Contrast-enhanced magnetic resonance microangiography reveals remodeling of the cerebral microvasculature in transgenic ArcAß mice.

ABSTRACT

Amyloid-ß (Aß) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcAß model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-µMRA). Three-dimensional gradient echo datasets with 60 µm isotropic resolution were acquired in 4- and 24-month-old arcAß mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-µMRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 µm) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20-80 µm) has been observed in 24-month-old arcAß mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and Aß deposition in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old arcAß mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of Aß and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-µMRA in mice.