Evidential Reasoning Advances Interpretable Real-World Disease Screening

Deep learning has brought significant progress to medical image classification, yet most existing methods still rely on isolated visual evidence and cannot effectively leverage similar cases or external knowledge. In clinical practice, diagnosis is typically supported by similar historical cases and their associated symptoms. To explicitly model this evidence-based diagnostic process, we propose a case-aware reasoning framework driven by multimodal knowledge graphs for medical image classification. Specifically, we construct a case-aware multimodal knowledge graph as a structured diagnostic memory, where diseases, images, and symptoms are hierarchically organized. Given an input image, our method adaptively retrieves similar cases from this memory and extracts their corresponding case-centered subgraphs. We further introduce a knowledge propagation and injection mechanism, in which an image-centric Graph Attention Network aggregates heterogeneous semantics into case-based features, followed by a bidirectional cross-modal attention mechanism that injects these features into visual representations for cross-modal alignment. To mitigate noisy retrieval, we design a confidence-calibrated decision refinement scheme that estimates the reliability of each retrieved case by jointly considering prediction confidence and sample similarity, and reweights its contribution to the final prediction, providing interpretable case-level evidence. Extensive experiments on multiple medical imaging datasets demonstrate that our approach consistently outperforms strong baselines, while ablation and qualitative analyses validate its effectiveness and interpretability. The code is available at https://anonymous.4open.science/r/MKG-CARE-8B7B.

Large-scale pretrained foundation models have revolutionized general medical screening, but often falter on rare diseases because such conditions are underrepresented in real-world clinical datasets. While retrieval-augmented diagnosis attempts to mitigate this, conventional static methods frequently succumb to the hubness problem, retrieving visually similar but semantically incorrect common diseases. To address this, we propose Evo-RAD, a self-evolving agentic framework that transforms evidence acquisition into a dynamic decision-making task. We formulate retrieval as a Markov Decision Process (MDP) where a graphbased agent observes the reference set state and executes actions to purge discordant evidence (DELETE), acquire pathologically consistent samples (INSERT), or conclude the evolution (TERMINATE). Optimized via Group Relative Policy Optimization (GRPO) with a homogeneityaware reward, the agent learns to maximize the diagnostic homogeneity of the support reference set. Experiments on retinal disease benchmarks show that Evo-RAD substantially improves rare-disease diagnosis, outperforming retinal foundation models by +21.04%, while also surpassing retrieval-based and parameter-efficient fine-tuning methods by +3.56%. Code is available at https://github.com/SDH-Lab/Evo-RAD.

Deep neural networks for medical image diagnosis often achieve high predictive accuracy while relying on spurious or clinically irrelevant visual cues, limiting their trustworthiness in practice. Post-hoc explanation methods are widely used to visualize model decisions in the form of saliency maps; however, these explanations do not influence how models learn during training, allowing non-causal or confounding features to persist. This motivates the incorporation of explanation supervision directly into the training objective to guide model attention toward clinically meaningful regions and promote clinically grounded decision-making. This paper presents a systematic approach to integrate explanation loss into model training and analyzes how different explanation loss designs and supervision strengths influence both predictive performance and spatial faithfulness of explanations. To quantitatively assess interpretability, two complementary explanation performance metrics-annotation coverage and saliency precision-are introduced, enabling rigorous evaluation beyond qualitative visualization. Our experimental results reveal a clear trade-off between explanation quality and explanation loss coefficients. Furthermore, quantitative statistical analysis yields consistently improved explanation alignment while maintaining comparable accuracy. Experiments were conducted on annotated chest X-ray datasets; however, the proposed framework is applicable to a broad range of annotated biomedical imaging modalities. Overall, these findings demonstrate that explanation supervision is not a monolithic design choice and provide practical guidance for incorporating explanation loss into training objectives under noisy clinical annotations.