Disentangling specific and off-target signals in tau PET imaging

项目摘要 tau聚集体的正电子发射断层扫描（PET）成像在tau蛋白的表达中起着越来越重要的作用。 阿尔茨海默病（AD）和其他tau蛋白病的诊断，并提供了新的见解， 这些疾病的病理生理学。已经开发出有前途的tau放射性示踪剂，但它们都受到 由于在与疾病直接相关的大脑区域中的脱靶结合而受到重要的限制 或在相邻区域。我们提出了一种新的方法，基于因素分析的动态 序列，以去除该污染信号对PET测量的贡献。我们期望我们 一种方法可以提高我们量化关键大脑区域tau聚集体中小信号变化的能力，这在 这将提高我们在早期诊断AD的能力，发现纵向研究的变化， 监测对未来疗法的反应。我们将描述所提出的方法的性能， 计算机模拟，并将评估该技术在实验测量获得的健康 对照组、轻度认知障碍（MCI）受试者和AD患者。

PROJECT SUMMARY Positron emission tomography (PET) imaging of tau aggregates plays an increasingly important role in the diagnosis of Alzheimer’s disease (AD) and other tauopathies, and has provided new insights into the pathophysiology of these diseases. Promising tau radiotracers have been developed, however they all suffer from important limitations due to off-target binding either in brain regions directly implicated in the disease process or in adjacent regions. We propose to develop a new approach based on factor analysis of dynamic sequences to remove the contribution of this contaminating signal to the PET measurements. We expect our approach to improve our ability to quantify small signal changes in tau aggregates in key brain regions, which in turn should improve our ability to diagnose AD in early stages, to detect changes in longitudinal studies and to monitor responses to future therapeutics. We will characterize the performance of the proposed method in computer simulations and will evaluate the technique in experimental measurements acquired in healthy controls, subjects with mild cognitive impairment (MCI) and AD patients.