Structural Development of Human Fetal Brain

人类胎儿大脑的结构发育

• 批准号: 8514172
• 负责人: Hao Huang
• 金额: $ 9.87万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514172
• 关键词: Anatomy; Anisotropy; Area; Atlases; Auditory area; Autistic Disorder; Autopsy; Brain; Brain Diseases; Cerebrum; Cognitive; Complex; Data; Data Set; Databases; Development; Diagnostic radiologic examination; Diffusion; Diffusion Magnetic Resonance Imaging; Event; Fetal Development; Foundations; Gene Expression; Gene Structure; Genes; Gestational Age; Goals; Growth; Histology; Human; Human Development; Image; Impairment; Language; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mental Retardation; Microscopic; Morphology; Motor; Neurobiology; Newborn Infant; Pregnancy; Premature Infant; Process; Radial; Reference Standards; Research; Resources; Schizophrenia; Series; Staging; Structure; Thick; Tissue-Specific Gene Expression; Tissues; Tubular formation; Weight; Work; axon growth; base; cognitive function; digital; extrastriate visual cortex; fetal; insight; interest; myelination; premature; relating to nervous system; somatosensory; synaptogenesis; technology development; two-dimensional; ultra high resolution; white matter

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.

描述（由申请人提供）：该项目的主要目标是利用超高分辨率扩散张量成像（DTI）定性和定量地描绘人类胎儿大脑的结构发育。 DTI 的结构测量结果将进一步与胎儿皮质板的基因谱相关。人脑极其复杂，但其起源却是一个简单的管状结构。其发育的特点是一系列精确组织的事件，这些事件构成了胎儿发育过程中剧烈结构变化的机制。揭示人类胎儿大脑发育不同阶段的详细解剖结构，并将解剖学变化与基因图谱关联起来，不仅有助于理解这一高度有序的过程，而且有助于了解智力低下、自闭症、精神分裂症、双相情感障碍和语言障碍等认知性大脑疾病的神经生物学基础。然而，这一时期人类大脑发育的解剖学研究却出奇地稀少，基于组织学的图谱最近才出现。我们的初步数据 (1-3) 和其他研究 (例如 4-9) 都支持 DTI 能够在宏观和微观层面上无创地描绘胎儿大脑结构。结构 DTI 图集将为早产儿诊断放射学提供参考标准，也是了解整个大脑结构发育的宝贵资源。从扩散张量和底板厚度测量得出的派系各向异性 (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令人耳目一新的窗口。这项研究是通过三个实验室（黄博士、Sestan 博士和 Yarowsky 博士）之间的合作而得以完成的。通过 Sestan 博士实验室对胎儿大脑 (10) 的基因分析，包含结构变化和基因表达之间关系的数据库可能会提供早期检测发育和认知大脑疾病的线索。在本提案中，我们将通过以下三个目标，重点开发将成为这一新研究领域重要组成部分的技术和数据库： 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。目标 2：描绘大脑壁结构测量的皮质图。目标 3：将整个皮质板的结构测量的时间变化与与突触形成、轴突生长和髓鞘形成的发育功能相关的量化基因表达相关联。