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Session: Poster session I
Session starts: Thursday 24 January, 15:00

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Bas Vis (Erasmus Medical Center)
Hilary Barrett (Erasmus Medical Center)
Frank Gijsen (Erasmus Medical Center)
Ali Akyildiz (Erasmus Medical Center)

Abstract:
Myocardial infarction and stroke are majorly caused by atherosclerotic plaque rupture, which correlates with high mechanical stresses in plaques1. A potential stress concentration location in plaques is the calcification-fibrous tissue interface. Histopathological examinations demonstrated plaque ruptures located at this interface2. This study aims to identify critical geometric features of calcification and fibrous tissue structure for stress concentrations, through a comprehensive morphometric analysis and implementing fibrous tissue anisotropy in a plaque calcification model for the first time. Histological cross-sections (n=65) of carotid plaques (n=16) were morphometrically analyzed for calcification-related geometric features and for fiber orientation patterns surrounding calcification. Based on these measurements, 145 finite element models (FEMs) were generated. Using anisotropic, hyperelastic material models; FEMs were solved for an intraluminal pressure of 140 mmHg, and plaque stresses were computed. Of the 145 calcified plaque regions analyzed, four distinct fiber patterns were identified: attached to calcification (40%), encircling (25%), pushed-aside (15%) and randomly distributed (10%). Most calcifications had the long axis oriented circumferentially, with the median[Q1:Q3] length/width ratio of 1.97 [1.23:3.02]. Calcification width/plaque thickness ranged from 0.02 to 0.96 with a median of 0.12. For attached fiber pattern, calcifications were evenly distributed over plaque thickness whereas for other three patterns calcifications were closer to outer edge. For attached fiber FEMs, max principal stress at calcification-fibrous tissue interface demonstrated a wide variation, with a median [Q1:Q3] of 277 [156:543] kPa. For pushed-aside pattern FEMs, the median [Q1:Q3] stress was 85 [41:165] kPa. Encircling and random pattern models showed stress values lower than 10 kPa. Multivariable regression analysis (r2=0.88) showed that interface stresses significantly positively correlated with calcification length/width ratio and this effect was amplified with increased calcification width/plaque thickness ratio. This study is to first to 1.)comprehensively evaluate calcification-related morphometric features in atherosclerotic plaques and fiber orientation patterns around calcifications, 2.)implement fibrous tissue anisotropy for stress analysis at calcification-fibrous tissue interface, and 3.)analyze the effect of morphometric features and fiber orientation on interface stresses. Study results demonstrate that combination of larger calcification length/width ratio, larger calcification width/plaque thickness, and attached fiber pattern significantly increases stresses at calcification-fibrous tissue interface, a plaque rupture location. References: [1] Cheng, G. C., Loree, H. M., Kamm, R. D., Fishbein, M. C., and Lee, R. T. (1993), Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: A structural analysis with histopathological correlation, Circulation, 87(4), 1179-1187. [2] Daemen M. J., Ferguson M. S., Gijsen F. J., Hippe D. S., Kooi M. E., Demarco K., van der Wal A. C., Yuan C., and Hatsukami T. S., Carotid plaque fissure: an underestimated source of intraplaque hemorrhage, Atherosclerosis 254, 102 (2016).