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

  • Angelika Hoffmann
  • Jörg Bredno
  • Michael F. Wendland
  • Nikita Derugin
  • Jason Hom
  • Tibor Schuster
  • Claus Zimmer
  • Hua Su
  • Peter T. Ohara
  • William L. Young
  • Max Wintermark
Original Article


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.


Ischemic stroke MRI Blood–brain barrier Hemorrhagic transformation 

Supplementary material

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


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Angelika Hoffmann
    • 1
    • 6
  • Jörg Bredno
    • 3
  • Michael F. Wendland
    • 2
  • Nikita Derugin
    • 4
  • Jason Hom
    • 2
  • Tibor Schuster
    • 5
  • Claus Zimmer
    • 6
  • Hua Su
    • 7
  • Peter T. Ohara
    • 8
  • William L. Young
    • 7
  • Max Wintermark
    • 1
    • 2
  1. 1.Department of Radiology, Neuroradiology DivisionUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Radiology, Neuroradiology SectionUniversity of California San FranciscoSan FranciscoUSA
  3. 3.CT and Nuclear Medicine, Imaging Physics and System AnalysisPhilips HealthcareSan JoseUSA
  4. 4.Department of NeurosurgeryUniversity of California San FranciscoSan FranciscoUSA
  5. 5.Institute of Medical Statistics and EpidemiologyTechnische Universität MünchenMunichGermany
  6. 6.Department of NeuroradiologyTechnische Universität MünchenMunichGermany
  7. 7.Department of Anesthesia and Perioperative Care, Neurosurgery and Neurology, Center for Cerebrovascular ResearchUniversity of California San FranciscoSan FranciscoUSA
  8. 8.Department of AnatomyUniversity of California San FranciscoSan FranciscoUSA

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