Abstract WP257: A New microCT-based Blood-Brain Barrier Imaging to Study Hemorrhagic Transformation of Ischemic Stroke

Background: The breakdown of the blood-brain barrier (BBB) can accelerate the progression of cerebral ischemic injury, and vice versa. Hemorrhagic transformation (HT) of ischemic stroke is linked with the loss of the BBB integrity, which has been reported to have a biphasic dynamics: a significant reduction in BBB permeability at 24h after reperfusion. Objectives: To develop a new microCT-based in vivo BBB imaging technique for small animals and investigate if (1) acute HT after ischemic stroke could be predicted with the severity of earlier BBB dysfunction and (2) BBB opening is biphasic regardless of the HT. Methods: Focal cerebral ischemia was induced by transient occlusion of middle cerebral artery (tMCAO) for 1h in 11-week-old C57/BL6 mice (n=29). Thereafter, serial microCT imaging was performed 5min after ipsi-lesional intra-carotid infusion of iopromide (240μl, 5min) at 4h, 24h, and 48h after the tMCAO. Then, animals were sacrificed after intravenous injection of 2% Evans-Blue (EB) and the extent of BBB damage was visualized in the ex vivo brain sections by measuring EB leakage with a near-infrared fluorescent (NIRF) imaging machine. Results: microCT signal due to the leakage of iopromide into the infarct lesion was clearly observed at 5min after each infusion at 4h, 24h, and 48h after stroke, which gradually decreased over 60~180min, and then completely disappeared. The iopromide-leakage on microCT corresponded closely with the EB-leakage on NIRF imaging and the infarct lesion on TTC staining. At 48h after tMCAO, the leakage of iopromide (arbibrary-unit, A.U.) was more extensive in the animals with parenchymal hematoma (n=13) than in those without (n=16): 26.3±11.7A.U. vs. 9.8±5.9A.U. (p Conclusions: We introduce a new BBB imaging technique for small animals in vivo and show that acute HT could not be predicted with earlier microCT BBB imaging. Regardless of the HT, the biphasic BBB opening was not observed.