Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.
The study evaluates and compares GPT-4 and GPT-4Vision for radiological tasks, suggesting GPT-4Vision may recognize radiological features from images, thereby enhancing its diagnostic potential over text-based descriptions.
Detecting misleading patterns in automated diagnostic assistance systems, such as those powered by Artificial Intelligence, is critical to ensuring their reliability, particularly in healthcare. Current techniques for evaluating deep learning models cannot visualize confounding factors at a diagnostic level. Here, we propose a self-conditioned diffusion model termed DiffChest and train it on a dataset of 515,704 chest radiographs from 194,956 patients from multiple healthcare centers in the United States and Europe. DiffChest explains classifications on a patient-specific level and visualizes the confounding factors that may mislead the model. We found high inter-reader agreement when evaluating DiffChest's capability to identify treatment-related confounders, with Fleiss' Kappa values of 0.8 or higher across most imaging findings. Confounders were accurately captured with 11.1% to 100% prevalence rates. Furthermore, our pretraining process optimized the model to capture the most relevant information from the input radiographs. DiffChest achieved excellent diagnostic accuracy when diagnosing 11 chest conditions, such as pleural effusion and cardiac insufficiency, and at least sufficient diagnostic accuracy for the remaining conditions. Our findings highlight the potential of pretraining based on diffusion models in medical image classification, specifically in providing insights into confounding factors and model robustness.
Large language models (LLMs) have broad medical knowledge and can reason about medical information across many domains, holding promising potential for diverse medical applications in the near future. In this study, we demonstrate a concerning vulnerability of LLMs in medicine. Through targeted manipulation of just 1.1% of the model's weights, we can deliberately inject an incorrect biomedical fact. The erroneous information is then propagated in the model's output, whilst its performance on other biomedical tasks remains intact. We validate our findings in a set of 1,038 incorrect biomedical facts. This peculiar susceptibility raises serious security and trustworthiness concerns for the application of LLMs in healthcare settings. It accentuates the need for robust protective measures, thorough verification mechanisms, and stringent management of access to these models, ensuring their reliable and safe use in medical practice.
A knowledge gap persists between Machine Learning (ML) developers (e.g., data scientists) and practitioners (e.g., clinicians), hampering the full utilization of ML for clinical data analysis. We investigated the potential of the chatGPT Advanced Data Analysis (ADA), an extension of GPT-4, to bridge this gap and perform ML analyses efficiently. Real-world clinical datasets and study details from large trials across various medical specialties were presented to chatGPT ADA without specific guidance. ChatGPT ADA autonomously developed state-of-the-art ML models based on the original study's training data to predict clinical outcomes such as cancer development, cancer progression, disease complications, or biomarkers such as pathogenic gene sequences. Strikingly, these ML models matched or outperformed their published counterparts. We conclude that chatGPT ADA offers a promising avenue to democratize ML in medicine, making advanced analytics accessible to non-ML experts and promoting broader applications in medical research and practice.
Computed Tomography (CT) scans provide detailed and accurate information of internal structures in the body. They are constructed by sending x-rays through the body from different directions and combining this information into a three-dimensional volume. Such volumes can then be used to diagnose a wide range of conditions and allow for volumetric measurements of organs. In this work, we tackle the problem of reconstructing CT images from biplanar x-rays only. X-rays are widely available and even if the CT reconstructed from these radiographs is not a replacement of a complete CT in the diagnostic setting, it might serve to spare the patients from radiation where a CT is only acquired for rough measurements such as determining organ size. We propose a novel method based on the transformer architecture, by framing the underlying task as a language translation problem. Radiographs and CT images are first embedded into latent quantized codebook vectors using two different autoencoder networks. We then train a GPT model, to reconstruct the codebook vectors of the CT image, conditioned on the codebook vectors of the x-rays and show that this approach leads to realistic looking images. To encourage further research in this direction, we make our code publicly available on GitHub: XXX.
