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Oct 15

BioFusionNet: Deep Learning-Based Survival Risk Stratification in ER+ Breast Cancer Through Multifeature and Multimodal Data Fusion

Breast cancer is a significant health concern affecting millions of women worldwide. Accurate survival risk stratification plays a crucial role in guiding personalised treatment decisions and improving patient outcomes. Here we present BioFusionNet, a deep learning framework that fuses image-derived features with genetic and clinical data to achieve a holistic patient profile and perform survival risk stratification of ER+ breast cancer patients. We employ multiple self-supervised feature extractors, namely DINO and MoCoV3, pretrained on histopathology patches to capture detailed histopathological image features. We then utilise a variational autoencoder (VAE) to fuse these features, and harness the latent space of the VAE to feed into a self-attention network, generating patient-level features. Next, we develop a co-dual-cross-attention mechanism to combine the histopathological features with genetic data, enabling the model to capture the interplay between them. Additionally, clinical data is incorporated using a feed-forward network (FFN), further enhancing predictive performance and achieving comprehensive multimodal feature integration. Furthermore, we introduce a weighted Cox loss function, specifically designed to handle imbalanced survival data, which is a common challenge in the field. The proposed model achieves a mean concordance index (C-index) of 0.77 and a time-dependent area under the curve (AUC) of 0.84, outperforming state-of-the-art methods. It predicts risk (high versus low) with prognostic significance for overall survival (OS) in univariate analysis (HR=2.99, 95% CI: 1.88--4.78, p<0.005), and maintains independent significance in multivariate analysis incorporating standard clinicopathological variables (HR=2.91, 95% CI: 1.80--4.68, p<0.005). The proposed method not only improves model performance but also addresses a critical gap in handling imbalanced data.

  • 4 authors
·
Feb 16, 2024

Clinically-Inspired Multi-Agent Transformers for Disease Trajectory Forecasting from Multimodal Data

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

  • 4 authors
·
Oct 25, 2022

ISLES 2024: The first longitudinal multimodal multi-center real-world dataset in (sub-)acute stroke

Stroke remains a leading cause of global morbidity and mortality, placing a heavy socioeconomic burden. Over the past decade, advances in endovascular reperfusion therapy and the use of CT and MRI imaging for treatment guidance have significantly improved patient outcomes and are now standard in clinical practice. To develop machine learning algorithms that can extract meaningful and reproducible models of brain function for both clinical and research purposes from stroke images - particularly for lesion identification, brain health quantification, and prognosis - large, diverse, and well-annotated public datasets are essential. While only a few datasets with (sub-)acute stroke data were previously available, several large, high-quality datasets have recently been made publicly accessible. However, these existing datasets include only MRI data. In contrast, our dataset is the first to offer comprehensive longitudinal stroke data, including acute CT imaging with angiography and perfusion, follow-up MRI at 2-9 days, as well as acute and longitudinal clinical data up to a three-month outcome. The dataset includes a training dataset of n = 150 and a test dataset of n = 100 scans. Training data is publicly available, while test data will be used exclusively for model validation. We are making this dataset available as part of the 2024 edition of the Ischemic Stroke Lesion Segmentation (ISLES) challenge (https://www.isles-challenge.org/), which continuously aims to establish benchmark methods for acute and sub-acute ischemic stroke lesion segmentation, aiding in creating open stroke imaging datasets and evaluating cutting-edge image processing algorithms.

  • 18 authors
·
Aug 20, 2024

Building Flexible, Scalable, and Machine Learning-ready Multimodal Oncology Datasets

The advancements in data acquisition, storage, and processing techniques have resulted in the rapid growth of heterogeneous medical data. Integrating radiological scans, histopathology images, and molecular information with clinical data is essential for developing a holistic understanding of the disease and optimizing treatment. The need for integrating data from multiple sources is further pronounced in complex diseases such as cancer for enabling precision medicine and personalized treatments. This work proposes Multimodal Integration of Oncology Data System (MINDS) - a flexible, scalable, and cost-effective metadata framework for efficiently fusing disparate data from public sources such as the Cancer Research Data Commons (CRDC) into an interconnected, patient-centric framework. MINDS offers an interface for exploring relationships across data types and building cohorts for developing large-scale multimodal machine learning models. By harmonizing multimodal data, MINDS aims to potentially empower researchers with greater analytical ability to uncover diagnostic and prognostic insights and enable evidence-based personalized care. MINDS tracks granular end-to-end data provenance, ensuring reproducibility and transparency. The cloud-native architecture of MINDS can handle exponential data growth in a secure, cost-optimized manner while ensuring substantial storage optimization, replication avoidance, and dynamic access capabilities. Auto-scaling, access controls, and other mechanisms guarantee pipelines' scalability and security. MINDS overcomes the limitations of existing biomedical data silos via an interoperable metadata-driven approach that represents a pivotal step toward the future of oncology data integration.

  • 5 authors
·
Sep 30, 2023

Spatial-ORMLLM: Improve Spatial Relation Understanding in the Operating Room with Multimodal Large Language Model

Precise spatial modeling in the operating room (OR) is foundational to many clinical tasks, supporting intraoperative awareness, hazard avoidance, and surgical decision-making. While existing approaches leverage large-scale multimodal datasets for latent-space alignment to implicitly learn spatial relationships, they overlook the 3D capabilities of MLLMs. However, this approach raises two issues: (1) Operating rooms typically lack multiple video and audio sensors, making multimodal 3D data difficult to obtain; (2) Training solely on readily available 2D data fails to capture fine-grained details in complex scenes. To address this gap, we introduce Spatial-ORMLLM, the first large vision-language model for 3D spatial reasoning in operating rooms using only RGB modality to infer volumetric and semantic cues, enabling downstream medical tasks with detailed and holistic spatial context. Spatial-ORMLLM incorporates a Spatial-Enhanced Feature Fusion Block, which integrates 2D modality inputs with rich 3D spatial knowledge extracted by the estimation algorithm and then feeds the combined features into the visual tower. By employing a unified end-to-end MLLM framework, it combines powerful spatial features with textual features to deliver robust 3D scene reasoning without any additional expert annotations or sensor inputs. Experiments on multiple benchmark clinical datasets demonstrate that Spatial-ORMLLM achieves state-of-the-art performance and generalizes robustly to previously unseen surgical scenarios and downstream tasks.

