Style-Aware and Uncertainty-Guided Approach to Semi-Supervised Domain Generalization in Medical Imaging

Deep learning has significantly advanced medical image analysis by enabling accurate, automated diagnosis across diverse clinical tasks such as lesion classification and disease detection. However, the practical deployment of these systems is still hindered by two major challenges: the limited availability of expert-annotated data and substantial domain shifts caused by variations in imaging devices, acquisition protocols, and patient populations. Although recent semi-supervised domain generalization (SSDG) approaches attempt to address these challenges, they often suffer from two key limitations: (i) reliance on computationally expensive uncertainty modeling techniques such as Monte Carlo dropout, and (ii) inflexible shared-head classifiers that fail to capture domain-specific variability across heterogeneous imaging styles. To overcome these limitations, we propose MultiStyle-SSDG, a unified semi-supervised domain generalization framework designed to improve model generalization in low-label scenarios. Our method introduces a multi-style ensemble pseudo-labeling strategy guided by entropy-based filtering, incorporates prototype-based conformity and semantic alignment to regularize the feature space, and employs a domain-specific multi-head classifier fused through attention-weighted prediction. Additionally, we introduce a dual-level neural-style transfer pipeline that simulates realistic domain shifts while preserving diagnostic semantics. We validated our framework on the ISIC2019 skin lesion classification benchmark using 5% and 10% labeled data. MultiStyle-SSDG consistently outperformed recent state-of-the-art methods such as FixMatch, StyleMatch, and UPLM, achieving statistically significant improvements in classification accuracy under simulated domain shifts including style, background, and corruption. Specifically, our method achieved 78.6% accuracy with 5% labeled data and 80.3% with 10% labeled data on ISIC2019, surpassing FixMatch by 4.9–5.3 percentage points and UPLM by 2.1–2.4 points. Ablation studies further confirmed the individual contributions of each component, and t-SNE visualizations illustrate enhanced intra-class compactness and cross-domain feature consistency. These results demonstrate that our style-aware, modular framework offers a robust and scalable solution for generalizable computer-aided diagnosis in real-world medical imaging settings.