Structural Development of Human Fetal Brain

项目描述（由申请人提供）：拟建项目的主要目标是利用超高分辨率弥散张量成像（DTI）定性和定量地描绘人类胎儿大脑的结构发育。DTI的结构测量将进一步与胎儿皮质板上的基因谱相关。人类的大脑异常复杂，但它的起源是一个简单的管状结构。它的发育以一系列精确组织的事件为特征，这些事件是胎儿发育过程中剧烈结构变化机制的基础。揭示人类胎儿大脑发育不同阶段的详细解剖结构，并将解剖变化与基因谱相关联，不仅有助于理解这一高度有序的过程，还有助于理解认知性脑障碍（如智力迟钝、自闭症、精神分裂症、双相情感障碍和语言障碍）的神经生物学基础。然而，这一时期人类大脑发育的解剖学研究却出奇地少，基于组织学的地图集直到最近才可用。我们的初步数据（1-3）和其他研究（例如4-9）都支持DTI能够在宏观和微观水平上无创地描绘胎儿大脑结构。结构DTI图谱将为早产儿影像学诊断提供参考标准，并为了解全脑结构发育提供宝贵资源。从扩散张量和亚板厚度测量中得出的各向异性（FA）为皮质成熟提供了有价值的见解。这两个测量值在空间上的独特变化伴随着皮质板不同位置的独特基因谱。表征特定基因表达的特征结构效应为理解大脑功能的形成提供了一个新的窗口。这项研究是由Huang博士、Sestan博士和Yarowsky博士这三个实验室合作完成的。Sestan博士的实验室对胎儿大脑进行了基因分析，将结构变化和基因表达之间的关系纳入数据库，可能会为早期发现发育和认知大脑障碍提供线索。在本提案中，我们将重点发展技术和数据库，这将是这个新的研究领域的重要组成部分，通过以下三个目标：目标1：建立人类胎儿大脑的二维（2D）和三维（3D）数字DTI/MRI图谱。目的2：描述脑壁结构测量的皮质映射。目的3：将皮质板上结构测量的时间变化与突触形成、轴突生长和髓鞘形成等发育功能相关的量化基因表达联系起来。

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.