  • 5 authors
·
Aug 11

Zero-Shot ECG Classification with Multimodal Learning and Test-time Clinical Knowledge Enhancement

Electrocardiograms (ECGs) are non-invasive diagnostic tools crucial for detecting cardiac arrhythmic diseases in clinical practice. While ECG Self-supervised Learning (eSSL) methods show promise in representation learning from unannotated ECG data, they often overlook the clinical knowledge that can be found in reports. This oversight and the requirement for annotated samples for downstream tasks limit eSSL's versatility. In this work, we address these issues with the Multimodal ECG Representation Learning (MERL}) framework. Through multimodal learning on ECG records and associated reports, MERL is capable of performing zero-shot ECG classification with text prompts, eliminating the need for training data in downstream tasks. At test time, we propose the Clinical Knowledge Enhanced Prompt Engineering (CKEPE) approach, which uses Large Language Models (LLMs) to exploit external expert-verified clinical knowledge databases, generating more descriptive prompts and reducing hallucinations in LLM-generated content to boost zero-shot classification. Based on MERL, we perform the first benchmark across six public ECG datasets, showing the superior performance of MERL compared against eSSL methods. Notably, MERL achieves an average AUC score of 75.2% in zero-shot classification (without training data), 3.2% higher than linear probed eSSL methods with 10\% annotated training data, averaged across all six datasets. Code and models are available at https://github.com/cheliu-computation/MERL

  • 6 authors
·
Mar 11, 2024

Cross-Modality Jailbreak and Mismatched Attacks on Medical Multimodal Large Language Models

Security concerns related to Large Language Models (LLMs) have been extensively explored, yet the safety implications for Multimodal Large Language Models (MLLMs), particularly in medical contexts (MedMLLMs), remain insufficiently studied. This paper delves into the underexplored security vulnerabilities of MedMLLMs, especially when deployed in clinical environments where the accuracy and relevance of question-and-answer interactions are critically tested against complex medical challenges. By combining existing clinical medical data with atypical natural phenomena, we redefine two types of attacks: mismatched malicious attack (2M-attack) and optimized mismatched malicious attack (O2M-attack). Using our own constructed voluminous 3MAD dataset, which covers a wide range of medical image modalities and harmful medical scenarios, we conduct a comprehensive analysis and propose the MCM optimization method, which significantly enhances the attack success rate on MedMLLMs. Evaluations with this dataset and novel attack methods, including white-box attacks on LLaVA-Med and transfer attacks on four other state-of-the-art models, indicate that even MedMLLMs designed with enhanced security features are vulnerable to security breaches. Our work underscores the urgent need for a concerted effort to implement robust security measures and enhance the safety and efficacy of open-source MedMLLMs, particularly given the potential severity of jailbreak attacks and other malicious or clinically significant exploits in medical settings. For further research and replication, anonymous access to our code is available at https://github.com/dirtycomputer/O2M_attack. Warning: Medical large model jailbreaking may generate content that includes unverified diagnoses and treatment recommendations. Always consult professional medical advice.

  • 7 authors
·
May 26, 2024

Multimodal AI predicts clinical outcomes of drug combinations from preclinical data

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

  • 10 authors
·
Mar 4

MMedPO: Aligning Medical Vision-Language Models with Clinical-Aware Multimodal Preference Optimization

The advancement of Large Vision-Language Models (LVLMs) has propelled their application in the medical field. However, Medical LVLMs (Med-LVLMs) encounter factuality challenges due to modality misalignment, where the models prioritize textual knowledge over visual input, leading to hallucinations that contradict information in medical images. Previous attempts to enhance modality alignment in Med-LVLMs through preference optimization have inadequately mitigated clinical relevance in preference data, making these samples easily distinguishable and reducing alignment effectiveness. To address this challenge, we propose MMedPO, a novel multimodal medical preference optimization approach that considers the clinical relevance of preference samples to enhance Med-LVLM alignment. MMedPO curates multimodal preference data by introducing two types of dispreference: (1) plausible hallucinations injected through target Med-LVLMs or GPT-4o to produce medically inaccurate responses, and (2) lesion region neglect achieved through local lesion-noising, disrupting visual understanding of critical areas. We then calculate clinical relevance for each sample based on scores from multiple Med-LLMs and visual tools, and integrate these scores into the preference optimization process as weights, enabling effective alignment. Our experiments demonstrate that MMedPO significantly enhances factual accuracy in Med-LVLMs, achieving substantial improvements over existing preference optimization methods by averaging 14.2% and 51.7% across the Med-VQA and report generation tasks. Our code are available in https://github.com/aiming-lab/MMedPO.

  • 6 authors
·
Dec 8, 2024

Towards Generalist Biomedical AI

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

  • 32 authors
·
Jul 26, 2023

MedSumm: A Multimodal Approach to Summarizing Code-Mixed Hindi-English Clinical Queries

In the healthcare domain, summarizing medical questions posed by patients is critical for improving doctor-patient interactions and medical decision-making. Although medical data has grown in complexity and quantity, the current body of research in this domain has primarily concentrated on text-based methods, overlooking the integration of visual cues. Also prior works in the area of medical question summarisation have been limited to the English language. This work introduces the task of multimodal medical question summarization for codemixed input in a low-resource setting. To address this gap, we introduce the Multimodal Medical Codemixed Question Summarization MMCQS dataset, which combines Hindi-English codemixed medical queries with visual aids. This integration enriches the representation of a patient's medical condition, providing a more comprehensive perspective. We also propose a framework named MedSumm that leverages the power of LLMs and VLMs for this task. By utilizing our MMCQS dataset, we demonstrate the value of integrating visual information from images to improve the creation of medically detailed summaries. This multimodal strategy not only improves healthcare decision-making but also promotes a deeper comprehension of patient queries, paving the way for future exploration in personalized and responsive medical care. Our dataset, code, and pre-trained models will be made publicly available.

