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IVUS Application in CAD

Review

Acta Cardiol Sin 2011;27:1-13

Clinical Application of Intravascular Ultrasound


in Coronary Artery Disease: An Update
Chia-Pin Lin,1 Junko Honye,2 Chi-Jen Chang1 and Chi-Tai Kuo1

Intravascular ultrasound (IVUS) employs a miniature ultrasound probe positioned at the tip of a coronary catheter to
emit ultrasound signal which is reflected from surrounding tissue and then reconstructed into a real-time
tomographic gray-scale image. IVUS directly images the vessel inside, allowing measurement of plaque morphology,
distribution and exact vessel composition. Recent technical developments enable processing of the backscattered
ultrasound radiofrequency signal underlying the gray-scale image. Therefore, IVUS can now provide more accurate
measurement of tissue properties than traditional gray-scale images by different methods of tissue characterization.
Thin-cap fibroatheroma by virtual histology was a proved risk factor for future cardiac events. Clinical trials
disclosed significant improvement in patient outcome and reduced complications by IVUS-guided percutaneous
coronary intervention (PCI), which can also provide more information in angiographic ambiguous lesions. 3-4 mm2
for non-left main (LM) lesion or 5.9-7.5 mm2 for LM lesion are considered the cut-off minimal lumen areas to
identify significant stenosis. After stenting, in-stent minimal area 90% of the average reference lumen area or
100% of the lumen area of the reference segment with the lowest lumen area are IVUS-acceptable. In conclusion,
IVUS is a powerful imaging modality which can provide more information before, during and after PCI to facilitate
the procedure. Therefore, it should be used more widely in order to improve clinical outcomes and quality of our
interventions.

Key Words:

Coronary artery disease Intravascular ultrasound Percutaneous coronary intervention


Tissue characterization

INTRODUCTION

ronary angiography (QCA) was the major imaging modality used to assess the severity of CAD and to determine the process of coronary atherosclerosis. However,
many studies have questioned its accuracy and reproducibility.2,3 During the last two decades, technical advances made slender catheters that generate real-time
intra-luminal ultrasound images of the coronary arteries
possible. This new imaging modality, intravascular ultrasound (IVUS), can evaluate the severity of CAD directly
inside the vessel and can easily detect the progression
and regression of atherosclerotic plaque during serial
follow-up. Angiography evaluates the coronary anatomy
as a planar silhouette of the lumen (lumenogram). Ultrasound, on the other hand, directly images the vessel in it,
allowing measurement of plaque morphology, distribution and exact vessel composition. By using this new
modality during percutaneous coronary intervention

Even though there have been major advances in diagnosis and treatment, coronary artery disease (CAD) remains a leading cause of morbidity and mortality in the
developed world, and it is also a growing cause of death
in developing countries.1 Traditionally, quantitative co-

Received: August 21, 2010


Accepted: December 30, 2010
1
First Cardiovascular Division, Department of Internal Medicine,
Chang Gung Memorial Hospital, Chang Gung University, College of
Medicine, Taiwan; 2Fuchu Keijinkai Hospital, Tokyo, Japan.
Address correspondence and reprint requests to: Dr. Chi-Tai Kuo,
First Cardiovascular Division, Department of Internal Medicine,
Chang Gung Memorial Hospital and Chang Gung University, College
of Medicine, No. 199, Tung-Hwa North Road, Taipei, Taiwan. Tel:
886-3-328-1200 ext. 8162; Fax: 886-3-327-1192; E-mail: chitai@
adm.cgmh.org.tw
1

Acta Cardiol Sin 2011;27:1-13

Chia-Pin Lin et al.

sclerotic changes because no lumen narrowing can be


detected until further plaque growth. Moreover, in a diffuse atherosclerotic lesion, angiography may fail to evaluate the severity of lumen narrowing since there is no
truly normal segment that can act as a reference site.

(PCI), many clinical trials have disclosed significant improvement in patients outcomes and reduced complications.4,5 Meanwhile, plenty of clinical pharmacological
trials employ IVUS to demonstrate their beneficial effects because it offers great value in precisely quantifying atherosclerosis progression or regression.6 This new
imaging modality can change our viewpoint in the treatment and evaluation of CAD.

