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层白质：基于示踪剂的组织学和 dMRI 纤维束成像验证

• 批准号: 10521896
• 负责人: NIKOLAOS MAKRIS
• 金额: $ 70.74万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 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/10521896
• 关键词: 3-Dimensional; Affect; Alzheimer' s Disease; Anatomy; 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; Multiple Sclerosis; Neuroanatomy; Neurologic; Pathway interactions; Play; Precentral gyrus; Primates; Prosencephalon; Reporting; Research; Resolution; Role; Scanning; Slide; Somatosensory Cortex; Source; Structure; System; Time; Tissues; Tracer; Translating; Validation; Work; autism spectrum disorder; base; chronic traumatic encephalopathy; connectome; data mining; data quality; density; design; ex vivo imaging; experimental study; human disease; improved; in vivo; nervous system disorder; neuroimaging; nonhuman primate; novel; organizational structure; relating to nervous system; systematic review; tractography; translation to humans; ultra high resolution; white matter

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5年的R01赠款中，标题为“揭开灵长类动物大脑的浅表白色物质：基于示踪剂 组织学和扩散MRI修剪验证：“我们将在灵长类动物中绘制浅表白质（SWM） 大脑使用实验道方法。 基于体内和超高分辨率的分辨率在同一恒河主中基于体内扩散MRI（DMRI）的片段 猕猴。游泳是位于前脑和你的大脑皮层之间 基础白质途径。 将U形纤维（U纤维）置于大脑沟下。 神经系统疾病，例如自闭症谱系障碍，多重扇贝病和阿尔茨海默氏病，以及 SWM的知识对于准确解释基于DMRI的拖拉机至关重要 SWM的基本联系神经解剖学是未知的，因为我们无法可视化 人脑中轴突的特定起源，终止和轨迹。 因此 人类灵长类动物（NHP）模型，但对NHP SWM的全面研究，从轨迹到轨迹。 终止，尚未进行，因此对人类的连通性和组织的了解 通过在NHP中进行侵入性研究来改善。 NHP大脑中SWM的首次详细详细的神经解剖研究，在NHP和翻译中进行了DMRI验证 为了实现这一目标，我们将使用一系列与DMRI一起使用的组织学技术 在马萨诸塞州综合医院（MGH）连接扫描仪质量优质的扫描 DMRI数据。 SWM连通性在恒河猴中。 神经解剖学病例构成了NHP中白质连接的基础 利用这个档案馆来组织额脑区域的游泳。 组织学方法，包括基于清晰度的组织清除和神经解剖学道，以询问 SWM的结构，地形和连接性，我们将产生Grouth数据 在同一动物中，体内和ex vivo dMri在执行神经解剖学的实验中， 允许基于组织学和神经成像的连接进行直接比较。 将DMRI数据传播到神经成像社区并举办竞争以确定最佳 SWM的拖拉术方法。 使用基于同源的人类连接项目数据集的比较。 SWM连通性的地面真理，并有助于改善NHP和人类黄铜中的DMRI拖拉术。