Brainstem connectomes related to Alzheimer's disease

摘要 与内侧颞叶和其他皮质区域相比，脑干很少受到关注。 在阿尔茨海默病(AD)的研究中。来自各种神经病理学研究的越来越多的证据，最近 然而，最新的Braak分期表明，最早的tau病理可能发生在脑干核团。 并传播到经内嗅觉皮质区域。而使用AV1451示踪剂的tau PET成像正在出现 作为测量皮质tau负荷的有力工具，由于分辨率低，它在研究脑干方面受到限制。 和脱离目标的绑定。另一方面，连接体成像技术的巨大进步使我们能够 以前所未有的细节研究大脑通路的完整性。使用多壳层扩散成像数据 人类连接组计划(HCP)，我们开发了用于计算纤维取向的新工具 分布(FOD)和隔室模型。这些工具已经成功地应用于重建 挑战人脑中的纤维通路。在这个项目中，我们将利用尖端的连接件和tau 来自美国国立卫生研究院资助的两项研究的PET成像数据和我们建立脑干图谱的新分析算法 用于AD研究的连接件。我们的目标是开发能够提供连接的使能技术 测量脑干以补充来自PET成像的皮质tau负荷。用新的脑干地图集 以及在这个项目中开发的相关软件工具，我们将能够检查脑干和 阿尔茨海默病病程中皮质萎缩。这些实验的发现将在活体内提供 AD前驱期tau病理Braak分期的证据。此外，脑干 连接体将能够在体内映射神经递质特定通路中的连接性变化 以及它们与AD患者行为症状的关系。总体而言，这项计划有三个具体目标：1. 使用连接组成像数据开发与AD相关的脑干通路图谱。2.检视两者的关系 阿尔茨海默病患者脑干核团和皮质tau病理的连接性改变。3.研究行为与心理健康的关系 阿尔茨海默病的症状和脑干连接。在这个项目中开发的所有地图集和软件工具将是 免费分发给研究团体。当我们开发这些用于研究AD的地图集和工具时，他们 在脑干发挥重要作用的其他神经疾病的研究中也应该有价值 角色。

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.