MECHANISM
IVUS is a miniature ultrasound probe positioned at
the tip of a coronary catheter. The probe emits ultrasound frequencies, typically at 20-45 MHz, and the signal is reflected from surrounding tissue and reconstructed into a real-time tomographic gray-scale image.11
The probe is inserted over the guiding wire and then
pushed beyond the lesion; the ultrasound catheter is then
withdrawn slowly for the imaging process. Ultrasound
waves are reflected at the interface of two different tissues. In coronary arteries, there are two clear borders
which can be defined: the lumen-intimal border and the
media-external elastic membrane (EEM) border (Figure
1). Blood speckle in the lumen reflects more weakly
than the echo signal from the intima, allowing for a clear
lumen-intimal border next to the IVUS catheter. At the
same time, the media is echolucent (faint echo signal),
which is manifest on the gray-scale image as a dark ring
outside the intima. The other clear border, the mediaEEM border, is between the dark media and echodense
(bright echo signal) adventitia. Manual or computer-assisted planimetry of these two borders allows precise

LIMITATIONS OF CORONARY ANGIOGRAPHY


Mason Sones, Jr. performed the worlds first coronary angiography in 1958 at the Cleveland Clinic, starting the modern era of percutaneous cardiovascular treatment.7 Although coronary angiography has contributed
greatly to clinical cardiology, this imaging modality may
have misled us regarding the true nature of the atherosclerotic process. Angiography is a lumenogram obtained by injecting contrast media into coronary arteries
in order to detect atherosclerotic disease and predict
coronary events. However, coronary disease is largely
not a disease of the lumen itself but an abnormality of
the vessel wall.8 In fact, most major coronary events occur at insignificantly and not highly stenotic lesions.
Once the plaque ruptures and a thrombus develops, a patient could experience unstable angina, acute myocardial
infarction (AMI), or sudden cardiac death. Therefore,
the size of the lumen and severity of narrowing are not
good predictors of cardiac events.9
Angiography depicts arteries as a planar silhouette
of the contrast-filled lumen. Since the angiogram is a
lumenogram, inadequate angiographic projection may
mislead interpretations of the luminal narrowing. Furthermore, the assessment of lesion severity requires a
comparison of the diseased lumen diameter and normal
segment, which might not always be truly normal if only
diagnosed with angiography.
In 1987, Glagov et al. proposed a new paradigm for
atherogenesis. 10 They suggested that initial atherosclerotic plaque growth leads to compensatory expansion
of the vessel wall (positive or expansive remodeling). In
later phases, after the remodeling fails to compensate for
the accumulation of plaque, lumen narrowing occurs,
and it is at this time that angiography can help. Because
of this process, angiography cannot detect early atheroActa Cardiol Sin 2011;27:1-13

Figure 1. Illustration of intravascular ultrasound image. Left:


Coronary plaque is composed of fibrotic tissue. Right: the same image
shows catheter (most inner circle), lumen-intimal area (middle circle),
external elastic membrane (EEM) area (outer circle) and artifact of
guiding wire (arrow). The echo-lucent ring indicates media layer
(asterisk), and the bright ring outside of EEM is the adventitia.

IVUS Application in CAD

of the probes rotating nature, a common artifact, nonuniform rotational distortion (NURD) can develop
(Figure 2). NURD is a result of the uneven drag of the
rotating transducer, resulting in cyclical oscillations in
rotational speed. NURD is a visible distortion of the image, which may be due to excessive tightening of the
hemostatic valve, a highly tortuous vessel, bending of
the guiding catheter, kinking of the imaging catheter, or
a too small lumen of the guiding catheter. One should
avoid images with NURD in doing measurements.
In phased array system, on the other hand, multiple
transducer elements in an annular array are activated sequentially, generating the image without any rotation.
The phased array can be programmed so that one set of
elements transmits while a second set simultaneously receives information. Because there is no protective sheath
needed, repeated saline flushing is not necessary for
electronic systems and the profile of the distal shaft is
smaller than in the mechanical system; however, such
differences have been reduced in recent years. Owing to
the phased array but non-rotating and long monorail design, NURD and guide-wire artifacts, respectively, do
not develop in electronic system. Furthermore, shorter
transducer-to-tip design can facilitate better visualization
of distal anatomy than the mechanical rotating system.
However, the ultrasound frequency of the electronic sys-

measurements of the lumen area, intima-media area, and


EEM area. On the basis of the backscattered echo signal
from various tissues, we can distinguish different tissues
from each other based on brightness in the gray-scale
image. In addition, recent approaches that use imageprocessing technology to analyze the radiofrequency of
backscattered echo signals can make tissue characterization more objective and detailed, which may influence
decision-making in daily practice, especially decisions in
acute coronary syndrome cases.

