Multiple Domain Generalization Using Category Information Independent of Domain Differences

We present MaskGen, a theoretically grounded and deliberately simple approach for domain generalization in 3D biomedical image segmentation. Modern segmentation models degrade sharply under shifts in modality, disease severity, clinical sites, and more, limiting their reliable adoption. Existing generalization methods address this using extreme augmentations, hand-engineered domain statistics mixing, or architectural redesigns that add significant implementation overhead while yielding inconsistent performance across biomedical settings. MaskGen instead presents a principled learning strategy with marginal overhead that utilizes both source-domain image intensities and domain-stable foundation model representations to train robust segmentation models. As a result, MaskGen achieves strong gains in both fully supervised and few-shot segmentation across broad clinical shifts in biomedical studies. Unlike prior approaches, MaskGen is architecture- and loss-agnostic, compatible with standard augmentation pipelines, easy to implement, and tackles arbitrary anatomical regions. Its implementation is freely available at https://github.com/sebodiaz/MaskGen.

Generalizing image classification across domains remains challenging in critical tasks such as fundus image-based diabetic retinopathy (DR) grading and resting-state fMRI seizure onset zone (SOZ) detection. When domains differ in unknown causal factors, achieving cross-domain generalization is difficult, and there is no established methodology to objectively assess such differences without direct metadata or protocol-level information from data collectors, which is typically inaccessible. We first introduce domain conformal bounds (DCB), a theoretical framework to evaluate whether domains diverge in unknown causal factors. Building on this, we propose GenEval, a multimodal Vision Language Models (VLM) approach that combines foundational models (e.g., MedGemma-4B) with human knowledge via Low-Rank Adaptation (LoRA) to bridge causal gaps and enhance single-source domain generalization (SDG). Across eight DR and two SOZ datasets, GenEval achieves superior SDG performance, with average accuracy of 69.2% (DR) and 81% (SOZ), outperforming the strongest baselines by 9.4% and 1.8%, respectively.

Domain generalization (DG) aims to improve the generalizability of computer vision models toward distribution shifts. The mainstream DG methods predominantly focus on learning domain invariance across domains, however, such methods overlook the untapped potential inherent in domain-specific information. While the prevailing practice of discriminative linear classifier has been tailored to domain-invariant features, it struggles when confronted with diverse domain-specific information, e.g., intra-class shifts, that exhibits multi-modality. To address these issues, we explore the theoretical implications of relying on domain-invariant features, revealing the crucial role of domain-specific information in mitigating the target risk for DG. Drawing from these insights, we propose Generative Classifier-driven Domain Generalization (GCDG), introducing a generative paradigm for the DG classifier based on Gaussian Mixture Models (GMMs) for each class across domains. GCDG consists of three key modules: Heterogeneity Learning Classifier~(HLC), Spurious Correlation Blocking~(SCB), and Diverse Component Balancing~(DCB). Concretely, HLC attempts to model the feature distributions and thereby capture valuable domain-specific information via GMMs. SCB identifies the neural units containing spurious correlations and perturbs them, mitigating the risk of HLC learning irrelevant spurious patterns. Meanwhile, DCB ensures a balanced contribution of components within HLC, preventing the underestimation or neglect of critical components. In this way, GCDG excels in capturing the nuances of domain-specific information characterized by diverse distributions. Extensive experiments show GCDG's comparable performance on five DG benchmarks and one face anti-spoofing dataset, seamlessly integrating into existing DG methods with consistent improvements.