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，在这些疾病中，细微的白质发育异常表明大脑连接改变。因此，有必要对大脑通路的正常模式和发育时间有一个清晰的认识，并解释白质通路的作用，以便更准确地诊断发育过程中大脑连接的细微障碍。在该项目的前期，我们优化了弥散磁共振采集和神经束造影重建参数，用于研究胎儿/儿童大脑的连接发育，并根据组织学确定了关键的神经束造影成分。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回归有关，以及这些通路出现半球不对称。我们在发育中的人类胎儿，新生儿和幼儿大脑中建立了高角分辨率磁共振成像/扩散谱成像（HARDI/DSI）具有最佳参数的潜力，可以定义发育中的大脑和小脑的连接解剖学。本R01的目的是通过增加与成像和组织学相比较的脑区域数量，以及增加标本/受试者数量和发育时间点，进一步证实初步发现，并更准确地确定人类胎儿、新生儿和幼儿大脑连接和形态发育的时间进程。在Aim 1中，我们将创建一个全面的人类胎儿、新生儿和幼儿大脑通路和大脑形态的体外发育图谱。在大脑和小脑的皮层和白质纤维通路的发展将被报道。纤维通路的形成/成熟与脑回结构之间的时空关系也将被研究。在目标2中，我们将用组织学验证目标1中的关键发现。在Aims 3中，我们将比较Aims 1中导出的体外神经束造影与临床上正常的新生儿和幼儿大脑的体内神经束造影。每个通路的轨迹和体积将通过共同登记体外和体内扩散数据作为组比较来评估。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.