Brain Imaging of Newborns with Fetal Alcohol Syndrome

描述（由申请人提供）：自1998年以来，我们一直在南非开普敦合作研究胎儿酒精综合征（FAS），那里是世界上FAS发病率最高的地方之一。2005年，我们获得资助，在南非实施了第一次功能磁共振成像研究。2008年，我们获得了R01奖，在学龄儿童中使用神经成像来检查与眨眼调节（EBC）相关的小脑神经回路。我们最近发现，眨眼调节是FAS和其他酒精相关疾病的一个非常可靠的潜在生物标志物。R01还包括资助招募酗酒的孕妇和产后6个月的EBC神经行为研究的对照组。胎儿酒精谱系障碍是一个全球性的公共卫生问题，其长期影响包括严重的神经认知障碍，在婴儿期很难诊断。对成人和儿童的核磁共振成像（MRI）研究表明，特定的大脑区域受到了不成比例的影响。在婴儿出生后的最初几周，体积MRI测量可以发现早期区域体积的差异，并提供比标准新生儿行为或神经学检查更敏感的未来神经预后指标。迄今为止，很少有研究使用MRI脑形态术对新生儿进行分割，这目前需要手工标记，因此对于大数据集来说过于劳动密集型。我们建议在产前暴露于酒精的新生儿中进行首次结构MRI研究。研究人员将招募两组孕妇——35名重度饮酒者和35名未饮酒的对照组。其目的是：(1)确定在产前大量饮酒的新生儿中，哪些大脑结构不成比例地小；(2)测试产前暴露相关的特定新生儿脑区体积减少是否能预测6个月时的神经行为表现缺陷；(3)使用信息论的注册技术来检查产前暴露的新生儿特定大脑结构的形状和位置的变化。将根据健康新生儿对照数据构建图谱，以验证和改进麻省总医院目前正在开发的自动分割工具，以便更快、更有效地标记婴儿大脑结构。

DESCRIPTION (provided by applicant): Since 1998, we have been collaborating on research on fetal alcohol syndrome (FAS) in Cape Town, South Africa, where the incidence of FAS is among the highest in the world. In 2005 we were funded to implement the first fMRI studies in South Africa and in 2008 were awarded an R01 to use neuroimaging in school-age children to examine the cerebellar neural circuitry related to eyeblink conditioning (EBC), which we recently identified as a strikingly reliable potential biomarker of FAS and other alcohol-related disorders. The R01 also includes funding to recruit heavy drinking pregnant women and controls for a neurobehavioral study of EBC at 6 months postpartum. Fetal alcohol spectrum disorder, a world-wide public health problem whose long-term effects include significant neurocognitive impairment, is difficult to diagnose in infancy. Magnetic resonance imaging (MRI) studies with adults and children have shown that specific brain regions are disproportionately affected. Volumetric MRI measures in the first weeks of life may detect early differences in regional volumes and provide a more sensitive index of future neurological outcome than standard newborn behavioral or neurological examinations. To date, few studies have been conducted using MRI cerebral morphometry segmentation in neonates, which currently requires hand labeling and is, therefore, too labor intensive for large data sets. We propose to conduct the first structural MRI study in newborns exposed prenatally to alcohol. Two groups of pregnant women will be recruited-35 heavy alcohol users and 35 non-exposed controls. The aims are (1) to determine which brain structures are disproportionately smaller in neonates with heavy prenatal alcohol exposure; (2) to test whether prenatal exposure- related volumetric reductions in specific neonatal brain regions predict neurobehavioral performance deficits at 6 months; and (3) to use information-theoretic registration techniques to examine alterations in shape and location of specific brain structures in prenatally exposed neonates. An atlas will be constructed from the data from healthy neonatal controls to validate and refine automated segmentation tools currently being developed at Massachusetts General Hospital to permit faster and more efficient labeling of infant brain structures. PUBLIC HEALTH RELEVANCE: Fetal alcohol syndrome (FAS) and alcohol-related disorders are an important worldwide health problem and a major public health issue in South Africa, whose long-term effects include significant, irreversible neurocognitive and behavioral impairment. Since FAS and alcohol-related disorders are difficult to diagnose in infancy, identification of morphological effects in specific brain regions in the neonate can advance understanding of the etiology of these disorders, improve diagnosis, and permit earlier identification of affected children. This research will also provide high quality neonatal neuroimaging data from healthy newborns to be used in refinement of automated methods for segmentation of infant brain scans.