EQUIPMENT
The equipment required to obtain such tomographic
images is comprised of three major components: a catheter with a miniaturized probe at the tip, a pullback device, and a console to reconstruct real-time images. The
use of a motorized pullback device at a constant speed
permits volumetric evaluation of the lesion and plaque
dimensions after longitudinal or 3-dimensional reconstruction. IVUS catheters currently available range from
2.6 to 3.5 French (outer diameter, 0.87-1.17 mm), are
suitable for examining distal coronary lesions and permit
examination of most stenotic lesions before PCI.12 Most
IVUS catheters are monorail system, which can facilitate
rapid exchange and can be placed through a 6-French
guiding catheter. For some specific probes, even a 5French guiding catheter can be used. Two different approaches to transducer design are commonly used: (1)
mechanical rotating devices and (2) electronically switched multi-element array system.
Mechanical rotating probes use a driving cable to
rotate at 1800 rpm (30 images per second). The probes
emit an ultrasound beam perpendicular to the catheter
and vessel. In this system, the imaging transducer is protected in a transparent sheath, which facilitates smooth
and uniform pullback. During IVUS examination, the
sheath as well as the probe is advanced beyond the lesion or the segment of interest and the probe is then
pulled back within the sheath either manually or motorized (usually 0.5 mm/s). However, small air bubbles between the probe and protective sheath can significantly
deteriorate image quality, and saline flushing is required
to provide a fluid environment for the ultrasound beam
before the probe is inserted in a coronary artery. Because

Figure 2. NURD, non-uniform rotational distortion (arrow).

Acta Cardiol Sin 2011;27:1-13

Chia-Pin Lin et al.

cular events.16,17
Despite the invasive nature of IVUS, its safety is
well established.18-20 Complication rates vary from 1% to
3%, and the most frequently reported adverse event is
transient coronary spasm, which can be easily resolved
by administering nitroglycerin. Major complications are
vessel dissection and closure, and these complications
occur in < 0.5% of cases; most of these events develop
during PCI.

tem is only 20 MHz, which means that it has poorer


image resolution than mechanical system.

ADVANTAGES OF ULTRASOUND IMAGING


The basic advantage of IVUS over angiography is
the penetrating nature of ultrasound, which allows direct
evaluation of not only the lumen but also the surrounding vessel wall. Unlike angiography, IVUS can directly
assess an atherosclerotic plaque and the remodeling of
arterial wall as well as diffuse lesions. Hence, it is more
sensitive than angiography for detecting vascular lesions, especially in the early phase. An IVUS study of
the hearts of cardiac transplant donors revealed significant coronary plaques even in very young (< 20 y/o) patients.13 This means that atherosclerotic risk factors begin affecting coronary arteries many decades before
symptoms appear, and IVUS, not angiography, can easily detect such damage. In almost all CAD patients,
IVUS detects more diffuse and extensive plaques within
coronary arteries than angiography. Therefore, IVUS
provides more information regarding CAD than angiography does.
IVUS can also detect plaques that have a high risk
of spontaneous rupture or the ruptured plaque with insignificantly angiographic finding. Some typical morphologic criteria, such as echolucent area located in the
positive remodeling segment covered by a thin fibrous
cap, can be identified by IVUS.14,15 However, most of
these studies were cross-sectional, which limited their
ability to identify real causal relationships. Recently, the
preliminary results of the first prospective IVUS virtual
histology follow-up study were announced, which suggested the combination of large plaque burden and a
large necrotic core with thin cap identified by virtual
histology are risk factors for future adverse cardiovas-

IVUS-BASED DETECTION OF PLAQUE


COMPOSITION
The IVUS probe generates an ultrasound signal and
receives the backscattered signal from tissue; this signal
is processed in real-time into a tomographic gray-scale
image. This image provides useful information for the
determination of vessel and lumen diameters and the severity and distribution of plaques. The gray-scale IVUS
image can also be used to characterize coronary plaque
composition on the basis of the echogenicity of different
structures.21 However, owing to the basic features of the
gray-scale images, such as operator-dependent interpretation, equipment settings, and limited resolution, grayscale IVUS is a suboptimal tool for accurately and reproducibly identifying plaque composition.22 However,
recent technical developments enable processing of the
backscattered ultrasound radiofrequency (RF) signal
underlying the gray-scale image. Therefore, IVUS can
now provide more accurate measurement of tissue properties than traditional gray-scale images. There are
three different RF data analysis methods now available:
autoregressive (AR) modeling, fast Fourier transform
(FFT), and a newly designed pattern recognition algorithm and mathematically defined spectral similarity system (Table 1).

