Automated grading of Knee Osteoarthritis (KOA) from radiographs is challenged by significant inter-observer variability and the limited robustness of deep learning models, particularly near critical decision boundaries. To address these limitations, this paper proposes a novel framework, Diffusion-based Counterfactual Augmentation (DCA), which enhances model robustness and interpretability by generating targeted counterfactual examples. The method navigates the latent space of a diffusion model using a Stochastic Differential Equation (SDE), governed by balancing a classifier-informed boundary drive with a manifold constraint. The resulting counterfactuals are then used within a self-corrective learning strategy to improve the classifier by focusing on its specific areas of uncertainty. Extensive experiments on the public Osteoarthritis Initiative (OAI) and Multicenter Osteoarthritis Study (MOST) datasets demonstrate that this approach significantly improves classification accuracy across multiple model architectures. Furthermore, the method provides interpretability by visualizing minimal pathological changes and revealing that the learned latent space topology aligns with clinical knowledge of KOA progression. The DCA framework effectively converts model uncertainty into a robust training signal, offering a promising pathway to developing more accurate and trustworthy automated diagnostic systems. Our code is available at https://github.com/ZWang78/DCA.
Osteoporosis, characterized by reduced bone mineral density (BMD) and compromised bone microstructure, increases fracture risk in aging populations. While dual-energy X-ray absorptiometry (DXA) is the clinical standard for BMD assessment, its limited accessibility hinders diagnosis in resource-limited regions. Opportunistic computed tomography (CT) analysis has emerged as a promising alternative for osteoporosis diagnosis using existing imaging data. Current approaches, however, face three limitations: (1) underutilization of unlabeled vertebral data, (2) systematic bias from device-specific DXA discrepancies, and (3) insufficient integration of clinical knowledge such as spatial BMD distribution patterns. To address these, we propose a unified deep learning framework with three innovations. First, a self-supervised learning method using radiomic representations to leverage unlabeled CT data and preserve bone texture. Second, a Mixture of Experts (MoE) architecture with learned gating mechanisms to enhance cross-device adaptability. Third, a multi-task learning framework integrating osteoporosis diagnosis, BMD regression, and vertebra location prediction. Validated across three clinical sites and an external hospital, our approach demonstrates superior generalizability and accuracy over existing methods for opportunistic osteoporosis screening and diagnosis.
Deep learning-based myocardial scar segmentation from late gadolinium enhancement (LGE) cardiac MRI has shown great potential for accurate and timely diagnosis and treatment planning for structural cardiac diseases. However, the limited availability and variability of LGE images with high-quality scar labels restrict the development of robust segmentation models. To address this, we introduce CLAIM: \textbf{C}linically-Guided \textbf{L}GE \textbf{A}ugmentation for Real\textbf{i}stic and Diverse \textbf{M}yocardial Scar Synthesis and Segmentation framework, a framework for anatomically grounded scar generation and segmentation. At its core is the SMILE module (Scar Mask generation guided by cLinical knowledgE), which conditions a diffusion-based generator on the clinically adopted AHA 17-segment model to synthesize images with anatomically consistent and spatially diverse scar patterns. In addition, CLAIM employs a joint training strategy in which the scar segmentation network is optimized alongside the generator, aiming to enhance both the realism of synthesized scars and the accuracy of the scar segmentation performance. Experimental results show that CLAIM produces anatomically coherent scar patterns and achieves higher Dice similarity with real scar distributions compared to baseline models. Our approach enables controllable and realistic myocardial scar synthesis and has demonstrated utility for downstream medical imaging task. Code is available at https://github.com/farheenjabeen/CLAIM-Scar-Synthesis.
An essential step in deploying medical imaging models is ensuring alignment with clinical knowledge and interpretability. We focus on mapping clinical concepts into the latent space of generative models to identify Concept Activation Vectors (CAVs). Using a simple reconstruction autoencoder, we link user-defined concepts to image-level features without explicit label training. The extracted concepts are stable across datasets, enabling visual explanations that highlight clinically relevant features. By traversing latent space along concept directions, we produce counterfactuals that exaggerate or reduce specific clinical features. Preliminary results on chest X-rays show promise for large pathologies like cardiomegaly, while smaller pathologies remain challenging due to reconstruction limits. Although not outperforming baselines, this approach offers a path toward interpretable, concept-based explanations aligned with clinical knowledge.
