The role of hemodynamic factors on the development, enlargement, and rupture of cerebral aneurysms: A combination of computational fluid dynamics analysis and an animal model study

Abstract

Predicting cerebral aneurysm rupture is still difficult since we do not have enough information about the risk factors for the aneurysm rupture. We studied the hemodynamic related factors for the development, enlargement, and rupture of cerebral aneurysms, using both an animal model of experimentally induced cerebral aneurysms and a computational fluid dynamics (CFD) simulation of human cerebral aneurysms. We introduce here our evidence suggesting that cerebral aneurysms develop near the apex of arterial bifurcations as a result of an increase in hemodynamic factors, particularly in wall shear stress. Aneurysms in our animal model developed at several sites along the circle of Willis, where blood flow is increased in compensation for unilateral common carotid artery ligation and experimental hypertension, suggesting that the enhanced hemodynamic stress is of primary importance. Our hemorheological studies in rats showed that the wall shear stress was increased and at its highest level at the distal end of the aneurysm orifice. Vascular endothelial cells can sense fluid shear stress caused by blood flow, change their shape and release several substances in response to the shear, and in turn regulate blood flow. During aneurysm formation, vascular endothelial cells may sense excessively high levels of wall shear stress over the physiological limit, which may initiate damage to vascular wall components, leading to aneurysm formation. In order to clarify the role of endothelial shear sensing on aneurysm formation, we examined the effect of blockage in the P2X4 purinoceptor, one of the vascular endothelial shear-sensors, on the frequency of aneurysm induction after aneurysm-inducing surgery. In a group of P2X4 purinoceptor knockout mice, the number of induced aneurysms was significantly smaller than that in the control wild-type mice group. The CFD analyses using 3-dimentional CT angiographic images of human cerebral aneurysms also indicated the tendency whereby the magnitude of wall shear stress at the aneurysm orifice is high only if the measured flow velocities derived from physiological data of individual patients were used as inlet boundary conditions. The data are consistent with the results found using an animal model. In order to examine more details of hemodynamics in human aneurysms and to clarify hemodynamic risk factors for enlargement and rupture of cerebral aneurysms with CFD techniques, we just started a multi-institutional prospective clinical study, named “Computational Fluid Dynamics Analysis of Blood Flow in Cerebral Aneurysms: Prospective Observational Study (CFD ABO Study)”.