Daily Papers

Transformer-based speech language models (SLMs) have significantly improved neural speech recognition and understanding. While existing research has examined how well SLMs encode shallow acoustic and phonetic features, the extent to which SLMs encode nuanced syntactic and conceptual features remains unclear. By drawing parallels with linguistic competence assessments for large language models, this study is the first to systematically evaluate the presence of contextual syntactic and semantic features across SLMs for self-supervised learning (S3M), automatic speech recognition (ASR), speech compression (codec), and as the encoder for auditory large language models (AudioLLMs). Through minimal pair designs and diagnostic feature analysis across 71 tasks spanning diverse linguistic levels, our layer-wise and time-resolved analysis uncovers that 1) all speech encode grammatical features more robustly than conceptual ones.

While recent multimodal large language models (MLLMs) have advanced automated ECG interpretation, they still face two key limitations: (1) insufficient multimodal synergy between time series signals and visual ECG representations, and (2) limited explainability in linking diagnoses to granular waveform evidence. We introduce GEM, the first MLLM unifying ECG time series, 12-lead ECG images and text for grounded and clinician-aligned ECG interpretation. GEM enables feature-grounded analysis, evidence-driven reasoning, and a clinician-like diagnostic process through three core innovations: a dual-encoder framework extracting complementary time series and image features, cross-modal alignment for effective multimodal understanding, and knowledge-guided instruction generation for generating high-granularity grounding data (ECG-Grounding) linking diagnoses to measurable parameters (e.g., QRS/PR Intervals). Additionally, we propose the Grounded ECG Understanding task, a clinically motivated benchmark designed to comprehensively assess the MLLM's capability in grounded ECG understanding. Experimental results on both existing and our proposed benchmarks show GEM significantly improves predictive performance (CSN 7.4% uparrow), explainability (22.7% uparrow), and grounding (24.8% uparrow), making it more suitable for real-world clinical applications. GitHub repository: https://github.com/lanxiang1017/GEM.git

By computing the rank correlation between attention weights and feature-additive explanation methods, previous analyses either invalidate or support the role of attention-based explanations as a faithful and plausible measure of salience. To investigate whether this approach is appropriate, we compare LIME, Integrated Gradients, DeepLIFT, Grad-SHAP, Deep-SHAP, and attention-based explanations, applied to two neural architectures trained on single- and pair-sequence language tasks. In most cases, we find that none of our chosen methods agree. Based on our empirical observations and theoretical objections, we conclude that rank correlation does not measure the quality of feature-additive methods. Practitioners should instead use the numerous and rigorous diagnostic methods proposed by the community.

Several studies have shown that speech and language features, automatically extracted from clinical interviews or spontaneous discourse, have diagnostic value for mental disorders such as schizophrenia and bipolar disorder. They typically make use of a large feature set to train a classifier for distinguishing between two groups of interest, i.e. a clinical and control group. However, a purely data-driven approach runs the risk of overfitting to a particular data set, especially when sample sizes are limited. Here, we first down-select the set of language features to a small subset that is related to a well-validated test of functional ability, the Social Skills Performance Assessment (SSPA). This helps establish the concurrent validity of the selected features. We use only these features to train a simple classifier to distinguish between groups of interest. Linear regression reveals that a subset of language features can effectively model the SSPA, with a correlation coefficient of 0.75. Furthermore, the same feature set can be used to build a strong binary classifier to distinguish between healthy controls and a clinical group (AUC = 0.96) and also between patients within the clinical group with schizophrenia and bipolar I disorder (AUC = 0.83).

Red blood cells (RBCs) are essential to human health, and their precise morphological analysis is important for diagnosing hematological disorders. Despite the promise of foundation models in medical diagnostics, comprehensive AI solutions for RBC analysis remain scarce. We present RedDino, a self-supervised foundation model designed for RBC image analysis. RedDino uses an RBC-specific adaptation of the DINOv2 self-supervised learning framework and is trained on a curated dataset of 1.25 million RBC images from diverse acquisition modalities and sources. Extensive evaluations show that RedDino outperforms existing state-of-the-art models on RBC shape classification. Through assessments including linear probing and nearest neighbor classification, we confirm its strong feature representations and generalization ability. Our main contributions are: (1) a foundation model tailored for RBC analysis, (2) ablation studies exploring DINOv2 configurations for RBC modeling, and (3) a detailed evaluation of generalization performance. RedDino addresses key challenges in computational hematology by capturing nuanced morphological features, advancing the development of reliable diagnostic tools. The source code and pretrained models for RedDino are available at https://github.com/Snarci/RedDino, and the pretrained models can be downloaded from our Hugging Face collection at https://huggingface.co/collections/Snarcy/reddino-689a13e29241d2e5690202fc

As deep learning models gain attraction in medical data, ensuring transparent and trustworthy decision-making is essential. In skin cancer diagnosis, while advancements in lesion detection and classification have improved accuracy, the black-box nature of these methods poses challenges in understanding their decision processes, leading to trust issues among physicians. This study leverages the CLIP (Contrastive Language-Image Pretraining) model, trained on different skin lesion datasets, to capture meaningful relationships between visual features and diagnostic criteria terms. To further enhance transparency, we propose a method called MedGrad E-CLIP, which builds on gradient-based E-CLIP by incorporating a weighted entropy mechanism designed for complex medical imaging like skin lesions. This approach highlights critical image regions linked to specific diagnostic descriptions. The developed integrated pipeline not only classifies skin lesions by matching corresponding descriptions but also adds an essential layer of explainability developed especially for medical data. By visually explaining how different features in an image relates to diagnostic criteria, this approach demonstrates the potential of advanced vision-language models in medical image analysis, ultimately improving transparency, robustness, and trust in AI-driven diagnostic systems.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Automated interpretation of electrocardiograms (ECG) has garnered significant attention with the advancements in machine learning methodologies. Despite the growing interest, most current studies focus solely on classification or regression tasks, which overlook a crucial aspect of clinical cardio-disease diagnosis: the diagnostic report generated by experienced human clinicians. In this paper, we introduce a novel approach to ECG interpretation, leveraging recent breakthroughs in Large Language Models (LLMs) and Vision-Transformer (ViT) models. Rather than treating ECG diagnosis as a classification or regression task, we propose an alternative method of automatically identifying the most similar clinical cases based on the input ECG data. Also, since interpreting ECG as images is more affordable and accessible, we process ECG as encoded images and adopt a vision-language learning paradigm to jointly learn vision-language alignment between encoded ECG images and ECG diagnosis reports. Encoding ECG into images can result in an efficient ECG retrieval system, which will be highly practical and useful in clinical applications. More importantly, our findings could serve as a crucial resource for providing diagnostic services in underdeveloped regions.

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.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

Medical imaging analysis plays a critical role in the diagnosis and treatment of various medical conditions. This paper focuses on chest X-ray images and their corresponding radiological reports. It presents a new model that learns a joint X-ray image & report representation. The model is based on a novel alignment scheme between the visual data and the text, which takes into account both local and global information. Furthermore, the model integrates domain-specific information of two types -- lateral images and the consistent visual structure of chest images. Our representation is shown to benefit three types of retrieval tasks: text-image retrieval, class-based retrieval, and phrase-grounding.

Objective: To transform heterogeneous clinical data from electronic health records into clinically meaningful constructed features using data driven method that rely, in part, on temporal relations among data. Materials and Methods: The clinically meaningful representations of medical concepts and patients are the key for health analytic applications. Most of existing approaches directly construct features mapped to raw data (e.g., ICD or CPT codes), or utilize some ontology mapping such as SNOMED codes. However, none of the existing approaches leverage EHR data directly for learning such concept representation. We propose a new way to represent heterogeneous medical concepts (e.g., diagnoses, medications and procedures) based on co-occurrence patterns in longitudinal electronic health records. The intuition behind the method is to map medical concepts that are co-occuring closely in time to similar concept vectors so that their distance will be small. We also derive a simple method to construct patient vectors from the related medical concept vectors. Results: For qualitative evaluation, we study similar medical concepts across diagnosis, medication and procedure. In quantitative evaluation, our proposed representation significantly improves the predictive modeling performance for onset of heart failure (HF), where classification methods (e.g. logistic regression, neural network, support vector machine and K-nearest neighbors) achieve up to 23% improvement in area under the ROC curve (AUC) using this proposed representation. Conclusion: We proposed an effective method for patient and medical concept representation learning. The resulting representation can map relevant concepts together and also improves predictive modeling performance.

Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

It is widely accepted that information derived from analyzing speech (the acoustic signal) and language production (words and sentences) serves as a useful window into the health of an individual's cognitive ability. In fact, most neuropsychological testing batteries have a component related to speech and language where clinicians elicit speech from patients for subjective evaluation across a broad set of dimensions. With advances in speech signal processing and natural language processing, there has been recent interest in developing tools to detect more subtle changes in cognitive-linguistic function. This work relies on extracting a set of features from recorded and transcribed speech for objective assessments of speech and language, early diagnosis of neurological disease, and tracking of disease after diagnosis. With an emphasis on cognitive and thought disorders, in this paper we provide a review of existing speech and language features used in this domain, discuss their clinical application, and highlight their advantages and disadvantages. Broadly speaking, the review is split into two categories: language features based on natural language processing and speech features based on speech signal processing. Within each category, we consider features that aim to measure complementary dimensions of cognitive-linguistics, including language diversity, syntactic complexity, semantic coherence, and timing. We conclude the review with a proposal of new research directions to further advance the field.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Future short or long-term space missions require a new generation of monitoring and diagnostic systems due to communication impasses as well as limitations in specialized crew and equipment. Machine learning supported diagnostic systems present a viable solution for medical and technical applications. We discuss challenges and applicability of such systems in light of upcoming missions and outline an example use case for a next-generation medical diagnostic system for future space operations. Additionally, we present approach recommendations and constraints for the successful generation and use of machine learning models aboard a spacecraft.

Automatic medical report generation (MRG) is of great research value as it has the potential to relieve radiologists from the heavy burden of report writing. Despite recent advancements, accurate MRG remains challenging due to the need for precise clinical understanding and the identification of clinical findings. Moreover, the imbalanced distribution of diseases makes the challenge even more pronounced, as rare diseases are underrepresented in training data, making their diagnostic performance unreliable. To address these challenges, we propose diagnosis-driven prompts for medical report generation (PromptMRG), a novel framework that aims to improve the diagnostic accuracy of MRG with the guidance of diagnosis-aware prompts. Specifically, PromptMRG is based on encoder-decoder architecture with an extra disease classification branch. When generating reports, the diagnostic results from the classification branch are converted into token prompts to explicitly guide the generation process. To further improve the diagnostic accuracy, we design cross-modal feature enhancement, which retrieves similar reports from the database to assist the diagnosis of a query image by leveraging the knowledge from a pre-trained CLIP. Moreover, the disease imbalanced issue is addressed by applying an adaptive logit-adjusted loss to the classification branch based on the individual learning status of each disease, which overcomes the barrier of text decoder's inability to manipulate disease distributions. Experiments on two MRG benchmarks show the effectiveness of the proposed method, where it obtains state-of-the-art clinical efficacy performance on both datasets.

