Large Language Models for Disease Diagnosis: A Scoping Review

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 growing attention in this field, many critical research questions remain under-explored. For instance, what diseases and LLM techniques have been investigated for diagnostic tasks? How can suitable LLM techniques and evaluation methods be selected for clinical decision-making? To answer these questions, we performed a comprehensive analysis of LLM-based methods for disease diagnosis. This scoping review examined the types of diseases, associated organ systems, relevant clinical data, LLM techniques, and evaluation methods reported in existing studies. Furthermore, we offered guidelines for data preprocessing and the selection of appropriate LLM techniques and evaluation strategies for diagnostic tasks. We also assessed the limitations of current research and delineated the challenges and future directions in this research field. In summary, our review outlined a blueprint for LLM-based disease diagnosis, helping to streamline and guide future research endeavors.

Interpretable Differential Diagnosis with Dual-Inference Large Language Models

Methodological advancements to automate the generation of differential diagnosis (DDx) to predict a list of potential diseases as differentials given patients' symptom descriptions are critical to clinical reasoning and applications such as decision support. However, providing reasoning or interpretation for these differential diagnoses is more meaningful. Fortunately, large language models (LLMs) possess powerful language processing abilities and have been proven effective in various related tasks. Motivated by this potential, we investigate the use of LLMs for interpretable DDx. First, we develop a new DDx dataset with expert-derived interpretation on 570 public clinical notes. Second, we propose a novel framework, named Dual-Inf, that enables LLMs to conduct bidirectional inference for interpretation. Both human and automated evaluation demonstrate the effectiveness of Dual-Inf in predicting differentials and diagnosis explanations. Specifically, the performance improvement of Dual-Inf over the baseline methods exceeds 32% w.r.t. BERTScore in DDx interpretation. Furthermore, experiments verify that Dual-Inf (1) makes fewer errors in interpretation, (2) has great generalizability, (3) is promising for rare disease diagnosis and explanation.

Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling

Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.

Deep learning with noisy labels in medical prediction problems: a scoping review

Objectives: Medical research faces substantial challenges from noisy labels attributed to factors like inter-expert variability and machine-extracted labels. Despite this, the adoption of label noise management remains limited, and label noise is largely ignored. To this end, there is a critical need to conduct a scoping review focusing on the problem space. This scoping review aims to comprehensively review label noise management in deep learning-based medical prediction problems, which includes label noise detection, label noise handling, and evaluation. Research involving label uncertainty is also included. Methods: Our scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched 4 databases, including PubMed, IEEE Xplore, Google Scholar, and Semantic Scholar. Our search terms include "noisy label AND medical / healthcare / clinical", "un-certainty AND medical / healthcare / clinical", and "noise AND medical / healthcare / clinical". Results: A total of 60 papers met inclusion criteria between 2016 and 2023. A series of practical questions in medical research are investigated. These include the sources of label noise, the impact of label noise, the detection of label noise, label noise handling techniques, and their evaluation. Categorization of both label noise detection methods and handling techniques are provided. Discussion: From a methodological perspective, we observe that the medical community has been up to date with the broader deep-learning community, given that most techniques have been evaluated on medical data. We recommend considering label noise as a standard element in medical research, even if it is not dedicated to handling noisy labels. Initial experiments can start with easy-to-implement methods, such as noise-robust loss functions, weighting, and curriculum learning.

A survey of recent methods for addressing AI fairness and bias in biomedicine

Artificial intelligence (AI) systems have the potential to revolutionize clinical practices, including improving diagnostic accuracy and surgical decision-making, while also reducing costs and manpower. However, it is important to recognize that these systems may perpetuate social inequities or demonstrate biases, such as those based on race or gender. Such biases can occur before, during, or after the development of AI models, making it critical to understand and address potential biases to enable the accurate and reliable application of AI models in clinical settings. To mitigate bias concerns during model development, we surveyed recent publications on different debiasing methods in the fields of biomedical natural language processing (NLP) or computer vision (CV). Then we discussed the methods that have been applied in the biomedical domain to address bias. We performed our literature search on PubMed, ACM digital library, and IEEE Xplore of relevant articles published between January 2018 and December 2023 using multiple combinations of keywords. We then filtered the result of 10,041 articles automatically with loose constraints, and manually inspected the abstracts of the remaining 890 articles to identify the 55 articles included in this review. Additional articles in the references are also included in this review. We discuss each method and compare its strengths and weaknesses. Finally, we review other potential methods from the general domain that could be applied to biomedicine to address bias and improve fairness.The bias of AIs in biomedicine can originate from multiple sources. Existing debiasing methods that focus on algorithms can be categorized into distributional or algorithmic.

