A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture
ABSTRACT The role of microcalcifications (μCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that μCalcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-μm resolution and undecalcified histology with special emphasis on calcified particles <50 μm in diameter. Our results reveal the presence of thousands of μCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 μCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these μCalcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the μCalc and surrounding tissue, μCalc size, and clustering. We found that local tissue stress could be increased fivefold when μCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 μm) if no μCalcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous μCalcs < 15 μm in the caps, not visible at 6.7-μm resolution, and that our failure to find any nonruptured caps between 30 and 66 μm is a strong indication that many of these caps contained μCalcs.
- SourceAvailable from: Jacques Ohayon
Computer Methods in Biomechanics and Biomedical Engineering 08/2014; 17 Suppl 1(sup1):16-7. DOI:10.1080/10255842.2014.931071 · 1.79 Impact Factor
- "These include intravascular ultrasound (IVUS) (Rioufol et al 2002, Carlier and Tanaka 2006), optical coherence tomography (OCT) (Jang et al 2002, Tearney et al 2008) and magnetic resonance imaging (IV-MRI) (Larose et al 2005, Briley-Saebo et al 2007). Diagnosis of high-risk atherosclerotic plaques remains problematic as the thickness of the fibrous cap alone is not a sufficient predictor of plaque stability (Virmani et al 2000, Ohayon et al 2008, Fleg et al 2012, Maldonado et al 2012). "
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- "With evidence that higher plaque stresses are linked to plaque rupture and the selection of critical stress value as the representative value, critical stress values have been used in several studies concerning plaque rupture and assessment. Vengrenyuk et al. (2006, 2008), Bluestein et al. (2008), Maldonado et al. (2012), Cardoso and Weinbaum (2013), and Kelly-Arnold et al. (2013) demonstrated that plaque cap with micro-calcification inclusions are associated with elevated stress levels and may be related to plaque rupture. Gao et al. (2011) studied carotid plaques and found that critical stress values from symptomatic patients were higher that from asymptomatic patients. "
ABSTRACT: Medical imaging and image-based modeling have made considerable progress in recent years in identifying atherosclerotic plaque morphological and mechanical risk factors which may be used in developing improved patient screening strategies. However, a clear understanding is needed about what we have achieved and what is really needed to translate research to actual clinical practices and bring benefits to public health. Lack of in vivo data and clinical events to serve as gold standard to validate model predictions is a severe limitation. While this perspective paper provides a review of the key steps and findings of our group in image-based models for human carotid and coronary plaques and a limited review of related work by other groups, we also focus on grand challenges and uncertainties facing the researchers in the field to develop more accurate and predictive patient screening tools.Journal of Biomechanics 01/2014; DOI:10.1016/j.jbiomech.2014.01.012 · 2.50 Impact Factor
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ABSTRACT: Spontaneous plaque rupture in mouse models of atherosclerosis is controversial, although numerous studies discuss so-called "vulnerable plaque" phenotypes in mice. We compared the morphology and biomechanics of two acute and one chronic murine model of atherosclerosis to human coronaries of the thin-cap fibroatheroma (TCFA) phenotype. Our acute models were ApoE(-/-) and LDLr(-/-) mice, both fed a high-fat diet for 8 weeks with simultaneous infusion of Angiotensin II, and our chronic mouse model was the ApoE(-/-) strain fed a regular chow diet for one year. We found that the mouse plaques from all three models exhibited significant morphological differences from human TCFA plaques, including the plaque burden, plaque thickness, eccentricity, and the amount of the vessel wall covered by lesion, as well as significant differences in the relative composition of plaques. These morphological differences suggested that the distribution of solid mechanical stresses in the walls may differ as well. Using a finite element analysis (FEA) computational solid mechanics model, we computed the relative distribution of stresses in the walls of murine and human plaques and found that although human TCFA plaques have the highest stresses in the thin fibrous cap, murine lesions do not have such stress distributions. Instead, local maxima of stresses were on the media and adventitia, away from the plaque. Our results suggest that if plaque rupture is possible in mice, it may be driven by a different mechanism than mechanics.AJP Heart and Circulatory Physiology 11/2012; 304(3). DOI:10.1152/ajpheart.00620.2012 · 4.01 Impact Factor