Stroke is the most common life-threatening neurological disease and the third leading cause of death in the United States One fourth of the deaths from cerebrovascular disease in the United States arise from hemorrhage and stroke associated with rupture of intracranial aneurysms. The endovascular treatment for intracranial aneurysms that is gradually replacing conventional surgery has focused on the intra-aneurysmal deposition of occlusive materials with no regard for the pathology of the disease our hypothesis is that the hemodynamics in the parent artery/aneurysm complex can be altered by the minimally invasive implantation of a flow divertor in the parent vessel. Scaffolding by the divertor initiates parent artery/aneurysm remodeling, leading to a cure of the lesion. The design parameters, i.e., axial and radial distensibility, filament diameter, pore size, and the material composition of the flow divertor will have to be tailored to the local hemodynamics for a permanent occlusion of the aneurysm, yet preventing vessel injury, acute thrombosis, or delayed stenosis inside the bioimplant. We propose to identify the optimal design of a flow divertor for endovascular bypass of intracranial aneurysms through two sequential but complementary approaches. In the first approach, vascular replicas of experimental aneurysm models in rabbit will be used in vitro to optimize the interaction between the flow divertor and the vascular hemodynamics. Thereafter, the most promising designs will be selected for implantation in an aneurysm model in rabbit to elucidate the remodeling of the vasculature in response to the implanted flow divertor. High spatio-temporal resolution data acquired from the bench top experiments will be correlated with the limited amount of data that can be obtained in vivo. The postmortem histopathological analysis of the in vivo data will provide definitive conclusions to observations made angiographically in vivo. The tasks will be accomplished through the following specific aims: 1) To construct elastomer replicas of the rabbit aneurysm model for bench top investigation using a mock circulation loop; 2) To evaluate the influence of the design parameters of the flow divertor on intra-aneurysmal flow in the elastomer replicas; 3(a) To construct elastase-induced bifurcation aneurysm model in rabbit; (b) To implant the optimized flow divertors in the rabbit aneurysm model and quantify indices of local hemodynamic changes by the divertor; and 4) To evaluate the efficacy of the optimized flow divertors in parent artery remodeling and aneurysm exclusion.
Showing the most recent 10 out of 16 publications
