RETT SYNDROME GENETICS, PATHOGENESIS & SEARCH FOR MARKER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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理解，作为改进诊断和治疗的第一步。这次合作的一个重要组成部分是核磁共振神经成像和核磁共振光谱成像。在这项研究的几个方面，与资源的合作是极其重要的。首先，患有Rett综合征的受试者中有很大一部分是儿童，他们需要一个特殊的环境来感到舒适地参与扫描。此外，许多患有Rett综合征的成年人有智力障碍，需要特别注意才能成功进行扫描。我们中心的磁体是所有1.5T和3T全身扫描仪中孔径最短的。孔可以从后面和前面进入，并允许受试者与其护理人员保持目光接触。这种对儿童友好的磁共振成像环境有望大大减少镇静的需求，因为儿童更放松。柯比中心还配备了一个模拟扫描仪，在那里，儿童或其他受试者可以接受训练，保持静止，并在磁铁中执行任务。Naidu博士和该中心的工作人员将与肯尼迪克里格中心的儿童心理学家一起，致力于优化儿童成像。后者很重要，因为预计这些儿童的功能测试可以以定量可重复的方式提供有关其行为的急需信息。Rett综合征研究项目涉及本资源申请中提出的所有开发项目。项目1中改进图像配准和处理的血流和氧合方法和技术的设计将用于检验Rett综合征中额叶血流量和氧代谢异常的假设（见下文）。项目2中的光谱学工具将用于确定正常儿童的神经递质和其他脑化学物质的水平。“项目3”将首次提供将Rett综合征患儿与正常儿童大脑中的神经网络进行比较的可能性。项目4对于建立大脑区域的形状，并将所有项目的结果结合在将被评估为发育阶段功能的总体图中至关重要。

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.