Disentangling specific and off-target signals in tau PET imaging

解开 tau PET 成像中的特定信号和脱靶信号

• 批准号: 10461941
• 负责人: Nicolas Jean Guehl
• 金额: $ 21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461941
• 关键词: Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Basal Ganglia; Binding; Blood; Bone Marrow; Brain; Brain region; Cardiac; Characteristics; Clinical; Clinical Research; Computer Simulation; Computer software; Data; Data Set; Dementia; Development; Disease; Elderly; Factor Analysis; Foundations; Functional disorder; Future; Generations; Goals; Image; Impaired cognition; Kinetics; Longitudinal Studies; Measurement; Measures; Meninges; Methodology; Methods; Monitor; Neurofibrillary Tangles; Neuronal Injury; Outcome Measure; Performance; Physiological Processes; Play; Positron-Emission Tomography; Process; Raclopride; Role; Signal Transduction; Structure; Structure of choroid plexus; Tauopathies; Techniques; Testing; Therapeutic; Time; Tracer; Work; base; disease diagnosis; fluorodeoxyglucose; human subject; improved; in vivo; in vivo imaging; insight; interest; kinetic model; mathematical model; mild cognitive impairment; neuroimaging; novel strategies; perfusion imaging; radiotracer; response; simulation; spatiotemporal; tau Proteins; tau aggregation

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.

项目概要 tau 聚集体的正电子发射断层扫描 (PET) 成像在 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研究已经开发出来，但它们都受到影响。 由于与疾病直接相关的大脑区域中的脱靶结合导致的重要限制 我们建议开发一种基于动态因素分析的新方法。 序列以消除这种污染信号对 PET 测量的影响。 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 转变应该提高我们在早期阶段诊断 AD、检测纵向研究的变化以及 我们将监测对未来治疗的反应。 计算机模拟并将评估在健康中获得的实验测量技术 对照组、轻度认知障碍 (MCI) 受试者和 AD 患者。