The accurate classification of lymphoma subtypes using hematoxylin and eosin (H&E)-stained tissue is complicated by the wide range of morphological features these cancers can exhibit. We present LymphoML - an interpretable machine learning method that identifies morphologic features that correlate with lymphoma subtypes. Our method applies steps to process H&E-stained tissue microarray cores, segment nuclei and cells, compute features encompassing morphology, texture, and architecture, and train gradient-boosted models to make diagnostic predictions. LymphoML's interpretable models, developed on a limited volume of H&E-stained tissue, achieve non-inferior diagnostic accuracy to pathologists using whole-slide images and outperform black box deep-learning on a dataset of 670 cases from Guatemala spanning 8 lymphoma subtypes. Using SHapley Additive exPlanation (SHAP) analysis, we assess the impact of each feature on model prediction and find that nuclear shape features are most discriminative for DLBCL (F1-score: 78.7%) and classical Hodgkin lymphoma (F1-score: 74.5%). Finally, we provide the first demonstration that a model combining features from H&E-stained tissue with features from a standardized panel of 6 immunostains results in a similar diagnostic accuracy (85.3%) to a 46-stain panel (86.1%).
We propose the Multimodal Clinical Benchmark for Emergency Care (MC-BEC), a comprehensive benchmark for evaluating foundation models in Emergency Medicine using a dataset of 100K+ continuously monitored Emergency Department visits from 2020-2022. MC-BEC focuses on clinically relevant prediction tasks at timescales from minutes to days, including predicting patient decompensation, disposition, and emergency department (ED) revisit, and includes a standardized evaluation framework with train-test splits and evaluation metrics. The multimodal dataset includes a wide range of detailed clinical data, including triage information, prior diagnoses and medications, continuously measured vital signs, electrocardiogram and photoplethysmograph waveforms, orders placed and medications administered throughout the visit, free-text reports of imaging studies, and information on ED diagnosis, disposition, and subsequent revisits. We provide performance baselines for each prediction task to enable the evaluation of multimodal, multitask models. We believe that MC-BEC will encourage researchers to develop more effective, generalizable, and accessible foundation models for multimodal clinical data.
Automatically generated reports from medical images promise to improve the workflow of radiologists. Existing methods consider an image-to-report modeling task by directly generating a fully-fledged report from an image. However, this conflates the content of the report (e.g., findings and their attributes) with its style (e.g., format and choice of words), which can lead to clinically inaccurate reports. To address this, we propose a two-step approach for radiology report generation. First, we extract the content from an image; then, we verbalize the extracted content into a report that matches the style of a specific radiologist. For this, we leverage RadGraph -- a graph representation of reports -- together with large language models (LLMs). In our quantitative evaluations, we find that our approach leads to beneficial performance. Our human evaluation with clinical raters highlights that the AI-generated reports are indistinguishably tailored to the style of individual radiologist despite leveraging only a few examples as context.
The recent success of general-domain large language models (LLMs) has significantly changed the natural language processing paradigm towards a unified foundation model across domains and applications. In this paper, we focus on assessing the performance of GPT-4, the most capable LLM so far, on the text-based applications for radiology reports, comparing against state-of-the-art (SOTA) radiology-specific models. Exploring various prompting strategies, we evaluated GPT-4 on a diverse range of common radiology tasks and we found GPT-4 either outperforms or is on par with current SOTA radiology models. With zero-shot prompting, GPT-4 already obtains substantial gains ($\approx$ 10% absolute improvement) over radiology models in temporal sentence similarity classification (accuracy) and natural language inference ($F_1$). For tasks that require learning dataset-specific style or schema (e.g. findings summarisation), GPT-4 improves with example-based prompting and matches supervised SOTA. Our extensive error analysis with a board-certified radiologist shows GPT-4 has a sufficient level of radiology knowledge with only occasional errors in complex context that require nuanced domain knowledge. For findings summarisation, GPT-4 outputs are found to be overall comparable with existing manually-written impressions.
