Investigation of techniques to quantify in vivo lesion volume based on comparison of water apparent diffusion coefficient (adc) maps with histology in focal cerebral ischemia of rats

Stroke lesion-volume estimates derived from calculated water apparent diffusion coefficient (ADC) maps provide a quantitative surrogate end-point for investigating the efficacy of drug treatment or studying the temporal evolution of cerebral ischemia. Methodology is described for estimating ischemic lesion volumes in a rat model of permanent middle cerebral artery occlusion (MCAO) based on absolute and percent-reduction threshold values of the water ADC at 3 h post-MCAO. Volume estimates derived from average ADC (ADCav) maps were compared with those derived from post-mortem histological sections. Optimum ADC thresholds were established as those that provided the best correlation and one-to-one correspondence between ADC- and histologically derived lesion-volume estimates. At 3 h post-MCAO, an absolute-ADCav threshold of 47 × 10−5 mm2/s (corresponding to a 33% reduction in ADCav based on a contralateral hemisphere comparison) provided the most accurate estimate of percent hemispheric lesion volume (%HLV). Experimental and data analysis issues for improving and validating the usefulness of DWI as a surrogate endpoint for the quantification of ischemic lesion volume are discussed.