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

Recently, Computer-Aided Diagnosis (CAD) systems have emerged as indispensable tools in clinical diagnostic workflows, significantly alleviating the burden on radiologists. Nevertheless, despite their integration into clinical settings, CAD systems encounter limitations. Specifically, while CAD systems can achieve high performance in the detection of lung nodules, they face challenges in accurately predicting multiple cancer types. This limitation can be attributed to the scarcity of publicly available datasets annotated with expert-level cancer type information. This research aims to bridge this gap by providing publicly accessible datasets and reliable tools for medical diagnosis, facilitating a finer categorization of different types of lung diseases so as to offer precise treatment recommendations. To achieve this objective, we curated a diverse dataset of lung Computed Tomography (CT) images, comprising 330 annotated nodules (nodules are labeled as bounding boxes) from 95 distinct patients. The quality of the dataset was evaluated using a variety of classical classification and detection models, and these promising results demonstrate that the dataset has a feasible application and further facilitate intelligent auxiliary diagnosis.

The rapid increase of computed tomography (CT) scans and their time-consuming manual analysis have created an urgent need for robust automated analysis techniques in clinical settings. These aim to assist radiologists and help them managing their growing workload. Existing methods typically generate entire reports directly from 3D CT images, without explicitly focusing on observed abnormalities. This unguided approach often results in repetitive content or incomplete reports, failing to prioritize anomaly-specific descriptions. We propose a new anomaly-guided report generation model, which first predicts abnormalities and then generates targeted descriptions for each. Evaluation on a public dataset demonstrates significant improvements in report quality and clinical relevance. We extend our work by conducting an ablation study to demonstrate its effectiveness.

Automated diagnosis prediction from medical images is a valuable resource to support clinical decision-making. However, such systems usually need to be trained on large amounts of annotated data, which often is scarce in the medical domain. Zero-shot methods address this challenge by allowing a flexible adaption to new settings with different clinical findings without relying on labeled data. Further, to integrate automated diagnosis in the clinical workflow, methods should be transparent and explainable, increasing medical professionals' trust and facilitating correctness verification. In this work, we introduce Xplainer, a novel framework for explainable zero-shot diagnosis in the clinical setting. Xplainer adapts the classification-by-description approach of contrastive vision-language models to the multi-label medical diagnosis task. Specifically, instead of directly predicting a diagnosis, we prompt the model to classify the existence of descriptive observations, which a radiologist would look for on an X-Ray scan, and use the descriptor probabilities to estimate the likelihood of a diagnosis. Our model is explainable by design, as the final diagnosis prediction is directly based on the prediction of the underlying descriptors. We evaluate Xplainer on two chest X-ray datasets, CheXpert and ChestX-ray14, and demonstrate its effectiveness in improving the performance and explainability of zero-shot diagnosis. Our results suggest that Xplainer provides a more detailed understanding of the decision-making process and can be a valuable tool for clinical diagnosis.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

Heart disease, also known as cardiovascular disease, is a prevalent and critical medical condition characterized by the impairment of the heart and blood vessels, leading to various complications such as coronary artery disease, heart failure, and myocardial infarction. The timely and accurate detection of heart disease is of paramount importance in clinical practice. Early identification of individuals at risk enables proactive interventions, preventive measures, and personalized treatment strategies to mitigate the progression of the disease and reduce adverse outcomes. In recent years, the field of heart disease detection has witnessed notable advancements due to the integration of sophisticated technologies and computational approaches. These include machine learning algorithms, data mining techniques, and predictive modeling frameworks that leverage vast amounts of clinical and physiological data to improve diagnostic accuracy and risk stratification. In this work, we propose to detect heart disease from ECG images using cutting-edge technologies, namely vision transformer models. These models are Google-Vit, Microsoft-Beit, and Swin-Tiny. To the best of our knowledge, this is the initial endeavor concentrating on the detection of heart diseases through image-based ECG data by employing cuttingedge technologies namely, transformer models. To demonstrate the contribution of the proposed framework, the performance of vision transformer models are compared with state-of-the-art studies. Experiment results show that the proposed framework exhibits remarkable classification results.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

Accurate diagnosis of Parkinson disease, especially in its early stages, can be a challenging task. The application of machine learning techniques helps improve the diagnostic accuracy of Parkinson disease detection but only few studies have presented work towards the prediction of disease progression. In this research work, Long Short Term Memory LSTM was trained using the diagnostic features on Parkinson patients speech signals, to predict the disease progression while a Multilayer Perceptron MLP was trained on the same diagnostic features to detect the disease. Diagnostic features selected using two well-known feature selection methods named Relief-F and Sequential Forward Selection and applied on LSTM and MLP have shown to accurately predict the disease progression as stage 2 and 3 and its existence respectively.

Diabetic retinopathy (DR) is a growing health problem worldwide and is a leading cause of visual impairment and blindness, especially among working people aged 20-65. Its incidence is increasing along with the number of diabetes cases, and it is more common in developed countries than in developing countries. Recent research in the field of diabetic retinopathy diagnosis is using advanced technologies, such as analysis of images obtained by ophthalmoscopy. Automatic methods for analyzing eye images based on neural networks, deep learning and image analysis algorithms can improve the efficiency of diagnosis. This paper describes an automatic DR diagnosis method that includes processing and analysis of ophthalmoscopic images of the eye. It uses morphological algorithms to identify the optic disc and lesions characteristic of DR, such as microaneurysms, hemorrhages and exudates. Automated DR diagnosis has the potential to improve the efficiency of early detection of this disease and contribute to reducing the number of cases of diabetes-related visual impairment. The final step was to create an application with a graphical user interface that allowed retinal images taken at cooperating ophthalmology offices to be uploaded to the server. These images were then analyzed using a developed algorithm to make a diagnosis.

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

Depression poses significant challenges to patients and healthcare organizations, necessitating efficient assessment methods. Existing paradigms typically focus on a patient-doctor way that overlooks multi-role interactions, such as family involvement in the evaluation and caregiving process. Moreover, current automatic depression detection (ADD) methods usually model depression detection as a classification or regression task, lacking interpretability for the decision-making process. To address these issues, we developed InterMind, a doctor-patient-family interactive depression assessment system empowered by large language models (LLMs). Our system enables patients and families to contribute descriptions, generates assistive diagnostic reports for doctors, and provides actionable insights, improving diagnostic precision and efficiency. To enhance LLMs' performance in psychological counseling and diagnostic interpretability, we integrate retrieval-augmented generation (RAG) and chain-of-thoughts (CoT) techniques for data augmentation, which mitigates the hallucination issue of LLMs in specific scenarios after instruction fine-tuning. Quantitative experiments and professional assessments by clinicians validate the effectiveness of our system.

Histology review is often used as the `gold standard' for disease diagnosis. Computer aided diagnosis tools can potentially help improve current pathology workflows by reducing examination time and interobserver variability. Previous work in cancer grading has focused mainly on classifying pre-defined regions of interest (ROIs), or relied on large amounts of fine-grained labels. In this paper, we propose a two-stage attention-based multiple instance learning model for slide-level cancer grading and weakly-supervised ROI detection and demonstrate its use in prostate cancer. Compared with existing Gleason classification models, our model goes a step further by utilizing visualized saliency maps to select informative tiles for fine-grained grade classification. The model was primarily developed on a large-scale whole slide dataset consisting of 3,521 prostate biopsy slides with only slide-level labels from 718 patients. The model achieved state-of-the-art performance for prostate cancer grading with an accuracy of 85.11\% for classifying benign, low-grade (Gleason grade 3+3 or 3+4), and high-grade (Gleason grade 4+3 or higher) slides on an independent test set.

Clinical machine learning research and AI driven clinical decision support models rely on clinically accurate labels. Manually extracting these labels with the help of clinical specialists is often time-consuming and expensive. This study tests the feasibility of automatic span- and document-level diagnosis extraction from unstructured Dutch echocardiogram reports. We included 115,692 unstructured echocardiogram reports from the UMCU a large university hospital in the Netherlands. A randomly selected subset was manually annotated for the occurrence and severity of eleven commonly described cardiac characteristics. We developed and tested several automatic labelling techniques at both span and document levels, using weighted and macro F1-score, precision, and recall for performance evaluation. We compared the performance of span labelling against document labelling methods, which included both direct document classifiers and indirect document classifiers that rely on span classification results. The SpanCategorizer and MedRoBERTa.nl models outperformed all other span and document classifiers, respectively. The weighted F1-score varied between characteristics, ranging from 0.60 to 0.93 in SpanCategorizer and 0.96 to 0.98 in MedRoBERTa.nl. Direct document classification was superior to indirect document classification using span classifiers. SetFit achieved competitive document classification performance using only 10\% of the training data. Utilizing a reduced label set yielded near-perfect document classification results. We recommend using our published SpanCategorizer and MedRoBERTa.nl models for span- and document-level diagnosis extraction from Dutch echocardiography reports. For settings with limited training data, SetFit may be a promising alternative for document classification.

WHO has declared that more than 2.2 billion people worldwide are suffering from visual disorders, such as media haze, glaucoma, and drusen. At least 1 billion of these cases could have been either prevented or successfully treated, yet they remain unaddressed due to poverty, a lack of specialists, inaccurate ocular fundus diagnoses by ophthalmologists, or the presence of a rare disease. To address this, the research has developed the Hybrid Trio-Network Model Algorithm for accurately diagnosing 12 distinct common and rare eye diseases. This algorithm utilized the RFMiD dataset of 3,200 fundus images and the Binary Relevance Method to detect diseases separately, ensuring expandability and avoiding incorrect correlations. Each detector, incorporating finely tuned hyperparameters to optimize performance, consisted of three feature components: A classical transfer learning CNN model, a two-stage CNN model, and a Siamese Network. The diagnosis was made using features extracted through this Trio-Model with Ensembled Machine Learning algorithms. The proposed model achieved an average accuracy of 97% and an AUC score of 0.96. Compared to past benchmark studies, an increase of over 10% in the F1-score was observed for most diseases. Furthermore, using the Siamese Network, the model successfully made predictions in diseases like optic disc pallor, which past studies failed to predict due to low confidence. This diagnostic tool presents a stable, adaptive, cost-effective, efficient, accessible, and fast solution for globalizing early detection of both common and rare diseases.

