Translational Stroke Research

, Volume 3, Issue 4, pp 508–516

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

Authors

  • Angelika Hoffmann
    • Department of Radiology, Neuroradiology DivisionUniversity of Virginia
    • Department of NeuroradiologyTechnische Universität München
  • Jörg Bredno
    • CT and Nuclear Medicine, Imaging Physics and System AnalysisPhilips Healthcare
  • Michael F. Wendland
    • Department of Radiology, Neuroradiology SectionUniversity of California San Francisco
  • Nikita Derugin
    • Department of NeurosurgeryUniversity of California San Francisco
  • Jason Hom
    • Department of Radiology, Neuroradiology SectionUniversity of California San Francisco
  • Tibor Schuster
    • Institute of Medical Statistics and EpidemiologyTechnische Universität München
  • Claus Zimmer
    • Department of NeuroradiologyTechnische Universität München
  • Hua Su
    • Department of Anesthesia and Perioperative Care, Neurosurgery and Neurology, Center for Cerebrovascular ResearchUniversity of California San Francisco
  • Peter T. Ohara
    • Department of AnatomyUniversity of California San Francisco
  • William L. Young
    • Department of Anesthesia and Perioperative Care, Neurosurgery and Neurology, Center for Cerebrovascular ResearchUniversity of California San Francisco
    • Department of Radiology, Neuroradiology DivisionUniversity of Virginia
    • Department of Radiology, Neuroradiology SectionUniversity of California San Francisco
Original Article

DOI: 10.1007/s12975-012-0212-7

Cite this article as:
Hoffmann, A., Bredno, J., Wendland, M.F. et al. Transl. Stroke Res. (2012) 3: 508. doi:10.1007/s12975-012-0212-7

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 2 h filament occlusion of the right MCA underwent MRI during occlusion, at 4 and 24 h 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 24 h, immediately following the last imaging study. BBBP changes were evaluated at baseline, 4 and 24 h 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 24 h, 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·100 g (marginal mean [95%CI]) during occlusion, at 4 and 24 h post reperfusion, respectively. The BBBP values on the infarcted and contralateral side were significantly different at 4 (p = 0.034) and 24 h post reperfusion (p = 0.031). The predictive value of BBBP in terms of macroscopic hemorrhage was highest 4 h 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 0.35 ml/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.

Keywords

Ischemic strokeMRIBlood–brain barrierHemorrhagic transformation

Supplementary material

12975_2012_212_MOESM1_ESM.doc (166 kb)
ESM 1(DOC 166 kb)

Copyright information

© Springer Science+Business Media, LLC 2012