MRI Blood–Brain Barrier Permeability Measurements to Predict Hemorrhagic Transformation in a Rat Model of Ischemic Stroke

Abstract

Permeability imaging might add valuable information in the risk assessment of hemorrhagic transformation. This study evaluates the predictive value of blood-brain barrier permeability (BBBP) measurements extracted from dynamic contrast-enhanced MRI for hemorrhagic transformation in ischemic stroke. Spontaneously hypertensive and Wistar rats with 2h filament occlusion of the right MCA underwent MRI during occlusion, at 4 and 24h post reperfusion. BBBP was imaged by DCE imaging and quantified by Patlak analysis. Cresyl-violet staining was used to characterize hemorrhage in sacrificed rats at 24h, immediately following the last imaging study. BBBP changes were evaluated at baseline, 4 and 24h after reperfusion. Receiver-operating characteristic (ROC) analysis was performed to determine the most accurate BBBP threshold to predict hemorrhagic transformation. In animals showing macroscopic hemorrhage at 24h, 95th BBBP percentile values ipsilateral were 0.323 [0.260, 0.387], 0.685 [0.385, 0.985], and 0.412 [0.210, 0.613] ml/min·100g (marginal mean [95%CI]) during occlusion, at 4 and 24h post reperfusion, respectively. The BBBP values on the infarcted and contralateral side were significantly different at 4 (p = 0.034) and 24h post reperfusion (p = 0.031). The predictive value of BBBP in terms of macroscopic hemorrhage was highest 4h after reperfusion (ROC area under the curve = 84%) with a high negative predictive value (98.3%) and limited positive predictive value (14.9%) for a threshold of 0.35ml/min·100g. Altered BBBP is a necessary but not sufficient condition to cause hemorrhagic transformation in rats with an infarct. Further research is needed to identify those additional risk factors that are required for hemorrhagic transformation to develop in the setting of ischemic stroke.