A Voxel-Wise T2 Distribution Framework for Lesion Severity Stratification and Treatment-Response Assessment in Stroke: Insights Into Suberoylanilide Hydroxamic Acid-Induced Neuroprotection.

PURPOSE: To evaluate lesion severity distribution in ischaemic brain lesions in spontaneously hypertensive rats (SHR) subjected to 90-min transient middle cerebral artery occlusion (tMCAO), and to determine whether epigenetically based neuroprotection modifies lesion severity profiles using a voxel-wise T2 distribution framework. THEORY AND METHODS: Stroke treatments are commonly evaluated by quantifying infarct size using histology or MRI, approaches that average across lesions and may obscure heterogeneous tissue responses. SHR underwent 90-min intraluminal MCAO and received suberoylanilide hydroxamic acid (SAHA) 4 h after reperfusion. Quantitative T2 maps were acquired at Days 1 and 8 postocclusion. Voxel-wise histogram analysis defined severity thresholds (T2 < 70 ms mild; 70-90 ms moderate; > 90 ms severe). Region-stratified RT-qPCR assessing neuronal, inflammatory, and apoptotic markers provided complementary biological context for interpreting region- and severity-resolved MRI patterns. RESULTS: Severity-bin stratification of voxel-wise T2 values quantified how lesion composition redistributed from severe toward moderate/mild classes across time and regions (cortex vs. subcortex) in association with SAHA treatment. Cortical molecular markers corroborated imaging-defined tissue preservation but did not resolve subcortical differences detected by voxel-wise MRI. Untreated animals exhibited partial spontaneous attenuation of extreme subcortical T2 abnormalities. Histogram descriptors correlated with behavioral outcomes. CONCLUSION: Voxel-wise T2 distribution analysis provides a complementary, severity-stratified description of lesion composition and its evolution over time, alongside conventional endpoints such as infarct volume and mean/median T2. The approach is readily applicable in preclinical MRI and is potentially translatable, warranting further validation across broader imaging settings.