Assessing The Vulnerable Plaque Plaque Necrotic Core Area
Assessing The Vulnerable Plaque: Plaque Necrotic Core Area, Fibrous Cap Thickness, Remodeling Index Acknowledgements Roderic Pettigrew, Ph. D. , M. D. Julie Heroux- NIH Director National Institute of Biomedical Imaging Saami Yazdani - CV Path and Bioengineering Ahmed Gharib, MD -NIH Jacques Ohayon, Ph. D-NIH CRT Vulnerable Plaque. Renu Summit Virmani, MD- CV Path February 22, 2010 US Department of Health & Human Services, National Institutes of Health
DISCLOSURES Roderic I. Pettigrew, Ph. D, MD I have no real or apparent conflicts of interest to report.
The Challenge: Preclinical VP S 3 S 2 S 1 Post Mortem (CVPath) S 2 (for LCX S 1 LAD: Imaged (3 sutures) L: Imaged (2 sutures; 1 in LOM and 1 in LM) RCA: CTO RC A LA D LC X
LAD (CVP 08030) S 3 TCFA Fibrous S 2 TCFA with Luminal Thrombus Micro Ca Thr NC S 1 NC NC Thr
Biomechanics of Atheroma Plaque Studies of Plaque Rupture • Computational, based on ruptured Coronary plaques • Mechanical testing of iliac, aortic plaques • Plaque rupture occurs at sites of high circumferential stress • Plaque rupture occurs when PCS > ~ 4000 mm. Hg (300 k. Pa) Large lipid core Thin fibrous cap < 100 µm Peak cap stress can predict plaque rupture Richardson et al. , Lancet 1989 – Loree et al. , Circ Res, 1992 - Cheng et al. , Circulation, 1993. ,
Critical Cap Thk microns What Are Morphologic Determinants of Vulnerability ? Plaque with large ess n k ic Simulations of 5500 Corethick and small h t p a morphologies Stenosisdeg, . , is more ec l b a t S vulerable for rupture. (mm) 200 175 150 125 100 75 50 25 0 Boundary of stability 75 ss ne k hic t p ca 8 e 70 0 r 1. 2. 3 u 6 1. 4 pt 50 0 re Ar t u o 1 4 5. C er i R 1. 6 3 0 ic al 1. 7 20 0 rot % ) Re c 1. 8 10 mod Ne s s ( 1 e v el i ne ti k a ng l c i Ind Re T h ex Ohayon J, …Pettigrew, Stable • Cap ~ 85 u • CCT ~75 u Am J Physiol 2008 q Unstable • Cap ~ 95 u • CCT ~ 120 u DN DP RI= DP/DN
Critical TCFA thickness (µm) 126 µm Remodeling Index
Plaque characteristics: Degree of stenosis = 77. 2 % Relative necrotic core thickness = 88. 1% Cap thickness range: [100 µm, 200µm] Computed Critical TCFA Cap Thickness = 126 µm Degree of stenosis % = 100 x Plaque area + Lumen area
3 D Plaque Assessment: Stenosis vs Longitudinal Extent
Summary 1. Plaque ruptures when Cap thickness stress exceeds ~ 300 k. Pa 2. Biomechanical Rupture determinants (morphologic): • Fibrous Cap Thickness • Necrotic Core Thickness • Remodeling Index 3. Complex combination of these 3 factors, not just Cap ~65 µ, predictive of rupture 4. Cell / Molecular features (macrophages, calcium) and 3 D variability needed 5. 3 -D: % Stenosis proportional to Plaque Length US Department of Health & Human Services, National Institutes of Health
Plaque characteristics: Plaque # NR-728 Degree of stenosis = 70 % Relative necrotic core thickness = 80% Cap thickness range: [69, 153 , 173 µm] 173µm 151µm 69µm Computed Critical TCFA Cap Thickness = 116 µm
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