Jinrui Fang

Joakim Nguyen, Jian Yu, Jinrui Fang et al.

Accurate diagnosis of pediatric brain tumors, starting with histopathology, presents unique challenges for deep learning, including severe data scarcity, class imbalance, and fine-grained morphologic overlap across diagnostically distinct subtypes. While pathology foundation models have advanced patch-level representation learning, their effective adaptation to weakly supervised pediatric brain tumor classification under limited data remains underexplored. In this work, we introduce an expert-guided contrastive fine-tuning framework for pediatric brain tumor diagnosis from whole-slide images (WSI). Our approach integrates contrastive learning into slide-level multiple instance learning (MIL) to explicitly regularize the geometry of slide-level representations during downstream fine-tuning. We propose both a general supervised contrastive setting and an expert-guided variant that incorporates clinically informed hard negatives targeting diagnostically confusable subtypes. Through comprehensive experiments on pediatric brain tumor WSI classification under realistic low-sample and class-imbalanced conditions, we demonstrate that contrastive fine-tuning yields measurable improvements in fine-grained diagnostic distinctions. Our experimental analyses reveal complementary strengths across different contrastive strategies, with expert-guided hard negatives promoting more compact intra-class representations and improved inter-class separation. This work highlights the importance of explicitly shaping slide-level representations for robust fine-grained classification in data-scarce pediatric pathology settings.

Xuan Wang, Zhongling Xu, Gopi Kannedhara et al.

Healthcare models are transitioning from unimodal prediction toward multimodal reasoning over heterogeneous diagnostic inputs. In computational pathology, for complex tumor subtypes where morphology alone can be challenging to distinguish, pathology reports and molecular measurements may provide additional diagnostic evidence alongside whole-slide images, yet existing models often fail to clarify how diverse signals assemble into recognizable diagnostic concepts. We propose ConceptM$^3$oE (Concept Multimodal MoE), which embeds concept formation directly within interaction-aware mixture-of-experts (MoE) pathways. The architecture decomposes evidence into modality-specific, redundant, and synergistic experts, which are then projected into structured concept bottlenecks mapping latent features to a hierarchy of morphology and biomarker concepts. To prevent the information loss typical of interpretable bottlenecks, we utilize residual pathways within each expert to allow task-relevant signals to flow both through the concepts and directly to the final task prediction, so that high performance is maintained alongside interpretability. Across an institutional pediatric brain tumor cohort and a public glioma cohort, the framework delivers competitive performance to unconstrained models while producing reasoning traces validated by an independent neuropathologist. In data-limited regimes, ConceptM$^3$oE improves limited-data performance, increasing macro-F1 from 56.41% to 66.70% at small training sizes compared to non-concept-informed baselines, while also showing faster training convergence consistent with the regularizing effect of concept learning. This work offers a scalable path toward high-performance medical AI that is inherently verifiable and better aligned with the complex decision-making of clinical practice.

Jian Yu, Joakim Nguyen, Jinrui Fang et al.

Accurate classification of pediatric central nervous system tumors remains challenging due to histological complexity and limited training data. While pathology foundation models have advanced whole-slide image (WSI) analysis, they often fail to leverage the rich, complementary information found in clinical text and tissue microarchitecture. To this end, we propose PathMoE, an interpretable multimodal framework that integrates H\&E slides, pathology reports, and nuclei-level cell graphs via an interaction-aware mixture-of-experts architecture built on state-of-the-art foundation models for each modality. By training specialized experts to capture modality uniqueness, redundancy, and synergy, PathMoE employs an input-dependent gating mechanism that dynamically weights these interactions, providing sample-level interpretability. We evaluate our framework on two dataset-specific classification tasks on an internal pediatric brain tumor dataset (PBT) and external TCGA datasets. PathMoE improves macro-F1 from 0.762 to 0.799 (+0.037) on PBT when integrating WSI, text, and graph modalities; on TCGA, augmenting WSI with graph knowledge improves macro-F1 from 0.668 to 0.709 (+0.041). These results demonstrate significant performance gains over state-of-the-art image-only baselines while revealing the specific modality interactions driving individual predictions. This interpretability is particularly critical for rare tumor subtypes, where transparent model reasoning is essential for clinical trust and diagnostic validation.

Jinrui Fang, Runhan Chen, Xu Yang et al.

Large language models (LLMs) achieve high accuracy in medical diagnosis when all clinical information is provided in a single turn, yet how they behave under multi-turn evidence accumulation closer to real clinical reasoning remains unexplored. We introduce MINT (Medical Incremental N-Turn Benchmark), a high-fidelity, multi-turn medical diagnosis benchmark comprising 1,035 cases with clinically labeled evidence shards, controlled turn granularity, and information-preserving decomposition. Through systematic evaluation of 11 LLMs on MINT, we uncover three persistent behavioral patterns that significantly impact diagnostic decisions: (1) intent to answer, models rush to answer before sufficient evidence has been observed, with over 55% of answers committed within the first two turns; (2) self-correction, incorrect-to-correct answer revisions occur at up to 10.6 times the rate of correct-to-incorrect flips, revealing a latent capacity for self-correction that premature commitment forecloses; and (3) strong lures, clinically salient information such as laboratory results trigger premature answering even when models are explicitly instructed to wait. We translate these findings into clinically actionable guidance: deferring the diagnostic question to later turns reduces premature answering and improves accuracy at the first point of commitment by up to 62.6%, while reserving salient clinical evidence for later turns prevents a catastrophic accuracy drop of up to 23.3% caused by premature commitment. Our work provides both a controlled evaluation framework and concrete recommendations for improving the reliability of LLMs in multi-turn medical diagnosis.

Philip DiGiacomo, Haoyang Wang, Jinrui Fang et al.

As AI chatbots gain adoption in clinical medicine, developing effective frameworks for complex, emerging diseases presents significant challenges. We developed and evaluated six Retrieval-Augmented Generation (RAG) corpus configurations for Long COVID (LC) clinical question answering, ranging from expert-curated sources to large-scale literature databases. Our evaluation employed an LLM-as-a-judge framework across faithfulness, relevance, and comprehensiveness metrics using LongCOVID-CQ, a novel dataset of expert-generated clinical questions. Our RAG corpus configuration combining clinical guidelines with high-quality systematic reviews consistently outperformed both narrow single-guideline approaches and large-scale literature databases. Our findings suggest that for emerging diseases, retrieval grounded in curated secondary reviews provides an optimal balance between narrow consensus documents and unfiltered primary literature, supporting clinical decision-making while avoiding information overload and oversimplified guidance. We propose Guide-RAG, a chatbot system and accompanying evaluation framework that integrates both curated expert knowledge and comprehensive literature databases to effectively answer LC clinical questions.