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.
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