Where to Look Matters: Rethinking Sub-Volume Sampling in 3D Medical Self-supervised Learning

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.

Self-supervised learning (SSL) is increasingly used in medical image analysis to reduce dependence on costly expert annotations by learning transferable representations from unlabeled data. However, SSL performance depends not only on model architecture, but also on whether the pretext task preserves information required by the downstream clinical objective. This review presents a task-oriented synthesis of SSL methods for medical imaging, focusing on how pretext-task design interacts with imaging modality, label availability, and downstream performance. We analyze 75 studies published from 2017 to 2025 and organize them into four paradigms: contrastive learning, non-contrastive and predictive learning, generative and reconstruction-based learning, and hybrid learning. Rather than cataloging methods chronologically, we examine how these paradigms support classification, segmentation, detection, reconstruction, and regression. The evidence suggests that no SSL strategy is universally optimal. Contrastive objectives generally encourage global discriminative representations and are well aligned with classification, but may underrepresent subtle or localized pathology. Spatial prediction, masked modeling, and reconstruction-based objectives better preserve anatomical structure and are often more suitable for segmentation and dense prediction. Hybrid methods can provide balanced representations, although they increase training complexity. Across modalities, SSL is most beneficial in low-label and few-shot regimes, but its effectiveness depends on modality-aware augmentation, pathology-preserving corruption, and clinically meaningful evaluation. We conclude with practical design guidelines and identify open challenges, including pathology-aware pretext tasks, resource-efficient training for high-dimensional data, and standardized evaluation protocols.

Self-supervised learning (SSL) has advanced medical image analysis be enabling learning form large unlabelled data. However, in brain magnetic resonance imaging (MRI), most 3D models remain specialized for either segmentation of classification, limiting their ability to generalize across datasets, imaging protocols,, and downstream tasks. This lack of transferability constrains the clinical utility of 3D MRI models, despite the availability of unlabeled volumetric data. We present Volta-3D, a self-supervised 3D Vision Transformer framework designed to learn transferable volumetric representations. Volta-3D jointly aligns global class-style tokens and local patch tokens within a student-teacher paradigm and enforces fine-grained structural reconstruction. This combined global-local alignment addresses the limited semantic diversity and subtle anatomical characteristics of brain MRI, which challenges existing SSL approaches. We evaluate Volta-3D on multiple out-of-distribution downstream tasks, including hippocampal segmentation and classification of sex and Alzheimer's disease versus healthy controls. Across all tasks, representations learned by Volta-3D outperform randomly initialized baselines, demonstrating improved transferability and robustness under domain shift. Hence jointly enforcing global semantic consistency and local structural learning during pretraining enables broader concept learning from unlabeled brain MRI data. Overall VolTA-3D supports effective multi-task downstream performance with task-specific pertaining, a step towards generalizable and clinically viable 3D models.