From Trajectories to Phenotypes: Disease Progression as Structural Priors for Multi-organ Imaging Representation Learning

Imaging-derived phenotypes (IDPs) summarize multi-organ physiology but provide only static snapshots of diseases that evolve over time. In contrast, longitudinal electronic health records encode disease trajectories through temporal dependencies among past diagnosis events and comorbidity structure. We hypothesize that IDPs and disease trajectories contain partially shared disease-relevant structure. We propose a trajectory-aware distillation framework that transfers structural knowledge from a generative disease trajectory Transformer into an organ-wise IDP encoder. A population-scale trajectory model trained on longitudinal diagnosis sequences produces subject-level embeddings that supervise IDP representation learning via geometry-preserving alignment. During downstream prediction, trajectory and imaging representations can also be fused via cross-attention. Across 159 diseases in the UK Biobank cohort, trajectory-aware pretraining consistently improves both discrimination (AUC) and time-to-onset prediction (MAE), with the largest gains for low-prevalence diseases. Similarity relationships in IDP embedding space also align with those in trajectory space, providing supportive evidence for partially aligned representation geometry. These results suggest that population-scale generative disease models can serve as structural priors for data-limited imaging modalities, improving robustness under realistic cohort constraints.

Enabling Ultra-Fast Cardiovascular Imaging Across Heterogeneous Clinical Environments with a Generalist Foundation Model and Multimodal Database

Multimodal cardiovascular magnetic resonance (CMR) imaging provides comprehensive and non-invasive insights into cardiovascular disease (CVD) diagnosis and underlying mechanisms. Despite decades of advancements, its widespread clinical adoption remains constrained by prolonged scan times and heterogeneity across medical environments. This underscores the urgent need for a generalist reconstruction foundation model for ultra-fast CMR imaging, one capable of adapting across diverse imaging scenarios and serving as the essential substrate for all downstream analyses. To enable this goal, we curate MMCMR-427K, the largest and most comprehensive multimodal CMR k-space database to date, comprising 427,465 multi-coil k-space data paired with structured metadata across 13 international centers, 12 CMR modalities, 15 scanners, and 17 CVD categories in populations across three continents. Building on this unprecedented resource, we introduce CardioMM, a generalist reconstruction foundation model capable of dynamically adapting to heterogeneous fast CMR imaging scenarios. CardioMM unifies semantic contextual understanding with physics-informed data consistency to deliver robust reconstructions across varied scanners, protocols, and patient presentations. Comprehensive evaluations demonstrate that CardioMM achieves state-of-the-art performance in the internal centers and exhibits strong zero-shot generalization to unseen external settings. Even at imaging acceleration up to 24x, CardioMM reliably preserves key cardiac phenotypes, quantitative myocardial biomarkers, and diagnostic image quality, enabling a substantial increase in CMR examination throughput without compromising clinical integrity. Together, our open-access MMCMR-427K database and CardioMM framework establish a scalable pathway toward high-throughput, high-quality, and clinically accessible cardiovascular imaging.