  • 10 authors
·
Jan 3, 2024

AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

  • 6 authors
·
May 13, 2024

Kvasir-VQA-x1: A Multimodal Dataset for Medical Reasoning and Robust MedVQA in Gastrointestinal Endoscopy

Medical Visual Question Answering (MedVQA) is a promising field for developing clinical decision support systems, yet progress is often limited by the available datasets, which can lack clinical complexity and visual diversity. To address these gaps, we introduce Kvasir-VQA-x1, a new, large-scale dataset for gastrointestinal (GI) endoscopy. Our work significantly expands upon the original Kvasir-VQA by incorporating 159,549 new question-answer pairs that are designed to test deeper clinical reasoning. We developed a systematic method using large language models to generate these questions, which are stratified by complexity to better assess a model's inference capabilities. To ensure our dataset prepares models for real-world clinical scenarios, we have also introduced a variety of visual augmentations that mimic common imaging artifacts. The dataset is structured to support two main evaluation tracks: one for standard VQA performance and another to test model robustness against these visual perturbations. By providing a more challenging and clinically relevant benchmark, Kvasir-VQA-x1 aims to accelerate the development of more reliable and effective multimodal AI systems for use in clinical settings. The dataset is fully accessible and adheres to FAIR data principles, making it a valuable resource for the wider research community. Code and data: https://github.com/Simula/Kvasir-VQA-x1 and https://huggingface.co/datasets/SimulaMet/Kvasir-VQA-x1

  • 3 authors
·
Jun 11 2

Multimodal Data Integration for Oncology in the Era of Deep Neural Networks: A Review

Cancer has relational information residing at varying scales, modalities, and resolutions of the acquired data, such as radiology, pathology, genomics, proteomics, and clinical records. Integrating diverse data types can improve the accuracy and reliability of cancer diagnosis and treatment. There can be disease-related information that is too subtle for humans or existing technological tools to discern visually. Traditional methods typically focus on partial or unimodal information about biological systems at individual scales and fail to encapsulate the complete spectrum of the heterogeneous nature of data. Deep neural networks have facilitated the development of sophisticated multimodal data fusion approaches that can extract and integrate relevant information from multiple sources. Recent deep learning frameworks such as Graph Neural Networks (GNNs) and Transformers have shown remarkable success in multimodal learning. This review article provides an in-depth analysis of the state-of-the-art in GNNs and Transformers for multimodal data fusion in oncology settings, highlighting notable research studies and their findings. We also discuss the foundations of multimodal learning, inherent challenges, and opportunities for integrative learning in oncology. By examining the current state and potential future developments of multimodal data integration in oncology, we aim to demonstrate the promising role that multimodal neural networks can play in cancer prevention, early detection, and treatment through informed oncology practices in personalized settings.

  • 5 authors
·
Mar 11, 2023

Harvard Glaucoma Detection and Progression: A Multimodal Multitask Dataset and Generalization-Reinforced Semi-Supervised Learning

Glaucoma is the number one cause of irreversible blindness globally. A major challenge for accurate glaucoma detection and progression forecasting is the bottleneck of limited labeled patients with the state-of-the-art (SOTA) 3D retinal imaging data of optical coherence tomography (OCT). To address the data scarcity issue, this paper proposes two solutions. First, we develop a novel generalization-reinforced semi-supervised learning (SSL) model called pseudo supervisor to optimally utilize unlabeled data. Compared with SOTA models, the proposed pseudo supervisor optimizes the policy of predicting pseudo labels with unlabeled samples to improve empirical generalization. Our pseudo supervisor model is evaluated with two clinical tasks consisting of glaucoma detection and progression forecasting. The progression forecasting task is evaluated both unimodally and multimodally. Our pseudo supervisor model demonstrates superior performance than SOTA SSL comparison models. Moreover, our model also achieves the best results on the publicly available LAG fundus dataset. Second, we introduce the Harvard Glaucoma Detection and Progression (Harvard-GDP) Dataset, a multimodal multitask dataset that includes data from 1,000 patients with OCT imaging data, as well as labels for glaucoma detection and progression. This is the largest glaucoma detection dataset with 3D OCT imaging data and the first glaucoma progression forecasting dataset that is publicly available. Detailed sex and racial analysis are provided, which can be used by interested researchers for fairness learning studies. Our released dataset is benchmarked with several SOTA supervised CNN and transformer deep learning models. The dataset and code are made publicly available via https://ophai.hms.harvard.edu/datasets/harvard-gdp1000.

  • 5 authors
·
Aug 25, 2023

Chest ImaGenome Dataset for Clinical Reasoning

Despite the progress in automatic detection of radiologic findings from chest X-ray (CXR) images in recent years, a quantitative evaluation of the explainability of these models is hampered by the lack of locally labeled datasets for different findings. With the exception of a few expert-labeled small-scale datasets for specific findings, such as pneumonia and pneumothorax, most of the CXR deep learning models to date are trained on global "weak" labels extracted from text reports, or trained via a joint image and unstructured text learning strategy. Inspired by the Visual Genome effort in the computer vision community, we constructed the first Chest ImaGenome dataset with a scene graph data structure to describe 242,072 images. Local annotations are automatically produced using a joint rule-based natural language processing (NLP) and atlas-based bounding box detection pipeline. Through a radiologist constructed CXR ontology, the annotations for each CXR are connected as an anatomy-centered scene graph, useful for image-level reasoning and multimodal fusion applications. Overall, we provide: i) 1,256 combinations of relation annotations between 29 CXR anatomical locations (objects with bounding box coordinates) and their attributes, structured as a scene graph per image, ii) over 670,000 localized comparison relations (for improved, worsened, or no change) between the anatomical locations across sequential exams, as well as ii) a manually annotated gold standard scene graph dataset from 500 unique patients.

