With the rise of medical foundation models and the growing availability of imaging data, scalable pretraining techniques offer a promising way to identify imaging biomarkers predictive of future disease risk. While current self-supervised methods for 3D medical imaging models capture local structural features like organ morphology, they fail to link pixel biomarkers with long-term health outcomes due to a missing context problem. Current approaches lack the temporal context necessary to identify biomarkers correlated with disease progression, as they rely on supervision derived only from images and concurrent text descriptions. To address this, we introduce time-to-event pretraining, a pretraining framework for 3D medical imaging models that leverages large-scale temporal supervision from paired, longitudinal electronic health records (EHRs). Using a dataset of 18,945 CT scans (4.2 million 2D images) and time-to-event distributions across thousands of EHR-derived tasks, our method improves outcome prediction, achieving an average AUROC increase of 23.7% and a 29.4% gain in Harrell’s C-index across 8 benchmark tasks. Importantly, these gains are achieved without sacrificing diagnostic classification performance. This study lays the foundation for integrating longitudinal EHR and 3D imaging data to advance clinical risk prediction.

Analyzing anatomic shapes of tissues and organs is pivotal for accurate disease diagnostics and clinical decision-making. One prominent disease that depends on anatomic shape analysis is osteoarthritis, which affects 30 million Americans. To advance osteoarthritis diagnostics and prognostics, we introduce ShapeMed-Knee, a 3D shape dataset with 9,376 high-resolution, medical-imaging-based 3D shapes of both femur bone and cartilage. Besides data, ShapeMed-Knee includes two benchmarks for assessing reconstruction accuracy and five clinical prediction tasks that assess the utility of learned shape representations. Leveraging ShapeMed-Knee, we develop and evaluate a novel hybrid explicit-implicit neural shape model which achieves up to 40% better reconstruction accuracy than a statistical shape model and two implicit neural shape models. Our hybrid models achieve state-of-the-art performance for preserving cartilage biomarkers (root mean squared error ≤ 0.05 vs. ≤ 0.07, 0.10, and 0.14). Our models are also the first to successfully predict localized structural features of osteoarthritis, outperforming shape models and convolutional neural networks applied to raw magnetic resonance images and segmentations (e.g., osteophyte size and localization 63% accuracy vs. 49-61%). The ShapeMed-Knee dataset provides medical evaluations to reconstruct multiple anatomic surfaces and embed meaningful disease-specific information. ShapeMed-Knee reduces barriers to applying 3D modeling in medicine, and our benchmarks highlight that advancements in 3D modeling can enhance the diagnosis and risk stratification for complex diseases. The dataset, code, and benchmarks are freely accessible.

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. MedAlign is provided under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.