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新技术的全面工具集 跨尺度成像轴突项目，并将部署此工具集以映射一个复杂的Cortico-系统 猕猴和人脑中皮质下的投影。我们将结合完整的优势 三种创新的显微镜技术。首先，极化敏感的光学相干断层扫描（PS-OCT） 将在微观筋膜的尺度上提供无标签的轴突取向成像，从而允许 我们在不需要轴突分割的情况下跟随束在整个大脑中。其次，全置光 - 清除和免疫标记部分的片片显微镜（LSM）将使我们能够在亚束上进行束缚。 微米尺度，解决各个轴突。第三，层次结构相对比断层扫描（HIP-CT）将使我们 为了对轴突及其​​微环境进行成像，以从几微米到亚的一系列尺度 微米。我们将缩放这三种显微镜技术，以形象大脑的大量亚体积（直到 半球的三分之二），其中包含运动，前和额叶皮层的皮层皮层项目。 在猕猴的大脑中，荧光示踪剂注射将允许直接验证我们的新型显微镜 技术。结合大量先前的示踪剂注射，猕猴数据还将 在皮质毛皮捆绑包中提供纤维的地形组织规则，然后我们将使用它 验证我们在人类大脑中的新型显微镜技术。在猕猴和人类标本中，我们将 还收集广泛的，尖端的，全脑扩散的MRI数据，该数据将提供非侵入性的链接 神经影像学。我们项目生成的前所未有的数据集将使研究发现可以两次使用 案例。在第一种用例中，我们将注释电动机，前和额叶皮层的项目 丘脑下核（STN）。我们将使用它们来提高我们对与临床相关的电路的理解 在邻近的邻近子区域中用深脑刺激治疗的四种疾病的改善 STN：肌张力障碍，图雷特综合症，帕金森氏病和强迫症。在第二个 用例，我们将研究从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得的DMRI信号。除了前所未有的 数据集和上述两个用例，该项目将生成最新的管道 跨越量表 获得的数据。我们将开发一个新颖的平台，用于与显微镜，示踪剂和MRI数据与 研究社区。这将远远超出静态数据存储库，从而使用户与数据进行交互 远程并提供针对黄金标准测试神经成像软件工具的“验证引擎” 该项目收集的验尸数据。如果成功，该项目将产生可扩展的验证 用于成像连接解剖结构的工具集，并直接将其与其在人类疾病研究中的应用联系起来。