DIFFUSION TENSOR MR IMAGING OF A MOUSE FASD MODEL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 胎儿酒精谱系障碍(FASD)是一个重大的公共卫生问题，其重要组成部分是中枢神经系统和颅面畸形。虽然消除FASD是临床和基础FASD研究的最终目标，但我们认识到，在不久的将来，产前接触酒精的不良影响将持续存在。为了更好地诊断和治疗受影响的个体，需要对乙醇引起的异常的全谱有更全面的了解。拟议的调查旨在为满足这一需求做出重大贡献。在这项工作中，扩散张量成像(DTI)，它允许在高分辨率(60微米或更低的各向同性)的中枢神经系统纤维束分析，将被应用于FASD小鼠模型的研究。以前使用该模型的研究确定了导致面部和中枢神经系统异常的关键暴露时间，这些异常与全面胎儿酒精综合症以及FASD的其他组成部分一致。拟议的研究将使用该模型以及急性和慢性乙醇治疗范例来检验总体假设，即在小鼠中，乙醇导致大脑和面部的结构异常，这与人类FASD的结构异常是一致的，并提供了信息。为此，我们建议利用DTI作为高通量筛查平台，提供全面的文献和发现乙醇诱导的中枢神经系统畸形，这种畸形是由产前酒精暴露在胚胎和早期胎儿发育阶段引起的。预计乙醇诱导的小鼠大脑结构异常将反映FASD儿童中观察到的缺陷模式，将为人类诊断测试提供信息，并将提供有助于降低FASD发病率的新信息。

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. Fetal Alcohol Spectrum Disorders (FASD), significant components of which are CNS and craniofacial abnormalities, are a major public health problem. While eliminating FASD is the ultimate goal for clinical and basic FASD research, we recognize that in the near future, adverse effects from prenatal ethanol exposure will persist. To better diagnose and treat affected individuals, a more complete understanding of the full spectrum of the ethanol-induced abnormalities is needed. The proposed investigations are designed to contribute significantly toward meeting this need. For this work, Diffusion Tensor Imaging (DTI), which allows CNS fiber tract analyses at a high resolution (60-micron or less isotropic), will be applied to the study of an FASD mouse model. Previous research using this model established critical exposure times that yield facial and CNS abnormalities consistent with full-blown Fetal Alcohol Syndrome, as well as other components of FASD. The proposed studies will employ this model and both acute and chronic ethanol treatment paradigms to test the overall hypothesis that in mice, ethanol induces structural abnormalities of the brain and face that are consistent with and informative for those in human FASD. To this end, utilizing DTI as high throughput screening platforms, we propose to provide comprehensive documentation and discovery of the ethanol-induced CNS dysmorphology that results from prenatal ethanol exposure at embryonic and early fetal stages of development. It is expected that the structural abnormalities of the brain that are induced by ethanol in mice will reflect the pattern of defects observed in children with FASD, will inform human diagnostic tests, and will provide new information to help reduce the incidence of FASD.