Disentangling specific and off-target signals in tau PET imaging

项目总结 正电子发射断层扫描(PET)对tau聚集体的成像在以下方面发挥越来越重要的作用 诊断阿尔茨海默病(AD)和其他肌萎缩侧索硬化症，并为 这些疾病的病理生理学。有希望的tau放射性示踪剂已经被开发出来，然而它们都受到了影响。 由于与疾病直接牵连的大脑区域的非靶点结合而产生的重要限制 进程或在相邻区域。我们提出了一种基于动态因子分析的新方法 序列，以消除该污染信号对PET测量的影响。我们期待我们的 提高我们量化关键大脑区域tau聚集体小信号变化的能力的方法，这在 TURN应该会提高我们在早期诊断AD的能力，在纵向研究中发现变化，并 监测对未来疗法的反应。我们将在下面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中获得的健康 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.