Linjie Mu

Linjie Mu, Yannian Gu, Zhongzhen Huang et al.

Large language models with reasoning capabilities have demonstrated impressive performance across a wide range of domains. In clinical applications, a transparent, step-by-step reasoning process provides physicians with strong evidence to support decision-making. While reinforcement learning has effectively enhanced reasoning performance in medical contexts, the clinical reliability of these reasoning processes remains limited because their accuracy and validity are often overlooked during training. To address this gap, we propose MedCEG, a framework that augments medical language models with clinically valid reasoning pathways by explicitly supervising the reasoning process through a Critical Evidence Graph (CEG). We curate a dataset of challenging clinical cases and algorithmically construct a CEG for each sample to represent a high-quality verifiable reasoning pathway. To guide the reasoning process, we introduce a Clinical Reasoning Procedure Reward, which evaluates Node Coverage, Structural Correctness, and Chain Completeness, thereby providing a holistic assessment of reasoning quality. Experimental results show that MedCEG surpasses existing methods in performance while producing clinically valid reasoning chains, representing a solid advancement in reliable medical AI reasoning. The code and models are available at https://github.com/LinjieMu/MedCEG.

Yannian Gu, Zhongzhen Huang, Linjie Mu et al.

Multimodal large language models (MLLMs) demonstrate considerable potential in clinical diagnostics, a domain that inherently requires synthesizing complex visual and textual data alongside consulting authoritative medical literature. However, existing benchmarks primarily evaluate MLLMs in end-to-end answering scenarios. This limits the ability to disentangle a model's foundational multimodal reasoning from its proficiency in evidence retrieval and application. We introduce the Clinical Understanding and Retrieval Evaluation (CURE) benchmark. Comprising $500$ multimodal clinical cases mapped to physician-cited reference literature, CURE evaluates reasoning and retrieval under controlled evidence settings to disentangle their respective contributions. We evaluate state-of-the-art MLLMs across distinct evidence-gathering paradigms in both closed-ended and open-ended diagnosis tasks. Evaluations reveal a stark dichotomy: while advanced models demonstrate clinical reasoning proficiency when supplied with physician reference evidence (achieving up to $73.4\%$ accuracy on differential diagnosis), their performance substantially declines (as low as $25.4\%$) when reliant on independent retrieval mechanisms. This disparity highlights the dual challenges of effectively integrating multimodal clinical evidence and retrieving precise supporting literature. CURE is publicly available at https://github.com/yanniangu/CURE.

Zhongzhen Huang, Yan Ling, Hong Chen et al.

We present PULSE, a medical reasoning agent that combines a domain-tuned large language model with scientific literature retrieval to support diagnostic decision-making in complex real-world cases. To evaluate its capabilities, we curated a benchmark of 82 authentic endocrinology case reports encompassing a broad spectrum of disease types and incidence levels. In controlled experiments, we compared PULSE's performance against physicians with varying levels of expertise-from residents to senior specialists-and examined how AI assistance influenced human diagnostic reasoning. PULSE attained expert-competitive accuracy, outperforming residents and junior specialists while matching senior specialist performance at both Top@1 and Top@4 thresholds. Unlike physicians, whose accuracy declined with disease rarity, PULSE maintained stable performance across incidence tiers. The agent also exhibited adaptive reasoning, increasing output length with case difficulty in a manner analogous to the longer deliberation observed among expert clinicians. When used collaboratively, PULSE enabled physicians to correct initial errors and broaden diagnostic hypotheses, but also introduced risks of automation bias. The study explores both serial and concurrent collaboration workflows, revealing that PULSE offers robust support across common and rare presentations. These findings underscore both the promise and the limitations of language model-based agents in clinical diagnosis, and offer a framework for evaluating their role in real-world decision-making.

Yakun Zhu, Zhongzhen Huang, Linjie Mu et al.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3, o1, and DeepSeek-R1, achieve only 51.12%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AI's diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Yongrui Yu, Zhongzhen Huang, Linjie Mu et al.

Radiology reporting is an essential yet time-consuming and error-prone task for radiologists in clinical examinations, especially for volumetric medical images. Rigorous quality control is also critical but tedious, ensuring that the final report meets clinical standards. Existing automated approaches, including radiology report generation methods and medical vision-language models, focus mainly on the report generation phase and neglect the crucial quality control procedure, limiting their capability to provide comprehensive support to radiologists. We propose Radiologist Copilot, an agentic AI assistant equipped with orchestrated tools designed for automated radiology reporting with quality control. Leveraging large language models as the reasoning backbone, the agentic system autonomously selects tools, plans, and executes actions, emulating the behavior of radiologists throughout the holistic radiology reporting process. The orchestrated tools include region localization, think with image paradigm directed region analysis planning, strategic template selection for report generation, quality assessment and feedback-driven adaptive refinement for quality control. Therefore, Radiologist Copilot facilitates accurate, complete, and efficient radiology reporting, assisting radiologists and improving clinical efficiency. Experimental results demonstrate that Radiologist Copilot significantly surpasses other state-of-the-art methods in radiology reporting. The source code will be released upon acceptance.

Linjie Mu, Zhongzhen Huang, Yannian Gu et al.

