Single-subject statistical mapping of acute brain hypoxia in the rat following middle cerebral artery occlusion: A microPET study

Abstract: No study so far has attempted to map the 3D topography of brain hypoxia in the individual rat in vivo following middle cerebral artery occlusion (MCAo). In a previous microPET study, we reported that 18F-fluoromisonidazole (18F-MISO) trapping in the brain after MCAo was specific for the hypoxic viable tissue. Here, we used 18F-MISO microPET to map the 3D topography of brain hypoxia in the acute stage of permanent distal MCAo in individual spontaneously hypertensive rats. Normal rats were also studied. 18F-MISO was intravenously injected approximately 1h after clip placement and PET data were acquired for 2 hours. Animals were sacrificed and the brains harvested 48h later for infarct mapping using standard histopathology. As expected, continuous 18F-MISO trapping was found over the affected relative to unaffected and control MCA cortex. Using single-subject voxel-based statistical mapping, tracer accumulation 90–120 min after injection was consistently significantly higher in the anterior MCA cortex (proximal relative to clip site) and gradually decreased towards posterior areas, a pattern consistent with the classic penumbra concept. The data also suggested that (i) a portion of the significant 18F-MISO trapping area may sit outside the contours of the final infarct despite the permanent MCAo, suggesting that 18F-MISO may be a marker not only of severe (penumbral) but also of milder (oligemic) hypoxia, and (ii) small portions of the final infarct may not exhibit early tracer trapping, suggesting that by the time the tracer was administered this tissue had already progressed to irreversible damage. This study shows the feasibility of single-subject mapping of brain hypoxia following MCAo in the rat, which has potential applications in pathophysiological investigations. [Copyright &y& Elsevier]