NEW APPLICATION OF INFRARED SPECTROSCOPY IN MEDICAL DIAGNOSIS

Prof. Jnos Mink

Department of Molecular Spectroscopy Institute of Structural Chemistry Chemical Research Center of the Hungarian Academy of Sciences H-1025-Budapest Pusztaszeri str. 59-67.

Chemical Research Center of HAS Department of Molecular Spectroscopy

Laboratories:

Infrared and Raman Spectroscopic Lab. ESR Spectroscopic Lab. NMR Spectroscopic Lab. Laser Spectroscopic Lab. Professors:

Lszl Biczk Gbor Keresztury Jnos Mink Lsz Nemes Antal Rockenbauer Tams Vidczy

28 16 young scientists / PhD students

University of Pannonia (Veszprm)

Research group: 5 (4) PhD / young scientists

PhD School: Material Science and Technology

Infrared and Raman Laboratory

Budapest:

2 FT-Raman systems FTIR Microscope with FPA detector (micro ATR) FTIR Microscope 2 FTIR spectrometer (ATR) FTIR emission system FTIR-GC system FTIR research grade 2 FTIR routine Far-IR system Open-path FTIR

Veszprm:

S 13 spectrometer

Extended Collaborations

Surface study: ATR; IRRAS; DRIFTS; EMISSION; LBfilms; coatings; polymer surfaces; dispersed catalysts; archeological samples

Analytical studies: HPLC-FTIR; GC-FTIR;TLC-Raman Environmental studies: atmospheric pollutants;

aerosol-microscopy

Theoretical studies: DFT; ab initio; Chemometrsics;

etc.

Medical applications: human hair and skin

One fingerprint

Four fingerprints

Discovery of the spectral effects

Hair: Narcotics in hair Effects of bleaching Effects of UV-radiation Skin: Moisture content Lipid content Effects of cosmetics (Literature)
Unexpected spectral differences

Spectral parameters
Band position
Band intensities Band widths

Spectral subtraction
First derivative Second derivative Band deconvolution

Statistical data processing

artificial neural network (ANN), principal component analysis (PCA) and factor analysis (FA), principal component regression (PCR), partial minimum squares (PMS), Cluster analysis (CA), generic algorithms (GA).

SKIN

Difference IR spectrum of two healthy patients is very small

1.4 1.2

Absorbance

.8

.6

.4

.2

difference
0

1750

1700

1650

1600

1550

1500

1450

Wavenumber (cm-1)

Spectral deviations between healthy and ill patients, exhibiting different RIAR values
.2 1550 RIAR 720 RIAR .1 20 RIAR .15

.05

Arbitrary

-.05

-.1

-.15 1700 1600 1500 1400 1300

-1

1200

1100

1000

900

Wavenumber(cm )

RIAR - Relative Infrared Analytical Risk

RIAR values Classifications Category of healthy condition

0-400 400-600

Healthy Weakly endangered

1 2

600-800
800-1800

Endangered
Highly endangered

3
4

Deviation of a healthy patients spectra from the averaged spectra of healthy patients (minimum 20-40 persons) RIAR Relative Infrared Analytical Risk
180 0
A ra nk a

160 0 140 0 120 0

R IA R

100 0 80 0 60 0 40 0 20 0 0 1 3 4 7 9 da y 10 11 12 14

Process of recovery monitored by infrared spectra of the skin belonging to a patient suffering in pancreas cancer. Green line is the limit value of healthy patients
1800 1600 1400 1220 1200
RIAR

1704

1000 800 600 400 200 0 1 64 day 147 164

Distribution between different types of diseases of 820 ill patients measured by FTIR spectra of their skin
Diseases of cardiovascular system Cancerous diseases Diseases of gastrointestinal segments Lesions of nervous system Diabetes Allergy Total 287 persons 270 persons 82 persons 74 persons 67 persons 40 persons 820 persons (35%) (33%) (10%) (9%) (8%) (5%)

