EnTrust: Modeling Inter-Modal Conflict for Trustworthy Multimodal Medical Image AnalysisDwarikanath Mahapatra, Abhijit Das, Behzad Bozorgtabar et al.
Multimodal medical imaging fuses complementary anatomical and functional information, yet modalities frequently disagree in pathologically heterogeneous regions. Current segmentation models handle this in one of two inadequate ways: deterministic fusion that averages away disagreement, or post-hoc uncertainty estimation decoupled from the fusion process that produces it. Both obscure the clinically critical question: why is this prediction unreliable? We present EnTrust, a framework that treats inter-modal conflict as the primary source of predictive uncertainty. Our EnFuse module decomposes multimodal features into three disentangled components: shared anatomical consensus (F_c), modality-specific cues (F_{u,m}), and spatially localized conflict signals (F_{cf}), with independence enforced via a cross-covariance objective. This structured decomposition conditions SegDiff, a diffusion-based generative segmentation model whose sampled hypotheses diverge specifically in regions of modal disagreement. TrustMap then translates this hypothesis divergence into calibrated, pixel-wise uncertainty using ensemble entropy, conflict-guided perturbation probing, and a learned calibration head, enabling clinicians to understand not only where predictions are uncertain, but why. Across four benchmarks spanning brain, cardiac, lesion, and oncology domains, EnTrust achieves state-of-the-art segmentation accuracy while reducing calibration error by 40% compared to the strongest baseline. Notably, it outperforms 5x deep ensembles using a single model at roughly half the memory footprint. Code and checkpoints are available at https://github.com/GenMI-Lab/EnTrust.git.
Graph-of-Differences: Anatomy-Structured Difference Alignment for Medical Image Re-IdentificationNichula Wasalathilaka, Abhijit Das, Imran Razzak et al.
Medical image re-identification (MedReID) enables longitudinal patient linkage but remains vulnerable to shortcut learning and often produces decisions that clinicians cannot audit against named anatomy. We propose Graph-of-Differences (GoD), which grounds identity comparisons in explicit anatomical structure. Each image is represented as an anatomy graph whose nodes correspond to named anatomical regions; given an image pair, soft node correspondence is established, and differences are computed over matched anatomy. A graph-level difference alignment objective ties these anatomy-matched differences to the global backbone difference, ensuring the retrieval signal is anchored in homologous structures rather than arbitrary spatial tokens. Explanations are defined over named graph nodes and quantitatively audited via node insertion/deletion tests, replacing unstable pixel heatmaps with verifiable structure-level evidence. On internal benchmarks, GoD improves Rank-1 by +7.1 pp on fundus and +3.1 pp on CXR over a strong frozen-backbone baseline, with further gains on zero-shot external transfers confirming that anatomy grounding improves both accuracy and generalization. Code is available at https://github.com/GenMI-Lab/GoD.git.
PROTON: Prototype-Based Test-Time Online OOD Detection for Medical VLMsAbhijit Das, Nichula Wasalathilaka, Yifan Lu et al.
Medical vision-language models (VLMs) enable zero-shot clinical image classification, yet reliably detecting out-of-distribution (OOD) inputs at deployment remains an open problem. No static scoring method works across all shift types: Maximum Concept Matching (MCM) on FLAIR achieves 76.4% AUROC for far-OOD but only 42.4% for covariate shifts such as ultra-wide-field fundus images, effectively random. We trace this to a structural mismatch: covariate-shifted inputs are indistinguishable from in-distribution samples in softmax space, yet occupy distinct regions in the VLM embedding space. To exploit this untapped signal, we propose PROTON (PROtotype-based Test-time ONline OOD detection), a lightweight post-hoc module that maintains an online prototype bank from high-confidence test predictions and adaptively fuses prototype distance with MCM scoring via stream-level variance statistics, requiring no model modification, training data, or prompt engineering. On the ophthalmology benchmark FLAIR + FIVES, PROTON improves MCM by +23.9 AUROC on covariate shift, +8.8 on semantic shift, and +8.1 on far-OOD, making it the only zero-shot method to improve all three without hierarchical prompts or labeled data. Code is available at https://github.com/GenMI-Lab/PROTON, and the project page is available at https://genmi-lab.github.io/PROTON.