianbroadbandpulsecentredon750kHz(thecentrefrequency
ofthetransducers)asshowninfigure16.19.Inthefrequencydomain,frequencydependentattenuationwasintroducedasaweightonamplitude,followedbyvelocity
dispersionasaweightonphase.Ineachcasetransformationtothetimedomainwascarriedout.Theresults

Page304

Figure16.19.
Receivedpulsespectrumafterpassagethrough
wateronly.

Figure16.20.
Simulated750kHzpulse(solidline),withdcp/df=84m
s1MHz1(dashedline)andwithdcp/df=84ms1
MHz1andBUA=80dBMHz1(dottedline).

areshowninfigure16.20.Themeanpulsevelocityandphasevelocityaresimilaratthetransducercentrefrequency.Deviationsbetweenthesevelocitiesmaybe
explainedintermsofBUAanddcp/df(dispersion)asfollows:
BUA 0anddcp/df>0

cc c<cp(f centre)

BUA 0anddcp/df<0

cc c>cp(f centre)

Page305

butthedeviationsarealwayslessthan2%andassuchfrequencydomainmethodsseemrelativelyrobustcomparedtotimedomainmethods.
Moreworkisneededintheinvestigationoftherelationshipbetweenthesevelocitymeasuresandbonepropertiesofclinicalrelevance.Inparticulartherelationship
betweenbonestrengthandtheadditionalvelocityparametersshouldbeinvestigatedasshouldtheinfluenceofporesizeandotherstructuralfeaturesonbothvelocity
andattenuation.AlthoughtherelationshipbetweenBUAandbonestructurehasbeenacceptedwefeelthatsimilarrelationshipsbetweenspeedofsoundand
structuralparametersmayhavebeenoverlookedinthemeasurementofbonevelocityusingcommerciallyavailablesystemsandcouldwellrepayfurtherinvestigation.
Acknowledgment
RSacknowledgesthefinancialsupportoftheGermanAcademicExchangeTransfer.
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[5]LangtonCM,PalmerSBandPorterRW1984ThemeasurementofbroadbandultrasonicattenuationincancellousboneEng.Med.138991
[6]ClarkeAJ,EvansJA,TruscottJGetal1994AphantomforthequantitativeultrasoundoftrabecularbonePhys.Med.Biol.39167787
[7]AaronJE,JohnsonDR,KanisJAetal1992AnadvancedmethodfortheanalysisofbonestructureComput.Biomed.Res.25116
[8]TavakoliMBandEvansJA1992TheeffectofbonestructureonultrasonicattenuationandvelocityUltrasonics3038995
[9]SerpeLandRhoJY1996ThenonlineartransitionperiodofbroadbandultrasoundattenuationasbonedensityvariesJ.Biomech.299636
[10]HanS,RhoJ,MedigeJandZivI1996UltrasoundvelocityandbroadbandattenuationoverawiderangeofbonemineraldensityOsteoporosisInt.62916
[11]HodgskinsonR,NjehCF,WhiteheadMAandLangtonCM1996ThenonlinearrelationshipbetweenBUAandporosityincancellousbonePhys.Med.
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[12]PedersenPCandOzcanHS1986UltrasoundpropertiesoflungtissueandtheirmeasurementsUltrasoundMed.Biol.1248399
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[15]O'DonnellM,JaynesETandMillerJG1978GeneralrelationshipbetweenultrasonicattenuationanddispersionJ.Acoust.Soc.Am.6319357
[16]DempsterDW1992BoneremodellingDisordersofBoneandMineralMetabolismedFLCoeandMJFavus(NewYork:Raven)