  • 12 authors
·
Jul 31, 2021

Interpretable graph-based models on multimodal biomedical data integration: A technical review and benchmarking

Integrating heterogeneous biomedical data including imaging, omics, and clinical records supports accurate diagnosis and personalised care. Graph-based models fuse such non-Euclidean data by capturing spatial and relational structure, yet clinical uptake requires regulator-ready interpretability. We present the first technical survey of interpretable graph based models for multimodal biomedical data, covering 26 studies published between Jan 2019 and Sep 2024. Most target disease classification, notably cancer and rely on static graphs from simple similarity measures, while graph-native explainers are rare; post-hoc methods adapted from non-graph domains such as gradient saliency, and SHAP predominate. We group existing approaches into four interpretability families, outline trends such as graph-in-graph hierarchies, knowledge-graph edges, and dynamic topology learning, and perform a practical benchmark. Using an Alzheimer disease cohort, we compare Sensitivity Analysis, Gradient Saliency, SHAP and Graph Masking. SHAP and Sensitivity Analysis recover the broadest set of known AD pathways and Gene-Ontology terms, whereas Gradient Saliency and Graph Masking surface complementary metabolic and transport signatures. Permutation tests show all four beat random gene sets, but with distinct trade-offs: SHAP and Graph Masking offer deeper biology at higher compute cost, while Gradient Saliency and Sensitivity Analysis are quicker though coarser. We also provide a step-by-step flowchart covering graph construction, explainer choice and resource budgeting to help researchers balance transparency and performance. This review synthesises the state of interpretable graph learning for multimodal medicine, benchmarks leading techniques, and charts future directions, from advanced XAI tools to under-studied diseases, serving as a concise reference for method developers and translational scientists.

  • 6 authors
·
May 3

A Multimodal Vision Foundation Model for Clinical Dermatology

Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks like skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here, we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin conditions, lesion segmentation, longitudinal monitoring, and metastasis prediction and prognosis. PanDerm achieved state-of-the-art performance across all evaluated tasks, often outperforming existing models when using only 10% of labeled data. We conducted three reader studies to assess PanDerm's potential clinical utility. PanDerm outperformed clinicians by 10.2% in early-stage melanoma detection through longitudinal analysis, improved clinicians' skin cancer diagnostic accuracy by 11% on dermoscopy images, and enhanced non-dermatologist healthcare providers' differential diagnosis by 16.5% across 128 skin conditions on clinical photographs. These results demonstrate PanDerm's potential to improve patient care across diverse clinical scenarios and serve as a model for developing multimodal foundation models in other medical specialties, potentially accelerating the integration of AI support in healthcare. The code can be found at https://github.com/SiyuanYan1/PanDerm.

  • 25 authors
·
Oct 19, 2024

Potential of Multimodal Large Language Models for Data Mining of Medical Images and Free-text Reports

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.

  • 14 authors
·
Jul 8, 2024

Bridging the Gap in Ophthalmic AI: MM-Retinal-Reason Dataset and OphthaReason Model toward Dynamic Multimodal Reasoning

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities with reinforcement learning paradigm. Although several multimodal reasoning models have been explored in the medical domain, most of them focus exclusively on basic reasoning, which refers to shallow inference based on visual feature matching. However, real-world clinical diagnosis extends beyond basic reasoning, demanding reasoning processes that integrate heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, the first ophthalmic multimodal dataset with the full spectrum of perception and reasoning. It encompasses both basic reasoning tasks and complex reasoning tasks, aiming to enhance visual-centric fundamental reasoning capabilities and emulate realistic clinical thinking patterns. Building upon MM-Retinal-Reason, we propose OphthaReason, the first ophthalmology-specific multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we specifically design a novel method called Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates the model's exploration depth using a shaped advantage mechanism. Comprehensive experiments demonstrate that our model achieves state-of-the-art performance on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 24.92\%, 15.00\%, 21.20\%, and 17.66\%. Project Page: https://github.com/lxirich/OphthaReason{link}.

  • 9 authors
·
Aug 22

SemiHVision: Enhancing Medical Multimodal Models with a Semi-Human Annotated Dataset and Fine-Tuned Instruction Generation

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

  • 7 authors
·
Oct 18, 2024

GMAI-VL & GMAI-VL-5.5M: A Large Vision-Language Model and A Comprehensive Multimodal Dataset Towards General Medical AI

Despite significant advancements in general artificial intelligence, such as GPT-4, their effectiveness in the medical domain (general medical AI, GMAI) remains constrained due to the absence of specialized medical knowledge. To address this challenge, we present GMAI-VL-5.5M, a comprehensive multimodal medical dataset created by converting hundreds of specialized medical datasets into meticulously constructed image-text pairs. This dataset features comprehensive task coverage, diverse modalities, and high-quality image-text data. Building upon this multimodal dataset, we propose GMAI-VL, a general medical vision-language model with a progressively three-stage training strategy. This approach significantly enhances the model's ability by integrating visual and textual information, thereby improving its ability to process multimodal data and support accurate diagnosis and clinical decision-making. Experimental evaluations demonstrate that GMAI-VL achieves state-of-the-art results across a wide range of multimodal medical tasks, such as visual question answering and medical image diagnosis. Our contributions include the development of the GMAI-VL-5.5M dataset, the introduction of the GMAI-VL model, and the establishment of new benchmarks in multiple medical domains. Code and dataset will be released at https://github.com/uni-medical/GMAI-VL.

