Moreno.nir vp.org acc02
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Moreno.nir vp.org acc02
- 1. Pedro R. Moreno, MD, FACC University of Kentucky Lexington, Kentucky Detection of Vulnerable Atherosclerotic Plaques By Near Infrared Spectroscopy
- 2. • Biological tissues have unique absorbance in the NIR wavelength range • NIR light has enough penetration that may obtain spectra through blood
- 3. 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
- 4. Advantages of Near-IR Spectroscopy For 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
- 5. 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
- 6. 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 Spectroscopy 198 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
- 7. 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)
- 8. Correlation of Blinded Near-IR Spectroscopy Results with Histologic Findings 99 Aortic samples HISTOLOGY LIPID POOL THIN CAP MACROPHAGES + - + - + - + - 35 4 4 56 13 6 4 76 37 6 7 49 NEAR-INFRARED SPECTROSCOPY Moreno PR, et al. Circulation 2002;105:923-927
- 9. • 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 Spectroscopy Results with Histologic Findings Lipid Pool Thin Cap Macrophages
- 10. 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
- 11. 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
- 12. 03-Coronary Tissue Scans 798 1198 1598 1998 2398 Variable 0.5 1.0 1.5 2.0 Response Normal Artery Fibrotic Plaque Lipid-Rich, Calcified Thick Cap Atheroma Thin Cap Atheroma Coronary Near-Infrared Spectra Moreno PR, et al. JACC 2001;37:356A
- 13. HISTOLOGY + - + - 21 2 1 46 NEAR-INFRARED SPECTROSCOPY • Sensitivity (%) 95 • Specificity (%) 96 • PPV (%) 91 • NPV (%) 98 Coronary Plaque Lipid Pool Detection by Near-IR Spectroscopy Moreno PR, et al. JACC 2001;37:356A Validation set (70 sections)
- 14. 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
- 15. 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
- 16. Moreno PR, et al. JACC 2001;37:3A In-vivo Detection of Groups of Lipid Plaques With a Near-IR Spectroscopy Catheter True (+) True (-) False (+) False (-) HISTOLOGY + - + - 19 0 5 6 NEAR-INFRARED SPECTROSCOPY Presence of lipid : Sensitivity: 79% Specificity: 100% Lipid area >0.75 mm2 : Sensitivity: 75% Specificity: 78%
- 17. 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
- 18. Percutaneous Coronary Near-IR Spectroscopy In 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
- 19. 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
- 20. Rx of VP Trial of Detection & Treatment of Vulnerable Plaque Patients with angina Cath Lab PTCA/ Stenting Near-IR Patients with TCFA* Randomize Placebo Patients w/out TCFA 1 year follow/up * TCFA=Thin-cap fibroatheroma UA=unstable angina - AMI: acute myocardial infarction - SCD=sudden cardiac death UA AMI SCD
- 21. 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.