Page307

INDEX
A
Absorbedpower,153
Absorptioncoefficient,30,58,130,152,178
measurementof,65
tissue,736
Accuracy,281
Acousticabsorber,401,141
Acousticemission,45
Acousticfountain,42
Acousticimpedance,273
Acousticintensity,152,178,181
Acousticloss,100
Acousticmicroscopy,36
Acousticoutput,27,129,133
trendsin,133
Acousticpower,40,42,92,130,133,137,242
measurementof,143
Acousticpressure,23,53,214
axialvariationof,78,14,19
positive,195
negative,23,131,137,203
Acousticpressurewaveform,142
Acousticsaturation,35
Acousticshock,23,47
Acousticstreaming,24,33,36,41,4652,129,2545
Acousticwavelength,4
Acousticworkingfrequency,138
Airbackingoftransducer,100
AIUM,30,205
Albunex,227
Alignment,hydrophone,29
Amnioticfluid,34,47,74
Anisotropyofscatter,82
Apodisation,11,1517,62
Array,transducer,956,102,121,155,191
1.5D,106
2D,106,160
aperiodic,159
concentricring,159
linear,103
noncoherent,158
phased,158,181
sectorvortex,159
sector,103
Artery,imageof,275
Astigmaticfocusing,20
Attenuation,57
measurementof,2925
Attenuationcoefficient,49,58,152,284
measurementof,65
tissue,736
Auditoryresponse,53
Autocorrelationdetection,123
Autocorrelationfunction,80
Autoregressionanalysis,120,124
B
Bmodeimaging,62,230,233,
acousticoutputfor,133
focusfor,146
temperaturerisefrom,131

Page308

B/A,23,45,61,284
measurementof,72
tissue823
Backscatter,284
Backscattercoefficient,59
Backscatteredpower,114
Bandwidth,27,29,36
Beambroadening,24
Beamforming,1035
Beamplot,180
Beamprofile,62,142
Beamwidth,133,157
Bergencode,31
Bioheattransfer,166
Bjerknesforces,213
Blood,47
scatteringfrom,75,7881
coolingby,178
Bloodflow,115
directionof,118,125
occlusionof,184
velocity,ascendingaorta,116
Bloodvessels,209
BMUS,138
Bone,130,287305
absorptionin,182
cortical,288
porosityof,296
speedofsoundin,78,297303
structureof,2957
trabecular,289
Bonephantom,295
Bonethermalindex,136
Brachytherapy,162
Brainlesions,182
Breasttumourtreatment,155,181
Broadbandmeasurementofattenuation,66
Broadbandultrasonicattenuation(BUA),2927
Bubbles,199219,2268,244
aggregationof,213,215,217
chemicaleffectsof,217
fragmentationof,207,212,217
growthof,203,206,217
harmonicgenerationby,211,231
nucleifor,132,206,214,244
populationsof,210
radiusof,200,203,215
resonanceof,200,206,210,230
scatteringfrom,199
shadowingfrom,199,206,218
temperaturerisein,244
Bulkmodulusofelasticity,284
tissue,285
C
Cableresonance,140
Calcaneus,290
Calibration,hydrophone,29,36,142
Calorimetry,144
CancerHospital,xxvi
Cardiacimaging,231
Cardiacresponse,523
Castoroil,68
Catalyst,activation,247
Cavitationnuclei,132,206,214,244
Cavitation,53,129,178,20119,229,242,254
inertial,131,201,207,215
noninertial,203
prompt,214
stable,131
transient,202
Celldeath,218
Centrefrequency,138
CHmodel,170
Characteristicspacing,284
Checksource,144
Chemicaleffectsfrombubbles,217
Choroidalblanching,52,183
Clutter,282
Clutterrejection,36,127
Collagen,scatterfrom,83
Colonimaging,226
Colourcoding,125
ColourDoppler,133,233