  • 18 authors
·
Nov 21, 2024 2

Advancing Multimodal Medical Capabilities of Gemini

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

  • 47 authors
·
May 6, 2024

Memory-Augmented Incomplete Multimodal Survival Prediction via Cross-Slide and Gene-Attentive Hypergraph Learning

Multimodal pathology-genomic analysis is critical for cancer survival prediction. However, existing approaches predominantly integrate formalin-fixed paraffin-embedded (FFPE) slides with genomic data, while neglecting the availability of other preservation slides, such as Fresh Froze (FF) slides. Moreover, as the high-resolution spatial nature of pathology data tends to dominate the cross-modality fusion process, it hinders effective multimodal fusion and leads to modality imbalance challenges between pathology and genomics. These methods also typically require complete data modalities, limiting their clinical applicability with incomplete modalities, such as missing either pathology or genomic data. In this paper, we propose a multimodal survival prediction framework that leverages hypergraph learning to effectively integrate multi-WSI information and cross-modality interactions between pathology slides and genomics data while addressing modality imbalance. In addition, we introduce a memory mechanism that stores previously learned paired pathology-genomic features and dynamically compensates for incomplete modalities. Experiments on five TCGA datasets demonstrate that our model outperforms advanced methods by over 2.3% in C-Index. Under incomplete modality scenarios, our approach surpasses pathology-only (3.3%) and gene-only models (7.9%). Code: https://github.com/MCPathology/M2Surv

  • 7 authors
·
Jun 24

GMAI-MMBench: A Comprehensive Multimodal Evaluation Benchmark Towards General Medical AI

Large Vision-Language Models (LVLMs) are capable of handling diverse data types such as imaging, text, and physiological signals, and can be applied in various fields. In the medical field, LVLMs have a high potential to offer substantial assistance for diagnosis and treatment. Before that, it is crucial to develop benchmarks to evaluate LVLMs' effectiveness in various medical applications. Current benchmarks are often built upon specific academic literature, mainly focusing on a single domain, and lacking varying perceptual granularities. Thus, they face specific challenges, including limited clinical relevance, incomplete evaluations, and insufficient guidance for interactive LVLMs. To address these limitations, we developed the GMAI-MMBench, the most comprehensive general medical AI benchmark with well-categorized data structure and multi-perceptual granularity to date. It is constructed from 285 datasets across 39 medical image modalities, 18 clinical-related tasks, 18 departments, and 4 perceptual granularities in a Visual Question Answering (VQA) format. Additionally, we implemented a lexical tree structure that allows users to customize evaluation tasks, accommodating various assessment needs and substantially supporting medical AI research and applications. We evaluated 50 LVLMs, and the results show that even the advanced GPT-4o only achieves an accuracy of 52%, indicating significant room for improvement. Moreover, we identified five key insufficiencies in current cutting-edge LVLMs that need to be addressed to advance the development of better medical applications. We believe that GMAI-MMBench will stimulate the community to build the next generation of LVLMs toward GMAI. Project Page: https://uni-medical.github.io/GMAI-MMBench.github.io/

  • 18 authors
·
Aug 6, 2024 2

Label Dependent Attention Model for Disease Risk Prediction Using Multimodal Electronic Health Records

Disease risk prediction has attracted increasing attention in the field of modern healthcare, especially with the latest advances in artificial intelligence (AI). Electronic health records (EHRs), which contain heterogeneous patient information, are widely used in disease risk prediction tasks. One challenge of applying AI models for risk prediction lies in generating interpretable evidence to support the prediction results while retaining the prediction ability. In order to address this problem, we propose the method of jointly embedding words and labels whereby attention modules learn the weights of words from medical notes according to their relevance to the names of risk prediction labels. This approach boosts interpretability by employing an attention mechanism and including the names of prediction tasks in the model. However, its application is only limited to the handling of textual inputs such as medical notes. In this paper, we propose a label dependent attention model LDAM to 1) improve the interpretability by exploiting Clinical-BERT (a biomedical language model pre-trained on a large clinical corpus) to encode biomedically meaningful features and labels jointly; 2) extend the idea of joint embedding to the processing of time-series data, and develop a multi-modal learning framework for integrating heterogeneous information from medical notes and time-series health status indicators. To demonstrate our method, we apply LDAM to the MIMIC-III dataset to predict different disease risks. We evaluate our method both quantitatively and qualitatively. Specifically, the predictive power of LDAM will be shown, and case studies will be carried out to illustrate its interpretability.

  • 5 authors
·
Jan 18, 2022

RadGraph: Extracting Clinical Entities and Relations from Radiology Reports

Extracting structured clinical information from free-text radiology reports can enable the use of radiology report information for a variety of critical healthcare applications. In our work, we present RadGraph, a dataset of entities and relations in full-text chest X-ray radiology reports based on a novel information extraction schema we designed to structure radiology reports. We release a development dataset, which contains board-certified radiologist annotations for 500 radiology reports from the MIMIC-CXR dataset (14,579 entities and 10,889 relations), and a test dataset, which contains two independent sets of board-certified radiologist annotations for 100 radiology reports split equally across the MIMIC-CXR and CheXpert datasets. Using these datasets, we train and test a deep learning model, RadGraph Benchmark, that achieves a micro F1 of 0.82 and 0.73 on relation extraction on the MIMIC-CXR and CheXpert test sets respectively. Additionally, we release an inference dataset, which contains annotations automatically generated by RadGraph Benchmark across 220,763 MIMIC-CXR reports (around 6 million entities and 4 million relations) and 500 CheXpert reports (13,783 entities and 9,908 relations) with mappings to associated chest radiographs. Our freely available dataset can facilitate a wide range of research in medical natural language processing, as well as computer vision and multi-modal learning when linked to chest radiographs.

