Why Invariance is Not Enough for Biomedical Domain Generalization and How to Fix It

Medical image segmentation is a critical task in computer-aided diagnosis and treatment planning. However, deep learning models often struggle to generalize across datasets due to domain shifts arising from variations in imaging protocols, scanner types, and patient populations. Traditional domain generalization (DG) methods utilize causal feature learning, adversarial consistency, and style augmentation to improve segmentation robustness. While effective, these approaches rely on explicit feature alignment, adversarial objectives, or handcrafted augmentations, which may not fully exploit the capabilities of foundation models. Recently, the Segment Anything Model (SAM) has demonstrated strong generalization capabilities in segmentation tasks. SAM-based DG methods attempt to improve medical image segmentation. However, these approaches primarily operate in the spatial domain and overlook frequency-based discrepancies that significantly affect model robustness. In this work, we propose Frequency-based Domain Generalization with SAM (FSAM), a novel framework that integrates Low-Rank Adaptation (LoRA) for efficient fine-tuning and a frequency adapter to incorporate frequency-domain representations for single-source domain generalization. FSAM enhances SAM's segmentation robustness by extracting domain-invariant high-frequency features, mitigating frequency-related domain shifts. Experimental results on fundus and prostate datasets demonstrate that FSAM outperforms existing traditional DG and SAM-based DG approaches in domain generalization. Codes and pre-trained models will be made available on GitHub.

Domain generalization is a technique aimed at enabling models to maintain high accuracy when applied to new environments or datasets (unseen domains) that differ from the datasets used in training. Generally, the accuracy of models trained on a specific dataset (source domain) often decreases significantly when evaluated on different datasets (target domain). This issue arises due to differences in domains caused by varying environmental conditions such as imaging equipment and staining methods. Therefore, we undertook two initiatives to perform segmentation that does not depend on domain differences. We propose a method that separates category information independent of domain differences from the information specific to the source domain. By using information independent of domain differences, our method enables learning the segmentation targets (e.g., blood vessels and cell nuclei). Although we extract independent information of domain differences, this cannot completely bridge the domain gap between training and test data. Therefore, we absorb the domain gap using the quantum vectors in Stochastically Quantized Variational AutoEncoder (SQ-VAE). In experiments, we evaluated our method on datasets for vascular segmentation and cell nucleus segmentation. Our methods improved the accuracy compared to conventional methods.

Hardware shifts, color variations, and changing patient characteristics between development and deployment routinely break trained medical image classifiers. Existing remedies fall short: standard color jittering provides insufficient diversity, while deep generative style transfer algorithms hallucinate features, destroy clinically relevant structures, and waste massive compute resources. To address this, we revisit classical statistical color matching and repurpose it as Colorist, a highly efficient data augmentation strategy that applies global mean-standard deviation matching directly in the RGB color space. We demonstrate that this training-free, fully interpretable approach safely generates structurally intact domain variations, outperforming deep generative models in structural fidelity and color alignment. Across out-of-distribution histopathology, peripheral blood, dermatology, and retinal datasets, it improves balanced accuracy by up to +9% over state-of-the-art domain generalization regularizers and by +13% over an unaugmented baseline. Moreover, by avoiding neural networks in the augmentation loop, Colorist preserves anatomical structure, minimizes carbon footprint, and integrates seamlessly into standard dataloaders. Together, these findings establish statistical matching as a safe, interpretable, yet overlooked alternative to deep architectures for clinical robustness. Source code is available at https://github.com/sdoerrich97/colorist.