Hemodynamic intervention is a promising endovascular treatment for intracranial aneurysms. However, little is known about hemodynamic and biological responses of realistic aneurysms to such intervention. Understanding the interaction between the blood flow dynamics and biological response is vital to improving the success of aneurysm treatments. We hypothesize that disruption of impacting flow will induce favorable aneurysmal wall remodeling and thrombotic occlusion of intracranial aneurysms. We combine an in vivo rabbit model and imaged-based computational fluid dynamics approach to test this hypothesis by addressing the following Specific Aims: 1) to quantify the hemodynamic effects of stenting in realistic aneurysm geometries; 2) to determine the effects of reduced wall shear stress on aneurysm growth; 3) to determine the effect of reduced wall shear stress on vascular remodeling factors; and 4) to develop endovascular prostheses to modify intra-aneurysmal flow into a thrombogenetic environment characterized by recirculation zones and long particle residence time. Scientific Significance: Quantitative understanding of the hemodynamic factors that induce favorable changes in the aneurysm pathology will help develop more effective treatment paradigms. The overall goal of this Award is for a well-established quantitative scientist and engineer in the area of fluid mechanics to make a career transition to a quantitative biomedical researcher with expertise in bioengineering, quantitative vascular biology, and transitional research on cerebrovascular disease and therapy. A multi-faceted plan is proposed to train in areas of translational neurovascular intervention, integrative cerebrovascular biology and medical imaging.
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