Table 1. The comparison of different tissue characterization models

Mechanism
Trade name
Company
Gray-scale resolution
Number of tissue typing

AR model

FFT model

Spectral similarity

Classification tree
IVUS-VH
Volcano
20 MHz
4

IB value
IB-IVUS
YD
40 MHz
5

Pattern recognition
iMap
Boston Scientific
40 MHz
4

AR, autoregressive; FFT, fast Fourier transform; IB, integrated backscatter; IVUS, intravascular ultrasound; VH, virtual histology.
Acta Cardiol Sin 2011;27:1-13

IVUS Application in CAD

FFT measured in decibels (dB).27 A color-coded tissue


map based on the IB values for different plaque components was then constructed. Unlike AR modeling, FFT
modeling divides tissues into 5 categories on the basis of
IB value: (1) calcification (-30 dB to -23 dB), (2) mixed
lesion (-55 dB to -30 dB), (3) fibrous tissue (-63 dB to
-55 dB), (4) lipid core or intimal hyperplasia (-73 dB to
-63 dB), and (5) thrombus (-88 dB to -80 dB). High
diagnostic sensitivity (84% for lipid pool, 94% for fibrotic, and 100% for calcification) was also found in
another autopsy study of 42 coronary arteries.28 However, such FFT modeling tissue characterization is only
available in Japan, and large-scale studies to confirm
this methods accuracy remain to be performed.

Autoregressive modeling
After the IVUS-RF data are obtained from coronary
arteries during pullbacks, AR modeling converts these
data into a spectrum graph that plots the strength of the
backscattered signal against frequency. The averaged
spectrum is then normalized and parameters are identified from it within the bandwidth 17-42 MHz.23 A classification tree is used to characterize atherosclerotic coronary plaques, and this tree has the following parameters:
(1) y-intercept, (2) maximum power, (3) mid-band fit,
(4) minimum power, (5) frequency at maximum power,
(6) frequency at minimum power, (7) slope of regression
line, and (8) integrated backscatter. Atherosclerotic coronary plaques can be characterized into four different
categories on the basis of their components: fibrotic,
fibro-fatty, necrotic, and calcified. An in vivo IVUS
mapping study generated 87-97% accurate predictions
after results were compared with histological sections
obtained by directional coronary atherectomy.24 However, in another in vivo study, IVUS had only 38-58%
diagnostic accuracy for assessing 60 lesions in an atherosclerotic porcine model. 25 Therefore, we still need
large-scale in vivo studies to validate this modeling
method. Meanwhile, eletrocardiogram-gating is required
by this method, which may limit its clinical convenience.26

Spectral similarity system


Recently, a newly designed pattern recognition algorithm was used to predict the tissue type of a given region of interest by comparing its RF spectrum against a
database (library) and also estimating the confidence of
prediction.29 Conceptually, this system characterizes a
tissue type by comparing the spectrum from a vessel
with spectra of known tissue types, using a mathematically defined measure to determine the similarity between the two spectra. Therefore, this system can provide the average confidence level for each tissue type
within the frame or entire lesion, which is a capability
that previous tissue characterization systems lack. This
system classifies plaques into four different tissue types:
fibrotic, necrotic, lipidic, and calcified. One example of
such system is shown in Figure 3. Recently, by the first

Fast Fourier transform modeling


Another tissue characterization method is direct
mapping of the region of interest, using its integrated
backscatter (IB) value. IB was calculated as the average
power of the ultrasound backscattered signal by using

Figure 3. Illustration of a lesion in angiography, gray-scale intravascular ultrasound and color-coded tissue characterization. Left: the
angiography showed a significant stenotic lesion (arrow) in the proximal right coronary artery. Middle: the gray-scale IVUS image of the culprit
lesion showed mixed echoic plaque without obvious calcification. Red and yellow circles indicate lumen and EEM area, respectively. Right:
color-coded tissue characterization by spectral similarity system of the culprit lesion showed fibrotic tissue (green) and lipidic tissue (pink).
5

