Biomechanical Simulation of Evolving Aortic Aneurysms for Designing Intervention

描述（由申请人提供）：腹主动脉瘤（AAA）最常见于65岁及以上的男性，因此该疾病的发病率在我们的老龄化人群中呈上升趋势。人们普遍认为，机械因素在AAA的自然史及其对治疗的反应中起着关键作用，但目前还没有广泛接受的工具来量化或预测AAA的机械生物学和生物力学。我们的总体目标是通过以下方式支持和扩展斯坦福大学Symbios国家生物医学计算中心的心血管流体动力学项目：（1）开发描述腹主动脉在动脉瘤疾病进展期间经历的复杂化学机械变化的新型本构关系，（2）在为患病动脉开发的定制非线性有限元代码中实现这些关系，（3）将该动脉力学代码与斯坦福大学生物流体力学代码连接，以使我们能够首次量化生长中的AAA的流体-固体生长力学，以及（4）使用参数研究以及在斯坦福大学和匹兹堡可从患者获得的数据来改进和验证该独特计算工具的预测能力。最后，斯坦福大学中心将确保合并后的软件包是可移植的、易于使用的和广泛可用的。为此，我们汇集了来自另外3个机构的专业知识：德克萨斯A&M大学的J. Humphrey，在开发软组织的复杂组成理论方面具有专业知识，包括动脉和脑动脉瘤的生长和重塑; Vorp在量化腹主动脉瘤和相关腔内血栓的生物力学特性方面具有专业知识，并进行了大量的腹主动脉瘤壁应力模拟;奥地利格拉兹科技大学的Holzapfel拥有计算生物固体力学方面的专业知识，特别是使用有限元来模拟复杂的动脉粥样硬化动脉和动脉球囊支架相互作用。这三个小组共同代表了斯坦福大学所需的专业知识。泰勒和C。扎林斯，在血管外科和疾病进展的动物模型方面具有专长。我们将共同开发第一个计算工具，用于预测腹主动脉瘤的自然病程和对干预的反应，腹主动脉瘤是美国第13大死亡原因，仅在美国，腹主动脉瘤破裂每年就造成15，000人死亡，因此代表了第13大死亡原因。众所周知，机械因素在这些病变的进展和最终破裂中起关键作用（例如，当壁应力超过强度时发生破裂），但是目前没有办法同时理解控制动脉瘤生物力学的血流动力学、壁力学和微观结构的演变变化。本研究提案是对PAR-07-249的回应：它将解决建立一个独特、全面的计算工具的需求，以更好地了解动脉瘤的自然史，并显著扩展斯坦福大学国家生物医学计算中心的心血管研究能力。

DESCRIPTION (provided by applicant): Abdominal aortic aneurysms (AAAs) are most common in men aged 65 and older, thus the incidence of this disease is on the rise in our aging population. It is universally agreed that mechanical factors play key roles in the natural history of AAAs and their response to treatment, yet there is no widely accepted tool to quantify or predict the mechanobiology and biomechanics of AAAs. Our overall goal is to support and extend the Cardio- vascular Fluid Dynamics Project at the Symbios National Center for Biomedical Computing at Stanford University by (1) developing novel constitutive relations that describe complex chemo-mechanical changes experienced by the abdominal aorta during the progression of aneurysmal disease, (2) implementing these relations in a custom nonlinear finite element code developed for diseased arteries, (3) interfacing this arterial mechanics code with the Stanford biofluid mechanics code to enable us to quantify, for the first time, the fluid- solid-growth mechanics of a growing AAA, and (4) using parametric studies as well as data available at Stanford and Pittsburgh from patients to refine and verify the predictive capability of this unique computational tool. Finally, the Stanford Center will ensure that the combined software packages will be portable, easily used, and widely available. Toward this end, we bring together expertise from 3 additional institutions: J. Humphrey, at Texas A&M University, has expertise in developing complex constitutive theories for soft tissues, including growth and remodeling of arteries and cerebral aneurysms; D. Vorp, at the University of Pittsburgh, has expertise in quantifying biomechanical properties of abdominal aortic aneurysms and associated intraluminal thrombi, and has performed numerous simulations of aneurysmal wall stress; and G. Holzapfel, at Graz University of Technology in Austria, has expertise in computational biosolid mechanics, particularly using finite elements to model complex atherosclerotic arteries and arterial-balloon-stent interactions. Together, these three groups represent the expertise needed to complement that at Stanford University: C. Taylor, with expertise in computational biofluid mechanics, and C. Zarins, with expertise in vascular surgery and animal models of disease progression. Together, we will develop the first computational tool that is designed to predict the natural history and responses to intervention of abdominal aortic aneurysms, the 13th leading cause of death in the U.S.A. Ruptured abdominal aortic aneurysms account for 15,000 deaths per year in the U.S.A. alone, thus representing the 13th leading cause of death. It is well known that mechanical factors play key roles in the progression and eventual rupture of these lesions (e.g., rupture occurs when wall stress exceeds strength), yet there is currently no way to understand simultaneously the evolving changes in blood flow dynamics, wall mechanics, and microstructure that govern the biomechanics of aneurysms. This research proposal is in response to PAR-07-249: it will both address the need to build a unique, comprehensive, computational tool to understand better the natural history of aneurysms and significantly extend the cardiovascular research capabilities at the Stanford University National Center for Biomedical Computing.