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.
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