Unraveling the Superficial White Matter of the Primate Brain: Tracer-Based Histology and dMRI Tractography Validation

解开灵长类动物大脑的浅表白质：基于示踪剂的组织学和 dMRI 纤维束成像验证

基本信息

批准号：
10650392
负责人：
NIKOLAOS MAKRIS
金额：
$ 68.24万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650392
关键词：
3-Dimensional Affect Alzheimer&apos s Disease Anatomy Animal Experiments Animals Antibodies Archives Area Autopsy Axon Brain Cells Cerebral cortex Cerebral sulcus Cerebrum Collection Communities Complement Data Data Set Diffusion Magnetic Resonance Imaging Disease Feedback Fiber Foundations General Hospitals Goals Grant Head Health Histologic Histological Techniques Histology Human Knowledge Label Literature Location MRI Scans Macaca Macaca mulatta Magnetic Resonance Imaging Maps Massachusetts Methods Modeling Modernization Monkeys Motor Motor Cortex Multiple Sclerosis Neuroanatomy Neurologic Pathway interactions Precentral gyrus Primates Prosencephalon Reporting Research Resolution Scanning Shapes Slide Somatosensory Cortex Source Structure System Time Tissues Tracer Translating Validation Visualization Work autism spectrum disorder chronic traumatic encephalopathy connectome data mining data quality density design ex vivo imaging experimental study human disease improved in vivo millimeter nervous system disorder neural neuroimaging nonhuman primate novel organizational structure systematic review tractography translation to humans ultra high resolution white matter

项目摘要

Abstract In this 5 year R01 grant entitled “Unraveling the superficial white matter of the primate brain: Tracer-based histology and diffusion MRI tractography validation,” we will map superficial white matter (SWM) in the primate cerebrum using experimental tract tracing methods. We will use this ground truth information to validate high- resolution in vivo and ultra-high resolution ex vivo diffusion MRI (dMRI) based tractography in the same rhesus macaque monkeys. The SWM is a continuous layer located between the cerebral cortex of the forebrain and the underlying white matter association pathways. It comprises axons that interconnect cerebral cortical areas, including U-shaped fibers (U-fibers) under the cerebral sulci. This axonal layer plays a role in a broad range of neurological conditions such as autism spectrum disorder, multiple sclerosis, and Alzheimer’s disease, and knowledge of the SWM is essential for accurately interpreting dMRI-based tractography. Critically, the fundamental connectional neuroanatomy of the SWM is largely unknown due to our inability to visualize the specific origins, terminations, and trajectories of axons in the human brain. Our knowledge of human SWM connectional neuroanatomy is thus derived almost exclusively from experimental tract tracing results in the non- human primate (NHP) model, but comprehensive studies of the NHP SWM, from origin through trajectory to termination, have not been performed. Therefore, knowledge of human SWM connectivity and organization can be improved by invasive tract tracing studies in the NHP. The goal of the proposed research is to carry out the first detailed neuroanatomical study of the SWM in the NHP brain, with dMRI validation in the NHP and translation to human brains. To achieve this goal, we will use a range of histological techniques in conjunction with dMRI scans obtained with the Massachusetts General Hospital (MGH) Connectom scanner to produce superior quality dMRI data. We will first datamine the research literature to produce a compendium of existing knowledge of SWM connectivity in the rhesus monkey. We will also examine the Pandya-Rosene Archive, a vast collection of neuroanatomy cases that has formed the foundation of data on white matter connections in the NHP. We will utilize this archive to chart the organization of the SWM in frontal brain areas. We will then use modern histological methods, including CLARITY-based tissue clearing and neuroanatomical tract tracing, to interrogate the structure, topography, and connectivity of the SWM, and thereby produce ground truth data. We will perform in vivo and ex vivo dMRI in the same animals in which we perform neuroanatomical tract tracing experiments, allowing for direct comparisons between histological and neuroimaging-based connectivity. Moreover, we will disseminate the dMRI data to the neuroimaging community and host a competition to determine the optimal tractography method for SWM. Finally, we will translate knowledge of SWM neuroanatomy to the human brain using homologically based comparisons with Human Connectome Project datasets. These data will provide ground truth of SWM connectivity and serve to improve dMRI tractography in NHP and human brains.

抽象的在这项为期 5 年的 R01 资助中，题为“解开灵长类动物大脑的浅层白质：基于示踪剂组织学和扩散 MRI 纤维束成像验证”，我们将绘制灵长类动物浅层白质 (SWM) 的图谱我们将使用这些地面实况信息来验证高通量大脑。在同一只恒河猴中进行基于高分辨率体内和超高分辨率离体扩散 MRI (dMRI) 的纤维束成像 SWM 是位于前脑和大脑皮层之间的连续层。它包括连接大脑皮层区域的轴突，包括脑沟下的U形纤维（U型纤维），该轴突层发挥着广泛的作用。神经系统疾病，例如自闭症谱系障碍、多发性硬化症和阿尔茨海默病，以及 SWM 的知识对于准确解释基于 dMRI 的纤维束成像至关重要。由于我们无法将 SWM 可视化，因此 SWM 的基本连接神经解剖学在很大程度上是未知的。我们对人类 SWM 的了解。因此，连接神经解剖学几乎完全源自非非实验性的实验束追踪结果。人类灵长类动物 (NHP) 模型，但对 NHP SWM 进行了全面研究，从起源到轨迹再到因此，人类 SWM 连接和组织的知识可以。通过 NHP 中的侵入性管道追踪研究来改进该研究的目标是开展首次对 NHP 大脑中的 SWM 进行详细的神经解剖学研究，并在 NHP 中进行 dMRI 验证并进行翻译为了实现这一目标，我们将结合使用一系列组织学技术和 dMRI。使用麻省总医院 (MGH) Connectom 扫描仪获得的扫描结果可提供卓越的质量我们将首先对研究文献进行数据挖掘，以生成现有知识的纲要。我们还将检查 Pandya-Rosene 档案，这是一个巨大的集合。神经解剖学案例已成为 NHP 中白质连接数据的基础。利用这个档案来绘制额叶脑区域 SWM 的组织图，然后我们将使用现代的方法。组织学方法，包括基于 CLARITY 的组织透明化和神经解剖学路径追踪，以询问 SWM 的结构、地形和连接性，从而产生地面实况数据。我们在同一动物中进行神经解剖束追踪实验的体内和离体 dMRI，允许直接比较基于组织学和神经影像的连接。将 dMRI 数据传播给神经影像学界并举办竞赛以确定最佳方案最后，我们将 SWM 神经解剖学知识转化为人脑。使用与人类连接组项目数据集的同源比较这些数据将提供。 SWM 连接的基本事实，并有助于改善 NHP 和人脑的 dMRI 纤维束成像。