Page309

Colourflowimaging,121
Compressibilityfluctuations,80
Contrastagents,27,126,22536
safetyof,22930,233
scatteringfrom,230
Contrastresolution,106,281
Corotidarterydisease,232
Correlationlength,63
Countercurrentpair,169
Coupling,67,154,158
Couplinggel,254
Cranialthermalindex,136
Crosscorrelationdetection,124
Curie,MarieandPierre,xxvii
Cylindricalfocus,20
Cystfluid,52,74
D
Decibel,58
Deepveinthrombosis,232
Densityfluctuations,80
Dentalultrasound,218
Depthoffield,145
Derating,30,130,135
Diagnosticultrasound,3,26,34,205,242,279
Dielectricconstant,95,101
Dielectricdisplacement,92
Diffraction,24,58
Diffractioncorrection,62
Directivity,1045
Directivityfunction,10
Displacement,imageof,266,2689
Dopplercontrast,227,230
Dopplereffect,113
Dopplersignal,originof,114
Dopplersystems,51,11327,134
acousticoutputfrom,133
focalzoneof,145
frequencyof,115,123,145
gatewidthof,145
temperaturerisefrom,131
Doppler,continuouswave,51,116
Drugdelivery,232,2345,2526
transdermal2535
DualenergyXrayabsorptiometry,287,296
Duplexscanning,120
Dwelltime,48
E
Ear,209
Echoamplitude,284
Echoenhancingagents,22536
EchoGen,227
Edgewave,9,112
Effectiveconductivity,170
Elasticmoduli,tissue,285
Elastography,264,286
Electromechanicalcouplingcoefficient,935
Electricfield,244
Electricaldischarge,202
ElectricalQ,101
Embolism,229
Embryo,54,132
Emulsification,246
Endocavitaryprobes,161
Energydensity,40,152,271
kinetic,44
potential,44
Equilibriumlength,169
Erosion,218
Errors,
attenuationmeasurement,67
scatteringmeasurement,71
speedofsoundmeasurement,69
Erythrocytes,80,114,219
Ethanol/watermixtures,70
Eulerianframeofreference,43
Excesspressure,43
Eye,3
F.
Farfield,5
FastFouriertransform,118,120
Fat,scatterfrom,83
FDA,134,206
Fetalheartmonitoring,4
Figureofmerit,281
FiniteamplitudemethodforB/A,72

Page310

Finiteamplitudeeffects,12
Finitedifferencemethod,31
Finiteelementmodel,12,98
Flowturbulence,80
Focaldepth,14,157
Focaldimensions,107,190
Focalgain,
amplitude,13
intensity,13,157
Focus,
acoustic,15
geometric,15
Focusedultrasoundsurgery,4,163,17784
Focusing,13,62,106
cylindrical,20
astigmatic,20
Fountain,acoustic,42
Fragmentation,246
Framerate,105,121,133
Fraunhoferregion,5
Freeradical,203,229,244,2501
Frequency,
acousticworking,138
centre,138
Doppler,115,123,145
optimal,154
Frequencydependenceofattenuation,73,76
Frequencyspectrumanalysis,116,119
Fresnelregion,5
Fullwidthhalfmaximum,157
Functionalstudies,233
Fusionofparticles,246
G
Gallstones,189
Gasbodies,208
stabilised,209
Gasphasecontrastmedia,228
Gaspockets,199
Gaussiandistribution,80,115
Gaussianfunction,105
Gaussianpulse,303
Gaussianweighting,16
Gel,45,132
coupling,195
agarose,2656
Geometricfocus,15
Gol'dbergnumber,25
Gratinglobes,107,159
Greentagging,126
Groupvelocity,68,303
H
Haematocrit,114
Haemolysis,218
Haemorrhage,52,229
Harmonicgeneration,24
Harmonicimaging,108,126,235
Harmonicsfrombubbles,211
Heatflux,165
Heattransfer,165
Heating,24,33,53,73,129,15272,1779
transducer,48,130
Heelmeasurement,2917
Hipfracture,287
Hotfilmanemometry,51
Hydrophone,13740,1924
alignmentof,29
calibrationof,29,36,142
capacitance,191
linearityof,29
membranetype,28,138,191
needletype,28,138,191
optical,191
preamplifierfor,13840
sizeof,29,137,140
Hydroxylradical,251
Hyperthermia,4,27,15164
Hypobaricactivation,228
I
IEC,30,1357,139
Imaging,
Bmode,230
harmonic108,235
Impedance,
acoustic,60,92,273
electrical,923

