Non-invasive MRI is widely used to assess and monitor ischemic stroke, yet conventional approaches often lack sensitivity to subtle microstructural changes and struggle to evaluate tissue viability across lesion, penumbra, and distal regions. In this study, frequency dependent diffusion tensor distribution imaging ( ω DTD) was combined with clustering of diffusion tensor distributions D ( ω ) and multivariate regression modeling to characterize ischemic tissue alterations in a whole brain section. Ex vivo ω DTD and histology were performed in rats subjected to middle cerebral artery occlusion (MCAO) or sham surgery (P = 11) 24 h after reperfusion. Lesions showed cell loss and an increased presence of smaller, likely glial, cells. A random forest (RF) model was used to explain and predict histological parameters from diffusion tensor imaging (DTI), manually bin resolved ω DTD features, and cluster resolved ω DTD parameters. Model performance was evaluated using leave one animal out cross validation (LOO CV). ω DTD features better represented cell number than DTI metrics ( ω DTD R ² = 0.73 vs. DTI R ² = 0.49), with similar advantages for nuclear area and circularity ( ω DTD R ² = 0.64 and 0.61 vs. DTI R ² = 0.40 and 0.35). The RF model further proved beneficial in capturing complex, nonlinear relationships between MRI parameters and tissue characteristics. Overall, these results indicate that ω DTD provides richer microstructural information than standard DTI, and that combining ω DTD with advanced machine learning methods enhances interpretation of ischemic tissue damage.