Contrast-enhanced MicroCT-based Analysis of Human Atheroma Biomechanics

在美国，每年有50万人死于所谓的“急性冠状动脉综合征”，其中一半以上是由于覆盖在动脉粥样硬化部位的薄纤维帽破裂所致。“动脉粥样硬化帽的破裂是一种非常复杂的现象，受其厚度以外的许多因素的影响。最近的有限元研究发现，薄帽中的最大应力通常远小于广泛接受的组织破裂阈值，这表明帽厚度不是唯一的甚至是最重要的标准。临界断裂应力阈值是多年前使用2D有限元建模建立的，其中血管壁层被认为是均匀的、各向同性的和弹性的，而实际上，血管中的组织组成，特别是动脉粥样化中的组织组成是不均匀的、非各向同性的和超弹性的。本研究的总体目标是研究冠状动脉形态、组织异质性和血流动力学对冠状动脉破裂生物力学的影响。这项研究将为开发成像、预防和可能逆转组织成分变化的新策略奠定基础，这些变化将稳定的斑块转变为易破裂的斑块。 这项工作的教育部分整合了心血管生物力学，先进的3D成像和多尺度有限元建模的多学科教育计划。PI将为本科生（通过学年和夏季研究机会）和研究生（博士研究）提供培训，并为代表性不足的高中生提供实习机会，让他们在实验室工作。这项研究将通过增加我们对易损斑块破裂的理解以及提供易损斑块风险的替代范例来推进心血管生物力学领域。为此，PI将使用实验室物理模型，对比增强高分辨率microCT成像，具有组织特定属性的流体-固体相互作用数值模型以及患有动脉粥样硬化的人类冠状动脉血管的机械测试。一种新的基于对比增强microCT的有限元建模方法，具有逼真的血管壁层形态和基于像素的组织组成，将提供更准确的三维空间应力分布和动脉粥样硬化帽破裂临界阈值的修订分析。这种方法也将被用来调查的实际机制启动的上限破裂。一般来说，对比增强高分辨率microCT成像和先进的数值模拟，预计将产生在稳定和脆弱的动脉粥样硬化在人类冠状动脉血管的成分-结构-功能关系的机制的见解。

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.