Accurate and safe medication recommendations are critical for effective clinical decision-making, especially in multimorbidity cases. However, existing systems rely on point-wise prediction paradigms that overlook synergistic drug effects and potential adverse drug-drug interactions (DDIs). We propose FLAME, a fine-grained list-wise alignment framework for large language models (LLMs), enabling drug-by-drug generation of drug lists. FLAME formulates recommendation as a sequential decision process, where each step adds or removes a single drug. To provide fine-grained learning signals, we devise step-wise Group Relative Policy Optimization (GRPO) with potential-based reward shaping, which explicitly models DDIs and optimizes the contribution of each drug to the overall prescription. Furthermore, FLAME enhances patient modeling by integrating structured clinical knowledge and collaborative information into the representation space of LLMs. Experiments on benchmark datasets demonstrate that FLAME achieves state-of-the-art performance, delivering superior accuracy, controllable safety-accuracy trade-offs, and strong generalization across diverse clinical scenarios. Our code is available at https://github.com/cxfann/Flame.
Existing medical RAG systems mainly leverage knowledge from medical knowledge bases, neglecting the crucial role of experiential knowledge derived from similar patient cases -- a key component of human clinical reasoning. To bridge this gap, we propose DoctorRAG, a RAG framework that emulates doctor-like reasoning by integrating both explicit clinical knowledge and implicit case-based experience. DoctorRAG enhances retrieval precision by first allocating conceptual tags for queries and knowledge sources, together with a hybrid retrieval mechanism from both relevant knowledge and patient. In addition, a Med-TextGrad module using multi-agent textual gradients is integrated to ensure that the final output adheres to the retrieved knowledge and patient query. Comprehensive experiments on multilingual, multitask datasets demonstrate that DoctorRAG significantly outperforms strong baseline RAG models and gains improvements from iterative refinements. Our approach generates more accurate, relevant, and comprehensive responses, taking a step towards more doctor-like medical reasoning systems.
Dermatological diagnosis represents a complex multimodal challenge that requires integrating visual features with specialized clinical knowledge. While vision-language pretraining (VLP) has advanced medical AI, its effectiveness in dermatology is limited by text length constraints and the lack of structured texts. In this paper, we introduce MAKE, a Multi-Aspect Knowledge-Enhanced vision-language pretraining framework for zero-shot dermatological tasks. Recognizing that comprehensive dermatological descriptions require multiple knowledge aspects that exceed standard text constraints, our framework introduces: (1) a multi-aspect contrastive learning strategy that decomposes clinical narratives into knowledge-enhanced sub-texts through large language models, (2) a fine-grained alignment mechanism that connects subcaptions with diagnostically relevant image features, and (3) a diagnosis-guided weighting scheme that adaptively prioritizes different sub-captions based on clinical significance prior. Through pretraining on 403,563 dermatological image-text pairs collected from education resources, MAKE significantly outperforms state-of-the-art VLP models on eight datasets across zero-shot skin disease classification, concept annotation, and cross-modal retrieval tasks. Our code will be made publicly available at https: //github.com/SiyuanYan1/MAKE.
The present research tackles the difficulty of predicting osteoporosis risk via machine learning (ML) approaches, emphasizing the use of explainable artificial intelligence (XAI) to improve model transparency. Osteoporosis is a significant public health concern, sometimes remaining untreated owing to its asymptomatic characteristics, and early identification is essential to avert fractures. The research assesses six machine learning classifiers: Random Forest, Logistic Regression, XGBoost, AdaBoost, LightGBM, and Gradient Boosting and utilizes a dataset based on clinical, demographic, and lifestyle variables. The models are refined using GridSearchCV to calibrate hyperparameters, with the objective of enhancing predictive efficacy. XGBoost had the greatest accuracy (91%) among the evaluated models, surpassing others in precision (0.92), recall (0.91), and F1-score (0.90). The research further integrates XAI approaches, such as SHAP, LIME, and Permutation Feature Importance, to elucidate the decision-making process of the optimal model. The study indicates that age is the primary determinant in forecasting osteoporosis risk, followed by hormonal alterations and familial history. These results corroborate clinical knowledge and affirm the models' therapeutic significance. The research underscores the significance of explainability in machine learning models for healthcare applications, guaranteeing that physicians can rely on the system's predictions. The report ultimately proposes directions for further research, such as validation across varied populations and the integration of supplementary biomarkers for enhanced predictive accuracy.
