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

Mixture-of-Experts (MoE) architectures achieve scalable learning by routing inputs to specialized subnetworks through conditional computation. However, conventional MoE designs assume homogeneous expert capability and domain-agnostic routing-assumptions that are fundamentally misaligned with medical imaging, where anatomical structure and regional disease heterogeneity govern pathological patterns. We introduce Regional Expert Networks (REN), the first anatomically-informed MoE framework for medical image classification. REN encodes anatomical priors by training seven specialized experts, each dedicated to a distinct lung lobe or bilateral lung combination, enabling precise modeling of region-specific pathological variation. Multi-modal gating mechanisms dynamically integrate radiomics biomarkers with deep learning (DL) features extracted by convolutional (CNN), Transformer (ViT), and state-space (Mamba) architectures to weight expert contributions at inference. Applied to interstitial lung disease (ILD) classification on a 597-patient, 1,898-scan longitudinal cohort, REN achieves consistently superior performance: the radiomics-guided ensemble attains an average AUC of $0.8646~\pm ~0.0467$ , a +12.5% improvement over the SwinUNETR single-model baseline (AUC 0.7685, ${p}={0}.{031}$ ). Lower-lobe experts reach AUCs of 0.88-0.90, outperforming DL baselines (CNN: 0.76-0.79) and mirroring known patterns of basal ILD progression. Evaluated under rigorous patient-level cross-validation, REN demonstrates strong generalizability and clinical interpretability, establishing a scalable, anatomically-guided framework potentially extensible to other structured medical imaging tasks. Code is available on our GitHub https://github.com/NUBagciLab/MoE-REN.