RETT SYNDROME GENETICS, PATHOGENESIS & SEARCH FOR MARKER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。Rett综合征项目的总体目标是提高对Rett综合征的遗传学和发病机制的了解，作为改善诊断和治疗的第一步。这种合作的一个重要组成部分是磁共振神经成像和磁共振光谱成像。在这项研究的几个方面，与资源的合作是极其重要的。首先，Rett综合征的受试者中有很大一部分是儿童，他们需要特殊的环境才能感到舒适地参与扫描。此外，许多患有Rett综合征的成年人患有智力低下，需要特别关注才能成功进行扫描。我们中心的磁铁是所有1.5T和3T全身扫描仪中口径最短的。内孔可以从后面和前面接触，并允许受试者与其照顾者保持眼神接触。这种适合儿童的磁共振成像环境预计将大大减少对镇静的需求，因为儿童更放心。柯比中心还包括一台模拟扫描仪，儿童或其他受试者可以在其中训练保持不动并在磁铁中执行任务。奈杜博士和该中心的工作人员将与肯尼迪·克里格的儿童心理学家一起，致力于优化儿童的成像。后者很重要，因为预计对这些儿童的功能测试可以以定量可重复的方式提供关于他们行为的迫切需要的信息。Rett综合征研究计划涉及本资源申请中提出的所有开发项目。项目1中用于改进图像配准和处理的流动和氧合方法和技术的设计将用于检验Rett综合征额叶血流和氧代谢异常的假说(见下文)。项目2中的光谱工具将用于确定正常儿童的神经递质和其他大脑化学物质的水平。项目3将首次提供比较Rett综合征儿童和正常儿童大脑连接的可能性。项目4在确定大脑区域的形状和综合所有项目的结果方面将是至关重要的，这些项目将作为发育阶段的一项功能进行评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The general goal of the Rett Syndrome program project is to improve the understanding of the genetics and pathogenesis of Rett syndrome, as a first step to improved diagnosis and treatment. A significant component of this collaboration is MR neuroimaging and MR spectroscopic imaging. There are several aspects to this research for which collaboration with the resource is extremely important. First of all, a large fraction of the subjects with Rett Syndrome are children, who require a special environment to feel comfortable to participate in the scanning. Also, many adults with Rett syndrome have mental retardation and need special attention in order to be scanned successfully. The magnets in our center have the shortest bore available of all whole-body 1.5T and 3T scanners. The bore is accessible from the back and the front and allows the subject to keep eye contact with its care giver. This child-friendly environment for MR imaging is expected to drastically reduce the requir ements for sedation because the child is more at ease. The Kirby Center also contains a mock scanner in which the children or other subjects can be trained to hold still and perform tasks in the magnet. Together with the child psychologists at Kennedy Krieger, Dr. Naidu and the Center staff will work on optimizing the imaging of children. The latter is important because it is expected that functional testing of these children can provide much needed information on their behavior in a quantitative reproducible manner. The Rett Syndrome research program relates to all of the development projects proposed in this resource application. The design of flow and oxygenation methods and techniques for improved image registration and processing in Project 1 will be used to examine the hypothesis of abnormal blood flow and oxygen metabolism in the frontal lobe in Rett syndrome (see below). The spectroscopy tools in project 2 will be used to determine levels of neurotransmitters and other brain chemicals with respect to normal children. Project 3 will, for the first time, provide the possibility to compare the wiring in the brains of children with Rett syndrome to that of normal children. Projects 4 will be crucial in establishing shapes of brain regions and in combining the results of all projects in general maps that will be assessed as a function of developmental stage.