Prompt learning is one of the most effective paradigms for adapting pre-trained vision-language models (VLMs) to the biomedical image classification tasks in few shot scenarios. However, most of the current prompt learning methods only used the text prompts and ignored the particular structures (such as the complex anatomical structures and subtle pathological features) in the biomedical images. In this work, we propose Biomed-DPT, a knowledge-enhanced dual modality prompt tuning technique. In designing the text prompt, Biomed-DPT constructs a dual prompt including the template-driven clinical prompts and the large language model (LLM)-driven domain-adapted prompts, then extracts the clinical knowledge from the domain-adapted prompts through the knowledge distillation technique. In designing the vision prompt, Biomed-DPT introduces the zero vector as a soft prompt to leverage attention re-weighting so that the focus on non-diagnostic regions and the recognition of non-critical pathological features are avoided. Biomed-DPT achieves an average classification accuracy of 66.14\% across 11 biomedical image datasets covering 9 modalities and 10 organs, with performance reaching 78.06\% in base classes and 75.97\% in novel classes, surpassing the Context Optimization (CoOp) method by 6.20\%, 3.78\%, and 8.04\%, respectively. Our code are available at \underline{https://github.com/Kanyooo/Biomed-DPT}.
Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.
Multimodal medical images play a crucial role in the precise and comprehensive clinical diagnosis. Diffusion model is a powerful strategy to synthesize the required medical images. However, existing approaches still suffer from the problem of anatomical structure distortion due to the overfitting of high-frequency information and the weakening of low-frequency information. Thus, we propose a novel method based on dynamic frequency balance and knowledge guidance. Specifically, we first extract the low-frequency and high-frequency components by decomposing the critical features of the model using wavelet transform. Then, a dynamic frequency balance module is designed to adaptively adjust frequency for enhancing global low-frequency features and effective high-frequency details as well as suppressing high-frequency noise. To further overcome the challenges posed by the large differences between different medical modalities, we construct a knowledge-guided mechanism that fuses the prior clinical knowledge from a visual language model with visual features, to facilitate the generation of accurate anatomical structures. Experimental evaluations on multiple datasets show the proposed method achieves significant improvements in qualitative and quantitative assessments, verifying its effectiveness and superiority.
Medical large language models (LLMs) research often makes bold claims, from encoding clinical knowledge to reasoning like a physician. These claims are usually backed by evaluation on competitive benchmarks; a tradition inherited from mainstream machine learning. But how do we separate real progress from a leaderboard flex? Medical LLM benchmarks, much like those in other fields, are arbitrarily constructed using medical licensing exam questions. For these benchmarks to truly measure progress, they must accurately capture the real-world tasks they aim to represent. In this position paper, we argue that medical LLM benchmarks should (and indeed can) be empirically evaluated for their construct validity. In the psychological testing literature, "construct validity" refers to the ability of a test to measure an underlying "construct", that is the actual conceptual target of evaluation. By drawing an analogy between LLM benchmarks and psychological tests, we explain how frameworks from this field can provide empirical foundations for validating benchmarks. To put these ideas into practice, we use real-world clinical data in proof-of-concept experiments to evaluate popular medical LLM benchmarks and report significant gaps in their construct validity. Finally, we outline a vision for a new ecosystem of medical LLM evaluation centered around the creation of valid benchmarks.
Previous work on clinical relation extraction from free-text sentences leveraged information about semantic types from clinical knowledge bases as a part of entity representations. In this paper, we exploit additional evidence by also making use of domain-specific semantic type dependencies. We encode the relation between a span of tokens matching a Unified Medical Language System (UMLS) concept and other tokens in the sentence. We implement our method and compare against different named entity recognition (NER) architectures (i.e., BiLSTM-CRF and BiLSTM-GCN-CRF) using different pre-trained clinical embeddings (i.e., BERT, BioBERT, UMLSBert). Our experimental results on clinical datasets show that in some cases NER effectiveness can be significantly improved by making use of domain-specific semantic type dependencies. Our work is also the first study generating a matrix encoding to make use of more than three dependencies in one pass for the NER task.
Medical Visual Question Answering (Med-VQA) represents a critical and challenging subtask within the general VQA domain. Despite significant advancements in general Visual Question Answering (VQA), multimodal large language models (MLLMs) still exhibit substantial limitations when handling multi-task VQA scenarios. These limitations manifest through erroneous spatial localization and misinterpretation of medical images, which primarily arise from two fundamental issues: inadequate image-text alignment and insufficient medical knowledge in general-purpose MLLMs for specialized medical applications. To address these issues, we introduce the Cross-Modal Clinical Knowledge Distiller (ClinKD), an innovative framework designed to enhance image-text alignment and establish more effective medical knowledge adaptation mechanisms, which enables MLLMs to adapt to medical knowledge. Our extensive experimental evaluations demonstrate that the ClinKD achieves state-of-the-art performance on the Med-GRIT-270k dataset, a challenging medical benchmark containing fine-grained multi-task QA pairs. The results indicate that our approach not only significantly improves image-text alignment but also effectively enables MLLMs to adapt to the medical knowledge. The source code for ClinKD is available at: https://github.com/overloadedHenry/ClinKD.
