Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology

Stroke. 2011 Jul;42(7):2054-60. doi: 10.1161/STROKEAHA.110.597997. Epub 2011 Jun 2.

Abstract

Background and purpose: We sought to validate the blood-brain barrier permeability measurements extracted from perfusion-weighted MRI through a relatively simple and frequently applied model, the Patlak model, by comparison with gold standard histology in a rat model of ischemic stroke.

Methods: Eleven spontaneously hypertensive rats and 11 Wistar rats with unilateral 2-hour filament occlusion of the right middle cerebral artery underwent imaging during occlusion at 4 hours and 24 hours after reperfusion. Blood-brain barrier permeability was imaged by gradient echo imaging after the first pass of the contrast agent bolus and quantified by a Patlak analysis. Blood-brain barrier permeability was shown on histology by the extravasation of Evans blue on fluorescence microscopy sections matching location and orientation of MR images. Cresyl-violet staining was used to detect and characterize hemorrhage. Landmark-based elastic image registration allowed a region-by-region comparison of permeability imaging at 24 hours with Evans blue extravasation and hemorrhage as detected on histological slides obtained immediately after the 24-hour image set.

Results: Permeability values in the nonischemic tissue (marginal mean ± SE: 0.15 ± 0.019 mL/min 100 g) were significantly lower compared to all permeability values in regions of Evans blue extravasation or hemorrhage. Permeability values in regions of weak Evans blue extravasation (0.23 ± 0.016 mL/min 100 g) were significantly lower compared to permeability values of in regions of strong Evans blue extravasation (0.29 ± 0.020 mL/min 100 g) and macroscopic hemorrhage (0.35 ± 0.049 mL/min 100 g). Permeability values in regions of microscopic hemorrhage (0.26 ± 0.024 mL/min 100 g) only differed significantly from values in regions of nonischemic tissue (0.15 ± 0.019 mL/min 100 g).

Conclusions: Areas of increased permeability measured in vivo by imaging coincide with blood-brain barrier disruption and hemorrhage observed on gold standard histology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiopathology*
  • Brain Ischemia / pathology*
  • Disease Models, Animal
  • Evans Blue / pharmacology
  • Hemorrhage / pathology
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods*
  • Male
  • Microscopy, Fluorescence / methods
  • Permeability
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Stroke / pathology*

Substances

  • Evans Blue