Quantitative Analysis of Relationships Among Hemodynamics, Thrombus, and Abdomina

描述（由申请人提供）：腹主动脉瘤（AAA）是腹部主动脉的局灶性扩大，其破裂是美国65岁以上男性猝死的第三大原因。更深入地了解疾病的病理生理学和患者特异性风险评估对于降低AAA相关死亡率至关重要。许多研究者认为异常壁面剪应力是动脉瘤扩张和破裂风险的潜在重要因素。然而，大多数AAAs在进展过程中会形成腔内血栓（ILT）层。ILT对AAA膨胀的作用是有争议的，ILT的存在增加了研究壁面剪切应力对AAA膨胀影响的复杂性。最近的研究也表明，AAA血流动力学在血栓形成及其生长中起着关键作用。然而，以往的研究只使用了一个时间点的患者特异性模型，并且主要集中在研究两个因素之间的关系（例如，壁剪应力与AAA扩张，ILT的存在与AAA扩张），这些研究未能成功地充分阐明多因素之间的关系。因此，本课题的主要目标是系统地

DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) is the focal enlargement of the aorta in the abdomen and its rupture is the 3rd leading cause of sudden death in men older than 65 years in the US. More in-depth understanding of the pathophysiology of the disease and patient-specific risk assessment are critically important in reducing AAA- related mortality. Many researchers considered abnormal wall shear stress as a potentially important factor in aneurysm expansion and rupture risk. Most AAAs, however, develop intraluminal thrombus (ILT) layers during the progression. The role of ILT on AAA expansion is controversial and the presence of ILT increases complexity in investigating the effect of wall shear stress on AAA expansion. Recent studies also suggest that hemodynamics in the AAA plays a critical role in thrombus formation and its growth. Previous studies, however, used patient-specific models taken from only one time point and have mostly focused on studying relationships between two factors (e.g., wall shear stress vs. AAA expansion, the presence of ILT vs. AAA expansion), which haven't been successful in fully elucidating relationships between multiple factors. Therefore, the main goal of this project is to systemically study these variables, to examine multiple hypotheses on their relationships, and to possibly develop correlations among them by using longitudinal data from AAA patients. Specific aims are to i) quantify geometric parameters for ILTs and the local expansion rates of AAAs using CT images taken at multiple times, ii) perform hemodynamic simulations with the geometric model constructed from each patient and use the Lagrangian particle method for computing the shear stress experienced by platelets, and iii) examine three hypotheses on the effect of hemodynamic factors in AAAs by using the results from Aim (i) and (ii) for multiple patients and develop correlations among AAA expansion, ILT formation, and hemodynamic parameters. To advance these goals, we have already initiated collaboration with a clinical research team in South Korea and acquired longitudinal images of small AAAs from eleven patients that have been taken with 6 to 24 month intervals with high resolution CT. We will use these longitudinal patient data for developing the proposed numerical simulations and testing of hypotheses on AAA expansion and thrombus formation using multivariate statistical analysis. In our hemodynamic simulations, we will use the Lagrangian particle method to trace the history of shear stress of platelets and to assess the dynamical effects of high shear for platelet activation at the proximal side of the geometrically complex AAA. The study presented in this proposal is a joint collaborative effort between the departments of Mechanical Engineering and Statistics at Michigan State University and the Department of Radiology at Seoul National University Hospital. The proposed research would help ultimately to determine growth rules for developing better computational models of AAAs, which will become an essential tool in clinical management and surgical treatment of the disease.