Interpretable Multimodal MRI-Clinical Fusion for Functional Outcome Prediction After Acute Ischemic Stroke

Abstract

This study evaluates the added prognostic value of day-1 multimodal MRI for predicting three-month functional outcome after acute ischemic stroke (AIS). Sixty-six AIS patients with ADC, DWI, FLAIR, and clinical data were analyzed. Three-dimensional pretrained ResNet embeddings were extracted from each MRI modality, reduced using fold-isolated principal component analysis, and combined with structured clinical variables and ADC-derived lesion biomarkers. Linear support vector machines were evaluated using eight-fold stratified group cross-validation across MRI modality combinations. Clinical-only modeling achieved strong performance (AUC = $0.899 \pm 0.151$), while MRI-only models showed limited discrimination (AUC $\approx$ $0.67$-$0.73$). Among multimodal configurations, FLAIR-clinical fusion achieved the highest mean cross-validated performance (AUC = $0.948 \pm 0.061$), followed by ADC-clinical fusion (AUC = $0.941 \pm 0.094$). Full ADC-DWI-FLAIR fusion did not consistently outperform single-modality clinical fusion. Feature-importance analysis identified age, NIHSS subscores, ADC lesion burden, and learned FLAIR representations as key contributors, while qualitative FLAIR activation maps showed responses over lesion-like regions. These findings suggest that compact day-1 FLAIR and ADC representations provide complementary prognostic information beyond clinical variables and support interpretable, data-efficient outcome prediction in AIS.