Daily Papers

Chest X-rays (CXR) are the most common medical imaging study and are used to diagnose multiple medical conditions. This study examines the impact of synthetic data supplementation, using diffusion models, on the performance of deep learning (DL) classifiers for CXR analysis. We employed three datasets: CheXpert, MIMIC-CXR, and Emory Chest X-ray, training conditional denoising diffusion probabilistic models (DDPMs) to generate synthetic frontal radiographs. Our approach ensured that synthetic images mirrored the demographic and pathological traits of the original data. Evaluating the classifiers' performance on internal and external datasets revealed that synthetic data supplementation enhances model accuracy, particularly in detecting less prevalent pathologies. Furthermore, models trained on synthetic data alone approached the performance of those trained on real data. This suggests that synthetic data can potentially compensate for real data shortages in training robust DL models. However, despite promising outcomes, the superiority of real data persists.

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

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

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

Machine learning models for medical image analysis often suffer from poor performance on important subsets of a population that are not identified during training or testing. For example, overall performance of a cancer detection model may be high, but the model still consistently misses a rare but aggressive cancer subtype. We refer to this problem as hidden stratification, and observe that it results from incompletely describing the meaningful variation in a dataset. While hidden stratification can substantially reduce the clinical efficacy of machine learning models, its effects remain difficult to measure. In this work, we assess the utility of several possible techniques for measuring and describing hidden stratification effects, and characterize these effects on multiple medical imaging datasets. We find evidence that hidden stratification can occur in unidentified imaging subsets with low prevalence, low label quality, subtle distinguishing features, or spurious correlates, and that it can result in relative performance differences of over 20% on clinically important subsets. Finally, we explore the clinical implications of our findings, and suggest that evaluation of hidden stratification should be a critical component of any machine learning deployment in medical imaging.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Small sample sizes are common in many disciplines, which necessitates pooling roughly similar datasets across multiple institutions to study weak but relevant associations between images and disease outcomes. Such data often manifest shift/imbalance in covariates (i.e., secondary non-imaging data). Controlling for such nuisance variables is common within standard statistical analysis, but the ideas do not directly apply to overparameterized models. Consequently, recent work has shown how strategies from invariant representation learning provides a meaningful starting point, but the current repertoire of methods is limited to accounting for shifts/imbalances in just a couple of covariates at a time. In this paper, we show how viewing this problem from the perspective of Category theory provides a simple and effective solution that completely avoids elaborate multi-stage training pipelines that would otherwise be needed. We show the effectiveness of this approach via extensive experiments on real datasets. Further, we discuss how this style of formulation offers a unified perspective on at least 5+ distinct problem settings, from self-supervised learning to matching problems in 3D reconstruction.

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

Blood vessels of the brain provide the human brain with the required nutrients and oxygen. As a vulnerable part of the cerebral blood supply, pathology of small vessels can cause serious problems such as Cerebral Small Vessel Diseases (CSVD). It has also been shown that CSVD is related to neurodegeneration, such as Alzheimer's disease. With the advancement of 7 Tesla MRI systems, higher spatial image resolution can be achieved, enabling the depiction of very small vessels in the brain. Non-Deep Learning-based approaches for vessel segmentation, e.g., Frangi's vessel enhancement with subsequent thresholding, are capable of segmenting medium to large vessels but often fail to segment small vessels. The sensitivity of these methods to small vessels can be increased by extensive parameter tuning or by manual corrections, albeit making them time-consuming, laborious, and not feasible for larger datasets. This paper proposes a deep learning architecture to automatically segment small vessels in 7 Tesla 3D Time-of-Flight (ToF) Magnetic Resonance Angiography (MRA) data. The algorithm was trained and evaluated on a small imperfect semi-automatically segmented dataset of only 11 subjects; using six for training, two for validation, and three for testing. The deep learning model based on U-Net Multi-Scale Supervision was trained using the training subset and was made equivariant to elastic deformations in a self-supervised manner using deformation-aware learning to improve the generalisation performance. The proposed technique was evaluated quantitatively and qualitatively against the test set and achieved a Dice score of 80.44 pm 0.83. Furthermore, the result of the proposed method was compared against a selected manually segmented region (62.07 resultant Dice) and has shown a considerable improvement (18.98\%) with deformation-aware learning.

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