New hypothesis for vulnerable plaque rupture due to microcalcifications in thin fibrous caps
Item
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Title
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New hypothesis for vulnerable plaque rupture due to microcalcifications in thin fibrous caps
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Identifier
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d_2009_2013:a896264dd262:10028
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identifier
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10041
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Creator
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Vengrenyuk, Yuliya,
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Contributor
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Sheldon Weinbaum
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Date
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2009
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biomedical engineering | atherosclerosis | calcification | plaque rupture | stress concentration
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Abstract
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This dissertation develops a new paradigm for the rupture of thin-cap fibroatheroma (TCFA), namely that minute (10-20 mum-diameter) cellular-level microcalcifications in the cap proper can cause local stress concentrations around these minute spherical inclusions that lead to cavitation induced interfacial debonding and rupture. The hypothesized rigid inclusions, which lie below the visibility of current in vivo imaging techniques, are detected herein for the first time in fibrous caps of human coronary lesions. First, I develop a three-dimensional (3D) theoretical model of a perfectly bonded spherical inclusion in a fibrous cap and obtain an infinite series solution for the stress concentration around the hypothesized solid inclusion (Vengrenyuk et al., 2006). The model predicts a nearly twofold increase in peak circumferential stress (PCS) at the inclusion interface which is sufficient to exceed the critical yield stress of the cap provided its thickness is < 65 mum in close agreement with the histological observations. Having demonstrated the quantitative feasibility of the hypothesis, I provide the first experimental evidence for the existence of these cellular-level microcalcifications in fibrous caps of autopsy specimens from human coronary lesions using confocal staining and micro-computed tomography (micro-CT) imaging techniques whose resolution far exceeds existing in vivo imaging methods. To further investigate the new paradigm for the rupture of TCFA, I develop a more sophisticated multi-level finite element model (FEM) of realistic 3D geometries of human coronary lesions based on high resolution micro-CT imaging (Vengrenyuk et al., 2008). The new model predicts that cellular-level calcifications by themselves may not be dangerous unless they lie in a region of high background stress. The most dangerous situations occur when (1) a microinclusion appears in close proximity to a region where the PCS is already high, (2) the microcalcification has an elongated shape, or (3) there are two microcalcifications in close proximity to one another. Finally, I apply histology based finite element analysis (FEA) to evaluate peak circumferential stresses in mouse aortic and brachiocephalic (BCA) lesions to test the hypothesis that these stresses are responsible for the greater stability of aortic lesions in mice. This analysis is able to both explain the greater stability of aortic lesions in mice and provide new insight into the BCA lesion as a model for the stability of human lesions with and without microcalcifications in their fibrous caps.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Engineering
