Developmental sensorimotor and cognitive pathways in infant cerebellum with multi-scale imaging

项目摘要 人类小脑的发育经历了一系列精确编程的过程， 从怀孕的第三个三个月到产后的第一年。由于新生儿成像技术的进步 技术，小脑损伤已越来越多地发现在早产儿和足月分娩 并发症虽然围产期小脑损伤和畸形已广泛与 运动、语言、认知和社会行为的发育迟缓，这些都是潜在的生物学过程 - 导致功能紊乱的原因还没有被完全理解。现有的研究报告相互矛盾 关于区域性小脑病变在运动和社会认知障碍中的作用的研究结果， 特别是在继发性小脑畸形中，对侧脑损伤是一个重大的挑战。 混淆因素。我们的探索性研究建议通过开发多尺度来解决这些有争议的发现 阐明一年级小脑神经结构和连接图的成像框架 发展该框架建立在我们100-500µ m分辨率离体磁共振成像的初步工作基础上。 共振成像（MRI）和扩散MRI以及3-10µ m分辨率自动连续切片 偏振敏感光学相干层析成像（as-PSOCT）。本质上，as-PSOCT使用固有的光学特性， 属性，并采用块面策略，以消除传统组织学中的组织变形， 细胞组织、髓鞘含量和纤维束的方向，体积测量中具有显微镜精度。 重建通过将其与相同样品上的离体MRI共配准，将获得细胞水平信息。 转移到整个大脑空间的坐标。研究设计将优化扫描方案， 复杂的折叠模式以及发育中的小脑中小而少的有髓纤维束。 将开发计算模型，以帮助跨模态配准、多分辨率图像融合和 白色物质纤维束成像。该项目的成功完成将首次产生高- 分辨率图，以表征小脑结构和连接在第一年的生活。该项目将 进一步了解人类小脑在高级认知功能中的作用。小脑寰椎 和连接图为未来人类神经发育迟缓的临床评估提供了参考 小脑此外，多尺度技术作为一个更普遍的，有趣的工具，神经科学 社区在大脑中进行细胞到系统水平的调查。

PROJECT SUMMARY Development of the human cerebellum undergoes a precisely programmed sequence of processes, spanning from the third trimester of pregnancy into the first postnatal year. Due to advances in neonatal imaging techniques, cerebellar injury has been increasingly detected in premature infants and full-terms with birth complications. Although perinatal cerebellar injury and malformation have been broadly associated with developmental delays in motor, language, cognition, and social behaviors, the underlying biological processes – causing the functional disorders – have not yet been fully understood. Existing studies have reported conflicting findings regarding the role regional cerebellum lesions play in motor and socio-cognitive disorders, which are especially challenging in secondary cerebellar malformation where contralateral cerebral injury is a substantial confounder. Our exploratory study proposes to address these controversial findings by developing a multi-scale imaging framework to elucidate the neuroarchitecture and connectivity maps of the first-year cerebellum development. The framework builds on our preliminary work of 100-500µm-resolution ex vivo magnetic resonance imaging (MRI) and diffusion MRI as well as 3-10µm-resolution automated serial-sectioning polarization sensitive optical coherence tomography (as-PSOCT). Essentially, as-PSOCT uses intrinsic optical properties and adopts a block-face strategy to eliminate tissue distortion in conventional histology and reveal cellular organizations, myelin content, and orientation of fiber tracts with microscopic precision in volumetric reconstruction. By co-registering it with the ex vivo MRI on the same sample, cellular level information will be transferred to the coordinates of the entire brain space. The study design will optimize scan protocols to uncover sophisticated folding patterns as well as small and less myelinated fiber tracts in the developing cerebellum. Computational models will be developed to aid cross-modality registration, multi-resolution image fusion and white matter tractography. The successful completion of this project will, for the first time, generate high- resolution maps to characterize cerebellar structure and connectivity within the first year of life. The project will advance our understanding of the role human cerebellum plays in higher cognitive functions. The cerebellar atlas and connectivity map offer a reference for future clinical evaluations in neurodevelopmental delays in the human cerebellum. Additionally, the multi-scale technique serves as a more general, intriguing tool for the neuroscience community to conduct cellular-to-system level investigations in the brain.