Effects of reperfusion on ADC and CBF pixel-by-pixel dynamics in stroke: characterizing tissue fates using quantitative diffusion and perfusion imaging

The effects of reperfusion on the spatiotemporal dynamics of transient (60 minutes) focal ischemic brain injury in rats were evaluated on a pixel-by-pixel basis using quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) measurements every 30 minutes for 3 hours and compared to post-mortem histology at 24 hours. Four biologically relevant clusters were classified based on ADC (0.53 +/- 0.02 x 10mm/s, SD) and CBF (0.30 +/- 0.09 ml/g/min) viability thresholds, namely: (1) the normal cluster with ADC and CBF \u3e thresholds; (2) the mismatch cluster with ADC \u3e threshold but CBF \u3c threshold; (3) the core cluster with ADC and CBF \u3c thresholds; and (4) non-nourishing reperfusion zone where ADC \u3c threshold but CBF \u3e threshold. The spatio-temporal progression of tissue volumes, ADC and CBF of each cluster were evaluated. Pixels of each cluster on the CBF-ADC space were mapped onto the image space. Following reperfusion, 28% of the core pixels and 90% of the mismatch (defined at 60 minutes) pixels were salvaged at 180 minutes, which correlated with histology. The ADC and CBF of subsequently salvaged tissues were significantly higher than those became infarcted. Salvaging core pixels indicated that reduced ADC was not synonymous with irreversible injury; duration of exposure and severity of reduced ADC and CBF were likely critical. Projection profiles showed a bimodal ADC, but uni-modal CBF, distributions. The ADC bimodal minima, obtained without histological correlation, were similar to the histology-derived ADC and CBF viability thresholds, and could have potential clinical applications. This study demonstrated a simple but powerful approach to evaluate, on a pixel-by-pixel basis, the spatio-temporal evolution of ischemic brain injury, and a potential for statistical prediction of tissue fate