Study of Down syndrome cortical development by MRI/DTI

描述（由申请人提供）：唐氏综合症（DS）是最常见的智力迟钝的遗传形式。退行性椎体滑移的特征之一是大脑皮层发育异常。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，髓鞘形成延迟。这些异常导致皮层组织和电路异常。由于缺乏足够的退行性椎体变性组织，很难确定皮层发育异常何时首次发生。新的脑成像方法，尤其是核磁共振成像，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。本实验将研究胎儿发育过程中退行性椎体滑移的皮质发育与正常人类发育的比较，并将退行性椎体滑移的皮质形成和生长与退行性椎体滑移的动物模型——16节段性三体小鼠（Ts65Dn）进行比较。许多在DS中重复三倍的21号染色体基因也在Ts65Dn中重复三倍，因此Ts65Dn和DS具有共同的遗传异常。利用高分辨率NM和原位水扩散的新方法，扩散张量成像（diffusion tensor imaging， DTI）将解析纤维束结构和皮层组织。我们将描述皮质区域的体积，描绘皮层的微观结构和主要纤维束的结构存在于胎儿时期。我们有一个独特的死后胎儿DS脑（妊娠18-26周），这是未来皮质组织形成的时期。我们将直接解决皮质体积和特定纤维束的大小和形状在退行性椎体滑移中异常的假设。在目的1中，我们将使用MRI表征胎儿DS和Ts65Dn皮质区域的体积。在Aim 2中，我们将使用DTI表征DS和Ts65Dn的皮质微观结构和纤维束结构。因此，我们不仅将描述DS和Ts65Dn的胎儿发育特征，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导致永久性皮质异常，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.