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stenosis, such as under-expansion or neointimal hyperplasia, and to guide selection of appropriate therapy (repeat balloon expansion or vascular brachytherapy); (3)
to evaluate undetermined coronary lesions, which are
difficult to image with angiography because of their
location; (4) to assess a suboptimal angiographic result
after PCI; (5) to establish the distribution and presence
of coronary calcium for which adjunctive rotational
atherectomy is considered; and (6) to determine the
plaque location and circumferential distribution for
guidance of directional coronary atherectomy.31 In addition, color-coded tissue mapping of a specific pattern
of culprit plaques in ACS patients can predict notorious
slow flow or no reflow phenomenon before intervention.32
Furthermore, by tissue characterization, it is possible to
identify vulnerable plaques, lipid-rich necrotic cores
covered by a thin fibrous cap (TCFA, thin-cap fibroatheroma), before rupture.23 Strategies for IVUS-guided
PCI are summarized in Figure 4.

clinical study that used this system reported a large proportion of necrotic tissue in the culprit lesion of an acute
coronary syndrome (ACS) patient with high confidence
levels and no reflow phenomenon.30 Since this mapping
modality is a newly developed system, further studies
are needed before it can be used in clinical settings.

IVUS-GUIDED PCI
IVUS-guided stenting has been proved to lead to a
21% reduction (from 18.7% to 15%) in major cardiac
adverse events as compared to angiographic-guided
stenting in a meta-analysis.4 This result was mainly because of a 38% reduction in target vessel revascularization in the IVUS-guided arm. According to the 2005
update of the PCI guidelines of the American College of
Cardiology/American Heart Association/Society of Cardiovascular Angiography and Interventions, there is no
class I indication for IVUS in PCI; however, several
class IIa indications are recommended: (1) to assess the
adequacy of stent expansion, including the extent of
stent apposition and the minimal luminal diameter within
the stent; (2) to determine the mechanism of stent re-

Before intervention
IVUS is a powerful tool for evaluating plaques
themselves and the surrounding anatomy before PCI.
Clear identification of the characteristics of culprit

Figure 4. Intravascular ultrasound-guided percutaneous coronary intervention (PCI) strategy. SB, side branch; LM, left main; EEM, external
elastic membrane.
Acta Cardiol Sin 2011;27:1-13

IVUS Application in CAD

the distal, proximal reference site and lesion site should


be evaluated during or online immediately after the pullback. Negative remodeling is frequently encountered at
the lesion site, especially in chronic total occlusion
(CTO) cases, making lesion sizing difficult. It is reasonable to size the stent to 0.8- to 0.9-folds of the minimal
diameter of the EEM at the distal reference site. In the
Multicenter Ultrasound Stenting in Coronaries study
(MUSIC) trial, in-stent minimal area 90% of the average reference lumen area or 100% of the lumen area of
the reference segment with the lowest lumen area was
suggested.35

plaques and vessels can help to improve clinical outcomes after interventions. Usually, the monorail-system
IVUS probe should be advanced at least 10 mm beyond
the culprit lesion after adequate systemic heparinization
and intracoronary administration of 100-200 mg nitroglycerin. During motorized or manual pullback at a constant speed, the image is recorded to a videotape or a
hard disk. Automatic pullback is usually recommended,
because we are able to obtain volumetric data. The entire
imaging process should be continued until back to the
aorta in all cases, and disengaging the guiding catheter
from the coronary artery is mandatory if an aorto-coronary lesion is suspected.33

Intermediate lesions
Although coronary angiography has been considered
the gold standard for evaluating the stenosis of coronary
arteries, indeterminate lesions are commonly encountered despite multiple angiographic projections because
of vessel overlapping, tortuosity, eccentricity, ostial/
bifurcation, or severe calcification. A study of 70 de
novo coronary lesions [not including the left main (LM)
coronary artery] used 4.0 mm2 as the cut-off minimal lumen area (MLA) to identify significant stenosis when
compared with stress myocardial perfusion scan results;
it revealed 80% sensitivity and 90% specificity. 36 Another study of 51 non-LM lesions used 3.0 mm2 as the
MLA criteria for maximizing the sensitivity (83%) and
specificity (92.3%) when a value of fractional flow reserve (FFR) < 0.75 was considered as significant in
determining inducible ischemia.37
It is more difficult and unreliable to assess the severity of LM lesions, making further revascularization
plans difficult. In an autopsy study, it has been demonstrated that angiographically significant lesions were
often mildly diseased. 38 Similar to non-LM stenosis,
IVUS provided a tomographic viewpoint of LM stenosis and was more sensitive in detecting vessel wall
characteristics and atherosclerosis than angiography.
When FFR < 0.75 was used as the gold standard for
detecting significant LM stenosis, a study of 55 patients
showed highest sensitivity and specificity by using an
MLA of 5.9 mm2 and minimal lumen diameter (MLD) of
2.8 mm as IVUS indicators.39 Another LM study with
clinical end-points has suggested that an MLA of 7.5
mm2 should be used as the cut-off value for performing
revascularization.40

