Characterizing Tissue Fate After Transient Cerebral Ischemia of Varying Duration Using Quantitative Diffusion and Perfusion Imaging

Abstract

The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient-cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28). Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical 60-minute transient ischemia and permanent ischemia group. ADC-derived lesions markedly decreased on reperfusion at 35 minutes to an average of 15+/-5% of prereperfusion lesion size (P<0.00001). At 24 hours, lesion volume as determined by T2 imaging increased again to 51+/-10% of prereperfusion lesion size. In the 95-minute group, ADC lesions only briefly decreased on reperfusion and then secondarily enlarged at 180 minutes, almost reaching prereperfusion lesion volume. Pixel-based analysis demonstrated that >85% of mismatch pixels were salvaged by reperfusion independent of ischemia duration. Recanalization at 35, 60, and 95 minutes resulted in recovery of 46%, 28%, and 9% of core pixels, respectively. Core and mismatch pixels that were ultimately salvaged had persistently higher (P<0.001) CBF values during ischemia in all reperfusion groups, associated with higher (P<0.05) ADC values. This study demonstrated substantial salvage of mismatch tissue after reperfusion independent of ischemia duration and substantial permanent recovery of initial core pixels with early reperfusion. Severity of CBF reduction during ischemia seems to be the main factor determining tissue fate.