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（公法111-5）资助的。“动脉粥样硬化斑块破裂是心脏病发作和中风等急性心血管事件的主要原因。 许多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使用基因工程，药物或饮食来改变。 然而，自发性斑块破裂是罕见的动脉粥样硬化小鼠，需要新的方法来关联小鼠斑块的病理学，其生物力学特性和稳定性，对破裂。 本研究将采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。使用三维数字图像相关（3D-DIC）（一种非接触式光学方法）测量拉伸载荷下正常动脉和斑块上的局部表面应变; 2.直接测量导致斑块从下方血管壁分离所需的力，以估计斑块-动脉断裂能量。 该项目的主要目标是将生物力学测量与基础组织结构相关联，特别是与临床上与人类斑块破裂相关的那些特征相关联。 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的问题，如果成功的话，这项研究将为研究动脉粥样硬化斑块破裂提供新的实验工具和计算方法，重点是小动物模型。 三维DIC的应用，以测量局部应变的微米长度尺度上可能会发现广泛的实用程序在力学研究的生物组织。 该项目将通过为南加州大学科学教育中心开发的SCienceLab外展计划提供教育/实验室体验模块，向地区高中学生介绍机械测试和数据分析。 该SCienceLab模块将是该计划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成立的生物医学工程项目。

"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.