BRAIN CONNECTS: Mapping Connectivity of the Human Brainstem in a Nuclear Coordinate System

大脑连接：在核坐标系中绘制人类脑干的连接性

• 批准号: 10664289
• 负责人: Bruce Fischl
• 金额: $ 147.18万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664289
• 关键词: 3-Dimensional; Algorithms; Alzheimer' s Disease; Anatomy; Architecture; Atlases; Axon; Brain; Brain Mapping; Brain Stem; Cell Nucleus; Cells; Complex; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Enrollment; Exhibits; Fascicle; Fiber; Fluorescence; Fluorescence Microscopy; Goals; Histological Techniques; Human; Image; Imaging technology; Immunohistochemistry; Individual; Label; Light; Magnetic Resonance Imaging; Manuals; Maps; Measurement; Measures; Microscopic; Microscopy; Molecular; Morphology; Myelin; Myelin Sheath; Neurologic; Neurons; Nuclear; Optical Coherence Tomography; Pathway interactions; Pattern; Planet Earth; Property; Protocols documentation; Resolution; Secure; Slice; Stains; Structure; System; Techniques; Technology; Text; Thick; Three-dimensional analysis; Tissue Expansion; Tissue imaging; Tissues; Traumatic Brain Injury; Validation; Visualization; cell type; cohort; connectome; deep learning; design; ex vivo imaging; histological image; human tissue; in vivo; innovation; meter; microscopic imaging; multi-scale atlas; neuroimaging; preservation; programs; rapid technique; scale up; tool; tractography; two-photon; ultra high resolution

Project Summary/Abstract (30 lines of text limit) The ~1 billion neurons that form the human brainstem are organized at multiple scales, ranging from their cell type-specific patterns of dendritic arborization, to local circuits embedded within large-scale projection systems spanning the brainstem, and a complex nuclear architecture. In this project, we will image across this vast range of scales to build technologies to create a multiscale atlas akin to Google Earth for the human brainstem to visualize brainstem-wide networks and zoom in to the level of individual, labeled cells and their connectivity at micrometer resolution within the context of individual nuclei. This dramatic advance will be made possible through the use of an array of imaging technologies, including light-sheet fluorescence microscopy (LSFM), tissue clearing, immunohisto-chemistry (IHC), 2-photon expansion microscopy (2PEM), magnetic resonance imaging (MRI) and newly developed techniques in polarization-sensitive optical coherence tomography (PS- OCT). PS-OCT in particular is a potentially transformative technology as it provides micrometer resolution over large volumes of tissue, images all of the tissue (as opposed to fluorescence), does not require mounting and staining, can be automated, is essentially distortion free as it images the tissue prior to cutting, and with innovations we propose in our project, allows direct measures of 3D axonal orientation. LSM-based IHC will provide molecular, morphological and spatial properties of cells and their projections that will enable us to nuclear boundaries to place the connections in a nuclear context, 2PEM will provide direct validation of the 3D-PSOCT, and the OCT will also enable us to remove the distortions induced by cutting and clearing, and transfer information to intact brainstem and whole-hemisphere MRI for quantitative atlasing and in vivo inference.

项目摘要/摘要（文本限制 30 行） 形成人类脑干的约 10 亿个神经元以多种尺度组织起来，从细胞到细胞 树突状树枝化的特定类型模式，到嵌入大规模投影系统中的局部电路 跨越脑干和复杂的核结构。在这个项目中，我们将在这个广阔的范围内进行成像 建立技术来创建类似于谷歌地球的多尺度地图集，供人类脑干 可视化脑干范围的网络并放大到单个标记细胞的水平及其连接性 单个原子核范围内的微米分辨率。这一巨大的进步将成为可能 通过使用一系列成像技术，包括光片荧光显微镜（LSFM）， 组织透明化, 免疫组织化学 (IHC), 2 光子扩张显微镜 (2PEM), 磁共振 成像（MRI）和新开发的偏振敏感光学相干断层扫描技术（PS- 华侨城）。 PS-OCT 尤其是一种潜在的变革性技术，因为它提供了微米分辨率 大量组织，对所有组织进行成像（与荧光相反），不需要安装和 染色可以自动化，基本上不会失真，因为它在切割之前对组织进行成像，并且 我们在项目中提出的创新允许直接测量 3D 轴突方向。基于 LSM 的 IHC 将 提供细胞的分子、形态和空间特性及其预测，使我们能够进行核分析 边界将连接置于核环境中，2PEM 将提供 3D-PSOCT 的直接验证， OCT 还将使我们能够消除因切割和清理以及转移而引起的扭曲 完整脑干和全半球 MRI 信息，用于定量图谱和体内推理。