Conditional Evidence Reconstruction and Decomposition for Interpretable Multimodal Diagnosis

Multimodal clinical decision-making requires reliable reasoning over heterogeneous evidence from electronic health records, medical images, and physiological signals. Existing models typically map these inputs directly to diagnoses without explicitly assessing evidence sufficiency, tool-use requirements, or diagnostic uncertainty. This paper presents MedTRACE, a tool-augmented multimodal clinical reasoning agent for evidence-grounded decision-making. MedTRACE uses modality-specific encoders to construct a unified patient-state representation and performs an iterative loop of hypothesis formation, toolaware deliberation, and evidence verification. It dynamically invokes visual grounding, evidence retrieval, and structured parsing tools to locate diagnosis-relevant regions, retrieve clinical knowledge and similar cases, and extract structured findings. The acquired evidence enters an evidence memory, where a consistency verifier confirms or revises the current hypothesis. MedTRACE outputs a diagnosis together with supporting evidence, an auditable reasoning trace, and calibrated confidence. Experiments on multiple multimodal clinical diagnosis benchmarks show that MedTRACE improves diagnostic accuracy by 5.4% and AUROC by 4.7 percentage points over the strongest baseline. It also improves evidenceselection F1 by 8.2 percentage points and visual-grounding IoU by 6.5 percentage points, reduces expected calibration error by 31.6%, and decreases unsupported diagnostic errors by 27.8%. These results demonstrate that active evidence acquisition and verification improve the accuracy, interpretability, and reliability of multimodal clinical decisionmaking.

Missing modalities are prevalent in real-world Alzheimer's disease (AD) assessment and pose a significant challenge to multimodal learning, particularly when the distribution of observed modality subsets differs between training and deployment. Such missingness pattern mismatch induces a conditional representation shift across modality subsets. Existing approaches that rely on implicit imputation or modality synthesis often fail to explicitly model modality availability and uncertainty, leading to overconfident dependence on synthesized features, reduced robustness, and miscalibrated uncertainty estimates. To address these limitations, we propose PRA-PoE, an incomplete multimodal learning framework that is equipped with Prototype-anchored Representation Alignment (PRA) and an Uncertainty-aware Product of Experts (UA-PoE) fusion mechanism. First, PRA uses learnable global prototypes and availability-conditioned tokens to encode modality availability, distinguish observed from missing modalities, re-synthesize features for missing modalities, and adaptively refine observed representations to align latent spaces across modality subsets, with the goal of reducing representation shift under varying missingness patterns. Second, UA-PoE models each modality as a Gaussian expert and performs closed-form Product of Experts fusion, where experts with higher uncertainty are automatically down-weighted via lower precision, improving uncertainty reliability. We evaluate PRA-PoE under a clinically realistic protocol by training with naturally missing data and testing on all non-empty modality combinations. PRA-PoE consistently outperforms the state-of-the-art across datasets, achieving a 5.4% relative improvement in average accuracy on ADNI and a 10.9% relative gain in average F1 on OASIS-3 over the strongest baseline across all non-empty modality subsets.

Multimodal models in oncology can produce accurate predictions, but accurate prediction does not reveal whether the model has learned biology that is shared across modalities, biology confined to one modality, or spurious correlations that reflect confounders rather than genuine biology. We introduce DECAT, a model-agnostic post-hoc evaluation framework that classifies multimodal representations into four diagnostic scenarios for a given task and modality, using five null-referenced metrics and a rule-based decision procedure. The framework operates on learned representations, requires no knowledge of which specific confounder is present, and returns indeterminate when the evidence is insufficient. We validate DECAT on synthetic data across four multimodal model classes (over 2,500 trained representations) and on real data from 8,979 TCGA patients, evaluating both multimodal embeddings and five pretrained pathology foundation models. Entangled models (e.g., CLIP) achieve near-perfect shared biology detection but falsely claim shared biology in the majority of cases where it is absent on real foundation model embeddings. This false claim rate increases with confound strength so that larger cohorts and stronger representations produce more confident but still incorrect diagnoses. Applied to both multimodal TCGA embeddings and five pathology foundation models without paired RNA, DECAT detects confounding invisible to AUROC without requiring the confounder labels, as confirmed by post-hoc stratification.