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.
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.
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.
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.
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.
Large Language Models (LLMs) have shown remarkable performance across various tasks, yet significant disparities remain for non-English languages, and especially native African languages. This paper addresses these disparities by creating approximately 1 million human-translated words of new benchmark data in 8 low-resource African languages, covering a population of over 160 million speakers of: Amharic, Bambara, Igbo, Sepedi (Northern Sotho), Shona, Sesotho (Southern Sotho), Setswana, and Tsonga. Our benchmarks are translations of Winogrande and three sections of MMLU: college medicine, clinical knowledge, and virology. Using the translated benchmarks, we report previously unknown performance gaps between state-of-the-art (SOTA) LLMs in English and African languages. Finally, using results from over 400 fine-tuned models, we explore several methods to reduce the LLM performance gap, including high-quality dataset fine-tuning (using an LLM-as-an-Annotator), cross-lingual transfer, and cultural appropriateness adjustments. Key findings include average mono-lingual improvements of 5.6% with fine-tuning (with 5.4% average mono-lingual improvements when using high-quality data over low-quality data), 2.9% average gains from cross-lingual transfer, and a 3.0% out-of-the-box performance boost on culturally appropriate questions. The publicly available benchmarks, translations, and code from this study support further research and development aimed at creating more inclusive and effective language technologies.
The development of larger models for medical image analysis has led to increased performance. However, it also affected our ability to explain and validate model decisions. Models can use non-relevant parts of images, also called spurious correlations or shortcuts, to obtain high performance on benchmark datasets but fail in real-world scenarios. In this work, we challenge the capacity of convolutional neural networks (CNN) to classify chest X-rays and eye fundus images while masking out clinically relevant parts of the image. We show that all models trained on the PadChest dataset, irrespective of the masking strategy, are able to obtain an Area Under the Curve (AUC) above random. Moreover, the models trained on full images obtain good performance on images without the region of interest (ROI), even superior to the one obtained on images only containing the ROI. We also reveal a possible spurious correlation in the Chaksu dataset while the performances are more aligned with the expectation of an unbiased model. We go beyond the performance analysis with the usage of the explainability method SHAP and the analysis of embeddings. We asked a radiology resident to interpret chest X-rays under different masking to complement our findings with clinical knowledge. Our code is available at https://github.com/TheoSourget/MMC_Masking and https://github.com/TheoSourget/MMC_Masking_EyeFundus
In clinical practice, decision-making relies heavily on established protocols, often formalised as rules. Concurrently, Machine Learning (ML) models, trained on clinical data, aspire to integrate into medical decision-making processes. However, despite the growing number of ML applications, their adoption into clinical practice remains limited. Two critical concerns arise, relevant to the notions of consistency and continuity of care: (a) accuracy - the ML model, albeit more accurate, might introduce errors that would not have occurred by applying the protocol; (b) interpretability - ML models operating as black boxes might make predictions based on relationships that contradict established clinical knowledge. In this context, the literature suggests using ML models integrating domain knowledge for improved accuracy and interpretability. However, there is a lack of appropriate metrics for comparing ML models with clinical rules in addressing these challenges. Accordingly, in this article, we first propose metrics to assess the accuracy of ML models with respect to the established protocol. Secondly, we propose an approach to measure the distance of explanations provided by two rule sets, with the goal of comparing the explanation similarity between clinical rule-based systems and rules extracted from ML models. The approach is validated on the Pima Indians Diabetes dataset by training two neural networks - one exclusively on data, and the other integrating a clinical protocol. Our findings demonstrate that the integrated ML model achieves comparable performance to that of a fully data-driven model while exhibiting superior accuracy relative to the clinical protocol, ensuring enhanced continuity of care. Furthermore, we show that our integrated model provides explanations for predictions that align more closely with the clinical protocol compared to the data-driven model.
