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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS045753-04
Application #
7156947
Study Section
Special Emphasis Panel (ZRG1-SSS-S (10))
Program Officer
Golanov, Eugene V
Project Start
2003-12-01
Project End
2008-05-31
Budget Start
2006-12-01
Budget End
2008-05-31
Support Year
4
Fiscal Year
2007
Total Cost
$287,688
Indirect Cost
Name
University of Miami School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Sadasivan, Chander; Fiorella, David J; Woo, Henry H et al. (2013) Physical factors effecting cerebral aneurysm pathophysiology. Ann Biomed Eng 41:1347-65
Sadasivan, Chander; Brownstein, Jeremy; Patel, Bhumika et al. (2013) IN VITRO QUANTIFICATION OF THE SIZE DISTRIBUTION OF INTRASACCULAR VOIDS LEFT AFTER ENDOVASCULAR COILING OF CEREBRAL ANEURYSMS. Cardiovasc Eng Technol 4:63-74
Trager, Asher L; Sadasivan, Chander; Lieber, Baruch B (2012) Comparison of the in vitro hemodynamic performance of new flow diverters for bypass of brain aneurysms. J Biomech Eng 134:084505
Hao, Qing; Lieber, Baruch B (2012) Dispersive Transport of Angiographic Contrast During Antegrade Arterial Injection. Cardiovasc Eng Technol 3:171-178
Lieber, Baruch B; Sadasivan, Chander (2010) Endoluminal scaffolds for vascular reconstruction and exclusion of aneurysms from the cerebral circulation. Stroke 41:S21-5
Lieber, Baruch B; Sadasivan, Chander; Hao, Qing et al. (2009) The mixability of angiographic contrast with arterial blood. Med Phys 36:5064-78
Sadasivan, Chander; Lieber, Baruch B (2009) Numerical Investigation of Coil Configurations That Provide Ultra-High Packing Density of Saccular Aneurysms. J Med Device 3:41005
Trager, Asher L; Sadasivan, Chander; Seong, Jaehoon et al. (2009) Correlation between angiographic and particle image velocimetry quantifications of flow diverters in an in vitro model of elastase-induced rabbit aneurysms. J Biomech Eng 131:034506
Sadasivan, Chander; Cesar, Liliana; Seong, Jaehoon et al. (2009) An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model. Stroke 40:952-8
Cesar, Liliana; Miskolczi, Laszlo; Lieber, Baruch B et al. (2009) Neurological deficits associated with the elastase-induced aneurysm model in rabbits. Neurol Res 31:414-9

Showing the most recent 10 out of 16 publications