Computational Analysis of Cerebral Aneurysm Evolution

描述（由申请人提供）：脑动脉瘤破裂是出血性中风的主要原因。由于未破裂性脑动脉瘤的检出率越来越高，而蛛网膜下腔出血的预后仍然很差，因此往往需要临床医生判断哪些动脉瘤容易进展和破裂。不幸的是，我们对脑动脉瘤的自然史的了解是有限的，因为动脉瘤的形成、生长和破裂的过程还没有被很好地理解。先前的研究已经确定了参与这些过程的主要因素：a)动脉血流动力学，b)壁生物力学和力学生物学，以及c)动脉瘤周围环境（PAE）。然而，对于这些因素的相对重要性，它们在个体受试者中的相互作用，以及它们在高危人群中的可变性，人们知之甚少。该项目的总体目标是双重的：a)更好地了解脑动脉瘤发展的机制，b)开发一个脑动脉瘤分析的综合系统。我们的工作假设是，脑动脉瘤的生长模式是由暴露于集中血流动力学壁剪切应力和骨-动脉瘤接触的缓解作用相关的局灶性壁损伤分布决定的。该项目将分为三个基本阶段。在第一阶段（开发），我们将开发和整合动脉瘤建模和表征工具和数据库。血流动力学建模套件将通过使用快速原型技术构建的患者特异性体外模型进行验证，并使用粒子图像测速仪和激光多普勒测速仪进行测量。在第二阶段（知识发现），将从加州大学洛杉矶分校现有的未破裂动脉瘤的计算机断层血管造影（CTA）图像的独特纵向数据库中选择一系列生长和稳定的动脉瘤，并对其进行建模，以确定与动脉瘤生长最相关的血流动力学和PAE特征以及壁损伤标志物。在III期（论证）中，我们将基于未破裂脑动脉瘤患者的纵向CTA数据进行动脉瘤演变的前瞻性研究，以评估II期确定的生长预测因子。该项目的具体目标是：1。开发脑动脉瘤表征系统2。血流动力学和PAE特征与动脉瘤生长的关系研究如果我们的假设被证明是正确的，并且该方法被成功实施，将对未破裂脑动脉瘤的临床治疗产生巨大的积极影响。

Description (provided by the applicant): Cerebral aneurysm rupture is a leading cause of hemorrhagic strokes. Because unruptured cerebral aneurysms are being more frequently detected and the prognosis of subarachnoid hemorrhage is still poor, clinicians are often required to judge which aneurysms are prone to progression and rupture. Unfortunately our understanding of the natural history of cerebral aneurysms is limited because the processes of aneurysm initiation, growth and rupture are not well understood. Previous studies have identified the major factors involved in these processes: a) arterial hemodynamics, b) wall biomechanics and mechanobiology, and c) peri-aneurysmal environment (PAE). However, little is known about the relative importance of these factors, their interaction in an individual subject, or their variability across at-risk populations. The overall objective of this project is twofold: a) to gain a better understanding of the mechanisms responsible for the progression of cerebral aneurysms, and b) to develop an integrated system for cerebral aneurysm analysis. Our working hypothesis is that the growth pattern of cerebral aneurysms is determined by the distribution of focal wall damage related to exposure to concentrated hemodynamic wall shear stress and the mitigating effect of bone-aneurysm contact. The project will be divided into three basic phases. In Phase I (development), we will develop and integrate aneurysm modeling and characterization tools and database. The hemodynamics modeling suite will be validated with patient-specific in vitro models constructed using rapid prototyping technology and measured with particle image velocimetry and laser Doppler velocimetry. In Phase II (knowledge discovery), a series of growing and stable aneurysms will be selected from a unique longitudinal database of computed tomography angiography (CTA) images of unruptured aneurysms existing at UCLA, and modeled in order to identify hemodynamic and PAE characteristics and wall damage markers that best correlate with aneurysm growth. In Phase III (demonstration), we will conduct a prospective study of aneurysm evolution based on longitudinal CTA data of patients with unruptured cerebral aneurysms in order to evaluate the growth predictors identified in Phase II. The Specific Aims of the project are to: 1. Develop a system for cerebral aneurysm characterization 2. Study associations of hemodynamic and PAE characteristics to aneurysm growth 3. Evaluate growth predictors using prospective longitudinal data of unruptured aneurysms If our hypotheses are proven to be correct, and the methodology is successfully implemented, there will be a huge positive impact upon the clinical management of unruptured brain aneurysms.