Liver cancer is a leading cause of mortality worldwide, and accurate Computed Tomography (CT)-based tumor segmentation is essential for diagnosis and treatment. Manual delineation is time-intensive, prone to variability, and highlights the need for reliable automation. While deep learning has shown promise for automated liver segmentation, precise liver tumor segmentation remains challenging due to the heterogeneous nature of tumors, imprecise tumor margins, and limited labeled data. We present SmoothSegNet, a novel deep learning framework that addresses these challenges with the three key designs: (1) A novel knowledge-informed label smoothing technique that distills knowledge from clinical data to generate smooth labels, which are used to regularize model training, reducing the overfitting risk and enhancing model performance; (2) A global and local segmentation framework that breaks down the main task into two simpler sub-tasks, allowing optimized preprocessing and training for each; and (3) Pre- and post-processing pipelines customized to the challenges of each subtask aimed to enhance tumor visibility and refines tumor boundaries. We apply the proposed model on a challenging HCC-TACE-Seg dataset and show that SmoothSegNet outperformed various benchmarks in segmentation performance, particularly at smaller tumors (<10cm). Our ablation studies show that the three design components complementarily contribute to the model improved performance. Code for the proposed method are available at https://github.com/lingchm/medassist-liver-cancer.
With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.
Medication Extraction and Mining play an important role in healthcare NLP research due to its practical applications in hospital settings, such as their mapping into standard clinical knowledge bases (SNOMED-CT, BNF, etc.). In this work, we investigate state-of-the-art LLMs in text mining tasks on medications and their related attributes such as dosage, route, strength, and adverse effects. In addition, we explore different ensemble learning methods (\textsc{Stack-Ensemble} and \textsc{Voting-Ensemble}) to augment the model performances from individual LLMs. Our ensemble learning result demonstrated better performances than individually fine-tuned base models BERT, RoBERTa, RoBERTa-L, BioBERT, BioClinicalBERT, BioMedRoBERTa, ClinicalBERT, and PubMedBERT across general and specific domains. Finally, we build up an entity linking function to map extracted medical terminologies into the SNOMED-CT codes and the British National Formulary (BNF) codes, which are further mapped to the Dictionary of Medicines and Devices (dm+d), and ICD. Our model's toolkit and desktop applications are publicly available (at \url{https://github.com/HECTA-UoM/ensemble-NER}).
Fundus Fluorescein Angiography (FFA) is a critical tool for assessing retinal vascular dynamics and aiding in the diagnosis of eye diseases. However, its invasive nature and less accessibility compared to Color Fundus (CF) images pose significant challenges. Current CF to FFA translation methods are limited to static generation. In this work, we pioneer dynamic FFA video generation from static CF images. We introduce an autoregressive GAN for smooth, memory-saving frame-by-frame FFA synthesis. To enhance the focus on dynamic lesion changes in FFA regions, we design a knowledge mask based on clinical experience. Leveraging this mask, our approach integrates innovative knowledge mask-guided techniques, including knowledge-boosted attention, knowledge-aware discriminators, and mask-enhanced patchNCE loss, aimed at refining generation in critical areas and addressing the pixel misalignment challenge. Our method achieves the best FVD of 1503.21 and PSNR of 11.81 compared to other common video generation approaches. Human assessment by an ophthalmologist confirms its high generation quality. Notably, our knowledge mask surpasses supervised lesion segmentation masks, offering a promising non-invasive alternative to traditional FFA for research and clinical applications. The code is available at https://github.com/Michi-3000/Fundus2Video.
Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.
The need for improved diagnostic methods in ophthalmology is acute, especially in the less developed regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and rare ophthalmic conditions. VisionUnite represents a significant advancement in ophthalmology, with broad implications for diagnostics, medical education, and understanding of disease mechanisms.
