Masked and Predictive Self-Supervised Foundation Models for 3D Brain MRI
Authors: Esra Ergün, Hersh Chandarana, Dan Sodickson, Gözde Ünal
Abstract
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.
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.
Self-supervised learning offers a compelling approach for medical imaging, where labeled data are scarce and acquisition costs are high. We present COJEPA, a self-supervised framework for volumetric brain MRI that combines a joint-embedding predictive architecture (JEPA) with a contrastive loss (CO), targeting two complementary properties: local predictivity and global discriminability. The model is trained without labels on T1-weighted structural MRI from two cohorts (HCP-YA and AABC, N=2286, ages 22 to 90), extending I-JEPA to 3D with foreground-aware block masking, a hierarchical convolutional patch embedding, and world-space sinusoidal positional encodings. We evaluate all three objectives across zero-shot twin retrieval, brain tumor segmentation (BraTS 2024), and age regression (OpenBHB). COJEPA achieves the best monozygotic twin recall at rank@1 (0.84), the best finetuning age MAE (2.55 years on OpenBHB 3.0T), and matches CO on BraTS whole-tumor Dice, demonstrating that the combined objective yields representations that are simultaneously discriminative and locally structured.
MRI preprocessing defines the input distribution seen by brain MRI foundation models, yet it is usually treated as routine data cleaning rather than a modeling choice. We ask how much preprocessing is worth its computational cost for self-supervised 3D MRI pretraining. Keeping the corpus, 3D ViT backbone, masking protocol, and downstream evaluations fixed, we compare a graded P0-P7 preprocessing spectrum for masked autoencoding (MAE) and joint-embedding predictive learning (JEPA) on 20,000 heterogeneous brain MRI volumes, then transfer the encoders to IDH prediction, MCI classification, brain age regression, and GLI/PED tumor segmentation. The results do not support a simple "more is better" rule. P0/P1 are numerically unstable, making P2 the lowest-cost feasible level; beyond P2, choosing the best feasible preprocessing level improves aggregate utility by only 3.4 percentage points for MAE and 1.8 percentage points for JEPA, with most paired gains statistically unresolved. Stronger preprocessing is beneficial only in selected regimes: IDH improves modestly, AGE and GLI/PED are often near or best at P2, and MCI shows the clearest empirical P7 gain. Cross-level MCI transfer further shows that much of the P7 advantage can be recovered by applying stronger preprocessing downstream, without requiring P7 throughout pretraining. These findings recast MRI preprocessing as a downstream-aware cost-utility decision rather than a default escalation pipeline. Code is available at https://github.com/PangJiangShuan/PreBrain.