High-resolution MRI of the mouse cerebral vasculature to study hemodynamic-induced vascular remodeling

Background: Hemodynamics is a driving factor behind remodeling of the cerebral vasculature, yet mechanisms of flowinduced remodeling remain incompletely understood. Studies employing serial imaging could help characterize hemodynamic-induced pathologic and physiologic remodeling of cerebral arteries. Methods: This preliminary study was performed us ing 4 mice. In 3, we induced flow-driven vascular remodeling in the Circle of Willis (CoW). This was done by ligation of the left common carotid artery (CCA), and the right external carot id and pterygopalatine arteries, which resulted in an increase of blood flow through the basilar artery and the right internal carotid artery. The remaining mouse was used as a wild-type control. In the 3 experimental mice, we performed 9.4 Tesla Magnetic Resonance Imaging (MRI) over a span of 3 months. 3D images were reconstructed for serial computational evaluation of gross morphological changes. These measurements were verified by the terminal vascular corrosion casting and scanning electron microscope imaging. Results: This study demonstrated the feasibility to distinguish and serially measure pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. We showed that these changes were characterized by compensatory arterial dilation and increased tortuosity on the anterior cerebral artery. From scanning electron microscope images, we also found that there was microscopic damage, akin to aneurysmal remodeling, at the right olfactory artery origin. Conclusions: MRI-based serial imaging has the potential to serially characterize gross morphological changes in the CoW in response to flow manipulation. In the future, combining this analysis with computational fluid dynamics simulations will help to define the hemodynamic environments corresponding to these and other pathologic remodeling changes in the mouse CoW.