The 7-point checklist (7PCL) is widely used in dermoscopy to identify malignant melanoma lesions needing urgent medical attention. It assigns point values to seven attributes: major attributes are worth two points each, and minor ones are worth one point each. A total score of three or higher prompts further evaluation, often including a biopsy. However, a significant limitation of current methods is the uniform weighting of attributes, which leads to imprecision and neglects their interconnections. Previous deep learning studies have treated the prediction of each attribute with the same importance as predicting melanoma, which fails to recognize the clinical significance of the attributes for melanoma. To address these limitations, we introduce a novel diagnostic method that integrates two innovative elements: a Clinical Knowledge-Based Topological Graph (CKTG) and a Gradient Diagnostic Strategy with Data-Driven Weighting Standards (GD-DDW). The CKTG integrates 7PCL attributes with diagnostic information, revealing both internal and external associations. By employing adaptive receptive domains and weighted edges, we establish connections among melanoma's relevant features. Concurrently, GD-DDW emulates dermatologists' diagnostic processes, who first observe the visual characteristics associated with melanoma and then make predictions. Our model uses two imaging modalities for the same lesion, ensuring comprehensive feature acquisition. Our method shows outstanding performance in predicting malignant melanoma and its features, achieving an average AUC value of 85%. This was validated on the EDRA dataset, the largest publicly available dataset for the 7-point checklist algorithm. Specifically, the integrated weighting system can provide clinicians with valuable data-driven benchmarks for their evaluations.
Concept bottleneck models (CBMs), which predict human-interpretable concepts (e.g., nucleus shapes in cell images) before predicting the final output (e.g., cell type), provide insights into the decision-making processes of the model. However, training CBMs solely in a data-driven manner can introduce undesirable biases, which may compromise prediction performance, especially when the trained models are evaluated on out-of-domain images (e.g., those acquired using different devices). To mitigate this challenge, we propose integrating clinical knowledge to refine CBMs, better aligning them with clinicians' decision-making processes. Specifically, we guide the model to prioritize the concepts that clinicians also prioritize. We validate our approach on two datasets of medical images: white blood cell and skin images. Empirical validation demonstrates that incorporating medical guidance enhances the model's classification performance on unseen datasets with varying preparation methods, thereby increasing its real-world applicability.
Multi-modal large language models (MLLMs) have been given free rein to explore exciting medical applications with a primary focus on radiology report generation. Nevertheless, the preliminary success in 2D radiology captioning is incompetent to reflect the real-world diagnostic challenge in the volumetric 3D anatomy. To mitigate three crucial limitation aspects in the existing literature, including (1) data complexity, (2) model capacity, and (3) evaluation metric fidelity, we collected an 18,885 text-scan pairs 3D-BrainCT dataset and applied clinical visual instruction tuning (CVIT) to train BrainGPT models to generate radiology-adherent 3D brain CT reports. Statistically, our BrainGPT scored BLEU-1 = 44.35, BLEU-4 = 20.38, METEOR = 30.13, ROUGE-L = 47.6, and CIDEr-R = 211.77 during internal testing and demonstrated an accuracy of 0.91 in captioning midline shifts on the external validation CQ500 dataset. By further inspecting the captioned report, we reported that the traditional metrics appeared to measure only the surface text similarity and failed to gauge the information density of the diagnostic purpose. To close this gap, we proposed a novel Feature-Oriented Radiology Task Evaluation (FORTE) to estimate the report's clinical relevance (lesion feature and landmarks). Notably, the BrainGPT model scored an average FORTE F1-score of 0.71 (degree=0.661; landmark=0.706; feature=0.693; impression=0.779). To demonstrate that BrainGPT models possess objective readiness to generate human-like radiology reports, we conducted a Turing test that enrolled 11 physician evaluators, and around 74% of the BrainGPT-generated captions were indistinguishable from those written by humans. Our work embodies a holistic framework that showcased the first-hand experience of curating a 3D brain CT dataset, fine-tuning anatomy-sensible language models, and proposing robust radiology evaluation metrics.