More than half of the 500,000 deaths each year in the U.S. caused by what is called "acute coronary syndrome" result from the rupture of the thin fibrous cap that covers an "atheroma", a site where the artery is "hardened." The rupture of an atheroma cap is a very complex phenomenon governed by many factors beyond its thickness. Recent finite element studies have found that the maximal stresses in thin caps are typically far less than the widely accepted threshold for tissue rupture, revealing that cap thickness is not the only or even the most important criterion. The critical rupture stress threshold was established many years ago using 2D finite element modeling in which the vessel wall layers were considered homogeneous, isotropic and elastic, while in reality, the tissue composition in blood vessels, particularly in atheromas is non-homogeneous, non-isotropic and hyperelastic. The overall goal of this research is to investigate the contribution of cap morphology, tissue heterogeneity, and blood flow dynamics on the biomechanics of cap rupture in human coronary vessels. This research will form the basis for developing new strategies for imaging, preventing and possibly reverting changes in tissue composition that transform a stable plaque into one vulnerable to rupture. The educational component of this effort integrates a multidisciplinary education plan on cardiovascular biomechanics, advanced 3D imaging, and multiscale finite-element modeling. The PIs will provide training to undergraduate students (through academic year and summer research opportunities) and graduate students (PhD research) and offer internships for underrepresented high-school students to work in the laboratory.
This research will advance the field of cardiovascular biomechanics by increasing our understanding of vulnerable plaque rupture as well as providing an alternative paradigm for vulnerable plaque risk. To this end, the PIs will use laboratory physical models, contrast-enhanced high-resolution microCT imaging, fluid-solid interaction numerical models with tissue specific properties and mechanical testing in human coronary vessels with atheromas. A novel contrast-enhanced microCT-based finite element modeling approach with realistic vessel wall layers morphology and pixel-based tissue composition will provide a more accurate 3D spatial distribution of stresses and a revised analysis of the critical threshold for atheroma cap rupture. This approach will also be used to investigate the actual mechanism of initiation of the cap rupture. In general, contrast-enhanced high-resolution microCT imaging and advanced numerical modeling are expected to yield mechanistic insights of the composition-structure-function relationship in both stable and vulnerable atheromas in human coronary vessels.
