Validation of In Vivo Magnetic Resonance Imaging Blood–Brain Barrier Permeability Measurements by Comparison With Gold Standard Histology
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.
- Received July 28, 2010.
- Accepted February 1, 2011.
- © 2011 American Heart Association, Inc.