Study of Down syndrome cortical development by MRI/DTI

描述(申请人提供)：唐氏综合症(DS)是最常见的精神发育迟滞的遗传形式。DS的一个特殊特征是大脑皮质发育异常。研究发现，皮质发育不全、板层异常、突触形成减少、树突状细胞发育异常以及髓鞘形成延迟。这些异常导致大脑皮层组织和回路的异常。由于缺乏足够的DS组织，很难确定皮质发育异常最早发生的时间。更新的脑成像方法，特别是核磁共振成像，使大脑发育的研究能够以三维方式进行，而不需要组织学方法的侵入性。目前的实验将与正常人类发育相比，研究DS胎儿发育期间皮质的发育，并将DS的皮质形成和生长与DS的动物模型--节段性三体16小鼠(Ts65Dn)进行比较。在DS中复制的许多相同的21号染色体基因在Ts65Dn中也是三重的，因此Ts65Dn和DS共享共同的遗传异常。利用高分辨率NM和原位解决水分扩散的新方法，将解决扩散张量成像(DTI)纤维束的结构和皮质组织问题。我们将描述皮质区域的体积，描绘皮质的微结构和胎儿时期存在的主要纤维束的结构。我们收集了独一无二的死后胎儿DS脑(妊娠18-26周)，这是未来皮质组织形成的时期。我们将直接解决这一假说，即皮质体积以及特定纤维束的大小和形状在DS中异常。在目标1中，我们将使用MRI来表征胎儿DS和Ts65Dn的皮质区域的体积。在目标2中，我们将使用DTI来表征DS和Ts65Dn的皮质微结构和纤维束结构。因此，我们不仅将描述DS和Ts65Dn的胎儿发育特征，而且还将确定它们的相似程度。胎儿新皮质发育过程中的缺陷可能会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.