FORESEE-MS: Toward Prospective Spatial Forecasting of Future Multiple Sclerosis Lesions from Baseline FLAIR MRI

Traditional multiple sclerosis (MS) image analysis has primarily focused on retrospectively detecting and segmenting lesions. This study investigates whether baseline FLAIR MRI can identify regions at risk for future lesion formation beyond population-level spatial patterns. We introduce FORESEE-MS, an evaluation protocol that uses a fold-specific population-prior atlas as a baseline and assesses predictions using pooled voxel-level discrimination (AUROC and AUPRC) and within-patient lesion localization (Recall@Top-K%), with patient-level bootstrap confidence intervals. We evaluated five deep learning models (3D U-Net, Attn+ResBlock+VAE, ViT, and two SwinUNETR variants) using 5-fold cross-validation on 39 subjects from the MSSEG-2 dataset. The atlas achieved the highest pooled voxel-level AUROC and AUPRC, with no deep learning model reliably outperforming it on either metric. However, the 3D U-Net and Attn+ResBlock+VAE achieved higher mean voxel-level within-patient Recall@Top-K% than the atlas at all evaluated thresholds, although most paired confidence intervals for the differences included zero. These findings suggest that baseline FLAIR may contain patient-specific predictive information, but in this small cohort, it remains uncertain whether this information improves lesion forecasting beyond a population-prior atlas.