Lesion length
Determining adequate lesion length and stent landing zone is crucial for PCI, especially in long and diffuse
lesions. In a quantitative IVUS analysis from the SIRIUS
trial, inadequate lesion coverage may contribute to edge
restenosis after deploying a sirolimus-eluting stent. 34
The baseline maximal reference plaque area was significantly larger in the edge restenosis group than in the
non-restenosis group (60.5% vs. 48.58%). Therefore, it
is reasonable to choose a stent-landing zone with a
plaque area of < 50%.
At least three methods exist to determine the lesion
length for further PCI planning. (1) Time-counting
method: Since the motorized pullback occurs at a constant
speed and detailed imaging time is also simultaneously
recorded, the lesion length can be easily determined with
the following equation: (pullback speed) (time taken by
the probe to travel from the distal reference site to the
proximal reference site). (2) Long-view method: Almost
all IVUS consoles can yield a reconstructed longitudinal
view during and after the imaging process. By identifying the proximal and distal reference sites, the lesion
length can be rapidly determined. (3) Marking technique:
In some pullback devices, the pullback distance can be
manually reset. In such circumstances, whenever the distal reference site is identified by angiography and IVUS,
one can obtain precise lesion length on the pullback device after resetting the distance to zero and manually pulling back the device to the proximal reference site.
Lesion diameter
The lumen and EEM cross-sectional area (CSA) of
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and a smaller percentage of fibrous component.32 Thrombus aspiration or distal protection device deployment
before PCI is recommended if such lesions are found.
Furthermore, sometimes interventionists may encounter
multiple borderline angiographic lesions without critical
narrowing during ACS intervention. IVUS as well as
tissue characterization may play an important role in
locating the culprit lesion where plaque rupture or TCFA
has developed.49

Pre-treatment before PCI


Several plaque characteristics such as the severity
and extent of calcification, arterial remodeling, plaque
distribution, and the presence of dissection or thrombi
can affect the decision to use a particular treatment before PCI. Some studies have reported that IVUS imaging
before PCI can influence operators decision making and
treatment strategy.41,42
With regard to calcified lesions, IVUS is more sensitive than angiography for determining the distribution
of calcification as circumferential or non-circumferential. During high-pressure balloon or stent inflation, vessel expansion tends to develop at compliant sites if
heterogeneous materials are involved. It means that in a
non-circumferential calcified lesion, vessel dissection or
even rupture may occur at the junction of calcified and
non-calcified plaques if high-pressure inflation is used.
In such a scenario, dilatation followed by stenting may
be prepared before PCI. With regard to circumferential
calcified lesions, especially superficial calcified plaques,
the delivery and expansion of balloons and stents may be
difficult. Plaque modification by rotablation or cutting
balloon before intervention is reasonable and can facilitate procedure success and also prevent balloon/stent
under-expansion.
With regard to bifurcation lesions, IVUS can detect
the distribution of plaques not only in the main branch
but also in the ostium of the side branch (SB). One study
revealed that SB occlusion occurred in 35% of the
plaque-containing lesions at the SB ostium after PCI as
compared to the 8.2% occlusion rate of plaque-free lesions at the SB ostium. 43 Therefore, wiring the SB to
protect it before PCI should be considered if IVUS reveals plaque involvement at the SB ostium.
In ACS patients, no reflow phenomenon during PCI
leads to an unfavorable outcome. Clinical factors associated with this phenomenon include age, male sex,
hyperglycemia, increased white blood cell count, and
absence of pre-infarction angina.44-46 The most consistent risk factors for this phenomenon, determined by
gray-scale IVUS, are the presence of an attenuated
plaque, thrombus, large plaque burden, lipid pool-like
imaging, and positive vessel remodeling. 47,48 Colorcoded tissue characterization has been proved to predict
such phenomena before PCI if lesions are observed to
have a higher percentage of necrotic core component
Acta Cardiol Sin 2011;27:1-13

