Joakim Nguyen

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.

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.

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.

Seungjun Yi, Joakim Nguyen, Huimin Xu et al.

Congenital heart disease (CHD) presents complex, lifelong challenges often underrepresented in traditional clinical metrics. While unstructured narratives offer rich insights into patient and caregiver experiences, manual thematic analysis (TA) remains labor-intensive and unscalable. We propose a fully automated large language model (LLM) pipeline that performs end-to-end TA on clinical narratives, which eliminates the need for manual coding or full transcript review. Our system employs a novel multi-agent framework, where specialized LLM agents assume roles to enhance theme quality and alignment with human analysis. To further improve thematic relevance, we optionally integrate reinforcement learning from human feedback (RLHF). This supports scalable, patient-centered analysis of large qualitative datasets and allows LLMs to be fine-tuned for specific clinical contexts.

Seungjun Yi, Joakim Nguyen, Terence Lim et al.

This position paper examines how large language models (LLMs) can support thematic analysis of unstructured clinical transcripts, a widely used but resource-intensive method for uncovering patterns in patient and provider narratives. We conducted a systematic review of recent studies applying LLMs to thematic analysis, complemented by an interview with a practicing clinician. Our findings reveal that current approaches remain fragmented across multiple dimensions including types of thematic analysis, datasets, prompting strategies and models used, most notably in evaluation. Existing evaluation methods vary widely (from qualitative expert review to automatic similarity metrics), hindering progress and preventing meaningful benchmarking across studies. We argue that establishing standardized evaluation practices is critical for advancing the field. To this end, we propose an evaluation framework centered on three dimensions: validity, reliability, and interpretability.

Seungjun Yi, Joakim Nguyen, Huimin Xu et al.

Thematic Analysis (TA) is a widely used qualitative method that provides a structured yet flexible framework for identifying and reporting patterns in clinical interview transcripts. However, manual thematic analysis is time-consuming and limits scalability. Recent advances in LLMs offer a pathway to automate thematic analysis, but alignment with human results remains limited. To address these limitations, we propose SFT-TA, an automated thematic analysis framework that embeds supervised fine-tuned (SFT) agents within a multi-agent system. Our framework outperforms existing frameworks and the gpt-4o baseline in alignment with human reference themes. We observed that SFT agents alone may underperform, but achieve better results than the baseline when embedded within a multi-agent system. Our results highlight that embedding SFT agents in specific roles within a multi-agent system is a promising pathway to improve alignment with desired outputs for thematic analysis.