Authors: Alec K. Peltekian, Gorkem Durak, Halil Ertugrul Aktas, Carrie Lynn Richardson, Mary Carns, Kathleen Aren, GR Scott Budinger, Anthony J. Esposito, Alexander Misharin, Alok Nidhi Choudhary, Ankit Agrawal, Ulas Bagci
Organizations: Department of Computer Science, Northwestern University McCormick School of Engineering and Applied Science, Chicago, IL, USA · Department of Radiology, Machine and Hybrid Intelligence Laboratory, Northwestern University Feinberg School of Medicine, Chicago, IL, USA · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA · Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA · Simpson Querrey Lung Institute for Translational Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USA · Department of Electrical and Computer Engineering, Northwestern University McCormick School of Engineering and Applied Science, Chicago, IL, USA
Mixture-of-experts (MoE) models combine specialized predictors under learned routing, offering a principled mechanism for leveraging heterogeneity in medical data. We present a hierarchical multimodal MoE for interstitial lung disease (ILD) classification that integrates a frozen, pre-trained imaging expert with structured electronic health records (EHR) via two-stage gating. A modality-level gate assigns patient-specific weights to imaging and EHR predictions, while a sub-gating module decomposes the EHR branch into clinically defined feature groups with learned, group-specific contributions. This design preserves stable imaging representations while enabling input-dependent clinical weighting and explicit EHR specialization. Under strict patient-level cross-validation, the model achieved the highest mean AUC among the evaluated methods (0.8750 +- 0.0443), compared with 0.8646 for imaging-only REN and 0.7685 for SwinUNETR. The framework extends interpretability across anatomical regions, imaging--EHR utilization, and clinically defined EHR feature groups.
Figures & tables
Figure 1: Overview of the proposed hierarchical multimodal MoE framework for ILD diagnosis. (A) CT pipeline: volumes are preprocessed and segmented into five lung lobes; five lobe-specific imaging experts operate on lobe-masked volumes; fixed radiomics-derived lobe-importance weights provide a fold-specific prior for aggregating expert representations. (B) EHR pipeline: structured variables are partitioned into clinically defined feature groups and processed by group-specific sub-experts; an EHR sub-gate aggregates sub-expert outputs into a single clinical representation. We additionally evaluate a selective EHR configuration via expert-subset selection (restricting to a targeted subset of feature groups) prior to EHR sub-gating. (C) Multimodal fusion: a modality gate adaptively weights imaging and clinical representations, followed by a classifier for ILD prediction.
Method
AUC ± SD [95% CI]
Change vs. SwinUNETR
p-value
Imaging-Only Baselines
SwinUNETR (Baseline)
0.7685±0.0759 [0.674, 0.863]
–
–
CNN (Baseline)
0.7584±0.0919 [0.667, 0.850]
−1.3%
–
Mamba (Baseline)
0.6775±0.0454 [0.632, 0.723]
−11.8%
–
ViT (Baseline)
0.6535±0.0356 [0.618, 0.689]
−15.0%
–
MoE Anatomically-Guided Imaging-Only (REN)
Table 1: Performance comparison using 5-fold patient-level cross-validation. Values are reported as mean ± SD across folds. Table p -values are from two-sided paired t -tests against SwinUNETR. The direct comparison between the selective hierarchical MoE and imaging-only REN is reported in the text.
Figure 2: Interpretability analysis of hierarchical MoE gating behavior. (A) Modality-level gate activations for the full hierarchical EHR configuration, stratified by ILD status. (B) Mean EHR sub-expert gate weights across clinical feature groups for the full hierarchy. (C) Relationship between modality-level gate activations and prediction confidence for the full hierarchy. (D-F) Corresponding analyses for the selective hierarchical EHR configuration.
AI models for multimodal medical imaging must balance modality-specific specialization with cross-modal shared representations, a trade-off that pure Mixture-of-Experts (MoE) architectures currently fail to satisfy. Expert-based routing improves in-domain learning but may sacrifice cross-modal signals, which appear particularly important for rare (low-prevalence) pathologies in our experiments. To resolve this, we introduce Generalist-Specialist-MoE (GS-MoE), a two-branch (MoE) architecture that couples a cross-modal generalist model with distinct modality-specific specialists (experts) via domain-constrained feature fusion. On RadImageNet (1.35M images, 165 pathologies, three modalities), GS-MoE recovers detection of six low-prevalence pathologies on which every baseline scores F1 = 0, with per-class gains up to +0.60 F1. It attains this while even slightly exceeding dense and specialist-only MoE aggregate baselines (MCC 0.770), while using ∼53% fewer active parameters at inference than the strongest investigated dense model.
Johannes Kaiser, Florian Braunmiller, Daniel Rückert +1
Chair for AI in Healthcare and Medicine, Technical University of Munich (TUM) and TUM University Hospital, Munich, Germany · Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany · Department of Computing, Imperial College London, UK
Multimodal clinical prediction faces three challenges: multiple foundation models (FMs) with complementary strengths per modality, pervasive missing modalities at training and test time, and sample-specific variation in modality contributions. We introduce MedMIX, a multimodal framework that combines intra-modality expert fusion, learned inter-modality fusion, and training-only large--small model collaboration for robust medical prediction under incomplete modalities. Within each modality, MedMIX aggregates complementary embeddings from multiple small expert models; across modalities, it performs learned fusion over available modalities; and during training, it leverages large teacher models to improve deployed representations without additional inference cost. Across three heterogeneous benchmarks (OpenI, MIMIC-IV-MM, and MMIST-ccRCC), MedMIX achieves consistently strong performance while remaining robust under controlled missing-modality perturbations, and further demonstrates sustained robustness under cross-cohort shift on MIMIC-III. These results highlight MedMIX as a practical framework that unifies within-modality expert collaboration, sample-specific cross-modality fusion, and efficient large--small model collaboration while remaining robust to incomplete modalities.
Seungik Cho, Anqi Li, Wei Qiu
Department of Electrical and Computer Engineering Rice University Houston, TX 77005
Multimodal survival prediction, a crucial yet challenging task, demands the integration of multimodal medical data (\eg Whole Slide Images (WSIs) and Genomic Profiles) to achieve accurate prognostic modeling. Given the inherent heterogeneity across modalities, the feature decoupling-fusion paradigm has emerged as a dominant approach. However, these methods have the following shortcomings: (1) fail to reduce the redundant information of modality features before decoupling, which negatively affects the feature decoupling and fusion effect;(2) lack the ability to model the fine-grained relationships of the features and capture the local information interactions between intra- and inter-modality features. To address these issues, we propose a Hierarchical Decoupling-Fusion Mixture-of-Experts (HDMoE) framework with two levels of MoE and Random Feature Reorganization (RFR) modules.In the first-level MoE, shared experts and routed experts are employed to remove redundant information and extract fine-grained specific features within each modality, while the second-level MoE facilitates fine-grained inter-modality feature decoupling. Besides, we design two RFR modules following each level of MoE to finely fuse intra- and inter-modality features, which can help the model capture more fine-grained relationships between modalities. Extensive experimental results on our private Liver Cancer (LC) and three TCGA public datasets confirm the effectiveness of our proposed method. Codes are available at https://github.com/ZJUMAI/HDMoE.
Huayi Wang, Haochao Ying, Yuyang Xu +5
Zhejiang University Hangzhou, China · Xinjiang University Urumqi, China · Hangzhou City University Hangzhou, China +1