Publication Date

2008-04-20

Availability

Open access

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

April 2008

First Committee Member

Baruch B. Lieber - Committee Chair

Second Committee Member

Weizhao Zhao - Committee Member

Third Committee Member

Fotios Andreopoulos - Committee Member

Fourth Committee Member

Brant D. Watson - Committee Member

Fifth Committee Member

Ajay K. Wakhloo - Committee Member

Abstract

Cerebral aneurysms are abnormal focal dilations of the cerebral vasculature that may rupture and cause a hemorrhagic stroke. More than a decade after seminal experimental studies showed the feasibility of successfully treating cerebral aneurysms by flow diversion, the potential of this modality is gradually being recognized in the clinical arena. A flow divertor is a metallic meshed tube that has its porosity (ratio of metal-free surface area to total surface area) and pore density (number of pores per unit surface area) optimized to facilitate occlusion of aneurysms. An appropriately designed flow divertor severely attenuates the flow exchange between the parent vessel and an aneurysm, resulting in the formation of intra-aneurysmal flow stasis zones which promote thrombosis. This study reports the results from implantation of three different configurations of a novel flow-diverting device in thirty elastase-induced aneurysm models in rabbits. Ten animals per device configuration were followed-up at 3 weeks (n=3), 3 months (n=3), and 6 months (n=4) and tissue explanted post-sacrifice was sent for histology. High-speed angiographic sequences were acquired before and immediately after device implantation, and at follow-up for each animal. Temporal variations in the angiographic contrast intensity within the aneurysms were recorded and subsequently corrected for respiratory motion. These aneurysmal contrast washout curves were fit to a mathematical model whose parameters served to quantify device performance. Angiographic quantification was supplemented by histomorphometric data to derive composite scores of the performance of each device configuration in effecting stable aneurysm occlusion. Performance scores showed that the device with a porosity of 70%, filament diameter of 38 microns, and pore density of 18 pores/mm^2 performed better than devices with 65% porosity, 51 micron filament diameter, 14 pores/mm^2 and 70% porosity, 51 micron filament diameter, 12 pores/mm^2 with relative efficacies of 100%, 86%, and 79%, respectively. Angiographic quantification further suggested a parameter, which could be employed to estimate long-term aneurysm occlusion probabilities immediately after treatment with any flow diversion device. A value of this parameter less than 30 predicts greater than 97% angiographic aneurysm occlusion over a period of six months with a sensitivity of 73% and specificity of 82%. Larger data sets are required to improve the validity of this test. The pore density of flow divertors, rather than porosity, was seen to be a critical modulating factor of device efficacy. Refinement of the best device configuration by further optimizing the pore density may yield yet better results.

Keywords

Angiography; Diffusion; Residence Time; Thrombosis; Lagged Normal Distribution; Washout Curve; Pore Density; Flow Diversion; Stent; Mathematical Modeling; Convection; Flow Exchange

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