  • 12 authors
·
Jun 28, 2021

A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

  • 19 authors
·
Jul 22, 2024

SpiroLLM: Finetuning Pretrained LLMs to Understand Spirogram Time Series with Clinical Validation in COPD Reporting

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.

  • 8 authors
·
Jul 21

MEXA: Towards General Multimodal Reasoning with Dynamic Multi-Expert Aggregation

Combining pre-trained expert models offers substantial potential for scalable multimodal reasoning, but building a unified framework remains challenging due to the increasing diversity of input modalities and task complexity. For instance, medical diagnosis requires precise reasoning over structured clinical tables, while financial forecasting depends on interpreting plot-based data to make informed predictions. To tackle this challenge, we introduce MEXA, a training-free framework that performs modality- and task-aware aggregation of multiple expert models to enable effective multimodal reasoning across diverse and distinct domains. MEXA dynamically selects expert models based on the input modality and the task-specific reasoning demands (i.e., skills). Each expert model, specialized in a modality task pair, generates interpretable textual reasoning outputs. MEXA then aggregates and reasons over these outputs using a Large Reasoning Model (LRM) to produce the final answer. This modular design allows flexible and transparent multimodal reasoning across diverse domains without additional training overhead. We extensively evaluate our approach on diverse multimodal benchmarks, including Video Reasoning, Audio Reasoning, 3D Understanding, and Medical QA. MEXA consistently delivers performance improvements over strong multimodal baselines, highlighting the effectiveness and broad applicability of our expert-driven selection and aggregation in diverse multimodal reasoning tasks.

  • 5 authors
·
Jun 20 2

Discrete Diffusion Models with MLLMs for Unified Medical Multimodal Generation

Recent advances in generative medical models are constrained by modality-specific scenarios that hinder the integration of complementary evidence from imaging, pathology, and clinical notes. This fragmentation limits their evolution into foundation models that can learn and reason across the full spectrum of biomedical data. We propose MeDiM, the first medical discrete diffusion model that learns shared distributions across modalities without modality-specific components. MeDiM unifies multiple generative tasks: translating between images and text, and jointly producing image-report pairs across domains in response to prompts. Built on a discrete diffusion framework, MeDiM bridges vision and language representations through a shared probabilistic space. To enable unified and flexible medical generation, we employ a multimodal large language model (MLLM) as the diffusion backbone, leveraging its prior knowledge and cross-modal reasoning. Two key designs are introduced: (1) removing the causal attention mask for bidirectional context, and (2) injecting continuous timestep embeddings for diffusion awareness. Experiments demonstrate high-fidelity medical generation (FID 16.60 on MIMIC-CXR and FID 24.19 on PathGen) and accurate report generation (METEOR 0.2650 and 0.2580). Jointly generated image-report pairs further enhance downstream performance (plus6.43 percent BLEU-1, plus18.57 percent BLEU-2, plus31.58 percent BLEU-3, plus4.80 percent METEOR), showing that MeDiM supports coherent and clinically grounded multimodal outputs.

UCSC-VLAA UCSC-VLAA
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Oct 7 2

Towards a clinically accessible radiology foundation model: open-access and lightweight, with automated evaluation

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

  • 27 authors
·
Mar 12, 2024

ChestX-Reasoner: Advancing Radiology Foundation Models with Reasoning through Step-by-Step Verification

Recent advances in reasoning-enhanced large language models (LLMs) and multimodal LLMs (MLLMs) have significantly improved performance in complex tasks, yet medical AI models often overlook the structured reasoning processes inherent in clinical practice. In this work, we present ChestX-Reasoner, a radiology diagnosis MLLM designed to leverage process supervision mined directly from clinical reports, reflecting the step-by-step reasoning followed by radiologists. We construct a large dataset by extracting and refining reasoning chains from routine radiology reports. Our two-stage training framework combines supervised fine-tuning and reinforcement learning guided by process rewards to better align model reasoning with clinical standards. We introduce RadRBench-CXR, a comprehensive benchmark featuring 59K visual question answering samples with 301K clinically validated reasoning steps, and propose RadRScore, a metric evaluating reasoning factuality, completeness, and effectiveness. ChestX-Reasoner outperforms existing medical and general-domain MLLMs in both diagnostic accuracy and reasoning ability, achieving 16%, 5.9%, and 18% improvements in reasoning ability compared to the best medical MLLM, the best general MLLM, and its base model, respectively, as well as 3.3%, 24%, and 27% improvements in outcome accuracy. All resources are open-sourced to facilitate further research in medical reasoning MLLMs.

  • 6 authors
·
Apr 29

seg2med: a segmentation-based medical image generation framework using denoising diffusion probabilistic models

In this study, we present seg2med, an advanced medical image synthesis framework that uses Denoising Diffusion Probabilistic Models (DDPM) to generate high-quality synthetic medical images conditioned on anatomical masks from TotalSegmentator. The framework synthesizes CT and MR images from segmentation masks derived from real patient data and XCAT digital phantoms, achieving a Structural Similarity Index Measure (SSIM) of 0.94 +/- 0.02 for CT and 0.89 +/- 0.04 for MR images compared to ground-truth images of real patients. It also achieves a Feature Similarity Index Measure (FSIM) of 0.78 +/- 0.04 for CT images from XCAT. The generative quality is further supported by a Fr\'echet Inception Distance (FID) of 3.62 for CT image generation. Additionally, seg2med can generate paired CT and MR images with consistent anatomical structures and convert images between CT and MR modalities, achieving SSIM values of 0.91 +/- 0.03 for MR-to-CT and 0.77 +/- 0.04 for CT-to-MR conversion. Despite the limitations of incomplete anatomical details in segmentation masks, the framework shows strong performance in cross-modality synthesis and multimodal imaging. seg2med also demonstrates high anatomical fidelity in CT synthesis, achieving a mean Dice coefficient greater than 0.90 for 11 abdominal organs and greater than 0.80 for 34 organs out of 59 in 58 test cases. The highest Dice of 0.96 +/- 0.01 was recorded for the right scapula. Leveraging the TotalSegmentator toolkit, seg2med enables segmentation mask generation across diverse datasets, supporting applications in clinical imaging, data augmentation, multimodal synthesis, and diagnostic algorithm development.

