Dense self-supervised learning (SSL) is a powerful paradigm for learning without annotations the local descriptors required to solve dense medical imaging tasks. We present Pix2Rep-v2, a framework for SSL of pixel- and voxel-level representations suitable for few-shot downstream applications. Pix2Rep-v2 addresses the main challenges of dense SSL by leveraging a redundancy reduction objective at the pixel-level with a principle of equivariance of dense representations, that scales efficiently to 3D or wide field-of-view applications. We evaluate our method on four datasets, across multiple tasks, multiple modalities and anatomical structures using multiple backbones in 2D and 3D, and under various data regimes. As an alternative to linear probing or full fine-tuning on the downstream task, we also propose an in-context variant, without downstream training, based on a dense prototype approach. Pix2Rep-v2 shows substantially higher data-efficiency in few-shot scenarios compared to fully supervised baselines, and is competitive with the state-of-the-art e.g., +9.3 Dice points in one-shot segmentation on the M&Ms-2 dataset. Our code and pre-trained models are publicly available at https://github.com/BioMedTP/pix2rep-v2.
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.
Dense prediction is a fundamental requirement for many medical vision tasks such as medical image restoration, registration, and segmentation. The most popular vision model, Convolutional Neural Networks (CNNs), has reached bottlenecks due to the intrinsic locality of convolution operations. Recently, transformers have been widely adopted for dense prediction for their capability to capture long-range visual dependence. However, due to the high computational complexity and large memory consumption of self-attention operations, transformers are usually used at downsampled feature resolutions. Such usage cannot effectively leverage the tissue-level textural information available only at the full image resolution. This textural information is crucial for medical dense prediction as it can differentiate the subtle human anatomy in medical images. In this study, we hypothesize that Multi-layer Perceptrons (MLPs) are superior alternatives to transformers in medical dense prediction where tissue-level details dominate the performance, as MLPs enable long-range dependence at the full image resolution. To validate our hypothesis, we develop a full-resolution hierarchical MLP framework that uses MLPs beginning from the full image resolution. We evaluate this framework with various MLP blocks on a wide range of medical dense prediction tasks including restoration, registration, and segmentation. Extensive experiments on six public well-benchmarked datasets show that, by simply using MLPs at full resolution, our framework outperforms its CNN and transformer counterparts and achieves state-of-the-art performance on various medical dense prediction tasks.
Modern self-supervised representation learning methods often relies on empirical heuristics that are not theoretically grounded. In this study we propose HyDeS, a theoretically grounded method based on multi-view mutual information maximization within an hyperspherical space using Shannon differential entropy with a non-parametric von Mises-Fisher density estimator. We show that HyDeS bias the trained model towards focusing on foreground features of the images and perform well on segmentation tasks such as VOC PASCAL, while it lags in fine-grained classification. We provide a detailed analysis of the induced latent space geometry and learning dynamics, that can be used for designing other theoretically grounded self-supervised learning methods.
Esteban Rodríguez-Betancourt, Edgar Casasola-Murillo