Medical image classification is a critical problem for healthcare, with the potential to alleviate the workload of doctors and facilitate diagnoses of patients. However, two challenges arise when deploying deep learning models to real-world healthcare applications. First, neural models tend to learn spurious correlations instead of desired features, which could fall short when generalizing to new domains (e.g., patients with different ages). Second, these black-box models lack interpretability. When making diagnostic predictions, it is important to understand why a model makes a decision for trustworthy and safety considerations. In this paper, to address these two limitations, we propose a new paradigm to build robust and interpretable medical image classifiers with natural language concepts. Specifically, we first query clinical concepts from GPT-4, then transform latent image features into explicit concepts with a vision-language model. We systematically evaluate our method on eight medical image classification datasets to verify its effectiveness. On challenging datasets with strong confounding factors, our method can mitigate spurious correlations thus substantially outperform standard visual encoders and other baselines. Finally, we show how classification with a small number of concepts brings a level of interpretability for understanding model decisions through case studies in real medical data.

Differential Diagnosis (DDx) is a fundamental yet complex aspect of clinical decision-making, in which physicians iteratively refine a ranked list of possible diseases based on symptoms, antecedents, and medical knowledge. While recent advances in large language models (LLMs) have shown promise in supporting DDx, existing approaches face key limitations, including single-dataset evaluations, isolated optimization of components, unrealistic assumptions about complete patient profiles, and single-attempt diagnosis. We introduce a Modular Explainable DDx Agent (MEDDxAgent) framework designed for interactive DDx, where diagnostic reasoning evolves through iterative learning, rather than assuming a complete patient profile is accessible. MEDDxAgent integrates three modular components: (1) an orchestrator (DDxDriver), (2) a history taking simulator, and (3) two specialized agents for knowledge retrieval and diagnosis strategy. To ensure robust evaluation, we introduce a comprehensive DDx benchmark covering respiratory, skin, and rare diseases. We analyze single-turn diagnostic approaches and demonstrate the importance of iterative refinement when patient profiles are not available at the outset. Our broad evaluation demonstrates that MEDDxAgent achieves over 10% accuracy improvements in interactive DDx across both large and small LLMs, while offering critical explainability into its diagnostic reasoning process.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.

We present a foundation model-derived method to identify highly informative tokens and events in electronic health records. Our approach considers incoming data in the entire context of a patient's hospitalization and so can flag anomalous events that rule-based approaches would consider within a normal range. We demonstrate that the events our model flags are significant for predicting downstream patient outcomes and that a fraction of events identified as carrying little information can safely be dropped. Additionally, we show how informativeness can help interpret the predictions of prognostic models trained on foundation model-derived representations.

Survey data can contain a high number of features while having a comparatively low quantity of examples. Machine learning models that attempt to predict outcomes from survey data under these conditions can overfit and result in poor generalizability. One remedy to this issue is feature selection, which attempts to select an optimal subset of features to learn upon. A relatively unexplored source of information in the feature selection process is the usage of textual names of features, which may be semantically indicative of which features are relevant to a target outcome. The relationships between feature names and target names can be evaluated using language models (LMs) to produce semantic textual similarity (STS) scores, which can then be used to select features. We examine the performance using STS to select features directly and in the minimal-redundancy-maximal-relevance (mRMR) algorithm. The performance of STS as a feature selection metric is evaluated against preliminary survey data collected as a part of a clinical study on persistent post-surgical pain (PPSP). The results suggest that features selected with STS can result in higher performance models compared to traditional feature selection algorithms.

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labelled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labelling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labelled data was available. Our findings indicate a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better on transfer and learning from a larger and diverse dataset.

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-mini, o1, and DeepSeek-R1, achieve only 45.82%, 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 AIs 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.

Generalist vision language models (VLMs) have made significant strides in computer vision, but they fall short in specialized fields like healthcare, where expert knowledge is essential. In traditional computer vision tasks, creative or approximate answers may be acceptable, but in healthcare, precision is paramount.Current large multimodal models like Gemini and GPT-4o are insufficient for medical tasks due to their reliance on memorized internet knowledge rather than the nuanced expertise required in healthcare. VLMs are usually trained in three stages: vision pre-training, vision-language pre-training, and instruction fine-tuning (IFT). IFT has been typically applied using a mixture of generic and healthcare data. In contrast, we propose that for medical VLMs, a fourth stage of specialized IFT is necessary, which focuses on medical data and includes information from domain expert models. Domain expert models developed for medical use are crucial because they are specifically trained for certain clinical tasks, e.g. to detect tumors and classify abnormalities through segmentation and classification, which learn fine-grained features of medical data-features that are often too intricate for a VLM to capture effectively especially in radiology. This paper introduces a new framework, VILA-M3, for medical VLMs that utilizes domain knowledge via expert models. Through our experiments, we show an improved state-of-the-art (SOTA) performance with an average improvement of ~9% over the prior SOTA model Med-Gemini and ~6% over models trained on the specific tasks. Our approach emphasizes the importance of domain expertise in creating precise, reliable VLMs for medical applications.

Medical Visual Language Models have shown great potential in various healthcare applications, including medical image captioning and diagnostic assistance. However, most existing models rely on text-based instructions, limiting their usability in real-world clinical environments especially in scenarios such as surgery, text-based interaction is often impractical for physicians. In addition, current medical image analysis models typically lack comprehensive reasoning behind their predictions, which reduces their reliability for clinical decision-making. Given that medical diagnosis errors can have life-changing consequences, there is a critical need for interpretable and rational medical assistance. To address these challenges, we introduce an end-to-end speech-driven medical VLM, SilVar-Med, a multimodal medical image assistant that integrates speech interaction with VLMs, pioneering the task of voice-based communication for medical image analysis. In addition, we focus on the interpretation of the reasoning behind each prediction of medical abnormalities with a proposed reasoning dataset. Through extensive experiments, we demonstrate a proof-of-concept study for reasoning-driven medical image interpretation with end-to-end speech interaction. We believe this work will advance the field of medical AI by fostering more transparent, interactive, and clinically viable diagnostic support systems. Our code and dataset are publicly available at SiVar-Med.

Most papers caution against using predictive models for disease stratification based on unselected radiomic features, as these features are affected by contouring variability. Instead, they advocate for the use of the Intraclass Correlation Coefficient (ICC) as a measure of stability for feature selection. However, the direct effect of segmentation variability on the predictive models is rarely studied. This study investigates the impact of segmentation variability on feature stability and predictive performance in radiomics-based prediction of Triple-Negative Breast Cancer (TNBC) subtype using Magnetic Resonance Imaging. A total of 244 images from the Duke dataset were used, with segmentation variability introduced through modifications of manual segmentations. For each mask, explainable radiomic features were selected using the Shapley Additive exPlanations method and used to train logistic regression models. Feature stability across segmentations was assessed via ICC, Pearson's correlation, and reliability scores quantifying the relationship between feature stability and segmentation variability. Results indicate that segmentation accuracy does not significantly impact predictive performance. While incorporating peritumoral information may reduce feature reproducibility, it does not diminish feature predictive capability. Moreover, feature selection in predictive models is not inherently tied to feature stability with respect to segmentation, suggesting that an overreliance on ICC or reliability scores for feature selection might exclude valuable predictive features.

Medical diagnostic applications require models that can process multimodal medical inputs (images, patient histories, lab results) and generate diverse outputs including both textual reports and visual content (annotations, segmentation masks, and images). Despite this need, existing medical AI systems disrupt this unified process: medical image understanding models interpret images but cannot generate visual outputs, while medical image generation models synthesize images but cannot provide textual explanations. This leads to gaps in data representation, feature integration, and task-level multimodal capabilities. To this end, we propose a multi-level framework that draws inspiration from diagnostic workflows through the Observation-Knowledge-Analysis (OKA) paradigm. Specifically, at the observation level, we construct UniMed-5M, a dataset comprising over 5.6M samples that reformat diverse unimodal data into multimodal pairs for foundational observation. At the knowledge level, we propose Progressive Curriculum Learning that systematically introduces medical multimodal knowledge. At the analysis level, we introduce UniMedVL, the first medical unified multimodal model for the simultaneous analysis of image understanding and generation tasks within a single architecture. UniMedVL achieves superior performance on five medical image understanding benchmarks, while matching specialized models in generation quality across eight medical imaging modalities. Crucially, our unified architecture enables bidirectional knowledge sharing: generation tasks enhance visual understanding features, demonstrating that integrating traditionally separate capabilities within a single medical framework unlocks improvements across diverse medical vision-language tasks. Code is available at https://github.com/uni-medical/UniMedVL.

Pathology, the microscopic examination of diseased tissue, is critical for diagnosing various medical conditions, particularly cancers. Traditional methods are labor-intensive and prone to human error. Digital pathology, which converts glass slides into high-resolution digital images for analysis by computer algorithms, revolutionizes the field by enhancing diagnostic accuracy, consistency, and efficiency through automated image analysis and large-scale data processing. Foundational transformer pretraining is crucial for developing robust, generalizable models as it enables learning from vast amounts of unannotated data. This paper introduces the Hibou family of foundational vision transformers for pathology, leveraging the DINOv2 framework to pretrain two model variants, Hibou-B and Hibou-L, on a proprietary dataset of over 1 million whole slide images (WSIs) representing diverse tissue types and staining techniques. Our pretrained models demonstrate superior performance on both patch-level and slide-level benchmarks, surpassing existing state-of-the-art methods. Notably, Hibou-L achieves the highest average accuracy across multiple benchmark datasets. To support further research and application in the field, we have open-sourced the Hibou-B model, which can be accessed at https://github.com/HistAI/hibou

Representation learning has been a critical topic in machine learning. In Click-through Rate Prediction, most features are represented as embedding vectors and learned simultaneously with other parameters in the model. With the development of CTR models, feature representation learning has become a trending topic and has been extensively studied by both industrial and academic researchers in recent years. This survey aims at summarizing the feature representation learning in a broader picture and pave the way for future research. To achieve such a goal, we first present a taxonomy of current research methods on feature representation learning following two main issues: (i) which feature to represent and (ii) how to represent these features. Then we give a detailed description of each method regarding these two issues. Finally, the review concludes with a discussion on the future directions of this field.

