用神经算子构建阿尔茨海默病患者数字孪生,预测蛋白扩散并优化治疗方案
Neural operator-based digital twins for modeling amyloid-$β$ and tau propagation and treatment optimization in Alzheimer's disease

- 基于数据驱动的神经算子学习,从稀疏影像中推断疾病演化方程
- 对淀粉样蛋白和τ蛋白的预测准确率分别达87%和81%
- 可生成个性化治疗策略,适合精准医疗与神经退行性疾病研究者
在个体层面准确预测淀粉样β和τ蛋白的时空演变,对改善阿尔茨海默病的诊断与治疗至关重要。本文构建患者特异性的数字孪生模型,利用反应-扩散动力学在皮层表面模拟这些生物标志物的传播。主要挑战在于其非线性聚集机制未知,需从稀疏、噪声大且异质的纵向PET影像数据中推断。为此,我们提出一种数据驱动框架,结合算子学习与降维表示,直接从临床观测中学习疾病演化规律。该方法在淀粉样β和τ蛋白预测上分别达到87%和81%的准确率。在此基础上,进一步建立受偏微分方程约束的最优控制问题,设计个性化治疗策略以调控病理蛋白传播。通过融合数据驱动建模与治疗优化,该数字孪生框架为理解疾病进展和实现神经退行性疾病精准干预提供了可解释且具预测能力的平台。
原文摘要 · Abstract (English)
Accurately predicting the spatiotemporal evolution of amyloid-$β$ and tau proteins at the individual level is critical for improving the diagnosis and treatment of Alzheimer's disease. We consider the problem of constructing patient-specific digital twins that model the propagation of these biomarkers on the cortical surface using reaction--diffusion dynamics. A major challenge is that the underlying nonlinear aggregation mechanisms are unknown and must be inferred from sparse, noisy, and heterogeneous longitudinal PET imaging data. To address this, we develop a data-driven framework that learns biomarker dynamics directly from clinical observations. The approach combines operator learning with reduced-order representations to infer governing equations of disease progression from data. Using this framework, we achieve predictive accuracies of 87\% for amyloid-$β$ and 81\% for tau. Building on the learned dynamics, we further formulate a PDE-constrained optimal control problem to design personalized therapeutic strategies that regulate pathological protein propagation. By integrating data-driven dynamical modeling with treatment optimization, the proposed digital twin framework provides an interpretable and predictive platform for understanding disease progression and enabling precision interventions in neurodegenerative disorders.
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