Improving Fairness of Automated Chest X-ray Diagnosis by Contrastive Learning

Purpose: Limited studies exploring concrete methods or approaches to tackle and enhance model fairness in the radiology domain. Our proposed AI model utilizes supervised contrastive learning to minimize bias in CXR diagnosis. Materials and Methods: In this retrospective study, we evaluated our proposed method on two datasets: the Medical Imaging and Data Resource Center (MIDRC) dataset with 77,887 CXR images from 27,796 patients collected as of April 20, 2023 for COVID-19 diagnosis, and the NIH Chest X-ray (NIH-CXR) dataset with 112,120 CXR images from 30,805 patients collected between 1992 and 2015. In the NIH-CXR dataset, thoracic abnormalities include atelectasis, cardiomegaly, effusion, infiltration, mass, nodule, pneumonia, pneumothorax, consolidation, edema, emphysema, fibrosis, pleural thickening, or hernia. Our proposed method utilizes supervised contrastive learning with carefully selected positive and negative samples to generate fair image embeddings, which are fine-tuned for subsequent tasks to reduce bias in chest X-ray (CXR) diagnosis. We evaluated the methods using the marginal AUC difference ($\delta$ mAUC). Results: The proposed model showed a significant decrease in bias across all subgroups when compared to the baseline models, as evidenced by a paired T-test (p<0.0001). The $\delta$ mAUC obtained by our method were 0.0116 (95\% CI, 0.0110-0.0123), 0.2102 (95% CI, 0.2087-0.2118), and 0.1000 (95\% CI, 0.0988-0.1011) for sex, race, and age on MIDRC, and 0.0090 (95\% CI, 0.0082-0.0097) for sex and 0.0512 (95% CI, 0.0512-0.0532) for age on NIH-CXR, respectively. Conclusion: Employing supervised contrastive learning can mitigate bias in CXR diagnosis, addressing concerns of fairness and reliability in deep learning-based diagnostic methods.

Towards long-tailed, multi-label disease classification from chest X-ray: Overview of the CXR-LT challenge

Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" $\unicode{x2013}$ there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification.

A scoping review on multimodal deep learning in biomedical images and texts

Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.

Evaluate underdiagnosis and overdiagnosis bias of deep learning model on primary open-angle glaucoma diagnosis in under-served patient populations

In the United States, primary open-angle glaucoma (POAG) is the leading cause of blindness, especially among African American and Hispanic individuals. Deep learning has been widely used to detect POAG using fundus images as its performance is comparable to or even surpasses diagnosis by clinicians. However, human bias in clinical diagnosis may be reflected and amplified in the widely-used deep learning models, thus impacting their performance. Biases may cause (1) underdiagnosis, increasing the risks of delayed or inadequate treatment, and (2) overdiagnosis, which may increase individuals' stress, fear, well-being, and unnecessary/costly treatment. In this study, we examined the underdiagnosis and overdiagnosis when applying deep learning in POAG detection based on the Ocular Hypertension Treatment Study (OHTS) from 22 centers across 16 states in the United States. Our results show that the widely-used deep learning model can underdiagnose or overdiagnose underserved populations. The most underdiagnosed group is female younger (< 60 yrs) group, and the most overdiagnosed group is Black older (>=60 yrs) group. Biased diagnosis through traditional deep learning methods may delay disease detection, treatment and create burdens among under-served populations, thereby, raising ethical concerns about using deep learning models in ophthalmology clinics.

Prior Knowledge Enhances Radiology Report Generation

Radiology report generation aims to produce computer-aided diagnoses to alleviate the workload of radiologists and has drawn increasing attention recently. However, previous deep learning methods tend to neglect the mutual influences between medical findings, which can be the bottleneck that limits the quality of generated reports. In this work, we propose to mine and represent the associations among medical findings in an informative knowledge graph and incorporate this prior knowledge with radiology report generation to help improve the quality of generated reports. Experiment results demonstrate the superior performance of our proposed method on the IU X-ray dataset with a ROUGE-L of 0.384$\pm$0.007 and CIDEr of 0.340$\pm$0.011. Compared with previous works, our model achieves an average of 1.6% improvement (2.0% and 1.5% improvements in CIDEr and ROUGE-L, respectively). The experiments suggest that prior knowledge can bring performance gains to accurate radiology report generation. We will make the code publicly available at https://github.com/bionlplab/report_generation_amia2022.