BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC)

大脑连接：神经回路大规模成像中心 (LINC)

• 批准号: 10672681
• 负责人: Suzanne N Haber
• 金额: $ 472.84万
• 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 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672681
• 关键词: 3-Dimensional; Anatomy; Area; Autopsy; Axon; Biological Markers; Brain; Cells; Censuses; Clinical; Cohort Studies; Collection; Communities; Complex; Data; Data Analyses; Data Set; Deep Brain Stimulation; Dictionary; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dystonia; Fascicle; Fiber; Funding Opportunities; Gilles de la Tourette syndrome; Goals; Human; Image; Individual; Injections; Internal Capsule; Label; Learning; Light; Link; Literature; Macaca; Magnetic Resonance Imaging; Maps; Measurement; Mental disorders; Methods; Microscopic; Microscopy; Modeling; Monkeys; Motor; Multimodal Imaging; Neuroanatomy; Obsessive-Compulsive Disorder; Optical Coherence Tomography; Osmium; Parkinson Disease; Pathway interactions; Phase; Prefrontal Cortex; Protocols documentation; Records; Reproducibility; Research; Resolution; Sampling; Signal Transduction; Software Tools; Specimen; Stains; Structure; Structure of subthalamic nucleus; System; Techniques; Testing; Three-Dimensional Imaging; Tracer; Training; Travel; Validation; clinically relevant; comparative; connectome; data acquisition; data dissemination; data integration; data repository; human disease; imaging biomarker; improved; in vivo; innovation; microCT; motor disorder; multimodality; neural circuit; neuroimaging; neuroregulation; new technology; non-invasive imaging; novel; novel imaging technology; quality assurance; segregation; sharing platform; side effect; submicron; technology validation; therapy outcome; tomography; tool; tractography; ultra high resolution; vector; white matter

Project summary: This project will develop and validate a comprehensive toolset of novel technologies for imaging axonal projections across scales, and will deploy this toolset to map a complex system of cortico- subcortical projections in the macaque and human brain. We will combine the complementary strengths of three innovative microscopy techniques. First, polarization-sensitive optical coherence tomography (PS-OCT) will provide label-free, undistorted imaging of axonal orientations at the scale of microscopic fascicles, allowing us to follow fascicles across the brain without the need for axon segmentation. Second, whole-mount light- sheet microscopy (LSM) of cleared and immunolabeled sections will allow us to image fascicles at the sub- micron scale, resolving individual axons. Third, hierarchical phase-contrast tomography (HiP-CT) will allow us to image both the axons and their micro-environment, at a range of scales from a few microns down to sub- micron. We will scale these three microscopy techniques up to image a large sub-volume of the brain (up to two thirds of a hemisphere) that contains subcortical projections of the motor, premotor, and prefrontal cortex. In the macaque brains, fluorescent tracer injections will allow direct validation of our novel microscopy techniques. In combination with an extensive collection of prior tracer injections, the macaque data will also provide the topographic organizational rules of fibers in cortico-subcortical bundles, which we will then use to validate our novel microscopy techniques in human brains. In both macaque and human specimens, we will also collect extensive, cutting-edge, whole-brain diffusion MRI data, which will provide the link to non-invasive neuroimaging. The unprecedented datasets generated by our project will enable research discovery in two use cases. In the first use case, we will annotate projections of the motor, premotor, and prefrontal cortex to the subthalamic nucleus (STN). We will use them to advance our understanding of circuits associated with clinical improvements in four diseases that are treated with deep-brain stimulation in neighboring subzones of the STN: dystonia, Tourette’s syndrome, Parkinson’s disease, and obsessive-compulsive disorder. In the second use case, we will investigate the mapping from the axonal orientations and microstructural features obtained from the microscopy data to dMRI signals acquired in the same brains. In addition to the unprecedented datasets and the two use cases described above, this project will generate state-of-the-art pipelines for pre- processing, co-registration, axon segmentation, tractography, and quantification, across the scales spanned by the acquired data. We will develop a novel platform for sharing the microscopy, tracer, and MRI data with the research community. This will go well beyond a static data repository, allowing the user to interact with the data remotely and providing a “validation engine” for testing neuroimaging software tools against the gold standard post mortem data collected by this project. If successful, this project will generate a scalable and validated toolset for imaging connectional anatomy, with a direct link it to its applications in the study of human disease.

项目摘要：该项目将开发并验证一套全面的新技术工具集，用于 对跨尺度的轴突投影进行成像，并将部署该工具集来绘制复杂的皮质系统 我们将结合猕猴和人类大脑的皮层下投射的互补优势。 三项创新的显微技术：第一，偏振敏感光学相干断层扫描（PS-OCT）。 将在微观束的尺度上提供无标记、无失真的轴突方向成像，从而允许 我们可以追踪整个大脑的神经束，而不需要轴突分割第二，整体安装光。 透明和免疫标记切片的片状显微镜（LSM）将使我们能够对子束进行成像 第三，分层相差断层扫描 (HiP-CT) 将使我们能够实现微米级分辨率。 以从几微米到亚微米的各种尺度对轴突及其​​微环境进行成像 我们将把这三种显微镜技术放大到对大脑的一个大的子体积进行成像（高达 半球的三分之二）包含运动皮质、前运动皮质和前额皮质的皮层下投射。 在猕猴大脑中，荧光示踪剂注射将允许直接验证我们的新型显微镜技术 结合之前大量收集的示踪剂注射数据，猕猴数据也将被结合起来。 提供皮质-皮质下束中纤维的拓扑组织规则，然后我们将用它来 我们将在猕猴和人类标本中验证我们的新颖显微镜技术。 还收集广泛的、尖端的、全脑扩散 MRI 数据，这将提供与非侵入性 我们的项目生成的前所未有的数据集将使研究发现具有两种用途。 在第一个用例中，我们将注释运动、前运动和前额皮质到 我们将利用它们来增进我们对与临床相关的回路的理解。 通过深部脑刺激治疗相邻分区的四种疾病得到改善 STN：肌张力障碍、抽动秽语综合征、帕金森病和强迫症。 用例，我们将研究所获得的轴突方向和微观结构特征的映射 从显微镜数据到在同一大脑中获取的 dMRI 信号，这都是前所未有的。 数据集和上述两个用例，该项目将为预生成最先进的管道 处理、共同配准、轴突分割、纤维束成像和量化，跨越尺度 我们将开发一个新的平台，与人们共享显微镜、示踪剂和 MRI 数据。 这将远远超出静态数据存储库的范围，允许用户与数据进行交互。 远程并提供“验证引擎”，用于根据黄金标准测试神经影像软件工具 如果成功，该项目将生成可扩展且经过验证的事后分析数据。 用于成像连接解剖学的工具集，与其在人类疾病研究中的应用有直接联系。