Structural Development of Human Fetal Brain

人类胎儿大脑的结构发育

• 批准号: 9247587
• 负责人: Hao Huang
• 金额: $ 50.46万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247587
• 关键词: 2 year old; Age; Anisotropy; Architecture; Area; Atlases; Auditory; Behavior; Behavior assessment; Behavioral; Brain; Cerebral cortex; Characteristics; Clinical Research; Collaborations; Development; Developmental Process; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Fingerprint; Four-dimensional; Functional Magnetic Resonance Imaging; Genetic Transcription; Goals; Head; Health; Human; Image; Infant; Infant Development; Infant Health; Intellectual functioning disability; Label; Life; Machine Learning; Magnetic Resonance Imaging; Magnetoencephalography; Maps; Measurement; Measures; Modality; Motor; Neurodevelopmental Disorder; Phase; Recruitment Activity; Reference Standards; Research Personnel; Resolution; Rest; Risk Assessment; Sensorimotor functions; Sensory; Staging; Structure; Structure-Activity Relationship; System; Techniques; Time; Visual; Work; abstracting; age related; aging brain; artemis; autism spectrum disorder; base; connectome; fetal; gray matter; histological image; imaging modality; indexing; infancy; insight; neuroimaging; neuronal circuitry; next generation; novel; prisma; relating to nervous system; somatosensory; spatiotemporal; transcriptomics; white matter

Abstract Despite its critical significance, little is known about the most dynamic phase of brain development in infancy: 0-2 years. To change the status quo, comprehensive and quantitative infant brain atlases as reference standards for precision health are needed. In addition, diffusion MRI (dMRI) has entered a new era in which dynamic cortical internal microstructural complexity, indexed by e.g. cortical mean kurtosis derived from diffusion kurtosis imaging (DKI), can be studied in the living infant brain noninvasively using more advanced multi-shell dMRI. Furthermore, multi-modality measures offer unparalleled insights into mechanistic structure- function and structure-behavior relationships. Work in the current cycle has focused on structural development of human fetal and preterm brains. Based on high resolution diffusion tensor imaging (DTI) of 150 brains, we have established the atlases and quantified cortical microstructure with cortical fractional anisotropy, validated by histological images and correlated with transcriptomic (RNA) expression. Building upon this work, in the next cycle, we will focus on brain development in infancy, immediately after the fetal period. Specifically, the goal is to establish next-generation dMRI atlases (quantitative UPenn-CHOP infant brain atlases) and to harness a more advanced cortical microstructural mean kurtosis measurement by delineating its 4D spatiotemporal frameworks as well as uncovering its relationship to brain function and behavior during infancy (0-2 years). 160 typically developing infants at 1, 3, 6, 12, 18, 24 months will be recruited. Advanced “connectome-quality” multi-band high-resolution multi-shell dMRI, resting state fMRI (rs-fMRI) and structural MRI will be acquired. High-quality whole-head magnetoencephalography (MEG) will also be acquired. Anatomical labels of all 122 major gray and white matter structures will be built up based on high contrasts from DTI-derived maps. The measurements of DTI-derived metrics will be used for the quantitative components of DTI atlases and age-dependent white matter tract trajectories (Aim 1). Mean kurtosis of the 4th order kurtosis tensor has been shown to be sensitive to cortical internal microstructural changes of infant brains. The spatiotemporal sensitivity of mean kurtosis measures to infant age and cortical region will be investigated (Aim 2). Furthermore, we will establish mechanistic structure-function relationships with multi- modality imaging, including not only multi-shell dMRI, but also rs-fMRI and MEG, all optimized for infant brains (Aim 3). The quantitative infant brain atlases and normal developmental trajectories will provide reference standards for “pre-“diagnostic risk assessment, filling a gap towards precision health for infants (e.g. Z-score maps). Infant cortical microstructure will be delineated noninvasively with 4D spatiotemporal frameworks. With multi-modality strength, the fundamental structure-function and structure-behavior mechanistic relations will set the stage for understanding aberrant brain development in neurodevelopmental disorders such as autistic spectrum disorder and intellectual disabilities in general.

摘要 尽管婴儿期的大脑发育具有重要意义，但人们对婴儿期大脑发育最活跃的阶段知之甚少： 0-2年为改变现状，全面、定量的婴幼儿脑图谱作为参考 需要精确的健康标准。此外，扩散MRI（dMRI）已经进入了一个新的时代， 动态皮质内部微结构复杂性，例如，皮质平均峰度， 扩散峰度成像（DKI），可以研究在活的婴儿大脑无创使用更先进的 多层dMRI。此外，多模态测量为机械结构提供了无与伦比的见解- 功能和结构-行为关系。本周期的工作重点是结构发展 人类胎儿和早产儿大脑。基于150例脑的高分辨率弥散张量成像（DTI），我们 建立了图谱，并量化了皮质各向异性分数的皮质微结构，验证了 通过组织学图像并与转录组（RNA）表达相关。在这项工作的基础上， 下一个周期，我们将集中在婴儿期的大脑发育，胎儿期后立即。具体而言是 目标是建立下一代dMRI图谱（定量UPenn-CHOP婴儿脑图谱）， 利用更先进的皮质微结构平均峰度测量， 时空框架以及揭示其与婴儿期大脑功能和行为的关系 (0-2年）。将招募160名1、3、6、12、18、24个月的典型发育婴儿。先进 “连接组质量”多波段高分辨率多壳层dMRI、静息态fMRI（rs-fMRI）和结构 将采集MRI。还将获得高质量的全头脑磁图（MEG）。 将基于高对比度建立所有122个主要灰质和白色物质结构的解剖标签 从DTI衍生的地图。DTI衍生指标的测量值将用于定量 DTI图谱的组成部分和年龄依赖性白色物质束轨迹（目标1）。第4个峰的平均峰度 阶峰度张量对婴儿大脑皮层内部微结构变化敏感 大脑平均峰度测量对婴儿年龄和皮层区域的时空敏感性将被 研究（目标2）。此外，我们将建立机械结构与功能的关系， 模态成像，不仅包括多壳dMRI，还包括rs-fMRI和MEG，所有这些都针对婴儿大脑进行了优化 (Aim（3）第三章。定量婴儿脑图谱和正常发育轨迹将提供参考 “预“诊断风险评估标准，填补了婴儿精确健康方面的空白（如Z评分 地图）。婴儿皮质微结构将划定非侵入性与4D时空框架。 具有多模态强度的基本结构-功能和结构-行为的机械关系 将为理解神经发育障碍中的异常大脑发育奠定基础， 自闭症谱系障碍和一般智力残疾。