Micro-CT based analysis of a new paradigm for vulnerable plaque rupture: cellular microcalcifications in fibrous caps.

In this paper, we further investigate the new paradigm for the rupture of thin cap fibroatheroma (TCFA) proposed in Vengrenyuk et al. (2006 PNAS 103:14678) using a multilevel micro-CT based 3D numerical modeling. The new paradigm proposes that the rupture of TCFA is due to stress-induced interfacial debonding of cellular--level, 10-20 microm microcalcifications in the fibrous cap proper. Such microcalcifications, which lie below the visibility of current in vivo imaging techniques, were detected for the first time using confocal microscopy and high resolution microcomputed tomography (micro-CT) imaging in Vengrenyuk et al. (2006) In the present study, we use high resolution (7 microm) micro-CT imaging to construct accurate geometries of both these microcalcifications and larger mm size macrocalcifications at the cap shoulders to evaluate their biomechanical stability. The analysis shows that cellular-level calcifications by themselves are not dangerous unless they lie in a region of high background stress. This high level of background stress only occurs in caps whose thickness is < approximately 80 microm. Whereas a spherical microcalcification will increase peak circumferential stress (PCS) by a factor of two, in agreement with previous local analytical solutions, this can be increased several fold by elongated microcalcifications. The most dangerous situation is when a microinclusion appears in close proximity to a region where the PCS is already high. This stress will be substantially increased if the inclusion is elongated. In contrast, macrocalcifications at the cap shoulders are shown to actually increase plaque stability.