Dominantly Inherited Alzheimer Network: Imaging Core

显性遗传阿尔茨海默病网络：成像核心

• 批准号: 10665740
• 负责人: Tammie Lee Smith Benzinger
• 金额: $ 115.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665740
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease patient; Amyloid; Amyloid deposition; Appearance; Autoradiography; Binding; Biological Markers; Biostatistics Core; Brain imaging; Brain region; Cerebrospinal Fluid; Cerebrum; Clinical; Clinical Trials Design; Collaborations; Cross-Sectional Studies; Cyclotrons; DNA Sequence Alteration; Data; Data Analyses; Data Set; Deposition; Diffusion; Diffusion Magnetic Resonance Imaging; Enrollment; Ensure; Evaluation; Functional Magnetic Resonance Imaging; Future; Genetic; Genotype; Good Clinical Practice; Guidelines; Hemorrhage; Image; Imaging Techniques; Immunohistochemistry; Impaired cognition; Inflammation; Informatics; Inherited; International; Late Onset Alzheimer Disease; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Methods; Monoamine Oxidase; Mutation; Nerve Degeneration; Neurofibrillary Tangles; Neuroimmune; Neurons; Participant; Pharmacologic Substance; Phenotype; Pittsburgh Compound-B; Positron-Emission Tomography; Process; Production; Productivity; Protocols documentation; Proxy; Psychometrics; Quality Control; Radiation Dose Unit; Reproducibility; Research; Research Personnel; Resources; Rest; Risk; Scanning; Siblings; Site; Source; Standardization; Synapses; Techniques; Testing; Tracer; Update; Visit; Work; arterial spin labeling; autosomal dominant Alzheimer' s disease; cohort; computerized data processing; density; disease-causing mutation; image processing; imaging approach; imaging biomarker; improved; indexing; innovation; longitudinal analysis; mutation carrier; neuroimaging; neuroinflammation; neuropathology; novel; performance site; perfusion imaging; pre-clinical; quality assurance; regional atrophy; repository; risk minimization; serial imaging; spectrograph; tau Proteins; tau aggregation; timeline; white matter; β-amyloid burden

Core G: Imaging Summary The imaging data set collected in the Dominantly Inherited Alzheimer Network (DIAN) participants to date represents a highly valuable resource for Alzheimer's disease (AD) research. It has supported cross sectional analysis of PET and MRI data to develop a timeline for imaging biomarkers in autosomal dominant AD (ADAD). With this renewal application, the DIAN Imaging Core will continue to obtain and analyze longitudinal imaging data that is fully integrated with clinical, psychometric and cerebrospinal fluid (CSF) biomarkers, and will allow for mutation-specific genotype-phenotype analysis. Imaging Core will be responsible for the acquisition, quality control, and analysis of the MRI and PET neuroimaging for DIAN. Carriers of AD-causing mutations and their non-carrier siblings are enrolled and followed in the Clinical Core through the international DIAN performance sites. Participants will undergo structural and functional MRI, amyloid PET, tau PET, and metabolic PET imaging every 2 years, in conjunction with their clinical visits. The source imaging data and post-processed data will be available to collaborating and outside investigators and will be distributed by the Informatics and Biostatistics cores. For tau PET, we will now obtain scans with the tracers [18F]-MK-6240, [18F]-AV-1451 (aka Flortaucipir, T807), and [18F]-PI-2620. Because no single tracer has the international distribution to reach all sites, each site is assigned one for the three tau PET tracers. Using multiple tracers maximizes the number of DIAN sites that can perform tau PET imaging. Including multiple tracers across the study diminishes the risk of choosing one tracer for such a large, international study of unique participants. Approximately 1/3 of participants will undergo imaging with each tracer. We recognize the limitations of using multiple tracers in the same study and have taken steps to minimize this risk. Based upon our preliminary work, each tracer is independently powered to detect significant effects (see Project 2, Approach). Further, our current proposal is adaptive. If our immunohistochemistry and autoradiographic work (Project 2) demonstrates that one candidate tracer is unsuitable (i.e. THK-5351 binding to monoamine oxidase B44), it will be replaced with another. Over the course of the proposal we will also work with Pharma partners to strengthen tracer availability to a wider international network.

核心G：成像摘要 迄今为止，在主要继承的阿尔茨海默网络（Dian）参与者中收集的成像数据集 代表了阿尔茨海默氏病（AD）研究的高度宝贵资源。它支持横截面 对PET和MRI数据的分析，以开发用于对常染色体显性AD中生物标志物成像的时间表 （Adad）。使用此续订应用，Dian Imaging Core将继续获得和分析纵向 与临床，心理测量和脑脊液（CSF）生物标志物完全集成的成像数据以及 将允许特异性基因型 - 表型分析。 成像核心将负责MRI和PET的获取，质量控制和分析 Dian神经影像。招募了引起广告的突变及其非载体兄弟姐妹的载体 紧随其后的是临床核心，通过国际戴安（Dian Dian）表演网站。参与者将经历 结构和功能性MRI，淀粉样蛋白宠物，Tau PET和代谢宠物成像，每2年 他们的临床访问。源成像数据和后处理的数据将用于协作和 外部研究人员将由信息学和生物统计学核心分发。 对于Tau Pet，我们现在将使用示踪剂[18F] -MK-6240，[18F] -AV-1451（又称Flortaucipir，t807），进行扫描 和[18F] -PI-2620。因为没有一个示踪剂可以到达所有站点，所以每个站点都是 为三个tau宠物示踪剂分配了一个。使用多个示踪剂可以最大化Dian站点的数量 可以执行tau宠物成像。整个研究中包括多个示踪剂会降低选择一个的风险 示踪了如此大型国际参与者的国际研究。大约1/3的参与者将经历 用每个示踪剂进行成像。我们认识到在同一研究中使用多个示踪剂的局限性，并且 采取步骤来最大程度地降低这种风险。根据我们的初步工作，每个示踪剂都独立使用 检测显着影响（请参阅项目2，方法）。此外，我们目前的建议是适应性的。如果我们 免疫组织化学和放射自显影工作（项目2）表明，一个候选示踪剂是 不合适的（即Thk-5351与单胺氧化酶B44结合），将其替换为另一个。在课程中 在提案中，我们还将与Pharma Partners合作，以加强对更广泛国际的示踪剂的可用性 网络。