Machine learning classification problems are widespread in bioinformatics, but the technical knowledge required to perform model training, optimization, and inference can prevent researchers from utilizing this technology. This article presents an automated tool for machine learning classification problems to simplify the process of training models and producing results while providing informative visualizations and insights into the data. This tool supports both binary and multiclass classification problems, and it provides access to a variety of models and methods. Synthetic data can be generated within the interface to fill missing values, balance class labels, or generate entirely new datasets. It also provides support for feature evaluation and generates explainability scores to indicate which features influence the output the most. We present CLASSify, an open-source tool for simplifying the user experience of solving classification problems without the need for knowledge of machine learning.

Feature selection is the problem of selecting a subset of features for a machine learning model that maximizes model quality subject to a budget constraint. For neural networks, prior methods, including those based on ell_1 regularization, attention, and other techniques, typically select the entire feature subset in one evaluation round, ignoring the residual value of features during selection, i.e., the marginal contribution of a feature given that other features have already been selected. We propose a feature selection algorithm called Sequential Attention that achieves state-of-the-art empirical results for neural networks. This algorithm is based on an efficient one-pass implementation of greedy forward selection and uses attention weights at each step as a proxy for feature importance. We give theoretical insights into our algorithm for linear regression by showing that an adaptation to this setting is equivalent to the classical Orthogonal Matching Pursuit (OMP) algorithm, and thus inherits all of its provable guarantees. Our theoretical and empirical analyses offer new explanations towards the effectiveness of attention and its connections to overparameterization, which may be of independent interest.

Recently computer-aided diagnosis has demonstrated promising performance, effectively alleviating the workload of clinicians. However, the inherent sample imbalance among different diseases leads algorithms biased to the majority categories, leading to poor performance for rare categories. Existing works formulated this challenge as a long-tailed problem and attempted to tackle it by decoupling the feature representation and classification. Yet, due to the imbalanced distribution and limited samples from tail classes, these works are prone to biased representation learning and insufficient classifier calibration. To tackle these problems, we propose a new Long-tailed Medical Diagnosis (LMD) framework for balanced medical image classification on long-tailed datasets. In the initial stage, we develop a Relation-aware Representation Learning (RRL) scheme to boost the representation ability by encouraging the encoder to capture intrinsic semantic features through different data augmentations. In the subsequent stage, we propose an Iterative Classifier Calibration (ICC) scheme to calibrate the classifier iteratively. This is achieved by generating a large number of balanced virtual features and fine-tuning the encoder using an Expectation-Maximization manner. The proposed ICC compensates for minority categories to facilitate unbiased classifier optimization while maintaining the diagnostic knowledge in majority classes. Comprehensive experiments on three public long-tailed medical datasets demonstrate that our LMD framework significantly surpasses state-of-the-art approaches. The source code can be accessed at https://github.com/peterlipan/LMD.

Choosing which properties of the data to use as input to multivariate decision algorithms -- a.k.a. feature selection -- is an important step in solving any problem with machine learning. While there is a clear trend towards training sophisticated deep networks on large numbers of relatively unprocessed inputs (so-called automated feature engineering), for many tasks in physics, sets of theoretically well-motivated and well-understood features already exist. Working with such features can bring many benefits, including greater interpretability, reduced training and run time, and enhanced stability and robustness. We develop a new feature selection method based on Distance Correlation (DisCo), and demonstrate its effectiveness on the tasks of boosted top- and W-tagging. Using our method to select features from a set of over 7,000 energy flow polynomials, we show that we can match the performance of much deeper architectures, by using only ten features and two orders-of-magnitude fewer model parameters.

Visual Language Models (VLMs) have demonstrated impressive capabilities in visual grounding tasks. However, their effectiveness in the medical domain, particularly for abnormality detection and localization within medical images, remains underexplored. A major challenge is the complex and abstract nature of medical terminology, which makes it difficult to directly associate pathological anomaly terms with their corresponding visual features. In this work, we introduce a novel approach to enhance VLM performance in medical abnormality detection and localization by leveraging decomposed medical knowledge. Instead of directly prompting models to recognize specific abnormalities, we focus on breaking down medical concepts into fundamental attributes and common visual patterns. This strategy promotes a stronger alignment between textual descriptions and visual features, improving both the recognition and localization of abnormalities in medical images.We evaluate our method on the 0.23B Florence-2 base model and demonstrate that it achieves comparable performance in abnormality grounding to significantly larger 7B LLaVA-based medical VLMs, despite being trained on only 1.5% of the data used for such models. Experimental results also demonstrate the effectiveness of our approach in both known and previously unseen abnormalities, suggesting its strong generalization capabilities.

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Recent advancements in Large Language Models (LLMs) have drawn increasing attention since the learned embeddings pretrained on large-scale datasets have shown powerful ability in various downstream applications. However, whether the learned knowledge by LLMs can be transferred to clinical cardiology remains unknown. In this work, we aim to bridge this gap by transferring the knowledge of LLMs to clinical Electrocardiography (ECG). We propose an approach for cardiovascular disease diagnosis and automatic ECG diagnosis report generation. We also introduce an additional loss function by Optimal Transport (OT) to align the distribution between ECG and language embedding. The learned embeddings are evaluated on two downstream tasks: (1) automatic ECG diagnosis report generation, and (2) zero-shot cardiovascular disease detection. Our approach is able to generate high-quality cardiac diagnosis reports and also achieves competitive zero-shot classification performance even compared with supervised baselines, which proves the feasibility of transferring knowledge from LLMs to the cardiac domain.

Recently, efficient fine-tuning of large-scale pre-trained models has attracted increasing research interests, where linear probing (LP) as a fundamental module is involved in exploiting the final representations for task-dependent classification. However, most of the existing methods focus on how to effectively introduce a few of learnable parameters, and little work pays attention to the commonly used LP module. In this paper, we propose a novel Moment Probing (MP) method to further explore the potential of LP. Distinguished from LP which builds a linear classification head based on the mean of final features (e.g., word tokens for ViT) or classification tokens, our MP performs a linear classifier on feature distribution, which provides the stronger representation ability by exploiting richer statistical information inherent in features. Specifically, we represent feature distribution by its characteristic function, which is efficiently approximated by using first- and second-order moments of features. Furthermore, we propose a multi-head convolutional cross-covariance (MHC^3) to compute second-order moments in an efficient and effective manner. By considering that MP could affect feature learning, we introduce a partially shared module to learn two recalibrating parameters (PSRP) for backbones based on MP, namely MP_{+}. Extensive experiments on ten benchmarks using various models show that our MP significantly outperforms LP and is competitive with counterparts at less training cost, while our MP_{+} achieves state-of-the-art performance.

Chromosome classification is critical for karyotyping in abnormality diagnosis. To expedite the diagnosis, we present a novel method named Varifocal-Net for simultaneous classification of chromosome's type and polarity using deep convolutional networks. The approach consists of one global-scale network (G-Net) and one local-scale network (L-Net). It follows three stages. The first stage is to learn both global and local features. We extract global features and detect finer local regions via the G-Net. By proposing a varifocal mechanism, we zoom into local parts and extract local features via the L-Net. Residual learning and multi-task learning strategies are utilized to promote high-level feature extraction. The detection of discriminative local parts is fulfilled by a localization subnet of the G-Net, whose training process involves both supervised and weakly-supervised learning. The second stage is to build two multi-layer perceptron classifiers that exploit features of both two scales to boost classification performance. The third stage is to introduce a dispatch strategy of assigning each chromosome to a type within each patient case, by utilizing the domain knowledge of karyotyping. Evaluation results from 1909 karyotyping cases showed that the proposed Varifocal-Net achieved the highest accuracy per patient case (%) 99.2 for both type and polarity tasks. It outperformed state-of-the-art methods, demonstrating the effectiveness of our varifocal mechanism, multi-scale feature ensemble, and dispatch strategy. The proposed method has been applied to assist practical karyotype diagnosis.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Pre-trained transformers are often fine-tuned to aid clinical decision-making using limited clinical notes. Model interpretability is crucial, especially in high-stakes domains like medicine, to establish trust and ensure safety, which requires human engagement. We introduce SUFO, a systematic framework that enhances interpretability of fine-tuned transformer feature spaces. SUFO utilizes a range of analytic and visualization techniques, including Supervised probing, Unsupervised similarity analysis, Feature dynamics, and Outlier analysis to address key questions about model trust and interpretability. We conduct a case study investigating the impact of pre-training data where we focus on real-world pathology classification tasks, and validate our findings on MedNLI. We evaluate five 110M-sized pre-trained transformer models, categorized into general-domain (BERT, TNLR), mixed-domain (BioBERT, Clinical BioBERT), and domain-specific (PubMedBERT) groups. Our SUFO analyses reveal that: (1) while PubMedBERT, the domain-specific model, contains valuable information for fine-tuning, it can overfit to minority classes when class imbalances exist. In contrast, mixed-domain models exhibit greater resistance to overfitting, suggesting potential improvements in domain-specific model robustness; (2) in-domain pre-training accelerates feature disambiguation during fine-tuning; and (3) feature spaces undergo significant sparsification during this process, enabling clinicians to identify common outlier modes among fine-tuned models as demonstrated in this paper. These findings showcase the utility of SUFO in enhancing trust and safety when using transformers in medicine, and we believe SUFO can aid practitioners in evaluating fine-tuned language models for other applications in medicine and in more critical domains.

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

Interpretability can improve the safety, transparency and trust of AI models, which is especially important in healthcare applications where decisions often carry significant consequences. Mechanistic interpretability, particularly through the use of sparse autoencoders (SAEs), offers a promising approach for uncovering human-interpretable features within large transformer-based models. In this study, we apply Matryoshka-SAE to the radiology-specialised multimodal large language model, MAIRA-2, to interpret its internal representations. Using large-scale automated interpretability of the SAE features, we identify a range of clinically relevant concepts - including medical devices (e.g., line and tube placements, pacemaker presence), pathologies such as pleural effusion and cardiomegaly, longitudinal changes and textual features. We further examine the influence of these features on model behaviour through steering, demonstrating directional control over generations with mixed success. Our results reveal practical and methodological challenges, yet they offer initial insights into the internal concepts learned by MAIRA-2 - marking a step toward deeper mechanistic understanding and interpretability of a radiology-adapted multimodal large language model, and paving the way for improved model transparency. We release the trained SAEs and interpretations: https://huggingface.co/microsoft/maira-2-sae.

