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（文本限制的30行） 形成人脑干的约10亿个神经元在多个尺度上组织起来 树突状木器化的特定类型模式，嵌入了大规模投影系统中的本地电路 跨越脑干和复杂的核结构。在这个项目中，我们将在这一广阔的范围内形象 制定技术的量表，以创建类似于Google Earth的多尺寸图集，以使人类的脑干 可视化脑干范围内的网络，并放大到个体，标记的单元格的水平及其连接性 在单个核的背景下的千分尺分辨率。这个戏剧性的进步将成为可能 通过使用一系列成像技术，包括灯页荧光显微镜（LSFM）， 组织清除，免疫史学化学（IHC），2光子膨胀显微镜（2PEM），磁共振 成像（MRI）和新开发的极化敏感光学相干断层扫描技术（PS- 十月）。 PS-OCT尤其是一种潜在的变革性技术，因为它提供了千分尺的分辨率 大量的组织，图像所有组织（与荧光相对），不需要安装，并且 染色，可以自动化，本质上是无失真的，因为它在切割前和 我们在项目中提出的创新允许直接测量3D轴突取向。基于LSM的IHC Will 提供细胞及其投影的分子，形态和空间特性，使我们能够核能 将连接置于核环境中的边界，2PEM将直接验证3D-PSOCT， OCT还将使我们能够消除切割和清除引起的扭曲，并转移 信息以完整的脑干和全半球MRI，以进行定量耕种和体内推断。