Development of Brain Connectivity in Human Fetus, Newborn, and Toddler Ages

描述（由申请人提供）：越来越多的人意识到脑回折叠的发育障碍可导致发育性神经系统疾病，如阅读障碍、精神分裂症和Rett综合征，许多研究表明，此类疾病中的白色发育存在细微异常，表明大脑连接性改变。因此，有必要对大脑通路的正常模式和发育时间进行清晰的描述，并解释白色物质通路的作用，以便更准确地诊断发育过程中大脑连接的细微障碍。在该项目的前一阶段，作为R21资助，我们优化了弥散MR采集和纤维束成像重建参数，用于研究胎儿/小儿大脑中的连接发育，并根据组织学确认了关键的纤维束成像组件。我们已经报道了纤维通路的发展顺序与大脑和小脑中的迁移通路的回归，以及新兴的半球不对称的通路。我们建立在发展中的人类胎儿，新生儿和幼儿的大脑，高角分辨率磁共振成像/扩散光谱成像（HARDI/DSI）与最佳参数有可能定义发育中的大脑和小脑的连接解剖。本R 01的目的是通过增加与成像和组织学相比的脑区数量以及增加样本/受试者数量和发育时间点，进一步证实初步发现，并更精确地确定人类胎儿、新生儿和幼儿大脑中大脑连接和形态测量学发育的时间过程。在目标1中，我们将创建一个全面的人类胎儿，新生儿和幼儿脑通路和脑形态体外发育图谱。将报告大脑和小脑皮质和白色物质中纤维通路的发育。纤维通路和脑回结构的形成/成熟之间的时空关系也将被检查。在目标2中，我们将用组织学验证目标1中的关键发现。在目标3中，我们将比较来自目标1的离体纤维束成像与出生后新生儿和幼儿大脑中临床正常的体内纤维束成像。将通过共配准离体和体内扩散数据作为组比较来评估每种途径的轨迹和体积。此外，还将评估个体差异。

DESCRIPTION (provided by applicant): There has been growing awareness of the fact that developmental disturbances of gyral folding can lead to developmental neurological disorders such as dyslexia, schizophrenia, and Rett syndrome, and a number of studies have shown subtle abnormal white matter development in such disorders suggesting altered brain connectivity. It is therefore essential to develop a clear picture of the normal patterns and timin of development of brain pathways, and to interpret the role of white matter pathways in order to more accurately diagnose subtle disorders of brain connectivity during development. In a previous stage of this project, funded as an R21, we optimized diffusion MR acquisition and tractography reconstruction parameters for the study of connectional development in the fetal/pediatric brain, and confirmed key tractography components against histology. We have reported the developmental orders of fiber pathways in relation with the regression of migration pathways in the cerebrum and cerebellum, and emerging hemispheric asymmetry of the pathways. We established in developing human fetal, newborn, and toddler brains that high-angular resolution magnetic resonance imaging / diffusion spectrum imaging (HARDI/DSI) with optimal parameters has the potential to define connectional anatomy of the developing cerebrum and cerebellum. The goal of this R01 is to further confirm the preliminary findings by increasing the number of brain areas compared with imaging and histology, as well as by increasing the numbers of specimens/subjects and developmental time-points, and to determine more precisely the time course of development of brain connectivity and morphometry in the human fetus, newborn, and toddler brains. In Aim 1, we will create a comprehensive developmental atlas of human fetal, newborn, and toddler brain pathways and brain morphology ex vivo. Development of fiber pathways in the cortex and white matter of the cerebral and cerebellum will be reported. The spatio-temporal relationships between the formation/maturation of fiber pathways and gyral structures will also be examined. In Aim 2, we will validate key findings in Aim 1 with histology. In Aim 3, we will compare ex vivo tractography derived from Aims 1 to clinically normal in vivo tractography in postnatal newborn and toddler brains. Trajectories and volume of each pathway will be assessed by co-registering ex vivo and in vivo diffusion data as a group comparison. In addition, individual variations will also be assessed.