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.

项目摘要 Tau聚集体的正电子发射断层扫描（PET）成像在 诊断阿尔茨海默氏病（AD）和其他tauopathies，并为此提供了新的见解 这些疾病的病理生理。有希望的tau radiotracers已经开发出来，但是他们都是受害者 来自直接与该疾病的大脑区域中的靶向结合引起的重要局限性 过程或相邻区域。我们建议基于动态因素分析开发一种新方法 去除该污染信号对PET测量值的贡献的序列。我们期望我们的 提高我们量化关键大脑区域中tau聚集体的小信号变化能力的方法， 转弯应提高我们在早期阶段诊断AD的能力，检测纵向研究的变化和 监视对未来治疗的反应。我们将表征提出方法的性能 计算机模拟，并将评估在健康中获得的实验测量中的技术 对照，轻度认知障碍（MCI）和AD患者的受试者。