Improved Animal Modeling of Saccular Aneurysms

描述（由申请人提供）：在美国，未破裂的颅内动脉瘤约占总人口的4-5%。一旦确诊，可能很难自信地推荐适当的治疗方法。手术可以治愈，但有17%的风险会产生严重的副作用。血管内放置闭塞装置的风险较低（5-7%），但永久性动脉瘤关闭率不理想；在许多情况下会出现随后的再生。观察有破裂的风险，这在大多数情况下是致命的，并对大多数幸存者造成神经损伤。为了改变未破裂颅内动脉瘤患者的严峻前景，建议建立一个成功的研究项目，重点研究在兔子身上建立的人类动脉瘤的现实模型。该模型已经经过了广泛的验证，并被用于更好地理解与动脉瘤破裂相关的血流改变的作用。在目前的提案中，我们将实现四个重要目标来进一步研究动脉瘤：1)应用先进的技术，包括基因组学和蛋白质组学，到模型；2)将动脉瘤形状（被许多研究者认为是动脉瘤破裂的预测因素）与动脉瘤内血流改变和血管壁功能紊乱相关联；3)应用该模型，提高对微创线圈在许多情况下无法闭塞动脉瘤的理解；4)通过分析线圈治疗后动脉瘤附近血流的相关性，了解线圈失效的机理。这些目标都将通过创建动脉瘤模型来实现，然后与由放射科医生、机械工程师、分子生物学家和计算机科学家组成的多学科、多机构团队合作，将先进的成像技术、分子生物学、基因组学和计算流体动力学研究应用到模型中。该计划将通过预防由自发性颅内动脉瘤破裂引起的灾难性事件来提高健康水平。

DESCRIPTION (provided by applicant): In the United States, unruptured intracranial aneurysms are present in approximately 4-5% of the general population. Once diagnosed, appropriate therapy may be difficult to recommend with confidence. Surgery is curative, but carries a 17% risk of serious side effects. Endovascular placement of occlusion devices involves lower risk (5-7%), but suboptimal rates of permanent aneurysm closure; subsequent regrowth occurs in many cases. Observation carries a risk of rupture, which is fatal in the majority of cases and neurologically damaging to the majority of survivors. With the objective of altering the grim outlook just described for persons harboring unruptured intracranial aneurysms, work is proposed to build upon a successful research program focused on the study of a realistic model of human aneurysms that is created in rabbits. This model has already undergone extensive validation and been used to better understand the role of altered flow in aneurysms as related to rupture. In the current proposal we will achieve four important aims to further aneurysm research: 1) applying advanced techniques, including genomics and proteomics, to the model; 2) correlating aneurysm shape, considered a predictor for rupture by many investigators, with altered flow and disturbed function of the vessel wall within aneurysms; 3) applying the model to improve the understanding of why minimally invasive coils fail to occlude aneurysms in many cases; and 4) correlating flow near aneurysms after coil treatment to understand mechanisms of coil failure. Each of these aims will be achieved by creating model aneurysms and then, working with a multidisciplinary, multi-institutional team comprising Radiologists, Mechanical Engineers, Molecular Biologists, and Computer Scientists, applying advanced imaging techniques, molecular biology, genomics, and computational fluid dynamics studies to the model. This program will enhance health by preventing the catastrophic events resulting from spontaneous rupture of intracranial aneurysms.