New Morphological Indexes for Atherosclerotic Plaque Rupture Prediction

Jacques Ohayon, PhD and Roderic I. Pettigrew, MD, PhD

Laboratory TIMC-IMAG/DyCTiM, UJF, CNRS UMR 5525, In³S
Faculty of Medicine  of Grenoble - 38706 La Tronche Cedex, France
Email: Jacques.Ohayon@imag.fr

Necrotic Core Thickness and Positive Arterial Remodeling Index: Emergent Biomechanical Factors for Evaluating the Risk of Plaque Rupture -  Am J Physiol Heart Circ Physiol., 295(2):H717-27, 2008 - Fibrous cap thickness (Capthick) is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Corearea) and the arterial remodeling index (Remodindex), on the other hand, are difficult to use as clinical morphological indices: literature data show a wide dispersion of Core-area thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Core-area and Remodindex, it remains unclear how these interact and affect peak cap stress (Capstress) - a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Capstress value was calculated on 5,500 idealized atherosclerotic vessel models, which had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty four non-ruptured plaques acquired by IVUS on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Capstress. It was found that: (i) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques; and (ii) in addition to cap thickness, necrotic core thickness - rather than area - was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone, but rather as a combination of cap thickness, necrotic core thickness and the arterial remodeling index.

Fig.1: Three-dimensional plot highlighting the influences of remodeling index and relative necrotic core thickness on critical cap thickness. The critical cap thickness is defined as the value at which cap stress reaches the critical or rupture point tensile stress. This result shows that there is no single such threshold, which rather depends strongly on remodeling index and relative necrotic core thickness. More interestingly, plaques with low remodeling index and a large relative necrotic core thickness can be seen to be more prone to rupture, with a high critical cap thickness. This finding may explain, on the one hand, the progression and growth of clinically silent lesions and, on the other, why plaques with relatively small stenoses have been observed  to frequently rupture.

Selected Publications

• Ohayon J, Mesnier N, Broisat A, Toczek J, Riou L, Tracqui P. Elucidating atherosclertic vulnerable plaque rupture by modeling cross substitution of ApoE-/- mouse and human plaque component stiffnesses. Biomechanics and Modeling in Mechanobiology. (in press), 2011.

•  Ohayon J, Gharib AM, Garcia A, Heroux J, Yazdani SK, Malvè M, Tracqui P, Martinez MA, Doblare M, Finet G, Pettigrew RI. Is arterial wall-strain stiffening and additional process responsible for atherosclerosis in coronary bifurcations? in vivo Study Based on Dynamic CT and MRI. Am J Physiol Heart Circ Physiol. 301(3):H1097-106, 2011.

• Broisat A, Toczek J, Mesnier N, Tracqui P, Ghezzi C, Ohayon J, Riou L. Assessing the low levels of mechanical stress in aortic atherosclerosis lesions from ApoE-/-mouse . Arterioscler Thromb Vasc Biol. 31(5):1007-10, 2011.

• Tracqui P, Broisat A, Toczek J, Mesnier N, Ohayon J, Riou L. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy . Journal of structural Biology 174(1):115-23, 2011.

• Heroux J, Gharib AM, Danthi NS, Cecchini S, Ohayon J, Pettigrew RI. High Affinity avb3 Integrin Targeted Optical Probe as a New Imaging Biomarker for Early Atherosclerosis: Initial Studies in Watanabe Rabbits. Mol Imaging Biol., 12(1):2-8, 2010.

•  Soloperto G, Keenan NG, Sheppard MN, Ohayon J, Wood N, Pennell DJ, Mohiaddin RH, Xu XY. A combined imaging, computational and histological analysis of a ruptured carotid plaque. Artery Research, 4(2):59-65, 2010.

•  Le Floc'h S, Cloutier G, Finet G, Tracqui P, Pettigrew RI, Ohayon J. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study. Phys. Med. Biol., 55:5701-5721, 2010.

•  Finet G., Huo Y, Riouffol G, Ohayon J, Guerin P, Kassab GS.  Structure-function relation in the coronary artery tree: from fluid dynamics to arterial bifurcations. EuroIntervention, 6:J10-J15, 2010.

•  Le Floc'h S, Ohayon J, Tracqui P, Finet G, Gharib AM, Maurice R, Cloutier G, Pettigrew RI. Vulnerable Atherosclerotic Plaque Elasticity Reconstruction Based on a Segmentation-Driven Optimization Procedure Using Strain Measurements: Theoretical Framework. IEEE Trans Med Imaging, 28(7):1126-37, 2009.

•  Kotys MS, Herzka DA, Vonken EJ, Ohayon J, Heroux J, Gharib AM, Stuber M, Pettigrew RI. Profile order and time-dependent artifacts in contrast-enhanced coronary MR angiography at 3T: origin and prevention. Magn Reson Med., 62(2):292-9, 2009.

•  Eskandari H, Salcudean SE, Rohling R, Ohayon J. Viscoelastic characterization of soft tissue from dynamic finite element models. Physics in Medicine and Biology, 53(22):6569-90, 2008.

•  Ohayon J, Finet G, Gharib AM, Herzka DA, Tracqui P, Heroux J, Rioufol G, Kotys MS, Elagha A, Pettigrew RI. Necrotic core thickness asnd positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 295(2):H717-27, 2008.

•  Ohayon J, Dubreuil O, Tracqui P, Le Floc'h S, Rioufol G, Chalabreysse L, Thivolet F, Pettigrew RI, Finet G. Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 293(3):H1987-96, 2007.

•  Boudou T., Ohayon J., Arntz Y., Finet G., Picart C., Tracqui P. An extended modeling of the micropipette aspiration experiment for the characterization of the Young’s modulus and Poisson’s ratio of adherent thin biological samples: Numerical and experimental studies. Journal of Biomechanics, 39:1677-85, 2006.

•  Boudou T., Ohayon J., Picart C., Tracqui P. Characterization of the Young’s modulus and Poisson’s ratio of polyacrylamide gels using micropipette aspiration technique. Biorheology, 43(6): 721-8, 2006.