Structural Development of Human Fetal Brain

摘要 尽管它具有重要的意义，但人们对婴儿大脑发育最活跃的阶段知之甚少： 0-2年。以改变现状、全面定量的婴幼儿脑图谱为参考 精准健康的标准是必要的。此外，弥散磁共振成像(DMRI)已经进入了一个新的时代 动态皮质内部微结构复杂性，由例如源自以下来源的皮质平均峰度来索引 弥散峰度成像(DKI)，可以在活体婴儿脑中进行无创性研究 多层核磁共振成像。此外，多模式措施提供了对机械结构的无与伦比的见解- 功能和结构-行为关系。本周期的工作重点是结构发展。 人类胎儿和早产儿的大脑。基于150个大脑的高分辨率扩散张量成像(DTI)，我们 建立了具有皮质分数各向异性的图谱并量化了皮质微观结构，验证了 通过组织学图像，并与转录(RNA)表达相关。在此工作的基础上，在 下一个周期，我们将关注婴儿时期的大脑发育，紧接在胎儿期之后。具体地说， 目标是建立下一代dMRI图谱(定量的UPenn-CHOP婴儿脑图谱)并 通过描绘其4D来驾驭更高级的皮质微结构平均峰度测量 时空框架及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。进阶 “Connectome-Quality”多频段高分辨率多层dmri、静息状态fmri(rs-fmri)和结构 将获得核磁共振成像。还将获得高质量的全头脑磁图(MEG)。 所有122个主要灰质和白质结构的解剖标签将基于高对比度建立 从DTI派生的映射。DTI衍生指标的测量将用于量化 DTI图谱的组成部分和与年龄相关的白质束轨迹(目标1)。四阶均值峰度 峰度顺序张量对婴儿大脑皮质内部微结构的变化很敏感 大脑。平均峰度度量对婴儿年龄和皮质区域的时空敏感性将是 调查(目标2)。此外，我们还将建立多层次的机械结构-功能关系。 模式成像，不仅包括多层dmri，还包括rs-fmri和meg，所有这些都针对婴儿的大脑进行了优化。 (目标3)。定量的婴儿脑图谱和正常发育轨迹将提供参考 “诊断前”风险评估标准，填补了婴儿精确健康方面的空白(例如Z-SCORE 地图)。婴儿皮质微结构将用4D时空框架非侵入性地描绘出来。 具有多模态强度的基本结构-功能和结构-行为力学关系 将为了解神经发育障碍的异常大脑发育奠定基础 自闭症谱系障碍和智力残疾。

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.