In the field of medical sciences, reliable detection and classification of brain tumors from images remains a formidable challenge due to the rarity of tumors within the population of patients. Therefore, the ability to detect tumors in anomaly scenarios is paramount for ensuring timely interventions and improved patient outcomes. This study addresses the issue by leveraging deep learning (DL) techniques to detect and classify brain tumors in challenging situations. The curated data set from the National Brain Mapping Lab (NBML) comprises 81 patients, including 30 Tumor cases and 51 Normal cases. The detection and classification pipelines are separated into two consecutive tasks. The detection phase involved comprehensive data analysis and pre-processing to modify the number of image samples and the number of patients of each class to anomaly distribution (9 Normal per 1 Tumor) to comply with real world scenarios. Next, in addition to common evaluation metrics for the testing, we employed a novel performance evaluation method called Patient to Patient (PTP), focusing on the realistic evaluation of the model. In the detection phase, we fine-tuned a YOLOv8n detection model to detect the tumor region. Subsequent testing and evaluation yielded competitive performance both in Common Evaluation Metrics and PTP metrics. Furthermore, using the Data Efficient Image Transformer (DeiT) module, we distilled a Vision Transformer (ViT) model from a fine-tuned ResNet152 as a teacher in the classification phase. This approach demonstrates promising strides in reliable tumor detection and classification, offering potential advancements in tumor diagnosis for real-world medical imaging scenarios.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Developing an interpretable system for generating reports in chest X-ray (CXR) analysis is becoming increasingly crucial in Computer-aided Diagnosis (CAD) systems, enabling radiologists to comprehend the decisions made by these systems. Despite the growth of diverse datasets and methods focusing on report generation, there remains a notable gap in how closely these models' generated reports align with the interpretations of real radiologists. In this study, we tackle this challenge by initially introducing Fine-Grained CXR (FG-CXR) dataset, which provides fine-grained paired information between the captions generated by radiologists and the corresponding gaze attention heatmaps for each anatomy. Unlike existing datasets that include a raw sequence of gaze alongside a report, with significant misalignment between gaze location and report content, our FG-CXR dataset offers a more grained alignment between gaze attention and diagnosis transcript. Furthermore, our analysis reveals that simply applying black-box image captioning methods to generate reports cannot adequately explain which information in CXR is utilized and how long needs to attend to accurately generate reports. Consequently, we propose a novel explainable radiologist's attention generator network (Gen-XAI) that mimics the diagnosis process of radiologists, explicitly constraining its output to closely align with both radiologist's gaze attention and transcript. Finally, we perform extensive experiments to illustrate the effectiveness of our method. Our datasets and checkpoint is available at https://github.com/UARK-AICV/FG-CXR.

Multimodal large language models (MLLMs) demonstrate significant potential in the field of medical diagnosis. However, they face critical challenges in specialized domains such as ophthalmology, particularly the fragmentation of annotation granularity and inconsistencies in clinical reasoning logic, which hinder precise cross-modal understanding. This paper introduces FundusExpert, an ophthalmology-specific MLLM with integrated positioning-diagnosis reasoning capabilities, along with FundusGen, a dataset constructed through the intelligent Fundus-Engine system. Fundus-Engine automates localization and leverages MLLM-based semantic expansion to integrate global disease classification, local object detection, and fine-grained feature analysis within a single fundus image. Additionally, by constructing a clinically aligned cognitive chain, it guides the model to generate interpretable reasoning paths. FundusExpert, fine-tuned with instruction data from FundusGen, achieves the best performance in ophthalmic question-answering tasks, surpassing the average accuracy of the 40B MedRegA by 26.6%. It also excels in zero-shot report generation tasks, achieving a clinical consistency of 77.0%, significantly outperforming GPT-4o's 47.6%. Furthermore, we reveal a scaling law between data quality and model capability (L propto N^{0.068}), demonstrating that the cognitive alignment annotations in FundusGen enhance data utilization efficiency. By integrating region-level localization with diagnostic reasoning chains, our work develops a scalable, clinically-aligned MLLM and explores a pathway toward bridging the visual-language gap in specific MLLMs. Our project can be found at https://github.com/MeteorElf/FundusExpert.

Accurate and interpretable multi-disease diagnosis remains a critical challenge in medical research, particularly when leveraging heterogeneous multimodal medical data. Current approaches often rely on single-modal data, limiting their ability to comprehensively understand complex diseases. To address this, we propose MedTVT-R1, a novel Multimodal Large Language Model (MLLM) framework designed to integrate clinical multimodal data for reasoning and diagnosing multiple diseases. We construct MedTVT-QA, a curated instruction dataset that provides question-answer pairs for physiological-level interpretations and disease-level diagnoses with a Chain of Evidence approach. MedTVT-R1 incorporates a modality perception layer to capture inter-modal dependencies and adaptively weight modality contributions. Additionally, we employ Group Relative Policy Optimization (GRPO)-based Reinforcement Fine-Tuning with a Jaccard Reward function to enhance diagnostic reasoning. Experimental results demonstrate MedTVT-R1's superiority in multimodal feature utilization and multi-disease diagnosis, offering significant potential for clinical applications such as diagnostic report generation and comorbidity reasoning. The dataset and code are available at https://github.com/keke-nice/MedTVT-R1.

The rapid and accurate detection of COVID-19 cases is critical for timely treatment and preventing the spread of the disease. In this study, a two-stage feature extraction framework using eight state-of-the-art pre-trained deep Convolutional Neural Networks (CNNs) and an autoencoder is proposed to determine the health conditions of patients (COVID-19, Normal, Viral Pneumonia) based on chest X-rays. The X-ray scans are divided into four equally sized sections and analyzed by deep pre-trained CNNs. Subsequently, an autoencoder with three hidden layers is trained to extract reproductive features from the concatenated ouput of CNNs. To evaluate the performance of the proposed framework, three different classifiers, which are single-layer perceptron (SLP), multi-layer perceptron (MLP), and support vector machine (SVM) are used. Furthermore, the deep CNN architectures are used to create benchmark models and trained on the same dataset for comparision. The proposed framework outperforms other frameworks wih pre-trained feature extractors in binary classification and shows competitive results in three-class classification. The proposed methodology is task-independent and suitable for addressing various problems. The results show that the discriminative features are a subset of the reproductive features, suggesting that extracting task-independent features is superior to the extraction only task-based features. The flexibility and task-independence of the reproductive features make the conceptive information approach more favorable. The proposed methodology is novel and shows promising results for analyzing medical image data.

Recently, intelligent analysis of lung nodules with the assistant of computer aided detection (CAD) techniques can improve the accuracy rate of lung cancer diagnosis. However, existing CAD systems and pulmonary datasets mainly focus on Computed Tomography (CT) images from one single period, while ignoring the cross spatio-temporal features associated with the progression of nodules contained in imaging data from various captured periods of lung cancer. If the evolution patterns of nodules across various periods in the patients' CT sequences can be explored, it will play a crucial role in guiding the precise screening identification of lung cancer. Therefore, a cross spatio-temporal lung nodule dataset with pathological information for nodule identification and diagnosis is constructed, which contains 328 CT sequences and 362 annotated nodules from 109 patients. This comprehensive database is intended to drive research in the field of CAD towards more practical and robust methods, and also contribute to the further exploration of precision medicine related field. To ensure patient confidentiality, we have removed sensitive information from the dataset.

Assessing scientific claims requires identifying, extracting, and reasoning with multimodal data expressed in information-rich figures in scientific literature. Despite the large body of work in scientific QA, figure captioning, and other multimodal reasoning tasks over chart-based data, there are no readily usable multimodal benchmarks that directly test claim verification abilities. To remedy this gap, we introduce a new benchmark MuSciClaims accompanied by diagnostics tasks. We automatically extract supported claims from scientific articles, which we manually perturb to produce contradicted claims. The perturbations are designed to test for a specific set of claim verification capabilities. We also introduce a suite of diagnostic tasks that help understand model failures. Our results show most vision-language models are poor (~0.3-0.5 F1), with even the best model only achieving 0.72 F1. They are also biased towards judging claims as supported, likely misunderstanding nuanced perturbations within the claims. Our diagnostics show models are bad at localizing correct evidence within figures, struggle with aggregating information across modalities, and often fail to understand basic components of the figure.

Medical imaging is widely used in clinical practice for diagnosis and treatment. Report-writing can be error-prone for unexperienced physicians, and time- consuming and tedious for experienced physicians. To address these issues, we study the automatic generation of medical imaging reports. This task presents several challenges. First, a complete report contains multiple heterogeneous forms of information, including findings and tags. Second, abnormal regions in medical images are difficult to identify. Third, the re- ports are typically long, containing multiple sentences. To cope with these challenges, we (1) build a multi-task learning framework which jointly performs the pre- diction of tags and the generation of para- graphs, (2) propose a co-attention mechanism to localize regions containing abnormalities and generate narrations for them, (3) develop a hierarchical LSTM model to generate long paragraphs. We demonstrate the effectiveness of the proposed methods on two publicly available datasets.

Despite extensive standardization, diagnostic interviews for mental health disorders encompass substantial subjective judgment. Previous studies have demonstrated that EEG-based neural measures can function as reliable objective correlates of depression, or even predictors of depression and its course. However, their clinical utility has not been fully realized because of 1) the lack of automated ways to deal with the inherent noise associated with EEG data at scale, and 2) the lack of knowledge of which aspects of the EEG signal may be markers of a clinical disorder. Here we adapt an unsupervised pipeline from the recent deep representation learning literature to address these problems by 1) learning a disentangled representation using beta-VAE to denoise the signal, and 2) extracting interpretable features associated with a sparse set of clinical labels using a Symbol-Concept Association Network (SCAN). We demonstrate that our method is able to outperform the canonical hand-engineered baseline classification method on a number of factors, including participant age and depression diagnosis. Furthermore, our method recovers a representation that can be used to automatically extract denoised Event Related Potentials (ERPs) from novel, single EEG trajectories, and supports fast supervised re-mapping to various clinical labels, allowing clinicians to re-use a single EEG representation regardless of updates to the standardized diagnostic system. Finally, single factors of the learned disentangled representations often correspond to meaningful markers of clinical factors, as automatically detected by SCAN, allowing for human interpretability and post-hoc expert analysis of the recommendations made by the model.

This paper presents our team's participation in the MEDIQA-ClinicalNLP2024 shared task B. We present a novel approach to diagnosing clinical dermatology cases by integrating large multimodal models, specifically leveraging the capabilities of GPT-4V under a retriever and a re-ranker framework. Our investigation reveals that GPT-4V, when used as a retrieval agent, can accurately retrieve the correct skin condition 85% of the time using dermatological images and brief patient histories. Additionally, we empirically show that Naive Chain-of-Thought (CoT) works well for retrieval while Medical Guidelines Grounded CoT is required for accurate dermatological diagnosis. Further, we introduce a Multi-Agent Conversation (MAC) framework and show its superior performance and potential over the best CoT strategy. The experiments suggest that using naive CoT for retrieval and multi-agent conversation for critique-based diagnosis, GPT-4V can lead to an early and accurate diagnosis of dermatological conditions. The implications of this work extend to improving diagnostic workflows, supporting dermatological education, and enhancing patient care by providing a scalable, accessible, and accurate diagnostic tool.

