Dataset-Specific Encoding of Image Content Underlies Cross-Dataset Failure in Brain MRI Foundation Models

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO

Brain magnetic resonance imaging (MRI) is central to neuroscience and clinical assessment, but models are commonly developed for individual diseases, populations or imaging protocols. Foundation models promise more general representations, yet they are usually pretrained once and can lose earlier capabilities when updated with new data. Here we show that Alcmaeon, a three-dimensional brain MRI foundation model pretrained without manual labels on more than 425,000 volumes and derived imaging maps, can be expanded sequentially across clinical domains. Alcmaeon combines volumetric encoding and latent diffusion generation with Graph-Blueprint Pruning (GBP), which protects network modules important to earlier domains while leaving the remaining capacity trainable. Across expansion from healthy ageing and neurodegeneration to developmental, psychiatric and tumour imaging, GBP showed less forgetting than sequential adaptation and elastic weight consolidation across voxel-level reconstruction measures, with its largest advantage after adaptation to tumour imaging. The blueprints provided an inspectable record of how model capacity was protected and reused. Representations from different model levels supported image synthesis, disease classification, survival modelling and postoperative prediction, although no single representation was optimal for every task. These findings provide a route towards brain MRI foundation models that can grow with emerging data while retaining earlier capabilities.

Brain foundation models are often tested with a probe. The model is frozen, a simple classifier is trained on its output, and the classifier's accuracy is taken as a sign of what pretraining learned. We show that this reading can be wrong unless two controls are reported with it. We probed three frozen 3-D brain-MRI models at five depths, on two independent multi-site cohorts (ABIDE-I and ABIDE-II). The site where a scan was acquired could be predicted at about 0.9, on a scale where 0 is chance and 1 is perfect. No clinical or demographic target came close. An untrained copy of the same model predicted site just as well on both cohorts. Untrained models of three architectures, each built with three random seeds, did the same on ABIDE-I. The raw image, shrunk to 12x12x12 voxels and given to no model at all, predicted site at 0.95. Pretraining did not create the site signal. It was already in the scans. We also looked for any clinical target on which pretraining beats an untrained model, and found no reliable case. Adjusting for age, sex and diagnosis left site prediction almost unchanged, and so did a 4.6-fold increase in the number of voxels. Resting-state fMRI from the same people showed the same pattern. Site was the most predictable attribute of brain connectivity (0.81), and it survived five untrained layers while age did not. We recommend reporting two controls with every probe of a brain foundation model: running the probe again on the untrained model, and on the raw input. We release the code for both.