detection of vulnerable plaque by nis

Pedro R. Moreno, MD, FACCUniversity of KentuckyLexington, Kentucky

Detection of Vulnerable Atherosclerotic Plaques

By Near Infrared Spectroscopy

• Biological tissues have unique absorbance in the NIR wavelength range• NIR light has enough penetration that may obtain spectra through blood

Tissue Evaluation by Near-IR Spectroscopy

Absorbance peaks are caused by: Combinations of fundamental bonds (C-H, C=C, C=O) Electron transitions in the heaviest atoms

Advantages of Near-IR SpectroscopyFor Vulnerable Plaque Research

• Analysis under 1 second

• Simultaneous, multi-component, non- destructive analysis

• Chemical, biological and molecular information

• Automated predictions using computer algorithms

• Detection limits can be very low (from picograms to planets)

• Cost per analysis is minimal (no reagents used)

Dempsey RJ & Lodder RA. Applied Spectroscopy 1996;50:18A-34A

Near-IR Spectroscopy to Identify Vulnerable Plaques

Studies 1998-2001

• Human aortic plaques in-vitro

• Human coronary plaques in-vitro

• Rabbit aortic plaques in-vivo• Coronary pig safety study

• Human coronary plaques in-vivo

Hypothesis

• NIRS will identify vulnerable

plaques (1)

Methods

• Spectrometer: InfraAlyzer 500 (2)

• H & E and Trichrome staining

Identification Algorithm Model (3,4)

• 50% - Training set (histology)

• 50% - Validation set

Plaque Composition by Near-IR Spectroscopy198 Human Aortic Plaques

1. Lipid pool (>30%), thin cap (< 65 µm), and macrophages 3. Chemometric software (Math 3.0, Matlab 5.1,Speakease IV Eta) 2. (Bran+Luebbe, Elmsford, N.Y.) 4. Regression by principal component analysis

Blinded prediction

Near-IR System

Near Infrared in Human Aortic Plaques

Moreno PR, et al. Circulation 2002;105:923-927

Lipid

Fibrotic

Thin Cap

Thick Cap

Macrophages

No Macrophages

(n=198)

Correlation of Blinded Near-IR SpectroscopyResults with Histologic Findings

99 Aortic samples

HISTOLOGY

LIPID POOL THIN CAP MACROPHAGES

+ - + - + -

+

-

35 4

4 56

13 6

4 76

37 6

7 49NEAR-INFRARED

SPECTROSCOPY

Moreno PR, et al. Circulation 2002;105:923-927

• Sensitivity (%) 90 77 84

• Specificity (%) 93 93 89

• PPV (%) 90 68 86

• NPV (%) 93 95 88

PPV:Positive Predictive Value; NPV:Negative Predictive Value

99 Aortic samples

Correlation of Blinded Near-IR SpectroscopyResults with Histologic Findings

Lipid Pool Thin Cap Macrophages


Studies 1998-2001





Coronary Composition by Near-IR Spectroscopy

147 Human Coronary Sections

Hypothesis• Lipid pool in coronary plaques

Methods

• Spectrometer: Foss/NIRSystems • H & E and Trichrome staining

Identification Algorithm Model

• Training Set (76 sections)

• Validation set (70 sections)

Blinded prediction

Spectrometer

Moreno PR, et al. JACC 2001;37:356A

03-Coronary Tissue Scans

798 1198 1598 1998 2398

Variable

0.5

1.0

1.5

2.0

Re

sp

on

se

Normal Artery Fibrotic Plaque

Lipid-Rich, Calcified Thick Cap Atheroma Thin Cap Atheroma

Coronary Near-Infrared Spectra


HISTOLOGY

+ -

+

-

21 2

1 46NEAR-INFRARED

SPECTROSCOPY • Sensitivity (%) 95

• Specificity (%) 96

• PPV (%) 91

• NPV (%) 98

Coronary Plaque Lipid Pool Detection by Near-IR Spectroscopy


Validation set (70 sections)


Studies 1998-2001





Identification of Lipid-rich Aortic Atherosclerotic Plaques in Living Rabbits With a Near-IR Spectroscopy Catheter

Hypothesis

• Normal vs. atherosclerotic plaques• Lipid-rich versus lipid-poor plaques

Model

• Atherosclerotic Rabbit Model• Pulsed 1% cholesterol x 8 months

• Normal rabbits (controls)

Near-IR Spectroscopy• Laser-driven catheter system

Histology

• H & E and Trichrome staining• Computerized planimetry (Zedex software)

Moreno PR, et al. JACC 2001; 37:3A:1039-21

Normal

Atherosclerotic

Normal


In-vivo Detection of Groups of Lipid Plaques With a Near-IR Spectroscopy Catheter

True (+)

True (-)

False (+)

False (-)

HISTOLOGY

+ -

+

-

19 0

5 6NEAR-INFRARED

SPECTROSCOPY

Presence of lipid : Sensitivity: 79% Specificity: 100%

Lipid area >0.75 mm2: Sensitivity: 75% Specificity: 78%


Studies 1998-2001





Percutaneous Coronary Near-IR SpectroscopyIn vivo: A Safety Study

Moreno PR and Fallon JT. University of Kentucky and Mount Sinai School of Medicine, August, 2001

Six Normal Swines• Percutaneous, over-the wire NIR coronary catheterization

performed in 2/3 coronary arteries

Results:• Successful coronary catheterization in all cases• Excellent angiographic and histologic results with not a

single case of dissection, thrombosis or perforation.

3 French NIR catheter

Near-IR Spectroscopy in Humans

3 French CatheterPhase I - Safety• Stable angina / PTCA-Stent * • Reference normal segment

Prospective Study • Angioplasty/stenting• Scan 3 major arteries

• Follow/up 12 months

• Correlation spectra/events

Rx of VP

Trial of Detection & Treatment of Vulnerable Plaque

Patients with angina

Cath LabPTCA/ Stenting

Near-IR

Patients with

TCFA*

Randomize

Placebo

Patients w/out TCFA

1 yearfollow/up

* TCFA=Thin-cap fibroatheromaUA=unstable angina - AMI: acute myocardial infarction - SCD=sudden cardiac death

UA AMI SCD

Near-IR Spectroscopy & Vulnerable Plaques

Conclusions

• NIR spectroscopy can identify features of plaque vulnerability in vitro and lipid-rich plaques in vivo, through blood.

• A catheter-based system has been tested in-vivo with excellent performance in both swine and human coronary arteries.

• Additional clinical data are needed to definitively apply this technique to risk stratify human atherosclerotic lesions in the cath lab.

detection of vulnerable plaque by nis

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