DIFFUSION TENSOR MR IMAGING OF A MOUSE FASD MODEL

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目的目的是快速推进DTI技术及其应用，以发现和记录酒精对出生前和出生后啮齿动物大脑的有害影响。一个主要的重点是实现比目前可能的更快的成像时间。这将允许从离体到体内标本的DTI分析的扩展。 为了补充成像的进步，新的方法，包括工具和软件的数据管理和分析也正在开发和应用到我们的分析胎儿和出生后的小鼠大脑。这些技术被用来扩展本实验室目前的研究胎儿酒精谱系障碍（FASD）的小鼠模型，并解决这一假设，即母亲的酒精（乙醇）管理有限的产前发展的非常早期阶段（相当于人类发育的第3周）的结果在永久性中枢神经系统损伤。 为了实现这一目标，正在努力实现三个具体目标。目标#1是开发新的DTI方法，使成像时间比目前可行的更快。这将通过使用主动染色技术、3D径向锁孔成像和应用于DTI的新型低温射频线圈来实现。 目标#2是快速开发一个软件框架，用于基于无偏图谱生成的新的自动化小鼠大脑数据分析。该分析方法将用于DTI属性和连接模式的逐体素分析，以及DTI纤维追踪特定分析。 目的#3是将先前目的中提出的方法应用于检查酒精对出生前和出生后小鼠大脑的影响。 为此，将在产前第17天（GD 17）或出生后第45和/或90天（PND 45，PND 90）检查对照小鼠和妊娠第7天暴露于酒精的小鼠的脑纤维束形态（包括微结构完整性）以及区域扩散参数的变化，如各向异性测量（例如，部分各向异性  FA和平均扩散率  MD）。 除了GD 17和PND 45和90脑的离体成像外，PND 45动物的子集将在体内成像。由于据报道产前酒精暴露与人类随后的酒精依赖有关，并且还增加了动物的酒精自我给药和偏好，因此在成像之前，将在许多行为电池中检查出生后动物，旨在评估其对急性酒精挑战的反应。预计除了快速提供可直接应用于其他啮齿动物模型和研究问题的工具和方法外，该挑战赠款项目还将提供有关产前酒精暴露的生物学（结构和功能）后果的重要新信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this project is to rapidly advance DTI technology and its application to discovery and documentation of alcohol's deleterious effects on the pre-and postnatal rodent brain. A major focus is on achieving faster imaging times than are currently possible. This will allow the extension of DTI analyses from ex vivo to in vivo specimens. To complement the advances in imaging, new methodologies including tools and software for data management and analyses are also being developed and applied to our analyses of the fetal and postnatal mouse brain. These techniques are being utilized to extend this laboratory's current investigation of fetal alcohol spectrum disorders (FASD) in a mouse model and to address the hypothesis that maternal alcohol (ethanol) administration limited to very early stages of prenatal development (corresponding to week 3 of human development) results in permanent central nervous system damage. To accomplish this, 3 specific aims are being addressed. Aim #1 is to develop new DTI methodologies that will allow faster imaging times than are currently feasible. This will be accomplished by the use of active staining techniques, 3D radial keyhole imaging, and a novel cryogenic radiofrequency coil applied to DTI. Aim #2 is to rapidly develop a software framework for a new, automated mouse brain data analysis based on an unbiased atlas generation. This analysis method will be used for voxel-wise analysis of DTI properties and connectivity patterns, as well as DTI fiber tractography-specific analysis. Aim #3 is to apply the methodologies advanced in the previous Aims to the examination of alcohol's effect on the pre- and postnatal mouse brain. For this, the brains of control mice and those exposed to alcohol on their 7th day of gestation, will be examined on their 17th prenatal day (GD 17), or their 45th and/or 90th postnatal day (PND 45, PND 90) for fiber tract morphology (including microstructural integrity) as well as for alterations in regional diffusion parameters such as measures of anisotropy (eg. fractional anisotropy  FA and mean diffusivity  MD). In addition to ex vivo imaging of the GD 17 and PND 45 and 90 brains, a subset of the PND 45 animals will be imaged in vivo. Since prenatal alcohol exposure is reportedly related to subsequent alcohol dependence in humans and also increases alcohol self administration and preference in animals, prior to imaging, the postnatal animals will be examined in a number of behavioral batteries designed to assess their reactions to acute alcohol challenge. It is expected that in addition to rapidly providing tools and approaches that can be directly applied to other rodent models and research questions, this Challenge grant project will provide important new information regarding the biological (both structural and functional) consequences of prenatal alcohol exposure.