Angioarchitectural changes in subacute cerebral venous thrombosis. A synchrotron-based micro- and nano-CT study

It is well known that recanalization of thrombosed cerebral sinuses occurs early but without marked influence on the long-term outcome and on final venous infarct volume on magnetic resonance imaging. To better understand the possible microvascular mechanisms behind these clinical observations, we evaluated the sequels of subacute superior sagittal sinus (SSS) thrombosis in rats using micro- and nano-CT imaging of the same specimen to provide large volume and high resolution CT image data respectively. SSS thrombosis was induced in 11 animals which were euthanized after 6h (n=4) or 6 weeks (n=7). Eight sham-operated rats served as controls. After infusion of contrast into the vasculature of the brains, these were isolated and scanned using micro-, nano-, and synchrotron-based micro-CT ((8 μm³), (900 nm)³, and (1.9 μm³) voxel sizes). The cross-sectional area of the superior sagittal sinus, microvessels and cortical veins were quantified. Tissue sections were stained against VEGF antigen. Immunohistochemistry was confirmed using quantitative rtPCR. SSS thrombosis led to a congestion of the bridging veins after 6h. After 6 weeks, a network of small vessels surrounding the occluded SSS was present with concurrent return towards the diameter of the draining bridging veins of controls. This microvascular network connected to cortical veins as demonstrated by nano- and synchrotron-based micro-CT. Also the volume fraction and number of cortical veins increased significantly. Immunohistochemistry in the region of the microsvascular network demonstrated a strong immunoreactivity against VEGF, confirmed by rtPCR. The sequel of subacute SSS thrombosis induced a network of microvessels ("venogenesis") draining the bridging veins. Also the volume fraction of cortical veins increased significantly.