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

Multiple Sclerosis (MS) is a chronic autoimmune disease that can significantly reduce the quality of life of a patient. Existing treatment options can only help slow down the progression of the disease. Therefore, early detection and precise monitoring of disease progression are important. Deep learning offers state-of-the-art models for detecting and segmenting MS lesions in brain MRI scans. However, most of these models are evaluated using the Dice score, without accounting for lesion-wise detection and segmentation performance or other metrics that quantify model performance in cases that are complex or confusing for human annotators, or in cases that are essential for disease detection and progression monitoring. In this paper, we highlight the need to rethink the evaluation of MS lesion segmentation models. In this context, we first present problem fingerprinting in detail to highlight what neurologists look for in brain MRI scans for MS detection and progression monitoring, and which metrics are required to properly quantify model performance in these contexts. Additionally, we present an analysis of state-of-the-art models on two open-source datasets using these metrics to highlight their usability for real-world deployment in hospitals.

Ultra-high field 7-tesla (7T) MRI improves visualization of multiple sclerosis (MS) white matter lesions (WML) but differs sufficiently in contrast and artifacts from 1.5-3T imaging - suggesting that widely used automated segmentation tools may not translate directly. We analyzed 7T FLAIR scans and generated reference WML masks from Lesion Segmentation Tool (LST) outputs followed by expert manual revision. As external comparators, we applied LST-LPA and the more recent LST-AI ensemble, both originally developed on lower-field data. We then trained 3D UNETR and SegFormer transformer-based models on 7T FLAIR at multiple resolutions (0.5x0.5x0.5^3, 1.0x1.0x1.0^3, and 1.5x1.5x2.0^3) and evaluated all methods using voxel-wise and lesion-wise metrics from the BraTS 2023 framework. On the held-out test set at native 0.5x0.5x0.5^3 resolution, 7T-trained transformers achieved competitive overlap with LST-AI while recovering additional small lesions that were missed by classical methods, at the cost of some boundary variability and occasional artifact-related false positives. On a held-out 7 T test set, our best transformer model (SegFormer) achieved a voxel-wise Dice of 0.61 and lesion-wise Dice of 0.20, improving on the classical LST-LPA tool (Dice 0.39, lesion-wise Dice 0.02). Performance decreased for models trained on downsampled images, underscoring the value of native 7T resolution for small-lesion detection. By releasing our 7T-trained models, we aim to provide a reproducible, ready-to-use resource for automated lesion quantification in ultra-high field MS research (https://github.com/maynord/7T-MS-lesion-segmentation).

3D FLAIR MRI is widely recommended as one of the standard MRI sequences for brain imaging in multiple sclerosis (MS), but publicly available MS datasets remain relatively small and vary across scanners, acquisition protocols, and lesion patterns. This scarcity and variability hinder the development of robust neuroimaging machine learning models and are particularly challenging for generative models that aim to synthesize images while preserving small, sparse lesions. We propose Lesion-DDPM, a 3D conditional diffusion framework for lesion-aware FLAIR synthesis that incorporates multi-level anatomical mask injection together with a lesion-weighted reconstruction loss to emphasize lesion voxels while maintaining global brain structure. Using a curated subset of the MSLesSeg dataset, we compare Lesion-DDPM with representative state-of-the-art GAN- and diffusion-based models, assessing both image-generation metrics and downstream 3D U-Net segmentation. In our experiments, Lesion-DDPM achieved the lowest lesion-region reconstruction error among all methods. In a downstream 3D U-Net lesion segmentation task, a model trained only on Lesion-DDPM-generated scans and evaluated on real MRIs reached a Dice score of 0.616 compared with 0.569 for the best competing synthetic dataset. When Lesion-DDPM images were added to the real training set, the Dice score further increased to 0.685.