标题： 海马tau沉积的几何建模：一种基于表面的协变量分析和非靶向污染检测框架 显示英文标题

标题： Geometric Modeling of Hippocampal Tau Deposition: A Surface-Based Framework for Covariate Analysis and Off-Target Contamination Detection

摘要： 我们引入了一个结合几何建模与疾病进展分析的框架，利用正电子发射断层扫描（PET）数据来研究阿尔茨海默病（AD）中的tau沉积。 专注于海马体，我们构建了一个主表面，以捕捉tau病理的空间分布和形态变化。 通过将体素投影到该表面上，我们通过双向投影距离和插值的标准摄取值比（SUVR）量化tau的覆盖范围、强度和厚度。 这种低维嵌入保留了空间特异性，同时减轻了多重比较问题。 使用两阶段回归模型与逆概率加权来分析协变量效应，以调整信号稀疏性和选择偏差。 使用SuStaIn模型，我们识别出AD的亚型和阶段，揭示了不同的tau动态：以边缘为主导的亚型在覆盖范围和厚度上表现出与年龄相关的非线性积累，而后部亚型在整个疾病进展过程中表现出均匀的SUVR增加。 基于模型的预测表明，海马体tau沉积遵循一种结构化的空间轨迹，随着厚度增加而双向扩展，而亚型差异突显了后部海马体的参与，这与全脑模式一致。 最后，主表面上的方向信号模式揭示了来自脉络丛的污染，展示了所提出框架在包括淀粉样蛋白PET在内的多种模态中的更广泛应用。 显示英文摘要

摘要： We introduce a framework combining geometric modeling with disease progression analysis to investigate tau deposition in Alzheimer's disease (AD) using positron emission tomography (PET) data. Focusing on the hippocampus, we construct a principal surface that captures the spatial distribution and morphological changes of tau pathology. By projecting voxels onto this surface, we quantify tau coverage, intensity, and thickness through bidirectional projection distances and interpolated standardized uptake value ratios (SUVR). This low-dimensional embedding preserves spatial specificity while mitigating multiple comparison issues. Covariate effects are analyzed using a two-stage regression model with inverse probability weighting to adjust for signal sparsity and selection bias. Using the SuStaIn model, we identify subtypes and stages of AD, revealing distinct tau dynamics: the limbic-predominant subtype shows age-related nonlinear accumulation in coverage and thickness, whereas the posterior subtype exhibits uniform SUVR increases across disease progression. Model-based predictions show that hippocampal tau deposition follows a structured spatial trajectory expanding bidirectionally with increasing thickness, while subtype differences highlight posterior hippocampal involvement consistent with whole-brain patterns. Finally, directional signal patterns on the principal surface reveal contamination from the choroid plexus, demonstrating the broader applicability of the proposed framework across modalities including amyloid PET.