用疾病演化轨迹指导多器官影像表型学习,提升低发病率疾病的预测能力。
From Trajectories to Phenotypes: Disease Progression as Structural Priors for Multi-organ Imaging Representation Learning

- 通过生成式轨迹模型将疾病演化结构迁移至影像编码器
- 在159种疾病中显著提升判别与发病时间预测性能,尤其对罕见病有效
- 适合需要小样本、强泛化能力的医学影像表型研究者
影像衍生表型(IDPs)可概括多器官生理状态,但仅提供疾病演化的静态快照。相反,纵向电子健康记录通过历史诊断事件间的时序依赖和共病结构,刻画疾病演化轨迹。我们假设IDPs与疾病轨迹包含部分共享的疾病相关结构。提出一种轨迹感知的知识蒸馏框架,将生成式疾病轨迹Transformer中的结构知识迁移到器官级IDP编码器中。基于英国生物银行队列的大规模轨迹模型生成个体嵌入,通过保持几何结构的对齐方式监督IDP表示学习。下游预测中,可通过交叉注意力融合轨迹与影像表示。在159种疾病上,轨迹感知预训练显著提升判别能力(AUC)与发病时间预测精度(MAE),对低患病率疾病提升最明显。IDP嵌入空间的相似性关系也与轨迹空间一致,支持表示几何的部分对齐。结果表明,大规模生成式疾病模型可作为数据有限影像模态的结构先验,增强真实队列约束下的鲁棒性。
原文摘要 · Abstract (English)
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.
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