After intervention
In the era of bare metal stent (BMS), post procedure
MLD has been proved to be one of the predictors of
restenosis by angiography.50 By IVUS, the MUSIC trial
has suggested that adequate stenting results in favorable
clinical and angiographic outcomes.34 Such strategy includes the following: (1) complete apposition of the
stent over its entire length against the vessel wall; (2)
in-stent minimal area 90% of the average reference
lumen area or 100% of the lumen area of the reference
segment with the lowest lumen area; and (3) symmetric
stent expansion defined by a minimal lumen diameter/
maximal lumen diameter of 0.7.
Under-expansion and incomplete stent
apposition (ISA) (Figure 5)
Stent expansion refers to the in-stent minimal area
after the stent is deployed, and stent apposition refers to
a condition in which the stent is in complete contact
with the vessel wall. In the bare-metal stent era, neointimal hyperplasia and suboptimal stent expansion
were strong factors for restenosis.51 In the Can Routine
Ultrasound Influence Stent Expansion (CRUISE) trial,
larger MLD and MLA were obtained in the IVUSguided group than in the angiographic-guided group.52
Such improved expansion with IVUS-guided stenting
resulted in a clinical benefit at the 9-month follow-up
in terms of target vessel revascularization. In the drugeluting stent (DES) era, neointimal hyperplasia was
largely suppressed, making stent under-expansion the
major mechanism for restenosis. 53 In a prospective
study, the post-procedural minimal stent area remained
a strong predictor of restenosis.54 Meanwhile, ISA has
been proved to be a major cause of acute/subacute stent
thrombosis (ST). Moreover, late/very late ST of DES
was also observed in patients with ISA.55 In that study,
8

IVUS Application in CAD

Figure 5. Example of left main (LM) incomplete stent apposition. Angiography of critical left anterior descending artery (LAD) stenosis (left upper
panel). Angiography after stenting from LAD to LM and kissing ballooning (middle upper panel). IVUS showed incomplete stent apposition (left
lower panel) where blood speckles presented between stent (inner circle of middle lower panel) and vessel wall (outer circle of middle lower panel).
After high-pressure dilatation with larger balloon, angiography (right upper panel) showed larger LM diameter and IVUS (right lower panel) also
revealed better stent apposition.

usually requires a longer stent than angiographicguided stenting. At the same time, intramural hematoma, defined as an accumulation of blood within
the medial space and displacement of the internal elastic membrane inward and the EEM outward, can be accurately evaluated with IVUS.59 Intramural hematoma
may accompany dissection and associated with higher
rate of non-Q-wave MI, repeated revascularization and
sudden cardiac death.60

the incidence of ISA was 77% in the very late ST group


and only 12% in the control group. Therefore, higher
pressure with larger balloon should be recommended
for post-dilation in order to obtain adequate stent expansion and apposition.
Complication survey
After PCI, IVUS is commonly used to detect the
morphological effects of angioplasty and complication
such as slow flow/no reflow, dissection, 56 intramural
hematoma,57 plaque prolapsed, or spasm. Six morphological patterns after angioplasty have been proposed
by researchers using IVUS.58 Meanwhile, coronary dissection is a common reason for acute closure during or
after PCI. According to the depth of the dissection, a
classification of intimal, medial, and adventitial dissection was proposed. 58 IVUS is more sensitive than
angiography for detecting dissection and can also
clearly identify the extent of dissection to guide further
stenting if flow-limiting dissection develops, which

APPLICATION OF CLINICAL RESEARCH


Because IVUS is more sensitive than angiography
for evaluating coronary plaque even in angiographically normal arteries, it has become a powerful tool for
evaluating plaque progression or regression trials with
various pharmacological interventions such as statins
and angiotensin-converting enzyme inhibitor. 6 In the
Reversal of Atherosclerosis with Aggressive Lipid
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FUTURE DIRECTIONS OF IVUS USAGE IN


TAIWAN

Lowering (REVERSAL) trial, IVUS demonstrated a


significant lower plaque progression rate in the intensive
lipid control arm than the moderate-treatment arm.61 In
A Study to Evaluate the Effect of Rosuvastatin on
Intravascular Ultrasound-Derived Coronary Atheroma
Burden (ASTEROID) trial, IVUS showed significant
atheroma volume regression after high-dose statin treatment.62 In a substudy of the Comparison of Amlodipine
vs. Enalapril to Limit Occurrences of Thrombosis
(CAMELOT) trial, IVUS showed atheroma progression
in the placebo group, a trend toward progression in the
enalapril group, and no progression in the amlodipine
group.63

