Study of Down syndrome cortical development by MRI/DTI

唐氏综合症皮质发育的MRI/DTI研究

• 批准号: 6513705
• 负责人: PAUL J YAROWSKY
• 金额: $ 19.61万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6513705
• 关键词: Downs syndrome; aneuploidy; brain mapping; brain morphology; cerebral cortex; clinical research; developmental disease /disorder; developmental neurobiology; disease /disorder model; embryo /fetus cell /tissue; fiber cell; human fetus tissue; laboratory mouse; magnetic resonance imaging; mammalian embryology; neuroimaging; postmortem

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.

描述（由申请人提供）：唐氏综合症（DS）是智力低下的最常见遗传形式。 DS的特定标志之一是脑皮质发育。研究发现皮质性下降，异常层压，突触发生降低，树突状发育异常以及髓鞘延迟。这些异常导致皮质组织和电路异常。由于缺乏足够的DS组织，因此很难首先确定皮质发育中何时发生异常。较新的大脑成像方法，尤其是MRI，可以在3维进行研究，而没有组织学方法的侵入性。与正常人类发育相比，本实验将研究DS胎儿发育过程中皮质的发育，并将DS的皮质形成和生长与DS动物模型（分段三体小鼠（TS65DN））进行比较。 DS中的21个相同染色体基因中的许多相同的染色体基因也在TS65DN中进行了三次，因此TS65DN和DS具有共同的遗传异常。使用高分辨率NM和解决原位水扩散的新方法，将解决扩散张量成像（DTI）纤维束结构和皮质组织。我们将表征皮质区域的体积，描述皮层的微观结构以及胎儿时期存在的主要纤维束的结构。我们有一个独特的尸体胎儿DS大脑（妊娠18-26周）的集合，这是未来皮质组织形成的时期。我们将直接解决以下假设：皮质体积以及特定纤维束的大小和形状在DS中是异常的。在AIM 1中，我们将使用MRI表征胎儿DS和TS65DN中皮质区域的体积。在AIM 2中，我们将使用DTI表征DS和TS65DN中的皮质微结构和纤维束结构。因此，我们不仅会表征DS和TS65DN中的胎儿发育，而且还确定它们的相似性。胎儿新皮质发育过程中的缺陷可能导致导致认知缺陷的永久性皮质异常。