B-MIM: Biased Masked Image Modeling for Generalizable Segmentation of Fine-Grained Anatomical Structures

Foundation models have transformed vision and language by learning general-purpose representations from large-scale unlabeled data, yet 3D medical imaging lacks analogous approaches. Existing self-supervised methods rely on low-level reconstruction or contrastive objectives that fail to capture the anatomical semantics critical for medical image analysis, limiting transfer to downstream tasks. We present MASS (MAsk-guided Self-Supervised learning), which treats in-context segmentation as the pretext task for learning general-purpose medical imaging representations. MASS's key insight is that automatically generated class-agnostic masks provide sufficient structural supervision for learning semantically rich representations. By training on thousands of diverse mask proposals spanning anatomical structures and pathological findings, MASS learns what semantically defines medical structures: the holistic combination of appearance, shape, spatial context, and anatomical relationships. We demonstrate effectiveness across data regimes: from small-scale pretraining on individual datasets (20-200 scans) to large-scale multi-modal pretraining on 5K CT, MRI, and PET volumes, all without annotations. MASS demonstrates: (i) few-shot segmentation on novel structures, (ii) matching full supervision with only 20-40% labeled data while outperforming self-supervised baselines by over 20 in Dice score in low-data regimes, and (iii) frozen-encoder classification on unseen pathologies that matches full supervised training with thousands of samples. Mask-guided self-supervised pretraining captures broadly generalizable knowledge, opening a path toward 3D medical imaging foundation models without expert annotations. Code is available: https://github.com/Stanford-AIMI/MASS.

Masked image modeling (MIM) is a highly effective self-supervised learning (SSL) approach to extract useful feature representations from unannotated data. Predominantly used random masking methods make SSL less effective for medical images due to the contextual similarity of neighboring patches, leading to information leakage and SSL simplification. Hierarchical shifted window (Swin) transformer, a highly effective approach for medical images cannot use advanced masking methods as it lacks a global [CLS] token. Hence, we introduced an attention guided masking mechanism for Swin within a co-distillation learning framework to selectively mask semantically co-occurring and discriminative patches, to reduce information leakage and increase the difficulty of SSL pretraining. However, attention guided masking inevitably reduces the diversity of attention heads, which negatively impacts downstream task performance. To address this, we for the first time, integrate a noisy teacher into the co-distillation framework (termed DAGMaN) that performs attentive masking while preserving high attention head diversity. We demonstrate the capability of DAGMaN on multiple tasks including full- and few-shot lung nodule classification, immunotherapy outcome prediction, tumor segmentation, and unsupervised organs clustering.

Methods: Nine SSL methods spanning four pretext-task families were pretrained from scratch using the same 10{,}412 3D CT scans (1.89~M 2D axial slices) covering varied disease sites. The pretrained Swin Transformer encoder from each method was integrated into a SwinUNETR-style segmentation network (Swin encoder with a 3D CNN decoder and skip connections) and fine-tuned on nine public segmentation tasks of varying complexity, including large abdominal organs, head-and-neck structures, and tumors from CT and MRI. Performance was assessed using Dice similarity coefficient (DSC). Fine-tuning convergence speed, transferability across modalities (CT-to-MRI), and feature-reuse patterns between few- and many-shot fine tuning were further analyzed using centered kernel alignment. Results: Self-distilled masked image transformer (SMIT), which combines masked image modeling (MIM) with local and global self-distillation, achieved the highest overall segmentation accuracy across the nine tasks, the fastest fine-tuning convergence, and the smallest few-shot-to-many-shot performance gap, indicating the strongest data efficiency. SMIT also showed the most consistent feature-reuse patterns between few- and many-shot fine tuning. MIM-based SimMIM and self-distillation methods (DINO, iBOT) outperformed contrastive learning and rotation prediction, which rely on image-level global representations. Differences between SSL methods were largest in the few-shot setting and narrowed as the size of the labeled fine-tuning dataset increased, indicating that the choice of SSL pretraining matters most under limited annotation budgets.