Study of Down syndrome cortical development by MRI/DTI

描述（由申请人提供）：唐氏综合征（DS）是最常见的遗传形式的精神发育迟滞。DS的特征之一是大脑皮质发育异常。研究发现皮质发育不全、层压异常、突触发生减少、树突发育异常和髓鞘形成延迟。这些异常导致异常的皮层组织和电路。由于缺乏足够的DS组织，很难确定皮质发育异常何时首次发生。较新的脑成像方法，特别是MRI，使大脑发育的研究可以在三维空间进行，而没有组织学方法的侵入性。本实验将研究发育的皮质在胎儿发育期间在DS相比，正常的人类发展，还比较皮质的形成和生长在DS与DS的动物模型，节段性三体16小鼠（Ts65Dn）。DS中的许多相同的21号染色体基因也在Ts65Dn中三重化，因此Ts65Dn和DS具有共同的遗传异常。使用高分辨率NM和原位分辨水扩散的新方法，将分辨扩散张量成像（DTI）纤维束结构和皮质组织。我们将描述皮质区域的体积，描绘皮质的微观结构和胎儿时期主要纤维束的结构。我们有一个独特的收集死后胎儿DS大脑（18 - 26周妊娠），一个时期的形成未来的皮质组织。我们将直接解决的假设，皮质体积和特定的纤维束的大小和形状是异常的DS。在目标1中，我们将使用MRI表征胎儿DS和Ts65Dn的皮质区域的体积。在目标2中，我们将使用DTI表征DS和Ts65Dn的皮质微结构和纤维束结构。因此，我们不仅将表征DS和Ts65Dn中的胎儿发育，还将确定它们的相似性。胎儿新皮质发育过程中的缺陷可能导致永久性的皮质异常，导致认知缺陷。

DESCRIPTION (provided by applicant): Down syndrome (DS) is the most common genetic form of mental retardation. One of the specific hallmarks of DS is anomalous cerebral cortical development. Studies have found cortical hypoplasia, abnormal lamination, reduced synaptogenesis, aberrant dendritic development, and a delay in myelination. These abnormalities lead to abnormal cortical organization and circuitry. Because of the lack of adequate DS tissue, it has been difficult to determine when abnormalities in cortical development first occur. Newer methods of brain imaging especially MRI have allowed studies of brain development to be done 3-dimensionally, without the invasiveness of histological methods. The present experiments will investigate development of the cortex during fetal development in DS compared to normal human development and also compare cortical formation and growth in DS with an animal model of DS, the segmental trisomy 16 mice (Ts65Dn). Many of the same chromosome 21 genes triplicated in DS are also triplicated in Ts65Dn and therefore Ts65Dn and DS share a common genetic abnormality. Using high resolution NM and the new method of resolving water diffusion in situ, diffusion tensor imaging (DTI) fiber bundle architecture and cortical organization will be resolved. We will characterize the volume of cortical regions, delineate the microstructure of the cortex and the architecture of major fiber bundles present during the fetal period. We have a unique collection of postmortem fetal DS brains (18-26 weeks gestation), a period of formation of future cortical organization. We will directly address the hypothesis that cortical volume and the size and shape of specific fiber bundles is abnormal in DS. In Aim 1, we will characterize the volume of cortical regions in fetal DS and Ts65Dn using MRI. In Aim 2, we will characterize cortical microstructure and fiber bundle architecture in DS and Ts65Dn using DTI. Thus we will not only characterize fetal development in DS and Ts65Dn, but also determine how similar they are. Defects during fetal neocortical development could lead to permanent cortical abnormalities responsible for cognitive deficits.