While large language models (LLMs) have shown promise in diagnostic dialogue, their capabilities for effective management reasoning - including disease progression, therapeutic response, and safe medication prescription - remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) through a new LLM-based agentic system optimised for clinical management and dialogue, incorporating reasoning over the evolution of disease and multiple patient visit encounters, response to therapy, and professional competence in medication prescription. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini's long-context capabilities, combining in-context retrieval with structured reasoning to align its output with relevant and up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialist physicians and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding of management plans in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. While AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE's strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.
Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.
We present a deep learning-based approach to studying dynamic clinical behavioral regimes in diverse non-randomized healthcare settings. Our proposed methodology - deep causal behavioral policy learning (DC-BPL) - uses deep learning algorithms to learn the distribution of high-dimensional clinical action paths, and identifies the causal link between these action paths and patient outcomes. Specifically, our approach: (1) identifies the causal effects of provider assignment on clinical outcomes; (2) learns the distribution of clinical actions a given provider would take given evolving patient information; (3) and combines these steps to identify the optimal provider for a given patient type and emulate that provider's care decisions. Underlying this strategy, we train a large clinical behavioral model (LCBM) on electronic health records data using a transformer architecture, and demonstrate its ability to estimate clinical behavioral policies. We propose a novel interpretation of a behavioral policy learned using the LCBM: that it is an efficient encoding of complex, often implicit, knowledge used to treat a patient. This allows us to learn a space of policies that are critical to a wide range of healthcare applications, in which the vast majority of clinical knowledge is acquired tacitly through years of practice and only a tiny fraction of information relevant to patient care is written down (e.g. in textbooks, studies or standardized guidelines).
Healthcare systems are struggling to meet the growing demand for neurological care, with challenges particularly acute in Alzheimer's disease and related dementias (ADRD). While artificial intelligence research has often focused on identifying patterns beyond human perception, implementing such predictive capabilities remains challenging as clinicians cannot readily verify insights they cannot themselves detect. We propose that large language models (LLMs) offer more immediately practical applications by enhancing clinicians' capabilities in three critical areas: comprehensive data collection, interpretation of complex clinical information, and timely application of relevant medical knowledge. These challenges stem from limited time for proper diagnosis, growing data complexity, and an overwhelming volume of medical literature that exceeds any clinician's capacity to fully master. We present a framework for responsible AI integration that leverages LLMs' ability to communicate effectively with both patients and providers while maintaining human oversight. This approach prioritizes standardized, high-quality data collection to enable a system that learns from every patient encounter while incorporating the latest clinical evidence, continuously improving care delivery. We begin to address implementation challenges and initiate important discussions around ethical considerations and governance needs. While developed for ADRD, this roadmap provides principles for responsible AI integration across neurology and other medical specialties, with potential to improve diagnostic accuracy, reduce care disparities, and advance clinical knowledge through a learning healthcare system.
Importance: Emergency department (ED) returns for mental health conditions pose a major healthcare burden, with 24-27% of patients returning within 30 days. Traditional machine learning models for predicting these returns often lack interpretability for clinical use. Objective: To assess whether integrating large language models (LLMs) with machine learning improves predictive accuracy and clinical interpretability of ED mental health return risk models. Methods: This retrospective cohort study analyzed 42,464 ED visits for 27,904 unique mental health patients at an academic medical center in the Deep South from January 2018 to December 2022. Main Outcomes and Measures: Two primary outcomes were evaluated: (1) 30-day ED return prediction accuracy and (2) model interpretability using a novel LLM-enhanced framework integrating SHAP (SHapley Additive exPlanations) values with clinical knowledge. Results: For chief complaint classification, LLaMA 3 (8B) with 10-shot learning outperformed traditional models (accuracy: 0.882, F1-score: 0.86). In SDoH classification, LLM-based models achieved 0.95 accuracy and 0.96 F1-score, with Alcohol, Tobacco, and Substance Abuse performing best (F1: 0.96-0.89), while Exercise and Home Environment showed lower performance (F1: 0.70-0.67). The LLM-based interpretability framework achieved 99% accuracy in translating model predictions into clinically relevant explanations. LLM-extracted features improved XGBoost AUC from 0.74 to 0.76 and AUC-PR from 0.58 to 0.61. Conclusions and Relevance: Integrating LLMs with machine learning models yielded modest but consistent accuracy gains while significantly enhancing interpretability through automated, clinically relevant explanations. This approach provides a framework for translating predictive analytics into actionable clinical insights.
Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.