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

描述(申请人提供)：胎儿酒精谱系障碍(FASD)，其重要组成部分是中枢神经系统(CMS)和颅面畸形，是一个主要的公共卫生问题。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。拟议的调查旨在与财团其他成员的调查结合起来，以满足这一需要。在这项工作中，高分辨率磁共振成像(MRI)可以提供29微米(或更少)的各向同性扫描和随后准确的3-D重建和节段分析，扩散张量成像(DTI)可以进行CMS纤维束分析，将应用于FASD小鼠模型的研究。之前利用这一模型进行的研究已经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MRI和DTI作为高通量筛查平台，以解决以下具体目标：1)提供全面的文献和发现因产前酒精暴露在胚胎和胎儿早期发育阶段而导致的中枢神经系统畸形；2)定义胚胎和/或早期胎儿阶段因产前酒精暴露而导致的面部畸形，并将其特征和严重程度与伴随的脑异常联系起来；以及3)确定脑或面部以外的区域可作为产前酒精暴露的诊断指标。拟议研究的结果将与其他财团成员的相应调查结果进行比较。预计乙醇诱导的小鼠大脑和面部结构异常将反映FASD儿童所观察到的缺陷模式，将为人类诊断试验提供信息，并将提供有助于降低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.