Whole-Slide Imaging allows for the capturing and digitization of high-resolution images of histological specimen. An automated analysis of such images using deep learning models is therefore of high demand. The transformer architecture has been proposed as a possible candidate for effectively leveraging the high-resolution information. Here, the whole-slide image is partitioned into smaller image patches and feature tokens are extracted from these image patches. However, while the conventional transformer allows for a simultaneous processing of a large set of input tokens, the computational demand scales quadratically with the number of input tokens and thus quadratically with the number of image patches. To address this problem we propose a novel cascaded cross-attention network (CCAN) based on the cross-attention mechanism that scales linearly with the number of extracted patches. Our experiments demonstrate that this architecture is at least on-par with and even outperforms other attention-based state-of-the-art methods on two public datasets: On the use-case of lung cancer (TCGA NSCLC) our model reaches a mean area under the receiver operating characteristic (AUC) of 0.970 $\pm$ 0.008 and on renal cancer (TCGA RCC) reaches a mean AUC of 0.985 $\pm$ 0.004. Furthermore, we show that our proposed model is efficient in low-data regimes, making it a promising approach for analyzing whole-slide images in resource-limited settings. To foster research in this direction, we make our code publicly available on GitHub: XXX.
As large language models (LLMs) like OpenAI's GPT series continue to make strides, we witness the emergence of artificial intelligence applications in an ever-expanding range of fields. In medicine, these LLMs hold considerable promise for improving medical workflows, diagnostics, patient care, and education. Yet, there is an urgent need for open-source models that can be deployed on-premises to safeguard patient privacy. In our work, we present an innovative dataset consisting of over 160,000 entries, specifically crafted to fine-tune LLMs for effective medical applications. We investigate the impact of fine-tuning these datasets on publicly accessible pre-trained LLMs, and subsequently, we juxtapose the performance of pre-trained-only models against the fine-tuned models concerning the examinations that future medical doctors must pass to achieve certification.
Multimodal deep learning has been used to predict clinical endpoints and diagnoses from clinical routine data. However, these models suffer from scaling issues: they have to learn pairwise interactions between each piece of information in each data type, thereby escalating model complexity beyond manageable scales. This has so far precluded a widespread use of multimodal deep learning. Here, we present a new technical approach of "learnable synergies", in which the model only selects relevant interactions between data modalities and keeps an "internal memory" of relevant data. Our approach is easily scalable and naturally adapts to multimodal data inputs from clinical routine. We demonstrate this approach on three large multimodal datasets from radiology and ophthalmology and show that it outperforms state-of-the-art models in clinically relevant diagnosis tasks. Our new approach is transferable and will allow the application of multimodal deep learning to a broad set of clinically relevant problems.
The success of Deep Learning applications critically depends on the quality and scale of the underlying training data. Generative adversarial networks (GANs) can generate arbitrary large datasets, but diversity and fidelity are limited, which has recently been addressed by denoising diffusion probabilistic models (DDPMs) whose superiority has been demonstrated on natural images. In this study, we propose Medfusion, a conditional latent DDPM for medical images. We compare our DDPM-based model against GAN-based models, which constitute the current state-of-the-art in the medical domain. Medfusion was trained and compared with (i) StyleGan-3 on n=101,442 images from the AIROGS challenge dataset to generate fundoscopies with and without glaucoma, (ii) ProGAN on n=191,027 from the CheXpert dataset to generate radiographs with and without cardiomegaly and (iii) wGAN on n=19,557 images from the CRCMS dataset to generate histopathological images with and without microsatellite stability. In the AIROGS, CRMCS, and CheXpert datasets, Medfusion achieved lower (=better) FID than the GANs (11.63 versus 20.43, 30.03 versus 49.26, and 17.28 versus 84.31). Also, fidelity (precision) and diversity (recall) were higher (=better) for Medfusion in all three datasets. Our study shows that DDPM are a superior alternative to GANs for image synthesis in the medical domain.