Quantitative Analysis of Relationships Among Hemodynamics, Thrombus, and Abdomina

描述(申请人提供)：腹主动脉瘤(AAA)是指腹主动脉局限性扩大，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有的风险评估对于降低AAA相关死亡率至关重要。许多研究人员认为，异常的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AAA在进展过程中会形成腔内血栓(ILT)层。ILT在AAA扩张中的作用是有争议的，ILT的存在增加了研究壁切应力对AAA扩张影响的复杂性。最近的研究还表明，AAA的血流动力学在血栓的形成和生长中起着关键作用。然而，以前的研究只使用了一个时间点的患者特有的模型，并且主要集中于研究两个因素之间的关系(例如，壁切应力与AAA扩大，ILT的存在与AAA扩大)，这还没有成功地完全阐明多个因素之间的关系。因此，本项目的主要目标是系统地 研究这些变量，检验关于它们关系的多个假设，并可能通过使用来自AAA患者的纵向数据来发展它们之间的相关性。具体目标是：i)使用多次拍摄的CT图像来量化ILT的几何参数和AAA的局部扩张率；ii)利用从每个患者构建的几何模型进行血流动力学模拟，并使用拉格朗日质点方法计算血小板所经历的切应力；iii)利用AIM(I)和(Ii)针对多个患者的结果，检验关于AAA中血流动力学因素影响的三个假设，并建立AAA扩张、ILT形成和血流动力学参数之间的相关性。为了推进这些目标，我们已经开始与韩国的一个临床研究团队合作，并从11名患者那里获得了小AAA的纵向图像，这些图像每隔6到24个月用高分辨率CT进行一次拍摄。我们将使用这些纵向患者数据来开发拟议的数字模拟，并使用多元统计分析对AAA扩张和血栓形成的假说进行测试。在我们的血液动力学模拟中，我们将使用拉格朗日粒子方法来追踪血小板的剪切应力历史，并评估高剪切对血小板激活的动态影响。 在几何复杂的AAA的近侧。这项提案中提出的研究是密歇根州立大学机械工程和统计系与首尔国立大学医院放射科的联合合作成果。这项拟议的研究最终将有助于确定AAA的生长规律，以开发更好的AAA计算模型，这将成为临床治疗和外科治疗的重要工具。

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.