Contrastive Joint-Embedding Prediction for Representation Learning in Structural MRI

Self-supervised foundation models have shown strong promise in medical imaging. However, existing MRI foundation-model studies have primarily emphasized segmentation and dense prediction tasks, while systematic investigation of self-supervised foundation models for MRI-based disease detection remains limited. In this work, we investigate two major self-supervised pretraining paradigms for MRI-based disease detection: reconstruction-based learning via Masked Autoencoders (MAE) and predictive representation learning via Joint Embedding Predictive Architectures (JEPA). We study the role of auxiliary objectives by introducing a novel spectral-domain reconstruction loss for MAE to enhance sensitivity to fine-grained anatomical structure, and by integrating variance--covariance regularization (VCR) within our JEPA framework to encourage decorrelated latent representations. Our models are pretrained on heterogeneous single-contrast MRI volumes in a contrast-agnostic setting, without modality concatenation. Across five downstream disease detection tasks, our results highlight the importance of self-supervised objective design for medical foundation model pretraining, demonstrating that the downstream benefit of each objective is determined by its relevance to the task's structure. Specifically, spectral regularization yields the largest improvements when the downstream discriminative signal is characterized by strong high-frequency anatomical structures, while covariance regularization is most beneficial when discriminative information spans multiple decorrelated feature dimensions. MAE with spectral-domain supervision consistently achieves superior downstream performance for MRI-based disease detection. These findings suggest that self-supervised objectives in medical imaging encode specific biases, and their downstream benefit is fundamentally conditioned on the task's structure.

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

Foundation models pretrained using self-supervised learning have transformed computer vision by learning transferable representations from large-scale unlabeled data. However, existing foundation models for neuroimaging remain limited by task-specific training, slice-based learning strategies, or relatively small pretraining datasets, restricting their generalizability across diverse brain MRI applications. In this work, we present BrainNext, a general-purpose self-supervised foundation model for volumetric brain MRI analysis. BrainNext combines masked autoencoder (MAE) pretraining with a native three-dimensional Bi-Directional xLSTM-UNet architecture to learn rich anatomical representations from 60,551 unlabeled brain MRI examinations spanning multiple MRI modalities. The pretrained model is subsequently adapted to downstream tasks through lightweight task-specific fine-tuning. We evaluate BrainNext on the Foundation Models for Medical Imaging (FOMO) 2025 Method Track, encompassing classification, segmentation, and brain-age estimation, where it achieved second place overall and ranked first in the meningioma segmentation task on the official FOMO 2025 challenge leaderboard, demonstrating strong transferability across heterogeneous neuroimaging tasks. These results highlight the potential of large-scale self-supervised pretraining to learn robust and transferable volumetric representations, establishing BrainNext as a scalable foundation model for diverse brain MRI applications.