Medical imaging plays a pivotal role in modern healthcare, with computed tomography pulmonary angiography (CTPA) being a critical tool for diagnosing pulmonary embolism and other thoracic conditions. However, the complexity of interpreting CTPA scans and generating accurate radiology reports remains a significant challenge. This paper introduces Abn-BLIP (Abnormality-aligned Bootstrapping Language-Image Pretraining), an advanced diagnosis model designed to align abnormal findings to generate the accuracy and comprehensiveness of radiology reports. By leveraging learnable queries and cross-modal attention mechanisms, our model demonstrates superior performance in detecting abnormalities, reducing missed findings, and generating structured reports compared to existing methods. Our experiments show that Abn-BLIP outperforms state-of-the-art medical vision-language models and 3D report generation methods in both accuracy and clinical relevance. These results highlight the potential of integrating multimodal learning strategies for improving radiology reporting. The source code is available at https://github.com/zzs95/abn-blip.

Chest X-rays play a pivotal role in diagnosing respiratory diseases such as pneumonia, tuberculosis, and COVID-19, which are prevalent and present unique diagnostic challenges due to overlapping visual features and variability in image quality. Severe class imbalance and the complexity of medical images hinder automated analysis. This study leverages deep learning techniques, including transfer learning on pre-trained models (AlexNet, ResNet, and InceptionNet), to enhance disease detection and classification. By fine-tuning these models and incorporating focal loss to address class imbalance, significant performance improvements were achieved. Grad-CAM visualizations further enhance model interpretability, providing insights into clinically relevant regions influencing predictions. The InceptionV3 model, for instance, achieved a 28% improvement in AUC and a 15% increase in F1-Score. These findings highlight the potential of deep learning to improve diagnostic workflows and support clinical decision-making.

Deep learning (DL) has proven highly effective for ultrasound-based computer-aided diagnosis (CAD) of breast cancers. In an automaticCAD system, lesion detection is critical for the following diagnosis. However, existing DL-based methods generally require voluminous manually-annotated region of interest (ROI) labels and class labels to train both the lesion detection and diagnosis models. In clinical practice, the ROI labels, i.e. ground truths, may not always be optimal for the classification task due to individual experience of sonologists, resulting in the issue of coarse annotation that limits the diagnosis performance of a CAD model. To address this issue, a novel Two-Stage Detection and Diagnosis Network (TSDDNet) is proposed based on weakly supervised learning to enhance diagnostic accuracy of the ultrasound-based CAD for breast cancers. In particular, all the ROI-level labels are considered as coarse labels in the first training stage, and then a candidate selection mechanism is designed to identify optimallesion areas for both the fully and partially annotated samples. It refines the current ROI-level labels in the fully annotated images and the detected ROIs in the partially annotated samples with a weakly supervised manner under the guidance of class labels. In the second training stage, a self-distillation strategy further is further proposed to integrate the detection network and classification network into a unified framework as the final CAD model for joint optimization, which then further improves the diagnosis performance. The proposed TSDDNet is evaluated on a B-mode ultrasound dataset, and the experimental results show that it achieves the best performance on both lesion detection and diagnosis tasks, suggesting promising application potential.

Expert interpretation of anatomical images of the human brain is the central part of neuro-radiology. Several machine learning-based techniques have been proposed to assist in the analysis process. However, the ML models typically need to be trained to perform a specific task, e.g., brain tumour segmentation or classification. Not only do the corresponding training data require laborious manual annotations, but a wide variety of abnormalities can be present in a human brain MRI - even more than one simultaneously, which renders representation of all possible anomalies very challenging. Hence, a possible solution is an unsupervised anomaly detection (UAD) system that can learn a data distribution from an unlabelled dataset of healthy subjects and then be applied to detect out of distribution samples. Such a technique can then be used to detect anomalies - lesions or abnormalities, for example, brain tumours, without explicitly training the model for that specific pathology. Several Variational Autoencoder (VAE) based techniques have been proposed in the past for this task. Even though they perform very well on controlled artificially simulated anomalies, many of them perform poorly while detecting anomalies in clinical data. This research proposes a compact version of the "context-encoding" VAE (ceVAE) model, combined with pre and post-processing steps, creating a UAD pipeline (StRegA), which is more robust on clinical data, and shows its applicability in detecting anomalies such as tumours in brain MRIs. The proposed pipeline achieved a Dice score of 0.642pm0.101 while detecting tumours in T2w images of the BraTS dataset and 0.859pm0.112 while detecting artificially induced anomalies, while the best performing baseline achieved 0.522pm0.135 and 0.783pm0.111, respectively.

Explaining deep learning models is essential for clinical integration of medical image analysis systems. A good explanation highlights if a model depends on spurious features that undermines generalization and harms a subset of patients or, conversely, may present novel biological insights. Although techniques like GradCAM can identify influential features, they are measurement tools that do not themselves form an explanation. We propose a human-machine-VLM interaction system tailored to explaining classifiers in computational pathology, including multi-instance learning for whole-slide images. Our proof of concept comprises (1) an AI-integrated slide viewer to run sliding-window experiments to test claims of an explanation, and (2) quantification of an explanation's predictiveness using general-purpose vision-language models. The results demonstrate that this allows us to qualitatively test claims of explanations and can quantifiably distinguish competing explanations. This offers a practical path from explainable AI to explained AI in digital pathology and beyond. Code and prompts are available at https://github.com/nki-ai/x2x.

In this paper we introduce Feature Gradients, a gradient-based search algorithm for feature selection. Our approach extends a recent result on the estimation of learnability in the sublinear data regime by showing that the calculation can be performed iteratively (i.e., in mini-batches) and in linear time and space with respect to both the number of features D and the sample size N . This, along with a discrete-to-continuous relaxation of the search domain, allows for an efficient, gradient-based search algorithm among feature subsets for very large datasets. Crucially, our algorithm is capable of finding higher-order correlations between features and targets for both the N > D and N < D regimes, as opposed to approaches that do not consider such interactions and/or only consider one regime. We provide experimental demonstration of the algorithm in small and large sample-and feature-size settings.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Chest X-rays are widely used to diagnose thoracic diseases, but the lack of detailed information about these abnormalities makes it challenging to develop accurate automated diagnosis systems, which is crucial for early detection and effective treatment. To address this challenge, we employed deep learning techniques to identify patterns in chest X-rays that correspond to different diseases. We conducted experiments on the "ChestX-ray14" dataset using various pre-trained CNNs, transformers, hybrid(CNN+Transformer) models and classical models. The best individual model was the CoAtNet, which achieved an area under the receiver operating characteristic curve (AUROC) of 84.2%. By combining the predictions of all trained models using a weighted average ensemble where the weight of each model was determined using differential evolution, we further improved the AUROC to 85.4%, outperforming other state-of-the-art methods in this field. Our findings demonstrate the potential of deep learning techniques, particularly ensemble deep learning, for improving the accuracy of automatic diagnosis of thoracic diseases from chest X-rays. Code available at:https://github.com/syednabilashraf/SynthEnsemble

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Mental distress like depression and anxiety contribute to the largest proportion of the global burden of diseases. Automated diagnosis systems of such disorders, empowered by recent innovations in Artificial Intelligence, can pave the way to reduce the sufferings of the affected individuals. Development of such systems requires information-rich and balanced corpora. In this work, we introduce a novel mental distress analysis audio dataset DEPAC, labeled based on established thresholds on depression and anxiety standard screening tools. This large dataset comprises multiple speech tasks per individual, as well as relevant demographic information. Alongside, we present a feature set consisting of hand-curated acoustic and linguistic features, which were found effective in identifying signs of mental illnesses in human speech. Finally, we justify the quality and effectiveness of our proposed audio corpus and feature set in predicting depression severity by comparing the performance of baseline machine learning models built on this dataset with baseline models trained on other well-known depression corpora.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

Attention Deficit Hyperactive Disorder (ADHD) is a common behavioral problem affecting children. In this work, we investigate the automatic classification of ADHD subjects using the resting state Functional Magnetic Resonance Imaging (fMRI) sequences of the brain. We show that the brain can be modeled as a functional network, and certain properties of the networks differ in ADHD subjects from control subjects. We compute the pairwise correlation of brain voxels' activity over the time frame of the experimental protocol which helps to model the function of a brain as a network. Different network features are computed for each of the voxels constructing the network. The concatenation of the network features of all the voxels in a brain serves as the feature vector. Feature vectors from a set of subjects are then used to train a PCA-LDA (principal component analysis-linear discriminant analysis) based classifier. We hypothesized that ADHD-related differences lie in some specific regions of the brain and using features only from those regions is sufficient to discriminate ADHD and control subjects. We propose a method to create a brain mask that includes the useful regions only and demonstrate that using the feature from the masked regions improves classification accuracy on the test data set. We train our classifier with 776 subjects and test on 171 subjects provided by The Neuro Bureau for the ADHD-200 challenge. We demonstrate the utility of graph-motif features, specifically the maps that represent the frequency of participation of voxels in network cycles of length 3. The best classification performance (69.59%) is achieved using 3-cycle map features with masking. Our proposed approach holds promise in being able to diagnose and understand the disorder.

Predictive process monitoring is a process mining task aimed at forecasting information about a running process trace, such as the most correct next activity to be executed. In medical domains, predictive process monitoring can provide valuable decision support in atypical and nontrivial situations. Decision support and quality assessment in medicine cannot ignore domain knowledge, in order to be grounded on all the available information (which is not limited to data) and to be really acceptable by end users. In this paper, we propose a predictive process monitoring approach relying on the use of a {\em transformer}, a deep learning architecture based on the attention mechanism. A major contribution of our work lies in the incorporation of ontological domain-specific knowledge, carried out through a graph positional encoding technique. The paper presents and discusses the encouraging experimental result we are collecting in the domain of stroke management.

Curating a large scale medical imaging dataset for machine learning applications is both time consuming and expensive. Balancing the workload between model development, data collection and annotations is difficult for machine learning practitioners, especially under time constraints. Causal analysis is often used in medicine and economics to gain insights about the effects of actions and policies. In this paper we explore the effect of dataset interventions on the output of image classification models. Through a causal approach we investigate the effects of the quantity and type of data we need to incorporate in a dataset to achieve better performance for specific subtasks. The main goal of this paper is to highlight the potential of causal analysis as a tool for resource optimization for developing medical imaging ML applications. We explore this concept with a synthetic dataset and an exemplary use-case for Diabetic Retinopathy image analysis.

