Structural Development of Human Fetal Brain

描述（由申请人提供）：拟议项目的主要目标是用超高分辨率扩散张量成像（DTI）定性和定量描绘人胎脑的结构发育。DTI的结构测量将进一步与胎儿皮质板的基因谱相关。人类的大脑是非常复杂的，但它的起源是一个简单的管状结构。其发展的特点是一系列准确组织的事件，其基础的机制，戏剧性的结构变化在胎儿发育。揭示人类胎儿大脑发育不同阶段的详细解剖结构，并将解剖结构变化与基因图谱相关联，不仅有助于理解这一高度有序的过程，而且有助于理解认知性大脑疾病的神经生物学基础，如精神发育迟滞，自闭症，精神分裂症，双相情感障碍和语言障碍。然而，这一时期人类大脑发育的解剖学研究令人惊讶地稀缺，基于组织学的图谱直到最近才变得可用。我们的初步数据（1-3）和其他研究（例如4-9）支持DTI能够在宏观和微观水平上无创地描绘胎儿脑结构。结构DTI图谱将为早产儿的诊断放射学提供参考标准，并为了解整个大脑的结构发育提供有价值的资源。部分各向异性（FA）来自扩散张量和厚度测量的subplate提供了宝贵的见解皮质成熟。这两个测量值的空间上独特的变化伴随着在皮层板的不同位置的独特的基因谱。表征特定基因表达的特征结构效应为理解脑功能的形成提供了一个令人耳目一新的窗口。这项研究是通过三个实验室之间的合作实现的：黄博士，Sestan博士和Yarowsky博士。通过Sestan博士实验室的胎儿大脑基因图谱分析，结合结构变化和基因表达之间关系的数据库可以提供在早期阶段检测发育和认知大脑障碍的线索。在本研究中，我们将通过以下三个目标专注于技术和数据库的开发，这些技术和数据库将成为这一新研究领域的重要组成部分：目标1：建立人胎儿脑的二维（2D）和三维（3D）数字DTI/MRI图谱。目的2：描述大脑壁结构测量的皮质标测。目标3：在整个皮质板的结构测量的时间变化相关的突触形成，轴突生长和髓鞘形成的发育功能相关的定量基因表达。

DESCRIPTION (provided by applicant): The major goal of the proposed project is to delineate the structural development of the human fetal brain both qualitatively and quantitatively with ultra high resolution diffusion tensor imaging (DTI). The structural measurements from DTI will be further correlated to the gene profiles across the fetal cortical plate. Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development is characterized by a series of accurately organized events which underlies the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development and correlating the anatomical changes to gene profiles aid in understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Our preliminary data (1-3) and other studies (e.g. 4-9) have supported that DTI is capable of noninvasively delineating the fetal brain structures at both macroscopic and microscopic level. The structural DTI atlas will provide reference standards for diagnostic radiology of premature newborns and a valuable resource to understand the structural development of the entire brain. Factional anisotropy (FA) derived from diffusion tensor and thickness measurements of the subplate provide valuable insights into the cortical maturation. The spatially unique changes of these two measurements are accompanied by the distinctive gene profiles at different locations of the cortical plate. Characterizing the featured structural effects of specific gene expression offers a refreshing window to understand the formation of the brain functions. This study is made possible by collaborating among the three labs: Dr. Huang, Dr. Sestan and Dr. Yarowsky. With gene profiling of the fetal brains (10) from Dr. Sestan's lab, the database incorporating the relationship between the structural changes and gene expression may provide the clues of detecting developmental and cognitive brain disorders at their early stages. In this proposal, we will focus on the development of technologies and databases that will be essential components for this new research field through the following three aims: Aim 1: To establish the two- dimensional (2D) and three-dimensional (3D) digital DTI/MRI atlas of human fetal brain. Aim 2: To delineate the cortical mapping of structural measurement in the cerebral wall. Aim 3: To correlate across the cortical plate the temporal changes of the structural measurements to the quantified gene expression related to developmental functions of synapse formation, axonal growth and myelination.