通过融合多中心数据特征提升阿尔茨海默病病因诊断准确率
Dementia Etiology Diagnosis via Collaborative Meta Knowledge Enhancement

- 将中心特异性采集信息、来源标识和模态指示作为嵌入注入Transformer,显式建模数据异质性
- 在7个独立队列中平均宏AUC达85.62%,较最强基线提升4.29个百分点
- 适合需要跨中心泛化能力的临床辅助诊断系统开发
尽管人工智能在多项医疗任务中表现优异,但因疾病症状复杂重叠,实现精准的痴呆病因诊断仍具挑战。通过整合多中心样本扩大数据规模虽可提升性能,但各中心间固有的数据异质性导致冲突。传统多任务学习框架未考虑关键元信息(如站点特定采集方式和模态可用性),难以应对异质性。为此,本文提出协同元知识增强(COME)框架,将多中心采集语义、源标识符和模态指示作为异质性感知嵌入注入统一Transformer架构,实现异质性的显式建模。此外,设计信任区域约束优化方案,通过参考模型正则化训练过程,防止虚假相关性。在七个独立队列上,本方法在域内表现达到最新水平,平均宏AUC为85.62%,较最强基线提升4.29点;在跨中心与跨序列评估中均保持优异的域外泛化能力。大量验证还证实模型预测与已知生物标志物(淀粉样蛋白、磷化tau)及临床严重程度高度一致,表明COME具备在真实世界中实现稳健且可解释痴呆诊断的潜力。
原文摘要 · Abstract (English)
Although artificial intelligence (AI) has shown promising performance in several medical tasks, accurate dementia etiology diagnosis with AI remains challenging due to complex overlapping symptoms among diseases. Scaling up the dataset size by combining the cross-center samples may bring a gain in the pursuit of performance, while the inherent data heterogeneity across centers or populations induces the conflict. Conventional multi-task learning paradigms offer a promising framework; however, they fail to consider critical meta information (e.g., site-specific acquisition and modality availability) to combat the heterogeneity. To address this challenge, we propose a Collaborative Meta Knowledge Enhancement (COME) framework for dementia etiology diagnosis, which injects multi-center acquisition semantics, source identifiers, and modality indicators as heterogeneity-aware embeddings into a unified Transformer architecture for scale-up training, enabling explicit modeling of heterogeneity. Besides, a trust-region constrained optimization scheme is designed to regularize the model from spurious correlations during training through a reference model. Across seven independent cohorts, our method achieves state-of-the-art in-domain performance with a mean macro-averaged AUC of 85.62% and a 4.29-point gain over the strongest baseline, while maintaining superior out-of-domain generalization under both cross-center and cross-sequence evaluations. Extensive validation also confirms the alignment between model predictions and established biomarkers (amyloid, tau) and clinical severity, highlighting the potential of COME to enable robust and interpretable dementia diagnostics in real-world settings.
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