In disentangling the heterogeneity observed in psychopathology, personality of the patients is considered crucial. While it has been demonstrated that personality traits are reflected in the language used by a patient, we hypothesize that this enables automatic inference of the personality type directly from speech utterances, potentially more accurately than through a traditional questionnaire-based approach explicitly designed for personality classification. To validate this hypothesis, we adopt natural language processing (NLP) and standard machine learning tools for classification. We test this on a dataset of recorded clinical diagnostic interviews (CDI) on a sample of 79 patients diagnosed with major depressive disorder (MDD) -- a condition for which differentiated treatment based on personality styles has been advocated -- and classified into anaclitic and introjective personality styles. We start by analyzing the interviews to see which linguistic features are associated with each style, in order to gain a better understanding of the styles. Then, we develop automatic classifiers based on (a) standardized questionnaire responses; (b) basic text features, i.e., TF-IDF scores of words and word sequences; (c) more advanced text features, using LIWC (linguistic inquiry and word count) and context-aware features using BERT (bidirectional encoder representations from transformers); (d) audio features. We find that automated classification with language-derived features (i.e., based on LIWC) significantly outperforms questionnaire-based classification models. Furthermore, the best performance is achieved by combining LIWC with the questionnaire features. This suggests that more work should be put into developing linguistically based automated techniques for characterizing personality, however questionnaires still to some extent complement such methods.

In the field of chest X-ray (CXR) diagnosis, existing works often focus solely on determining where a radiologist looks, typically through tasks such as detection, segmentation, or classification. However, these approaches are often designed as black-box models, lacking interpretability. In this paper, we introduce Interpretable Artificial Intelligence (I-AI) a novel and unified controllable interpretable pipeline for decoding the intense focus of radiologists in CXR diagnosis. Our I-AI addresses three key questions: where a radiologist looks, how long they focus on specific areas, and what findings they diagnose. By capturing the intensity of the radiologist's gaze, we provide a unified solution that offers insights into the cognitive process underlying radiological interpretation. Unlike current methods that rely on black-box machine learning models, which can be prone to extracting erroneous information from the entire input image during the diagnosis process, we tackle this issue by effectively masking out irrelevant information. Our proposed I-AI leverages a vision-language model, allowing for precise control over the interpretation process while ensuring the exclusion of irrelevant features. To train our I-AI model, we utilize an eye gaze dataset to extract anatomical gaze information and generate ground truth heatmaps. Through extensive experimentation, we demonstrate the efficacy of our method. We showcase that the attention heatmaps, designed to mimic radiologists' focus, encode sufficient and relevant information, enabling accurate classification tasks using only a portion of CXR. The code, checkpoints, and data are at https://github.com/UARK-AICV/IAI

Lung cancer stands as the preeminent cause of cancer-related mortality globally. Prompt and precise diagnosis, coupled with effective treatment, is imperative to reduce the fatality rates associated with this formidable disease. This study introduces a cutting-edge deep learning framework for the classification of lung cancer from CT scan imagery. The research encompasses a suite of image pre-processing strategies, notably Canny edge detection, and wavelet transformations, which precede the extraction of salient features and subsequent classification via a Multi-Layer Perceptron (MLP). The optimization process is further refined using the Dragonfly Algorithm (DA). The methodology put forth has attained an impressive training and testing accuracy of 99.82\%, underscoring its efficacy and reliability in the accurate diagnosis of lung cancer.

Anomaly detection (AD) aims at detecting abnormal samples that deviate from the expected normal patterns. Generally, it can be trained merely on normal data, without a requirement for abnormal samples, and thereby plays an important role in rare disease recognition and health screening in the medical domain. Despite the emergence of numerous methods for medical AD, the lack of a fair and comprehensive evaluation causes ambiguous conclusions and hinders the development of this field. To address this problem, this paper builds a benchmark with unified comparison. Seven medical datasets with five image modalities, including chest X-rays, brain MRIs, retinal fundus images, dermatoscopic images, and histopathology images, are curated for extensive evaluation. Thirty typical AD methods, including reconstruction and self-supervised learning-based methods, are involved in comparison of image-level anomaly classification and pixel-level anomaly segmentation. Furthermore, for the first time, we systematically investigate the effect of key components in existing methods, revealing unresolved challenges and potential future directions. The datasets and code are available at https://github.com/caiyu6666/MedIAnomaly.

Objective: To improve prediction of Chronic Kidney Disease (CKD) progression to End Stage Renal Disease (ESRD) using machine learning (ML) and deep learning (DL) models applied to an integrated clinical and claims dataset of varying observation windows, supported by explainable AI (XAI) to enhance interpretability and reduce bias. Materials and Methods: We utilized data about 10,326 CKD patients, combining their clinical and claims information from 2009 to 2018. Following data preprocessing, cohort identification, and feature engineering, we evaluated multiple statistical, ML and DL models using data extracted from five distinct observation windows. Feature importance and Shapley value analysis were employed to understand key predictors. Models were tested for robustness, clinical relevance, misclassification errors and bias issues. Results: Integrated data models outperformed those using single data sources, with the Long Short-Term Memory (LSTM) model achieving the highest AUC (0.93) and F1 score (0.65). A 24-month observation window was identified as optimal for balancing early detection and prediction accuracy. The 2021 eGFR equation improved prediction accuracy and reduced racial bias, notably for African American patients. Discussion: Improved ESRD prediction accuracy, results interpretability and bias mitigation strategies presented in this study have the potential to significantly enhance CKD and ESRD management, support targeted early interventions and reduce healthcare disparities. Conclusion: This study presents a robust framework for predicting ESRD outcomes in CKD patients, improving clinical decision-making and patient care through multi-sourced, integrated data and AI/ML methods. Future research will expand data integration and explore the application of this framework to other chronic diseases.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR.

The Feature Selection Library (FSLib) introduces a comprehensive suite of feature selection (FS) algorithms for MATLAB, aimed at improving machine learning and data mining tasks. FSLib encompasses filter, embedded, and wrapper methods to cater to diverse FS requirements. Filter methods focus on the inherent characteristics of features, embedded methods incorporate FS within model training, and wrapper methods assess features through model performance metrics. By enabling effective feature selection, FSLib addresses the curse of dimensionality, reduces computational load, and enhances model generalizability. The elimination of redundant features through FSLib streamlines the training process, improving efficiency and scalability. This facilitates faster model development and boosts key performance indicators such as accuracy, precision, and recall by focusing on vital features. Moreover, FSLib contributes to data interpretability by revealing important features, aiding in pattern recognition and understanding. Overall, FSLib provides a versatile framework that not only simplifies feature selection but also significantly benefits the machine learning and data mining ecosystem by offering a wide range of algorithms, reducing dimensionality, accelerating model training, improving model outcomes, and enhancing data insights.

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

Coronary artery disease (CAD) remains the leading cause of death globally and invasive coronary angiography (ICA) is considered the gold standard of anatomical imaging evaluation when CAD is suspected. However, risk evaluation based on ICA has several limitations, such as visual assessment of stenosis severity, which has significant interobserver variability. This motivates to development of a lesion classification system that can support specialists in their clinical procedures. Although deep learning classification methods are well-developed in other areas of medical imaging, ICA image classification is still at an early stage. One of the most important reasons is the lack of available and high-quality open-access datasets. In this paper, we reported a new annotated ICA images dataset, CADICA, to provide the research community with a comprehensive and rigorous dataset of coronary angiography consisting of a set of acquired patient videos and associated disease-related metadata. This dataset can be used by clinicians to train their skills in angiographic assessment of CAD severity and by computer scientists to create computer-aided diagnostic systems to help in such assessment. In addition, baseline classification methods are proposed and analyzed, validating the functionality of CADICA and giving the scientific community a starting point to improve CAD detection.

Medical imaging plays a crucial role in diagnosis, with radiology reports serving as vital documentation. Automating report generation has emerged as a critical need to alleviate the workload of radiologists. While machine learning has facilitated report generation for 2D medical imaging, extending this to 3D has been unexplored due to computational complexity and data scarcity. We introduce the first method to generate radiology reports for 3D medical imaging, specifically targeting chest CT volumes. Given the absence of comparable methods, we establish a baseline using an advanced 3D vision encoder in medical imaging to demonstrate our method's effectiveness, which leverages a novel auto-regressive causal transformer. Furthermore, recognizing the benefits of leveraging information from previous visits, we augment CT2Rep with a cross-attention-based multi-modal fusion module and hierarchical memory, enabling the incorporation of longitudinal multimodal data. Access our code at https://github.com/ibrahimethemhamamci/CT2Rep

Current vision-language models (VLMs) in medicine are primarily designed for categorical question answering (e.g., "Is this normal or abnormal?") or qualitative descriptive tasks. However, clinical decision-making often relies on quantitative assessments, such as measuring the size of a tumor or the angle of a joint, from which physicians draw their own diagnostic conclusions. This quantitative reasoning capability remains underexplored and poorly supported in existing VLMs. In this work, we introduce MedVision, a large-scale dataset and benchmark specifically designed to evaluate and improve VLMs on quantitative medical image analysis. MedVision spans 22 public datasets covering diverse anatomies and modalities, with 30.8 million image-annotation pairs. We focus on three representative quantitative tasks: (1) detection of anatomical structures and abnormalities, (2) tumor/lesion (T/L) size estimation, and (3) angle/distance (A/D) measurement. Our benchmarks show that current off-the-shelf VLMs perform poorly on these tasks. However, with supervised fine-tuning on MedVision, we significantly enhance their performance across detection, T/L estimation, and A/D measurement, demonstrating reduced error rates and improved precision. This work provides a foundation for developing VLMs with robust quantitative reasoning capabilities in medical imaging. Code and data are available at https://medvision-vlm.github.io.