  • 8 authors
·
Apr 12

Large Language Models Illuminate a Progressive Pathway to Artificial Healthcare Assistant: A Review

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

  • 11 authors
·
Nov 3, 2023

Dolphin v1.0 Technical Report

Ultrasound is crucial in modern medicine but faces challenges like operator dependence, image noise, and real-time scanning, hindering AI integration. While large multimodal models excel in other medical imaging areas, they struggle with ultrasound's complexities. To address this, we introduce Dolphin v1.0 (V1) and its reasoning-augmented version, Dolphin R1-the first large-scale multimodal ultrasound foundation models unifying diverse clinical tasks in a single vision-language framework.To tackle ultrasound variability and noise, we curated a 2-million-scale multimodal dataset, combining textbook knowledge, public data, synthetic samples, and general corpora. This ensures robust perception, generalization, and clinical adaptability.The Dolphin series employs a three-stage training strategy: domain-specialized pretraining, instruction-driven alignment, and reinforcement-based refinement. Dolphin v1.0 delivers reliable performance in classification, detection, regression, and report generation. Dolphin R1 enhances diagnostic inference, reasoning transparency, and interpretability through reinforcement learning with ultrasound-specific rewards.Evaluated on U2-Bench across eight ultrasound tasks, Dolphin R1 achieves a U2-score of 0.5835-over twice the second-best model (0.2968) setting a new state of the art. Dolphin v1.0 also performs competitively, validating the unified framework. Comparisons show reasoning-enhanced training significantly improves diagnostic accuracy, consistency, and interpretability, highlighting its importance for high-stakes medical AI.

  • 19 authors
·
Sep 30

End-To-End Prediction of Knee Osteoarthritis Progression With Multi-Modal Transformers

Knee Osteoarthritis (KOA) is a highly prevalent chronic musculoskeletal condition with no currently available treatment. The manifestation of KOA is heterogeneous and prediction of its progression is challenging. Current literature suggests that the use of multi-modal data and advanced modeling methods, such as the ones based on Deep Learning, has promise in tackling this challenge. To date, however, the evidence on the efficacy of this approach is limited. In this study, we leveraged recent advances in Deep Learning and, using a Transformer approach, developed a unified framework for the multi-modal fusion of knee imaging data. Subsequently, we analyzed its performance across a range of scenarios by investigating multiple progression horizons -- from short-term to long-term. We report our findings using a large cohort (n=2421-3967) derived from the Osteoarthritis Initiative dataset. We show that structural knee MRI allows identifying radiographic KOA progressors on par with multi-modal fusion approaches, achieving an area under the ROC curve (ROC AUC) of 0.70-0.76 and Average Precision (AP) of 0.15-0.54 in 2-8 year horizons. Progression within 1 year was better predicted with a multi-modal method using X-ray, structural, and compositional MR images -- ROC AUC of 0.76(0.04), AP of 0.13(0.04) -- or via clinical data. Our follow-up analysis generally shows that prediction from the imaging data is more accurate for post-traumatic subjects, and we further investigate which subject subgroups may benefit the most. The present study provides novel insights into multi-modal imaging of KOA and brings a unified data-driven framework for studying its progression in an end-to-end manner, providing new tools for the design of more efficient clinical trials. The source code of our framework and the pre-trained models are made publicly available.

  • 4 authors
·
Jul 3, 2023

RAD: Towards Trustworthy Retrieval-Augmented Multi-modal Clinical Diagnosis

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.

  • 7 authors
·
Sep 24

Cascaded Multi-Modal Mixing Transformers for Alzheimer's Disease Classification with Incomplete Data

Accurate medical classification requires a large number of multi-modal data, and in many cases, different feature types. Previous studies have shown promising results when using multi-modal data, outperforming single-modality models when classifying diseases such as Alzheimer's Disease (AD). However, those models are usually not flexible enough to handle missing modalities. Currently, the most common workaround is discarding samples with missing modalities which leads to considerable data under-utilization. Adding to the fact that labeled medical images are already scarce, the performance of data-driven methods like deep learning can be severely hampered. Therefore, a multi-modal method that can handle missing data in various clinical settings is highly desirable. In this paper, we present Multi-Modal Mixing Transformer (3MAT), a disease classification transformer that not only leverages multi-modal data but also handles missing data scenarios. In this work, we test 3MT for AD and Cognitively normal (CN) classification and mild cognitive impairment (MCI) conversion prediction to progressive MCI (pMCI) or stable MCI (sMCI) using clinical and neuroimaging data. The model uses a novel Cascaded Modality Transformer architecture with cross-attention to incorporate multi-modal information for more informed predictions. We propose a novel modality dropout mechanism to ensure an unprecedented level of modality independence and robustness to handle missing data scenarios. The result is a versatile network that enables the mixing of arbitrary numbers of modalities with different feature types and also ensures full data utilization missing data scenarios. The model is trained and evaluated on the ADNI dataset with the SOTRA performance and further evaluated with the AIBL dataset with missing data.

