Brainstem connectomes related to Alzheimer's disease

与阿尔茨海默病相关的脑干连接体

• 批准号: 9524584
• 负责人: Yonggang Shi
• 金额: $ 245.73万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9524584
• 关键词: Adopted; Affect; Aging; Algorithmic Analysis; Alzheimer' s Disease; Anatomy; Area; Atlases; Atrophic; Attention; Autopsy; Behavior; Behavioral; Behavioral Symptoms; Binding; Brain; Brain Stem; Brain imaging; Cell Nucleus; Collaborations; Communities; Complement; Computational algorithm; Computer software; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Event; Fiber; Funding; Genetic; Goals; Histology; Human; Image; Imaging Techniques; Late Onset Alzheimer Disease; Limbic System; Magnetic Resonance Imaging; Maps; Measures; Medial; Mediating; Modeling; Nerve Degeneration; Neurotransmitters; Pathology; Pathway interactions; Patients; Phase; Play; Positron-Emission Tomography; Predisposition; Protocols documentation; Public Health; Reporting; Research; Research Personnel; Resolution; Resources; Role; Severity of illness; Software Tools; Staging; Symptoms; System; Techniques; Technology; Temporal Lobe; Testing; Tracer; United States National Institutes of Health; Update; Validation; behavior change; behavior prediction; behavioral impairment; brain pathway; cerebral atrophy; cholinergic; cohort; connectome; dorsal raphe nucleus; entorhinal cortex; experimental study; human data; improved; in vivo; locus ceruleus structure; nervous system disorder; neuroimaging; neuropathology; novel; tau Proteins; tool; web site

Abstract Compared with the medial temporal lobe and other cortical regions, little attention has been paid to the brainstem in Alzheimer's disease (AD) research. Increasing evidence from various neuropathology studies and recently updated Braak staging, however, suggested that the earliest tau pathology may occur in the brainstem nuclei and propagate to trans-entorhinal cortical regions. While tau PET imaging with the AV1451 tracer is emerging as a powerful tool for measuring cortical tau burden, it is limited for studying the brainstem due to low resolution and off-target binding. On the other hand, great advances in connectome imaging techniques have enabled us to study the integrity of brain pathways with unprecedented detail. Using multi-shell diffusion imaging data from the Human Connectome Project (HCP), we have developed novel tools for computing the fiber orientation distributions (FODs) and compartment models. These tools have been successfully applied to reconstruct challenging fiber pathways in the human brain. In this project, we will leverage cutting-edge connectome and tau PET imaging data from two NIH-funded studies and our novel analysis algorithms to build atlases of brainstem connectomes for AD research. Our goal is to develop the enabling techniques that can provide connectivity measures of brainstem to complement cortical tau burdens from PET imaging. With the novel brainstem atlases and associated software tools developed in this project, we will be able to examine the relation of brainstem and cortical atrophy during the disease course of AD. The findings from such experiments will provide in vivo evidence about the Braak staging of tau pathology in the prodromal phase of AD. In addition, the brainstem connectomes will enable the in vivo mapping of the connectivity changes in neurotransmitter-specific pathways and their relation to behavior symptoms in AD patients. Overall there are three specific aims in this project: 1. To develop atlases of brainstem pathways related to AD using connectome imaging data. 2. To examine the relation of connectivity changes in brainstem nuclei and cortical tau pathology in AD. 3. To study the relation of behavioral symptoms and brainstem connectivity in AD. All atlases and software tools developed in this project will be distributed freely to the research community. While we develop these atlases and tools for studying AD, they should also be valuable in research about other neurological disorders where the brainstem plays an important role.

抽象的 与内侧颞叶和其他皮质区域相比，对脑干几乎没有关注 在阿尔茨海默氏病（AD）研究中。来自各种神经病理学研究的越来越多的证据 但是，更新的Braak分期表明，最早的tau病理可能发生在脑干核中 并传播到跨内性皮质区域。而AV1451示踪剂的tau宠物成像正在出现 作为测量皮质tau负担的强大工具，由于低分辨率而言，它限制了研究脑干 和靶向绑定。另一方面，Connectome成像技术的巨大进步使我们能够 用前所未有的细节研究大脑通路的完整性。使用来自多壳扩散成像数据 人类连接组项目（HCP），我们开发了用于计算纤维取向的新颖工具 分布（FOD）和车厢模型。这些工具已成功地用于重建 挑战人脑中的纤维途径。在这个项目中，我们将利用尖端的连接组和tau 来自两项NIH资助的研究和我们的新颖分析算法以构建脑干地图的宠物成像数据 广告研究的连接组。我们的目标是开发可以提供连通性的能力技术 脑干的衡量标准以补充宠物成像的皮质tau负担。带有新颖的脑干地图 以及该项目开发的相关软件工具，我们将能够研究脑干和 AD疾病过程中的皮质萎缩。此类实验的发现将提供体内 关于AD前阶段中Tau病理学的BRAAK分期的证据。另外，脑干 连接组将使神经递质特异性途径中连通性变化的体内映射 及其与AD患者的行为症状有关。总体而言，该项目有三个具体的目标：1。 使用Connectome成像数据开发与AD相关的脑干途径的地图。 2。检查关系 AD中脑干核和皮质TAU病理学的连通性变化。 3。研究行为的关系 AD中的症状和脑干连通性。该项目中开发的所有图书馆和软件工具将是 自由分发给研究社区。当我们开发这些图形和研究广告的工具时，它们 在有关脑干发挥重要作用的其他神经系统疾病的研究中也应该很有价值 角色。