Page311

Invivomeasurements,66,69
Inflammatorydisease,233
Insertionmeasurement,65,290
Intensity,152,178,181
axialdistributionof,156
outputbeam,136
pulseaverage,47,53,132
temporalaverage,53,129,137,152,178
Intensityloss,24
Interstitialprobes,162
Intestine,gasbodiesin,132
Intraocularpressure,183
J
Jetting,202,208,217,244
K
Kidney,scatterfrom,82
KLMmodel,98,99
KramersKronig,303
KZKequation,31
L
Lagrangianframeofreference,43
Langevin,xxvii
Laseranemometry,48,51
Lastaxialmaximum,8,16
Leadzirconatetitanate,945,100,101,139,163,181
Lenses,15,96,158
Lesion,35
brain,182
shapeof,179
Levovist,227
Linearity,hydrophone,29
Liquidmixing,246
Lithotripsy,4,27,181,18995,218,229
Liver,scatteringfrom,75,8081
Lung,gascavitiesin,74,132
M
Machnumber,24
Macromoleculefracture,247
Magneticresonanceimaging,52,182,2639
contrastagentsfor,230
Masonmodel,97
Matchinglayer,quarterwavelength,100
MayneordWV,xxvi
MayneordPhillipsMemorialTrust,xxv
Mechanicalindex,132,2046
Membranepermeability,219
MI,132,2046
Microperfusion,235
Microstreaming,132,208,211
Modecoupling,transducer,934
Modelstones,194
Modulationtransferfunction,283
Momentumdensity,43
Multigated,pulsedDoppler,121
Muscle,scatteringfrom,78,81
N
Nearfield,45,64,254
Neurosensoryresponse,523
NMRimaging,281
Noise,279,2812
acoustic,63,140
Nonlinearbubbleoscillation,200,211
Nonlinearpropagation,2336,139,179
fieldmodelsfor,3143
Nonlinearpropagationparameter,23,26
NPLBeamCalibrator,142
Nyquistcriterion,115,118,134
O.
Observer,282
Oculartumours,treatmentof,183
Ophthalmology,3
Osteoporosis,287305
OutputDisplayStandard,135
P
Painreceptors,52
Paintingout,181
Palpation,263
Parabolicapproximation,31
Particledisplacement,53,266,2689
Particlevelocity,23
Penetrationdepth,3

Page312

Pennes'bioheattransferequation,166
Perfusion,127,166,177
Perfusionlength,132,138
Peripheralarterydisease,232
Phasecancellation,67,295
Phasequadraturedetection,1168
Phasevariations,64
Phasevelocity,23,68,300
PhillipsCES,xxvi
Physiotherapytransducers,5,16
Physiotherapy,ultrasound,4,34,2512,255
Piezoelectricelement,93
Piezoelectricstress,92
Piezoelectricity,xxvii,913
Pistonsource,4
Placentalflow,233
Planarintegration,145
Plasticwelding,241
Pointspreadfunction,63,108,273
Polymerdegradation,24850
Polyvinylidenefluoride,28,138,142,192
Positioningsystems,191
hydrophone,142
targettissue,158
PowerDoppler,126
Powersensor,140
Precision,281
Pressureimpulseresponsefunction,11,15
Pressuresensitivepaper,194
Probes:seeArrayandTransducer
Prostategland,161,181,183
Pulseenergy,138,195
Pulseenhancementofbubbles,215
Pulselength,4,10
Pulsepressuresquaredintegral,135,141
Pulseprofile,12,16,20
Pulserepetitionfrequency,132
Pulsespectrum,10,32,304
Pulsevelocity,mean,303
PulsedDoppler,118
Pulsedfields,102
PVDF,28,138,142,192
PZT,945,100,101,139,163,181
Q
Q,electrical,101
Quartzpizolectrique,xxvii
Quartzwind,39,46
R
Radiationforce,39,270
onbubble,129,2124
Radiationforcebalance,41,1434
Radiationpressure,3945,255
Langevin,40
measurementusingbubble,45
Rayleigh,445
Radiationpressuregradient,42
Radiationreactance,92
Radiationresistance,92,99
Radiationstresstensor,43
Radiotherapy,151,154
simultaneoushyperthermiaand,155
Rayleighdistance,5
Rayleighdistribution,60,63
RayleighLord,xxvii,201,218
Rayleighscattering,79,114
Rectalprobe,161,183
Rectifieddiffusion,132,210,212,215
Reflection,401,60
Refraction,268
Relaxation,73
Renalarterystudies,232
Renalstones,198
Replicapulse,112
Resolutioncell,63
Resolution,spatial,107,280
Resonance,
bubble,200,206,210,230
hydrophone,29
transducer,92,101
RichardsonLF,xxvii
Rotatingchamber,251
Rouleaux,114