  • 6 authors
·
Oct 1, 2022

MODMA dataset: a Multi-modal Open Dataset for Mental-disorder Analysis

According to the World Health Organization, the number of mental disorder patients, especially depression patients, has grown rapidly and become a leading contributor to the global burden of disease. However, the present common practice of depression diagnosis is based on interviews and clinical scales carried out by doctors, which is not only labor-consuming but also time-consuming. One important reason is due to the lack of physiological indicators for mental disorders. With the rising of tools such as data mining and artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. However, good quality physiological data for mental disorder patients are hard to acquire. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and audio data from clinically depressed patients and matching normal controls. All our patients were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes not only data collected using traditional 128-electrodes mounted elastic cap, but also a novel wearable 3-electrode EEG collector for pervasive applications. The 128-electrodes EEG signals of 53 subjects were recorded as both in resting state and under stimulation; the 3-electrode EEG signals of 55 subjects were recorded in resting state; the audio data of 52 subjects were recorded during interviewing, reading, and picture description. We encourage other researchers in the field to use it for testing their methods of mental-disorder analysis.

  • 26 authors
·
Feb 20, 2020

Sensing Cardiac Health Across Scenarios and Devices: A Multi-Modal Foundation Model Pretrained on Heterogeneous Data from 1.7 Million Individuals

Cardiac biosignals, such as electrocardiograms (ECG) and photoplethysmograms (PPG), are of paramount importance for the diagnosis, prevention, and management of cardiovascular diseases, and have been extensively used in a variety of clinical tasks. Conventional deep learning approaches for analyzing these signals typically rely on homogeneous datasets and static bespoke models, limiting their robustness and generalizability across diverse clinical settings and acquisition protocols. In this study, we present a cardiac sensing foundation model (CSFM) that leverages advanced transformer architectures and a generative, masked pretraining strategy to learn unified representations from vast, heterogeneous health records. Our model is pretrained on an innovative multi-modal integration of data from multiple large-scale datasets (including MIMIC-III-WDB, MIMIC-IV-ECG, and CODE), comprising cardiac signals and the corresponding clinical or machine-generated text reports from approximately 1.7 million individuals. We demonstrate that the embeddings derived from our CSFM not only serve as effective feature extractors across diverse cardiac sensing scenarios, but also enable seamless transfer learning across varying input configurations and sensor modalities. Extensive evaluations across diagnostic tasks, demographic information recognition, vital sign measurement, clinical outcome prediction, and ECG question answering reveal that CSFM consistently outperforms traditional one-modal-one-task approaches. Notably, CSFM exhibits robust performance across multiple ECG lead configurations from standard 12-lead systems to single-lead setups, and in scenarios where only ECG, only PPG, or a combination thereof is available. These findings highlight the potential of CSFM as a versatile and scalable solution, for comprehensive cardiac monitoring.

  • 13 authors
·
Jun 23

HINT: Hierarchical Interaction Network for Trial Outcome Prediction Leveraging Web Data

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

  • 5 authors
·
Feb 8, 2021

EndoBench: A Comprehensive Evaluation of Multi-Modal Large Language Models for Endoscopy Analysis

Endoscopic procedures are essential for diagnosing and treating internal diseases, and multi-modal large language models (MLLMs) are increasingly applied to assist in endoscopy analysis. However, current benchmarks are limited, as they typically cover specific endoscopic scenarios and a small set of clinical tasks, failing to capture the real-world diversity of endoscopic scenarios and the full range of skills needed in clinical workflows. To address these issues, we introduce EndoBench, the first comprehensive benchmark specifically designed to assess MLLMs across the full spectrum of endoscopic practice with multi-dimensional capacities. EndoBench encompasses 4 distinct endoscopic scenarios, 12 specialized clinical tasks with 12 secondary subtasks, and 5 levels of visual prompting granularities, resulting in 6,832 rigorously validated VQA pairs from 21 diverse datasets. Our multi-dimensional evaluation framework mirrors the clinical workflow--spanning anatomical recognition, lesion analysis, spatial localization, and surgical operations--to holistically gauge the perceptual and diagnostic abilities of MLLMs in realistic scenarios. We benchmark 23 state-of-the-art models, including general-purpose, medical-specialized, and proprietary MLLMs, and establish human clinician performance as a reference standard. Our extensive experiments reveal: (1) proprietary MLLMs outperform open-source and medical-specialized models overall, but still trail human experts; (2) medical-domain supervised fine-tuning substantially boosts task-specific accuracy; and (3) model performance remains sensitive to prompt format and clinical task complexity. EndoBench establishes a new standard for evaluating and advancing MLLMs in endoscopy, highlighting both progress and persistent gaps between current models and expert clinical reasoning. We publicly release our benchmark and code.

  • 8 authors
·
May 29

MM-DINOv2: Adapting Foundation Models for Multi-Modal Medical Image Analysis

Vision foundation models like DINOv2 demonstrate remarkable potential in medical imaging despite their origin in natural image domains. However, their design inherently works best for uni-modal image analysis, limiting their effectiveness for multi-modal imaging tasks that are common in many medical fields, such as neurology and oncology. While supervised models perform well in this setting, they fail to leverage unlabeled datasets and struggle with missing modalities, a frequent challenge in clinical settings. To bridge these gaps, we introduce MM-DINOv2, a novel and efficient framework that adapts the pre-trained vision foundation model DINOv2 for multi-modal medical imaging. Our approach incorporates multi-modal patch embeddings, enabling vision foundation models to effectively process multi-modal imaging data. To address missing modalities, we employ full-modality masking, which encourages the model to learn robust cross-modality relationships. Furthermore, we leverage semi-supervised learning to harness large unlabeled datasets, enhancing both the accuracy and reliability of medical predictions. Applied to glioma subtype classification from multi-sequence brain MRI, our method achieves a Matthews Correlation Coefficient (MCC) of 0.6 on an external test set, surpassing state-of-the-art supervised approaches by +11.1%. Our work establishes a scalable and robust solution for multi-modal medical imaging tasks, leveraging powerful vision foundation models pre-trained on natural images while addressing real-world clinical challenges such as missing data and limited annotations.

  • 7 authors
·
Sep 8

OpenMEDLab: An Open-source Platform for Multi-modality Foundation Models in Medicine

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

  • 20 authors
·
Feb 27, 2024