MAGNETIC RESONANCE AND DIFFUSION TENSOR IMAGING OF A MOUSE FASD MODEL U01

描述（由申请人提供）：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（CMS）和颅面异常。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，产前乙醇暴露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，需要更全面地了解乙醇引起的异常。拟议的调查旨在与其他财团成员的调查相结合，以满足这一需要。对于这项工作，高分辨率磁共振成像（MRI），可以提供29微米（或更小）的各向同性扫描和随后的精确三维重建和片段分析，以及扩散张量成像（DTI），允许CMS纤维束分析，将应用于FASD小鼠模型的研究。先前利用该模型的研究已经确定了产生面部和中枢神经系统异常的临界暴露时间，这些异常与成熟的胎儿酒精综合征以及FASD的其他组成部分一致。拟议的研究将采用该模型和急性和慢性乙醇治疗范式来检验总体假设，即在小鼠中，乙醇诱导大脑和面部结构异常，这与人类FASD的结构异常一致并提供信息。为此，利用MRI和DTI作为高通量筛选平台，我们提出以下具体目标：1)提供全面的文献和发现乙醇诱导的中枢神经系统畸形，这些畸形是由胚胎和胎儿早期发育阶段产前乙醇暴露引起的；2)定义由胚胎期和/或胎儿早期乙醇暴露导致的面部畸形，并将其特征和严重程度与伴随的大脑异常联系起来；3)识别除大脑或面部以外可能作为产前乙醇暴露诊断指标的区域。建议的研究结果将与其他联盟成员的相应调查结果进行比较。预计乙醇在小鼠中诱导的脑和面部结构异常将反映FASD儿童中观察到的缺陷模式，将为人类诊断测试提供信息，并将提供有助于减少FASD发病率的新信息。

DESCRIPTION (provided by applicant): Fetal Alcohol Spectrum Disorders (FASD), significant components of which are Central Nervous System (CMS) and craniofacial abnormalities, are a major public health problem. While eliminating FASD is the ultimate goal for both 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 integrate with those of other consortium members in meeting this need. For this work, both high resolution Magnetic Resonance Imaging (MRI), which can provide 29 micron (or less) isotropic scans and subsequent accurate 3-D reconstructions and segmental analyses, and Diffusion Tensor Imaging (DTI), which allows CMS fiber tract analyses, will be applied to the study of an FASD mouse model. Previous research utilizing this model has established critical exposure times that yield facial and CNS abnormalities that are 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 MRI and DTI as high throughput screening platforms, we propose to address the following specific aims : 1) 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; 2) to define the facial dysmorphology that results from prenatal ethanol exposure during embryonic and/or early fetal stages and to relate their character and severity to accompanying abnormalities of the brain; and 3) to identify regions other than the brain or face that may serve as diagnostic indicators of prenatal ethanol exposure. The results of the proposed studies will be compared to those of corresponding investigations by other consortium members. It is expected that the structural abnormalities of the brain and face 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 that will be helpful in reducing the incidence of FASD.