World models offer a principled framework for simulating future states under interventions, but realizing such models in complex, high-stakes domains like medicine remains challenging. Recent large language models (LLMs) have achieved strong performance on static medical reasoning tasks, raising the question of whether they can function as dynamic medical world models capable of simulating disease progression and treatment outcomes over time. In this work, we show that LLMs only incorporating medical knowledge struggle to maintain consistent patient states under sequential interventions, leading to error accumulation in long-horizon clinical simulation. To address this limitation, we introduce EHRWorld, a patient-centric medical world model trained under a causal sequential paradigm, together with EHRWorld-110K, a large-scale longitudinal clinical dataset derived from real-world electronic health records. Extensive evaluations demonstrate that EHRWorld significantly outperforms naive LLM-based baselines, achieving more stable long-horizon simulation, improved modeling of clinically sensitive events, and favorable reasoning efficiency, highlighting the necessity of training on causally grounded, temporally evolving clinical data for reliable and robust medical world modeling.

Linjie Mu, Zhongzhen Huang, Shengqian Qin et al.

Large vision-language models (LVLMs) have shown great promise in medical applications, particularly in visual question answering (MedVQA) and diagnosis from medical images. However, existing datasets and models often fail to consider critical aspects of medical diagnostics, such as the integration of historical records and the analysis of disease progression over time. In this paper, we introduce MMXU (Multimodal and MultiX-ray Understanding), a novel dataset for MedVQA that focuses on identifying changes in specific regions between two patient visits. Unlike previous datasets that primarily address single-image questions, MMXU enables multi-image questions, incorporating both current and historical patient data. We demonstrate the limitations of current LVLMs in identifying disease progression on MMXU-\textit{test}, even those that perform well on traditional benchmarks. To address this, we propose a MedRecord-Augmented Generation (MAG) approach, incorporating both global and regional historical records. Our experiments show that integrating historical records significantly enhances diagnostic accuracy by at least 20\%, bridging the gap between current LVLMs and human expert performance. Additionally, we fine-tune models with MAG on MMXU-\textit{dev}, which demonstrates notable improvements. We hope this work could illuminate the avenue of advancing the use of LVLMs in medical diagnostics by emphasizing the importance of historical context in interpreting medical images. Our dataset is released at github: https://github.com/linjiemu/MMXU.

Yakun Zhu, Zhongzhen Huang, Qianhan Feng et al.

Medical care follows complex clinical pathways that extend beyond isolated physician-patient encounters, emphasizing decision-making and transitions between different stages. Current benchmarks focusing on static exams or isolated dialogues inadequately evaluate large language models (LLMs) in dynamic clinical scenarios. We introduce CP-Env, a controllable agentic hospital environment designed to evaluate LLMs across end-to-end clinical pathways. CP-Env simulates a hospital ecosystem with patient and physician agents, constructing scenarios ranging from triage and specialist consultation to diagnostic testing and multidisciplinary team meetings for agent interaction. Following real hospital adaptive flow of healthcare, it enables branching, long-horizon task execution. We propose a three-tiered evaluation framework encompassing Clinical Efficacy, Process Competency, and Professional Ethics. Results reveal that most models struggle with pathway complexity, exhibiting hallucinations and losing critical diagnostic details. Interestingly, excessive reasoning steps can sometimes prove counterproductive, while top models tend to exhibit reduced tool dependency through internalized knowledge. CP-Env advances medical AI agents development through comprehensive end-to-end clinical evaluation. We provide the benchmark and evaluation tools for further research and development at https://github.com/SPIRAL-MED/CP_ENV.

Zhongzhen Huang, Kui Xue, Yongqi Fan et al.

Large-scale language models (LLMs) have achieved remarkable success across various language tasks but suffer from hallucinations and temporal misalignment. To mitigate these shortcomings, Retrieval-augmented generation (RAG) has been utilized to provide external knowledge to facilitate the answer generation. However, applying such models to the medical domain faces several challenges due to the lack of domain-specific knowledge and the intricacy of real-world scenarios. In this study, we explore LLMs with RAG framework for knowledge-intensive tasks in the medical field. To evaluate the capabilities of LLMs, we introduce MedicineQA, a multi-round dialogue benchmark that simulates the real-world medication consultation scenario and requires LLMs to answer with retrieved evidence from the medicine database. MedicineQA contains 300 multi-round question-answering pairs, each embedded within a detailed dialogue history, highlighting the challenge posed by this knowledge-intensive task to current LLMs. We further propose a new \textit{Distill-Retrieve-Read} framework instead of the previous \textit{Retrieve-then-Read}. Specifically, the distillation and retrieval process utilizes a tool calling mechanism to formulate search queries that emulate the keyword-based inquiries used by search engines. With experimental results, we show that our framework brings notable performance improvements and surpasses the previous counterparts in the evidence retrieval process in terms of evidence retrieval accuracy. This advancement sheds light on applying RAG to the medical domain.

Zhongzhen Huang, Linjie Mu, Yakun Zhu et al.

Effective clinical decision-making depends on iterative, multimodal reasoning across diverse sources of evidence. The recent emergence of multimodal reasoning models has significantly transformed the landscape of solving complex tasks. Although such models have achieved notable success in mathematics and science, their application to medical domains remains underexplored. In this work, we propose \textit{MedE$^2$}, a two-stage post-training pipeline that elicits and then enhances multimodal reasoning for medical domains. In Stage-I, we fine-tune models using 2,000 text-only data samples containing precisely orchestrated reasoning demonstrations to elicit reasoning behaviors. In Stage-II, we further enhance the model's reasoning capabilities using 1,500 rigorously curated multimodal medical cases, aligning model reasoning outputs with our proposed multimodal medical reasoning preference. Extensive experiments demonstrate the efficacy and reliability of \textit{MedE$^2$} in improving the reasoning performance of medical multimodal models. Notably, models trained with \textit{MedE$^2$} consistently outperform baselines across multiple medical multimodal benchmarks. Additional validation on larger models and under inference-time scaling further confirms the robustness and practical utility of our approach.