Abstract
Foundation models provide powerful representations for brain MRI analysis, but their predictions remain difficult to interpret in anatomically meaningful terms. Clinical assessment of brain MRI is commonly organized around anatomically defined structures and regional abnormalities, whereas conventional explanation methods typically produce voxel- or patch-level importance maps that do not explicitly quantify the contributions of individual brain regions. To address this mismatch, we propose RegionFM, an interpretable framework that integrates anatomical segmentation with brain MRI foundation-model embeddings. RegionFM first divides each MRI scan into anatomical regions and constructs a separate MRI volume for each region. A frozen foundation model then encodes each region into an embedding, and a region-additive logistic model combines these embeddings such that every anatomical region contributes an explicit scalar term to the final prediction. This formulation supports both subject-level and cohort-level analyses of regional contributions. We evaluate RegionFM on cognitive-impairment classification using embeddings from multiple pretrained brain MRI foundation models. The results show that RegionFM maintains performance comparable to less interpretable fine-tuning approaches while providing anatomically grounded explanations. Randomized embedding ablations yield near-chance performance, indicating that the predictions rely on meaningful structure captured by the foundation-model embeddings rather than simple feature statistics. Overall, RegionFM better aligns model explanations with anatomy-based clinical reasoning while maintaining competitive predictive performance.
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Aug 10, 2026cs.CV
Frozen foundation-model (FM) embeddings are increasingly used as off-the-shelf brain-MRI representations, on the assumption that they capture anatomy. We audit what they actually encode and find that acquisition site is a large, intrinsic component of the representation. Across two independent cohorts (ABIDE-I, ABIDE-II), three frozen 3-D encoders (brain-pretrained, CT-pretrained, and randomly initialized), and every network depth, site is linearly decodable at roughly 0.9 balanced accuracy at deep layers, exceeding the decodability of every clinical or demographic variable (sex, age, autism diagnosis) at every layer. The effect is intrinsic rather than learned: a randomly initialized encoder is already a ~0.9 site classifier on both cohorts and across three architecture families (Swin, ViT, ResNet), and site is decodable at ~0.95 directly from the raw downsampled image with no encoder, so the fingerprint reflects low-level image statistics that any encoder preserves rather than a product of pretraining. Residualizing measured population covariates leaves site decodability essentially unchanged, indicating an acquisition- rather than population-driven effect. A nonlinear probe matches the linear one, so the fingerprint is fully linearly accessible. The site subspace is removable post hoc by iterative null-space projection or ComBat (site decodability 0.94 -> 0.07/0.00), and is a site-attribution concern for shared or federated embeddings; but for dense segmentation this removal is not free, because site and anatomy occupy an entangled linear subspace (a matched-rank random-direction projection is Dice-neutral, whereas removing the site subspace is destructive). We recommend site-audited use of frozen brain-MRI FMs and release an open audit toolkit.
Saman Rahbar
Jul 30, 2026cs.CV
Medical foundation models (FMs) are increasingly used for brain MRI analysis. However, their evaluation remains dominated by high-resource datasets, leaving generalization to African cohorts underexplored. We assess whether FMs generalize equally to African and non-African brain MRI data across two tasks: dementia classification using a Nigerian dataset and brain tumor segmentation using BraTS-Africa. We evaluate two generalist FMs (BrainIAC, 3DINO) and two segmentation-specific FMs (MedSAM2, Medical-SAM2) against a from-scratch baseline. For classification, FMs provide limited gains (highest ROC-AUC of 0.86 with BrainIAC), whereas for segmentation they consistently improve performance, reaching up to 0.86 Dice with MedSAM2. Performance differences between African and non-African cohorts are inconsistent and appear more related to dataset size than data origin. These results suggest that FMs do not exhibit an inherent bias against African cohorts, and highlight the limited availability and diversity of African neuroimaging datasets as the main barrier to robust evaluation and deployment.
Kaouther Mouheb, Gonzalo Esteban Mosquera Rojas, Juancito van Leeuwen +2
May 3, 2026cs.CV
Brain MRI foundation models learn rich representations of anatomy, but interpreting what clinical information they encode remains an open problem. Standard sparse autoencoders (SAEs) suffer from severe feature collapse in deep transformer layers, and in Alzheimer's disease (AD) research, aging confounds nearly every clinical variable, making naive annotation unreliable. We propose GeoSAE, a geometry-guided SAE framework that uses the foundation model's learned manifold structure to prevent feature collapse and annotates each surviving feature via age-deconfounded partial correlations. Applied to ~14k T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging biomarkers and Lifestyle (AIBL) datasets, GeoSAE identifies a compact, fully interpretable feature set that predicts mild cognitive impairment (MCI)-to-AD conversion (AUC 0.746) using only 2% of the embedding dimensions, while comorbidity-annotated features achieve only chance-level performance. The identified features replicate across cohorts without retraining (r=0.97) and localize to neuroanatomically distinct regions consistent with Braak staging. This shows that geometry-guided SAEs can extract interpretable, biomarkers from frozen brain MRI foundation models.
Favour Nerrise, Lucy Yin, Mohammad H. Abbasi +2