Against the Flow: Coil Arrangement and Design Modulate Hemodynamics and Clotting in Model Saccular Bifurcation Intracranial Aneurysm In Vitro 209 views

Intracranial aneurysm (IA) healing after endovascular coiling has been studied extensively in silico and in vivo; however, it is still unclear what causes IAs to recur. In vitro models of IA thrombosis contribute to an understanding of why IAs recur by providing a way to interrogate acute healing mechanisms and to screen treatments. In this work, novel models of saccular bifurcation IA thrombosis were developed and used to explore how coil properties drive hemodynamics and clot formation. Two parallel plate flow chambers were designed: one to model thrombosis at the neck of a bifurcation IA and another to analyze thrombosis within a coiled “sac”. Clots were formed in the presence of coils during fluorescence imaging of fibrin polymerization and flow tracers. Clots were analyzed post-fixation using scanning electron microscopy. Comparisons with clotted coils in the absence of flow indicate that arterial shear rates were required to produce clot structure similar to that observed in vivo and differences in clotting on coils with different packing densities and designs. In order to determine whether coil arrangement and local packing density affect thrombosis, a coil arrangement was analyzed in which filler coiled coils were arranged parallel to one another to create areas of high local packing density. Slower flow with nondivergent streamlines and larger clots were observed around these coils compared to coils arranged circumferentially. Clot distribution over time was also affected by coiled coil arrangement. To determine whether coil secondary shape facilitates thrombosis, rectangular wires were braided together to create a novel braided coil design that was compared to the coiled coil design. In the neck model, braided coils produced more circular flow patterns and denser platelet-fibrin clot structure than coiled coils, but clot accumulation was not dependent on coil design. In the sac model, coiled coils reduced flow velocity and correlated with fibrous mesh clot when located at the neck. Braided coils promoted flow disturbances and faster velocities that correlated with less clot formation and dense platelet-fibrin clot structures. These results suggest that slow flow with nondivergent streamlines around coils may be optimal for the formation of large fibrous clots, and that framing coil design may have a stronger influence on coil structure within the sac than filling coil design. These results indicate that coil arrangement and design influence hemodynamics and thrombosis in coiled IAs. Extracellular matrix structure modulates cell behavior; therefore, coil arrangement and design likely impact cellularization and subsequent healing in IAs. Further studies are necessary to elucidate the effects of coil-mediated IA hemodynamics and clot structure on cellularization.

PHD (Doctor of Philosophy)

Intracranial aneurysm; Endovascular coil; Thrombosis

English

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2018-04-23