IVUS-guided PCI accounts for approximately 5%8% of procedures in the United States,8 and the number
in our country is likely lower than that. Since IVUS has
been proved to improve clinical outcomes in various
studies, it should be used more frequently in daily practice.56,57,65 In order to do so, the crossing ability, pushing
ability, tracking ability, and image quality should be improved; it should be made more easy to use; and the system interface should be more user-friendly. Meanwhile,
the cost of the system is also a key point influencing decisions about performing IVUS-guided PCI, especially if
it is not covered by national health insurance. Reducing
the cost of IVUS-guided PCI is another critical issue that
needs to be addressed if this procedure is to be popularized. Furthermore, holding IVUS-specific workshops or
conferences with experts will also help.

IVUS VERSUS OPTICAL COHERENCE


TOMOGRAPHY (OCT)
Intravascular OCT is a high-resolution optical intravascular imaging modality, which is approximately 10
times higher in resolution than IVUS. It uses near-infrared light rather than ultrasound, which may allow evaluation of not only intravascular microanatomy but also
neointimal formation and stent apposition. However,
there are some limitations of OCT in clinical use. First,
blood cells can interfere with OCT imaging; therefore,
vessel occlusion with a balloon, followed by continuous
flushing with lactated Ringers solution, is mandatory
for OCT examination. Second, limited visual depth is a
limitation of OCT; it prohibits the assessment of large
coronary vessels and deeper structures, so that IVUS is
still more useful in terms of assisting PCI. Recently, new
generation frequency-domain OCT (FD-OCT) has demonstrated some advantage over conventional time-domain OCT (TD-OCT) and has been developed for clinical use64 (Table 2).

SUMMARY
IVUS provides more detailed information than conventional angiography. Its safety and significant influence on daily decision-making in the catheterization
laboratory have been proved. IVUS evaluation before
and after PCI can improve clinical outcome and resolve
doubts about ambiguous lesions. Tissue characterization
is a new technique that is based on signal analysis,
which provides further information for lesion survey and
complication prevention. IVUS is also a powerful tool
for atherosclerotic evaluation for pharmacological treatment. OCT is another tomographic modality for evaluating coronary anatomy in more detail. However, increased procedure difficulty and limited visual depth

Table 2. The differences between intravascular ultrasound (IVUS), time-domain optical coherence tomography (TD-OCT) and
frequency-domain optical coherence tomography (FD-OCT)

Mechanism
Axial resolution (mm)
Lateral resolution (mm)
Frame rate (image/sec)
Catheter size (inches)
Pullback speed (mm/sec)

Acta Cardiol Sin 2011;27:1-13

IVUS

TD-OCT

FD-OCT

Ultrasound
100-150
150-300
30
0.08-0.12
0.5

Near infrared
10-20
20-40
15.6
0.016
1.0-2.0

Near infrared
10-20
20-40
100
0.016
20

10

IVUS Application in CAD


103:2705-10.
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15. Birgelen CV, Klinkhart W, Mintz GS, et al. Plaque distribution
and vascular remodeling of ruptured and nonruptured coronary
plaques in the same vessel: an intravascular ultrasound study in
vivo. J Am Coll Cardiol 2001;37;1864-70.
16. Stone GW, Maehara A, Lansky AJ, et al. A prospective naturehistory study of coronary atherosclerosis. N Engl J Med 2011;
364:226-35.
17. Conti CR. Finding the vulnerable plaque. Clin Cardiol 2010;
33:320-1.
18. Hausmann D, Erbel R, Alibelli-Chemarin MJ, et al. The safety of
intravascular ultrasound: a multicenter survey of 2207 examinations. Circulation 1995;91:623-30.
19. Guedes A, Keller PF, LAllier PL, et al. Long-term safety of
intravascular ultrasound in nontransplant, nonintervened, atherosclerotic coronary arteries. J Am Coll Cardiol 2005;45:559-64.
20. Batkoff BW, Linker DT. Safety of intravascular ultrasound: data
from a multicenter European registry. Cathet Cardiovasc Diagn
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21. Bose D, Birgelen CV, Erbel R. Intravascular ultrasound for the
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restrain its clinical use. Finally, the use of IVUS in our


country remains low because of various reasons. System
improvements, reduction in costs, and frequent IVUSspecific conferences could lead to IVUS being used
more widely, thus improving clinical outcomes and the
quality of our interventions.

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