QUANTITATION OF BIOMECHANICAL DETERMINANTS OF HUMAN AAA

我们的长期目标是定量确定作用于人胸腹主动脉的不同血流动力，这些力会导致管壁的生物力学应力和应变，随着时间的推移可能会导致主动脉壁的机械故障和动脉瘤扩大。由于肾下腹主动脉特别容易形成动脉瘤，而胸主动脉是有阻力的，我们将对这两段主动脉进行比较，以确定动脉瘤形成的易感因素。我们的假设是，血流动力和累积的生物力学应力和应变，以及遗传易感性和叠加的动脉粥样硬化和体液因素共同导致主动脉壁组织衰竭和动脉瘤的形成。这些因素同时存在，并在腹主动脉被放大，使其更容易发生AAA。我们将对人类腹主动脉和胸主动脉的结构、成分和生物力学特性进行表征和对比，并确定与年龄相关的主动脉壁的变化。利用磁共振成像技术，我们将无创性地评估年轻(20-35岁)和老年(60-75岁)正常成人以及AAA患者的胸、腹主动脉血流。我们将测定腹主动脉和胸主动脉的三维脉动流场和主动脉壁应变的差异。物理模型和活体动物实验将被用来验证磁共振测量，并开发和验证计算方法来模拟和预测主动脉壁的生物力学应力和应变。这些数据将被用来构建人体胸腹主动脉的计算模型，该模型描述了运动状态、心输出量和血压变化等多种条件下的三维脉动流动环境，并量化了实时的主动脉壁应力和应变模式。类似地，我们将构建一个人体腹主动脉瘤的计算生物力学模型，该模型将能够计算随时间累积的主动脉壁应力负荷。这将用于预测组织衰竭和动脉瘤扩大的模型，并将有助于评估旨在改变主动脉壁组织特征和基质结构的治疗策略，以及评估治疗策略，如主动脉支架移植和腹主动脉瘤的开放修复。

Our long term objective is to quantitively define the varying hemodynamic forces which act on the human thoracoabdominal aorta resulting in biomechanical stresses and strains in the vessel wall which may over time result in mechanical failure of the aortic wall and aneurysmal enlargement. Since the infrarenal abdominal aorta is particularly prone to aneurysm formation and the thoracic aorta is resistant, we will compare the two segments of aorta to determine predisposing factors for aneurysm formation. Our hypothesis is that hemodynamic forces and cumulative biomechanical stresses and strains, along with genetic susceptibility and superimposed atherogenic and humoral factors combine to result in aortic wall tissue failure and aneurysm formation. These factors, coincide, and are magnified in the abdominal aorta making it more prone to AAA. We will characterize and contrast the structural, compositional and biomechanical properties of the abdominal and thoracic aorta in humans and determine age related changes of the aortic wall. Utilizing MR imaging techniques, we will noninvasively assess thoracic and abdominal aortic blood flow in young (20-35 year old) and old (60-75 year old) normal adults as well as in patients with AAA. We will determine the 3 dimensional pulstaile flow field and quantitate differences in aortic wall strain between the abdominal and thoracic aorta. Physical models and in vivo animal experiments will be used to validate MR measurements and to develop and validate computational methods to model and predict biomechanical stress and strain of the aortic wall. These data will be used to construct a computational model of the human thoracoabdominal aorta which characterizes the 3 D pulsatile flow environment under a wide variation of conditions, such as changes in exercise states, cardiac output and blood pressure and quantify the real time aortic wall stress and strain pattern. Similarly, we will construct a computational biomechanical model of a human abdominal aortic aneurysm which will enable calculation of cumulative aortic wall stress loads over time. This will be used for predictive modeling of tissue failure and aneurysm enlargement and will be useful to evaluate strategies for therapies aimed at altering aortic wall tissue characteristics and matrix structure as well as in evaluating treatment strategies such as aortic stent grafts and open repair of the abdominal aortic aneurysms.