Novel Experimental and Theoretical Approaches to Understand Biomechanics of Atherosclerotic Plaque Rupture

该奖项是根据2009年《美国复苏和再投资法案》(Public Law 111-5)资助的。许多关于动脉粥样硬化的研究使用小鼠作为动物模型，因为斑块的结构和组成可以很容易地通过基因工程、药物或饮食改变。然而，自发性斑块破裂在动脉粥样硬化小鼠中是罕见的，需要新的方法将小鼠斑块的病理与其生物力学特性和对破裂的稳定性联系起来。本项目将应用两种新的方法来研究小鼠动脉粥样硬化斑块的生物力学行为：1.使用非接触式光学方法--三维数字图像相关(3D-DIC)测量正常动脉和斑块在拉伸载荷下的局部表面应变；2.直接测量导致斑块从基础血管壁上脱落所需的力，以估计斑块-动脉断裂能量。该项目的一个主要目标是将生物力学测量与潜在的组织结构联系起来，特别是与临床上与人类斑块破裂有关的特征联系起来。另一个目标是将经典断裂力学的分析方法应用于斑块破裂问题。如果成功，这项研究将提供新的实验工具和计算方法来研究动脉粥样硬化斑块破裂，重点是小动物模型。应用3-D DIC在微米尺度上测量局部应变，很可能在生物组织的力学研究中找到广泛的用途。该项目将通过为南加州大学科学教育中心开发的SCienceLab推广计划提供教育/实验室体验模块，向该地区的高中生介绍机械测试和数据分析。这个SCienceLab模块将是该项目中第一个专注于工程概念的模块。该项目还将有助于加强南加州大学新设立的生物医学工程计划。

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."Atherosclerotic plaque rupture is the leading cause of acute cardiovascular events such as heart attack and stroke. Many studies of atherosclerosis use mice as an animal model, since plaque structure and composition can easily be altered using genetic engineering, drugs, or diet. However, spontaneous plaque rupture is rare in atherosclerotic mice, necessitating new approaches to relate the pathology of mouse plaques to their biomechanical properties and stability against rupture. This project will apply two novel approaches to study the biomechanical behavior of mouse atherosclerotic plaques: 1. measurement of local surface strains on normal arteries and plaques under tensile loading using three-dimensional digital image correlation (3D-DIC), a non-contacting optical method; 2. direct measurement of the forces necessary to cause detachment of the plaque from the underlying vessel wall, in order to estimate plaque-artery fracture energy. A primary goal of the project is to correlate biomechanical measurements with underlying tissue structure, particularly with those features which have been clinically associated with plaque rupture in humans. An additional goal is to apply analytical methods derived from classic fracture mechanics to the problem of plaque rupture.If successful, this research will provide new experimental tools and computational approaches to study atherosclerotic plaque rupture, with an emphasis on small animal models. Application of 3-D DIC to measure local strains on the micrometer length scale is likely to find broad utility in mechanical studies of biological tissues. The project will offer an introduction to mechanical testing and data analysis to area high school students by providing an educational/laboratory experience module for the SCienceLab outreach program developed by the USC Center for Science Education. This SCienceLab module will be the first in the program to focus on engineering concepts. The project will also help to strengthen the newly established Biomedical Engineering Program at USC.