While hundreds of artificial intelligence (AI) algorithms are now approved or cleared by the US Food and Drugs Administration (FDA), many studies have shown inconsistent generalization or latent bias, particularly for underrepresented populations. Some have proposed that generative AI could reduce the need for real data, but its utility in model development remains unclear. Skin disease serves as a useful case study in synthetic image generation due to the diversity of disease appearance, particularly across the protected attribute of skin tone. Here we show that latent diffusion models can scalably generate images of skin disease and that augmenting model training with these data improves performance in data-limited settings. These performance gains saturate at synthetic-to-real image ratios above 10:1 and are substantially smaller than the gains obtained from adding real images. As part of our analysis, we generate and analyze a new dataset of 458,920 synthetic images produced using several generation strategies. Our results suggest that synthetic data could serve as a force-multiplier for model development, but the collection of diverse real-world data remains the most important step to improve medical AI algorithms.
We present RadGraph2, a novel dataset for extracting information from radiology reports that focuses on capturing changes in disease state and device placement over time. We introduce a hierarchical schema that organizes entities based on their relationships and show that using this hierarchy during training improves the performance of an information extraction model. Specifically, we propose a modification to the DyGIE++ framework, resulting in our model HGIE, which outperforms previous models in entity and relation extraction tasks. We demonstrate that RadGraph2 enables models to capture a wider variety of findings and perform better at relation extraction compared to those trained on the original RadGraph dataset. Our work provides the foundation for developing automated systems that can track disease progression over time and develop information extraction models that leverage the natural hierarchy of labels in the medical domain.
Medicine, by its nature, is a multifaceted domain that requires the synthesis of information across various modalities. Medical generative vision-language models (VLMs) make a first step in this direction and promise many exciting clinical applications. However, existing models typically have to be fine-tuned on sizeable down-stream datasets, which poses a significant limitation as in many medical applications data is scarce, necessitating models that are capable of learning from few examples in real-time. Here we propose Med-Flamingo, a multimodal few-shot learner adapted to the medical domain. Based on OpenFlamingo-9B, we continue pre-training on paired and interleaved medical image-text data from publications and textbooks. Med-Flamingo unlocks few-shot generative medical visual question answering (VQA) abilities, which we evaluate on several datasets including a novel challenging open-ended VQA dataset of visual USMLE-style problems. Furthermore, we conduct the first human evaluation for generative medical VQA where physicians review the problems and blinded generations in an interactive app. Med-Flamingo improves performance in generative medical VQA by up to 20\% in clinician's rating and firstly enables multimodal medical few-shot adaptations, such as rationale generation. We release our model, code, and evaluation app under https://github.com/snap-stanford/med-flamingo.
Recent advances in zero-shot learning have enabled the use of paired image-text data to replace structured labels, replacing the need for expert annotated datasets. Models such as CLIP-based CheXzero utilize these advancements in the domain of chest X-ray interpretation. We hypothesize that domain pre-trained models such as CXR-BERT, BlueBERT, and ClinicalBERT offer the potential to improve the performance of CLIP-like models with specific domain knowledge by replacing BERT weights at the cost of breaking the original model's alignment. We evaluate the performance of zero-shot classification models with domain-specific pre-training for detecting low-prevalence pathologies. Even though replacing the weights of the original CLIP-BERT degrades model performance on commonly found pathologies, we show that pre-trained text towers perform exceptionally better on low-prevalence diseases. This motivates future ensemble models with a combination of differently trained language models for maximal performance.
Medical data poses a daunting challenge for AI algorithms: it exists in many different modalities, experiences frequent distribution shifts, and suffers from a scarcity of examples and labels. Recent advances, including transformers and self-supervised learning, promise a more universal approach that can be applied flexibly across these diverse conditions. To measure and drive progress in this direction, we present BenchMD: a benchmark that tests how modality-agnostic methods, including architectures and training techniques (e.g. self-supervised learning, ImageNet pretraining), perform on a diverse array of clinically-relevant medical tasks. BenchMD combines 19 publicly available datasets for 7 medical modalities, including 1D sensor data, 2D images, and 3D volumetric scans. Our benchmark reflects real-world data constraints by evaluating methods across a range of dataset sizes, including challenging few-shot settings that incentivize the use of pretraining. Finally, we evaluate performance on out-of-distribution data collected at different hospitals than the training data, representing naturally-occurring distribution shifts that frequently degrade the performance of medical AI models. Our baseline results demonstrate that no modality-agnostic technique achieves strong performance across all modalities, leaving ample room for improvement on the benchmark. Code is released at https://github.com/rajpurkarlab/BenchMD .