REN: Anatomically-Informed Mixture-of-Experts for Interstitial Lung Disease Diagnosis

Mixture-of-Experts (MoE) architectures have significantly contributed to scalable machine learning by enabling specialized subnetworks to tackle complex tasks efficiently. However, traditional MoE systems lack domain-specific constraints essential for medical imaging, where anatomical structure and regional disease heterogeneity strongly influence pathological patterns. Here, we introduce \textit{Regional Expert Networks (REN)}, the first anatomically-informed MoE framework tailored specifically for medical image classification. REN leverages anatomical priors to train seven specialized experts, each dedicated to distinct lung lobes and bilateral lung combinations, enabling precise modeling of region-specific pathological variations. Multi-modal gating mechanisms dynamically integrate radiomics biomarkers and deep learning (DL) features (CNN, ViT, Mamba) to weight expert contributions optimally. Applied to interstitial lung disease (ILD) classification, REN achieves consistently superior performance: the radiomics-guided ensemble reached an average AUC of 0.8646 +- 0.0467, a +12.5\% improvement over the SwinUNETR baseline (AUC 0.7685, p=0.031). Region-specific experts further revealed that lower-lobe models achieved AUCs of 0.88-0.90, surpassing DL counterparts (CNN: 0.76-0.79) and aligning with known disease progression patterns. Through rigorous patient-level cross-validation, REN demonstrates strong generalizability and clinical interpretability, presenting a scalable, anatomically-guided approach readily extensible to other structured medical imaging applications. Code is available on our GitHub: https://github.com/NUBagciLab/MoE-REN.