Page313

S
Safety,contrastagents,22930,233
Saline,70,226,227
Sawtoothwaveform,23
Scandepth,146
Scanlinedensity,133
Scanwidth,146
Scattering,5761
coefficient,58
coherence,60
crosssection,58
dimensions,812
fractionoftotalattenuation,75
measurementof,70
tissueproperties,75,79,84
Scatteringfrombubbles,199
Scatteringfromcontrastmaterial,230
Selffocusing,9
Sensitivity,280
Sensoryreceptors,53
Shadowingfrombubbles,199,206,218
Shear,244,247
forces,208
Shearmodulus,284
imageof,269
tissue,26470,285
Shearviscosity,73
Shearwavepropagation,266,268
Shock,23,47
distance,planewave,25
parameter,24
Sidelobes,10,30,35
suppressionof,106
Signaltonoiseratio,279,283,284
Skin,2535
Skinburn,180
Skinimaging,3
Snell'slaw,60
Softtissuethermalindex,136
Solvents,245
Sonosalpingography,226,227
Sonochemistry24152
Sonoluminescence,201,251
Sonophoresis,256
Sonoview,228
Sparkdischarge,190
Spatialresolution,3,13,122,107,280
Specificabsorptionrate(SAR),153,155,164
Speckletracking,124
Speckle,63,2812
Spectrumanalysis,116
Speedofsound,4,23,61,284,291
frequencydispersionof,77
measurementof,68,78,297303
temperaturedependenceof,78
tissue,768
Standingwaves,129,213
Stiffness,2669
Stimulatedemission,231,235
Streaming,24,33,36,41,4652,129,2545
risetime,48
inblood,49
visualisationof,501
Subharmonicgeneration,211
Substitution,measurementby,65
Surfacewavesonbubbles,201,207
Surgery,17784
Symmetry,beam,4
T
Temperature,
dependenceofattenuationon,76
ingasbubble,201
profile,155
Tensilestrengthoftissue,54
Terephthalateion,251
Therapeuticultrasound,4,34,2512,255
Thermal,
conductivity,165,171,177
convection,165
dose,164
models,16471
Thermalindex,1356

Page314

ThermodynamicmethodforB/A,72
Threedimensionaldisplay,126
Timeofflightmeasurement,68
Tissueablation,152,177
Tissuecharacterisation,284
Tissue,elasticproperties,26376
Toleranceofpatient,171
Trachea,209
Transdermaldrugdelivery,2535
Transducer,
chemical,191
coaxialandconfocal,2701
conical,15
couplingof,295
curvilinear,146
designof,99102
electromagnetic,191
impedanceof,93
magnetostrictive,243,191
modelsfor,91,969
physiotherapy,5,16
piezoelectric,243
rectangular,11,1720
sector,146
selfheatingof,1301
sphericalbowl,135
square,32
ultrasoundfocused,11,135,32,151,1568,191
ultrasoundplane,412,32,1546
Transducerloss,99
Transittime,234
Triggering,141
Tumourtreatment,15584
Turbulentflow,80
U
Ultrasoundcleaningtank,131,218,241,243
Ultrasoundinterferometer,66
Ultrasoundfrequency,3,245
Ultrasoundpropertiesoftissues,7383
Ultrasoundstimulatedacousticemission,2705
Underwaterecholocation,xxvii
Urine,34
V
Velocitydispersion,68,302
Velocityofsound,seeSpeedofsound
group,68,303
meanpulse,303
phase,23
Velocityscale,Doppler,145
Vesseldensity,168
Vesselsize,168
Viscosity,467
Visualphysiology,282
Vitreoushumor,52,76
W
Watercoupling,291
Waterforacousticmeasurements,30,42,141,195
Waterreference,70
Waterstandoff,154,177,181
Water/CCl4interface,72
Water/ethanolmixtures,70
WFUMB,129
WJmodel,170
WJLmodel,170
Worstcasescenarios,168
Worstcasevalues,145
X.
Xraycontrastagents,2256,229,230
Xrayimaging,190,192
Z
Zerocrossingcounter,120
Zerocrossing,2979
Zoom,
read,133
write,133,137,146