This paper presents a comparison of six machine learning (ML) algorithms: GRU-SVM (Agarap, 2017), Linear Regression, Multilayer Perceptron (MLP), Nearest Neighbor (NN) search, Softmax Regression, and Support Vector Machine (SVM) on the Wisconsin Diagnostic Breast Cancer (WDBC) dataset (Wolberg, Street, & Mangasarian, 1992) by measuring their classification test accuracy and their sensitivity and specificity values. The said dataset consists of features which were computed from digitized images of FNA tests on a breast mass (Wolberg, Street, & Mangasarian, 1992). For the implementation of the ML algorithms, the dataset was partitioned in the following fashion: 70% for training phase, and 30% for the testing phase. The hyper-parameters used for all the classifiers were manually assigned. Results show that all the presented ML algorithms performed well (all exceeded 90% test accuracy) on the classification task. The MLP algorithm stands out among the implemented algorithms with a test accuracy of ~99.04%.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Sleep is an essential component of human physiology, contributing significantly to overall health and quality of life. Accurate sleep staging and disorder detection are crucial for assessing sleep quality. Studies in the literature have proposed PSG-based approaches and machine-learning methods utilizing single-modality signals. However, existing methods often lack multimodal, multilabel frameworks and address sleep stages and disorders classification separately. In this paper, we propose a 1D-Vision Transformer for simultaneous classification of sleep stages and sleep disorders. Our method exploits the sleep disorders' correlation with specific sleep stage patterns and performs a simultaneous identification of a sleep stage and sleep disorder. The model is trained and tested using multimodal-multilabel sensory data (including photoplethysmogram, respiratory flow, and respiratory effort signals). The proposed method shows an overall accuracy (cohen's Kappa) of 78% (0.66) for five-stage sleep classification and 74% (0.58) for sleep apnea classification. Moreover, we analyzed the encoder attention weights to clarify our models' predictions and investigate the influence different features have on the models' outputs. The result shows that identified patterns, such as respiratory troughs and peaks, make a higher contribution to the final classification process.

Intent is defined for understanding spoken language in existing works. Both textual features and acoustic features involved in medical speech contain intent, which is important for symptomatic diagnosis. In this paper, we propose a medical speech classification model named DRSC that automatically learns to disentangle intent and content representations from textual-acoustic data for classification. The intent representations of the text domain and the Mel-spectrogram domain are extracted via intent encoders, and then the reconstructed text feature and the Mel-spectrogram feature are obtained through two exchanges. After combining the intent from two domains into a joint representation, the integrated intent representation is fed into a decision layer for classification. Experimental results show that our model obtains an average accuracy rate of 95% in detecting 25 different medical symptoms.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

LLMs for clinical decision support often fail under small but clinically meaningful input shifts such as masking a symptom or negating a finding, despite high performance on static benchmarks. These reasoning failures frequently go undetected by standard NLP metrics, which are insensitive to latent representation shifts that drive diagnosis instability. We propose a geometry-aware evaluation framework, LAPD (Latent Agentic Perturbation Diagnostics), which systematically probes the latent robustness of clinical LLMs under structured adversarial edits. Within this framework, we introduce Latent Diagnosis Flip Rate (LDFR), a model-agnostic diagnostic signal that captures representational instability when embeddings cross decision boundaries in PCA-reduced latent space. Clinical notes are generated using a structured prompting pipeline grounded in diagnostic reasoning, then perturbed along four axes: masking, negation, synonym replacement, and numeric variation to simulate common ambiguities and omissions. We compute LDFR across both foundation and clinical LLMs, finding that latent fragility emerges even under minimal surface-level changes. Finally, we validate our findings on 90 real clinical notes from the DiReCT benchmark (MIMIC-IV), confirming the generalizability of LDFR beyond synthetic settings. Our results reveal a persistent gap between surface robustness and semantic stability, underscoring the importance of geometry-aware auditing in safety-critical clinical AI.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Extraction of relevant pathological terms from radiology reports is important for correct image label generation and disease population studies. In this letter, we compare the performance of some known application program interface (APIs) for the task of thoracic abnormality extraction from radiology reports. We explored several medical domain specific annotation tools like Medical Text Indexer(MTI) with Non-MEDLINE and Mesh On Demand(MOD) options and generic Natural Language Understanding (NLU) API provided by the IBM cloud. Our results show that although MTI and MOD are intended for extracting medical terms, their performance is worst compared to generic extraction API like IBM NLU. Finally, we trained a DNN-based Named Entity Recognition (NER) model to extract the key concept words from radiology reports. Our model outperforms the medical specific and generic API performance by a large margin. Our results demonstrate the inadequacy of generic APIs for pathology extraction task and establish the importance of domain specific model training for improved results. We hope that these results motivate the research community to release larger de-identified radiology reports corpus for building high accuracy machine learning models for the important task of pathology extraction.

Chronic Obstructive Pulmonary Disease (COPD), a major chronic respiratory disease with persistent airflow limitation, is a leading global cause of disability and mortality. Respiratory spirogram time series, routinely collected during pulmonary function tests (PFTs), play a critical role in the early detection of repsiratory diseases and in monitoring lung function over time. However, most current AI models for COPD diagnosis are limited to outputting classification results without providing a rationale for their diagnostic process, while current Large Language Models (LLMs) cannot understand spirograms yet, which severely limits their clinical trust and adoption. To tackle this challenge, we leverage a cohort of 234,028 individuals from the UK Biobank (UKB) to propose SpiroLLM, the first multimodal large language model that can understand spirogram. The model extracts morphological features from respiratory curves via a SpiroEncoder and aligns them with PFT numerical values in a unified latent space using a SpiroProjector, ultimately empowering a large language model to generate a comprehensive diagnostic report. Experimental results confirm that SpiroLLM achieved a diagnostic AUROC of 0.8980 (95% CI: 0.8820-0.9132). In a robustness test with missing core data, it maintained a 100% valid response rate, far surpassing the 13.4% of a text-only model and showcasing the superiority of its multimodal design. This work demonstrates the substantial potential of deeply fusing physiological signals with large language models, establishing a new paradigm for the next generation of interpretable and reliable clinical decision support tools.

Generating accurate and clinically meaningful radiology reports from chest X-ray images remains a significant challenge in medical AI. While recent vision-language models achieve strong results in general radiology report generation, they often fail to adequately describe rare but clinically important pathologies like fractures. This work addresses this gap by developing specialized models for fracture pathology detection and description. We train fracture-specific vision-language models with encoders from MAIRA-2 and CheXagent, demonstrating significant improvements over general-purpose models in generating accurate fracture descriptions. Analysis of model outputs by fracture type, location, and age reveals distinct strengths and limitations of current vision-language model architectures. We publicly release our best-performing fracture-reporting model, facilitating future research in accurate reporting of rare pathologies.

Automated diagnostic systems (ADS) have shown significant potential in the early detection of polyps during endoscopic examinations, thereby reducing the incidence of colorectal cancer. However, due to high annotation costs and strict privacy concerns, acquiring high-quality endoscopic images poses a considerable challenge in the development of ADS. Despite recent advancements in generating synthetic images for dataset expansion, existing endoscopic image generation algorithms failed to accurately generate the details of polyp boundary regions and typically required medical priors to specify plausible locations and shapes of polyps, which limited the realism and diversity of the generated images. To address these limitations, we present Polyp-Gen, the first full-automatic diffusion-based endoscopic image generation framework. Specifically, we devise a spatial-aware diffusion training scheme with a lesion-guided loss to enhance the structural context of polyp boundary regions. Moreover, to capture medical priors for the localization of potential polyp areas, we introduce a hierarchical retrieval-based sampling strategy to match similar fine-grained spatial features. In this way, our Polyp-Gen can generate realistic and diverse endoscopic images for building reliable ADS. Extensive experiments demonstrate the state-of-the-art generation quality, and the synthetic images can improve the downstream polyp detection task. Additionally, our Polyp-Gen has shown remarkable zero-shot generalizability on other datasets. The source code is available at https://github.com/CUHK-AIM-Group/Polyp-Gen.

Large Multimodal Models (LMMs) have shown remarkable progress in the field of medical Visual Question Answering (Med-VQA), achieving high accuracy on existing benchmarks. However, their reliability under robust evaluation is questionable. This study reveals that state-of-the-art models, when subjected to simple probing evaluation, perform worse than random guessing on medical diagnosis questions. To address this critical evaluation problem, we introduce the Probing Evaluation for Medical Diagnosis (ProbMed) dataset to rigorously assess LMM performance in medical imaging through probing evaluation and procedural diagnosis. Particularly, probing evaluation features pairing original questions with negation questions with hallucinated attributes, while procedural diagnosis requires reasoning across various diagnostic dimensions for each image, including modality recognition, organ identification, clinical findings, abnormalities, and positional grounding. Our evaluation reveals that top-performing models like GPT-4V and Gemini Pro perform worse than random guessing on specialized diagnostic questions, indicating significant limitations in handling fine-grained medical inquiries. Besides, models like LLaVA-Med struggle even with more general questions, and results from CheXagent demonstrate the transferability of expertise across different modalities of the same organ, showing that specialized domain knowledge is still crucial for improving performance. This study underscores the urgent need for more robust evaluation to ensure the reliability of LMMs in critical fields like medical diagnosis, and current LMMs are still far from applicable to those fields.

Oral cancer is highly common across the globe and is mostly diagnosed during the later stages due to the close visual similarity to benign, precancerous, and malignant lesions in the oral cavity. Implementing computer aided diagnosis systems early on has the potential to greatly improve clinical outcomes. This research intends to use deep learning to build a multiclass classifier for sixteen different oral lesions. To overcome the challenges of limited and imbalanced datasets, the proposed technique combines stratified data splitting and advanced data augmentation and oversampling to perform the classification. The experimental results, which achieved 83.33 percent accuracy, 89.12 percent precision, and 77.31 percent recall, demonstrate the superiority of the suggested model over state of the art methods now in use. The suggested model effectively conveys the effectiveness of oversampling and augmentation strategies in situations where the minority class classification performance is noteworthy. As a first step toward trustworthy computer aided diagnostic systems for the early detection of oral cancer in clinical settings, the suggested framework shows promise.

A ubiquitous feature of data of our era is their extra-large sizes and dimensions. Analyzing such high-dimensional data poses significant challenges, since the feature dimension is often much larger than the sample size. This thesis introduces robust and computationally efficient methods to address several common challenges associated with high-dimensional data. In my first manuscript, I propose a coherent approach to variable screening that accommodates nonlinear associations. I develop a novel variable screening method that transcends traditional linear assumptions by leveraging mutual information, with an intended application in neuroimaging data. This approach allows for accurate identification of important variables by capturing nonlinear as well as linear relationships between the outcome and covariates. Building on this foundation, I develop new optimization methods for sparse estimation using nonconvex penalties in my second manuscript. These methods address notable challenges in current statistical computing practices, facilitating computationally efficient and robust analyses of complex datasets. The proposed method can be applied to a general class of optimization problems. In my third manuscript, I contribute to robust modeling of high-dimensional correlated observations by developing a mixed-effects model based on Tsallis power-law entropy maximization and discussed the theoretical properties of such distribution. This model surpasses the constraints of conventional Gaussian models by accommodating a broader class of distributions with enhanced robustness to outliers. Additionally, I develop a proximal nonlinear conjugate gradient algorithm that accelerates convergence while maintaining numerical stability, along with rigorous statistical properties for the proposed framework.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.