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

描述(申请人提供)：人们越来越意识到这样一个事实，即脑回折叠的发育障碍会导致发育性神经障碍，如诵读困难、精神分裂症和雷特综合征，一些研究表明，在这些障碍中，脑白质发育轻微异常，提示大脑连接性改变。因此，为了更准确地诊断发育过程中大脑连接的细微障碍，有必要对大脑通路的正常模式和时间进行清晰的描述，并解释白质通路的作用。在这个项目的前一阶段，作为R21资助，我们优化了磁共振扩散成像和脑束成像重建参数，用于研究胎儿/儿童脑内的连接发育，并确认了关键的脑束成像成分与组织学对照。我们已经报道了纤维通路的发育顺序与大脑和小脑中迁移通路的退化以及通路出现的半球不对称有关。我们在发育中的人类胎儿、新生儿和幼儿大脑中证实，具有最佳参数的高角分辨率磁共振成像/扩散谱成像(HARDI/DSI)具有定义发育中的大脑和小脑的连接解剖的潜力。R01的目标是通过与成像和组织学相比增加大脑区域的数量，以及通过增加样本/受试者的数量和发育时间点来进一步证实初步发现，并更准确地确定人类胎儿、新生儿和幼儿大脑的大脑连通性和形态测量的发展时间进程。在目标1中，我们将创建一份全面的人类胎儿、新生儿和蹒跚学步儿童的脑通路和脑形态的体外发育图谱。在大脑和小脑的皮质和白质中纤维通路的发展将被报道。我们还将研究纤维通路的形成/成熟与脑回结构之间的时空关系。在目标2中，我们将用组织学来验证目标1中的关键发现。在目标3中，我们将比较来自AIMS 1的体外气管造影术和出生后新生儿和幼儿大脑的临床正常体内气管造影术。每条途径的轨迹和体积将通过共同登记体外和体内扩散数据作为小组比较来评估。此外，还将对个体差异进行评估。

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.