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

项目总结 人类小脑的发育经历了一系列精确编程的过程，跨越 从怀孕的第三个月到出生后的第一年。由于新生儿成像技术的进步 随着技术的发展，越来越多的早产儿和足月新生儿发现小脑损伤。 并发症。尽管围产期小脑损伤和畸形广泛地与 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过程 -导致功能障碍-还没有完全了解。现有的研究已经报道了相互矛盾的 关于小脑局部病变在运动和社会认知障碍中所起作用的研究结果 尤其是对侧脑损伤严重的继发性小脑畸形 混血儿。我们的探索性研究建议通过开发多量表来解决这些有争议的发现 用于阐明第一年小脑神经结构和连接图的成像框架 发展。该框架建立在我们的100-500微米分辨率体外磁性的初步工作基础上 磁共振成像(MRI)和扩散磁共振成像以及3-10微米分辨率的自动连续切片 偏振敏感光学相干层析成像(AS-PSOCT)。本质上，AS-PSOCT使用本征光纤 特性，并采用块面策略，消除了传统组织学中的组织扭曲，揭示了 细胞组织、髓鞘含量和纤维束的取向，在体积测量中具有微观精度 重建。通过将其与体外核磁共振在同一样本上共同注册，细胞水平信息将被 转移到整个大脑空间的坐标。研究设计将优化扫描方案，以揭示 发育中的小脑中有复杂的折叠图案以及较小且较少的有髓纤维束。 将开发计算模型，以帮助跨通道配准、多分辨率图像融合和 脑白质描记术。该项目的成功完成将第一次产生高度的- 分辨率图用于描述出生一年内的小脑结构和连接性。该项目将 促进我们对人类小脑在高级认知功能中所扮演的角色的理解。小脑地形图 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，多尺度技术为神经科学提供了一种更通用、更有趣的工具。 社区在大脑中进行细胞到系统水平的研究。

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.