Results of measurements for 380 patients declaring themselves as healthy in accordance of their genial state of health
Qualification Numbers Percent 40% 36% 24%

Healthy or weakly 152 endangered

Endangered
Highly endangered

137 91

Results of 39 diabetic patients and 59 healthy persons analyzed by Principal Component Analysis (PCA)
0.6

healthy
0.4 0.2 0

diabetic
-0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4

8.2

8.4

8.6

8.8

9.2

HAIR

Infrared spectra of untreated (lower trace) and bleached (upper trace) female hair sample. The difference spectrum is given below (dashed line, with 5x ordinate expansion)

Comparison of human hair infrared spectra of a healthy (lower trace, full line) and a breast cancer patient (upper trace, dashed line)

Absorbance

0.5 A.U.

1800

1700

1600

1500

1400

1300

1200

1100

1000

900

Wavenumber(cm-1)

Difference spectrum of healthy and breast cancer patients hair samples

0.02 A.U.

Absorbance
1800

1700

1600

1500

1400

1300

1200

1100

1000

900

Wavenumber(cm-1)

Plot of PCA scores for infrared spectra of hair samples

-Healthy female scores (negative), -healthy male scores (positive), -breast cancer patients scores

Partners
Stockholm University (Electron Microscopy) Institute fr Innovative Diagnostik (Ulm) Municipal Clinic (XVI District, Budapest)

LaborTrading Ltd./Varian (Instrumentation)

Scheme I

PRE-DIAGNOSIS BY OPTICAL METHODS

(Involves WP 1.1 - WP 1.9 work packages)

Measurement

WP 1.1 WP 1.3

EXPERIMENTAL METHODS IN LABORATORIES

IR measurements
Patient Skin Hair (in situ) (laboratory)

MEDICAL CONTROL IN HOSPITAL

Full diagnosis and therapy

Preliminary evaluation

Categories of health conditions WP 1.2 WP 1.4

Classification RIAR software Hair 1 2 3 4 Skin 1 2 3 4 Preliminary comparison with medical control of health conditions (4 categories)

Repeating the measurement checking the diagnosis

Disagreement

Agreement

Category 1 = healthy library (averaging)

IR spectra IR images
(Selected samples)

Category 2-4
EM structures (Selected samples) Structures Classes of similarities Hair A B C D Type of illnesses Illness diagnosis from hospitals

Chemometric (Statistical data processing)

WP 1.5 WP 1.6 WP 1.7 WP 1.8

Chemometric Categories 2-4 Classes of similarities Skin A B C D Hair B D E -

Chemometric Classes of similarities Hair B C D Illness specific libraries

A B C D E F

WP 1.9

SUMMARY OF THE YEARS RESULTS SUMMARY OF TWO THE RESULTS

Transmission FT-IR imaging of human hair

Cuticle

Cortex

Medulla

Images based on the absorption of the CH stretching band (collagen) (A), the Amide I band (protein) (B), of hair

ADVANTAGES

Detection (health condition) Prevention (early diagnosis) Monitoring Diagnosis (under investigation)

CHALLANGING

Simple methods Quick measurement (hair: ~1 min, skin: ~ min) Not invasive and painless Relative cheap Screening test in mass measures Patients showed very positive attitudes

PhD students and young co-workers

Lszl Kocsis

va Pfeifer

Viktria Komlsi

Veronika Gombs

Bernadett Ills

Lszl Hajba

Co-workers

Zsuzsanna Kovcs Dr. Judith Mihly Dr. Zoltn Bacsik Katalin Mdly

Csaba Nmeth

Dr. Gbor Keresztury

Dr. Kroly Hberger

It was my great pleasure to be with you:

Thanks for Jenny, Carolyn, Jennifer, Kevin, Imre, Glenn,
Chris, Mark, George, Baijn and Sam

Special thanks for April H. Foley, Ambassador of

United States

Thanks for your kind attention!!!