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

多尺度成像婴儿小脑发育感觉运动和认知通路

• 批准号: 10461075
• 负责人: Hui Wang
• 金额: $ 25.2万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-03 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461075
• 关键词: Address; Adopted; Age; Age-Months; Anatomy; Atlases; Autopsy; Biological Markers; Biological Process; Birth; Brain; Brain Stem; Cell Nucleus; Cells; Cerebellar Cortex; Cerebellar malformation; Cerebellum; Cerebrum; Cognition; Cognition Disorders; Cognitive; Communities; Computer Models; Conflict (Psychology); Contralateral; Data Set; Development; Developmental Delay Disorders; Diffusion Magnetic Resonance Imaging; Dorsal; Engineering; Face; Fiber; Functional disorder; Future; Goals; Growth; Histology; Human; Image; Imaging Device; Imaging Techniques; Individual; Infant; Injury; Intervention; Investigation; Knowledge; Language; Lateral; Lesion; Life; Link; Live Birth; Lobular; Lobule; Magnetic Resonance Imaging; Maps; Medial; Mediating; Microscopic; Modality; Morphology; Motor; Myelin; Neonatal; Neural Pathways; Neurosciences; Optical Coherence Tomography; Optics; Pathway interactions; Pattern; Perinatal; Play; Positioning Attribute; Prefrontal Cortex; Premature Infant; Procedures; Process; Property; Protocols documentation; Reporting; Research; Research Design; Resolution; Rest; Role; Sampling; Scanning; Seminal; Sensorimotor functions; Social Behavior; Structure; System; Techniques; Temporal Lobe; Thick; Third Pregnancy Trimester; Time; Tissue Sample; Tissues; Training; Work; algorithm development; cognitive function; critical period; delivery complications; developmental disease; in vivo; in vivo imaging; malformation; multidisciplinary; neonatal hypoxic-ischemic brain injury; neurodevelopment; postnatal; postnatal development; preservation; reconstruction; research clinical testing; targeted treatment; tool; tractography; ultra high resolution; white matter

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.

项目概要 人类小脑的发育经历了一系列精确编程的过程，涵盖 由于新生儿影像学的进步，从妊娠晚期到产后第一年。 随着技术的进步，早产儿和足月儿中越来越多地发现小脑损伤 尽管围产期小脑损伤和畸形与并发症广泛相关。 运动、语言、认知和社会行为的发育迟缓，以及潜在的生物过程 – 导致功能障碍 – 尚未完全理解，现有的研究报道了相互矛盾的情况。 关于区域小脑损伤在运动和社会认知障碍中的作用的研究结果是 对侧脑损伤严重的继发性小脑畸形尤其具有挑战性 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。 阐明第一年小脑神经结构和连接图的成像框架 该框架建立在我们 100-500μm 分辨率离体磁性的初步工作之上。 磁共振成像 (MRI) 和扩散 MRI 以及 3-10 µm 分辨率自动连续切片 偏振敏感光学相干断层扫描 (as-PSOCT) 本质上，as-PSOCT 使用本征光学。 特性并采用块面策略来消除传统组织学中的组织扭曲并揭示 细胞组织、髓磷脂含量和纤维束的方向，在体积上具有微观精度 通过将其与同一样本上的离体 MRI 共同配准，可以得到细胞水平的信息。 转移到整个大脑空间的坐标该研究设计将优化扫描协议以发现。 发育中的小脑具有复杂的折叠模式以及小而少髓鞘的纤维束。 将开发计算模型以帮助跨模态配准、多分辨率图像融合和 该项目的成功完成将首次产生高 该项目将绘制分辨率图来表征生命第一年内的小脑结构和连接性。 我们对人类高级小脑在高级认知功能中的作用的理解小脑图谱。 和连接图为未来人类神经发育迟缓的临床评估提供参考 此外，多尺度技术是神经科学的一种更通用、更有趣的工具。 社区在大脑中进行细胞到系统级别的研究。