Brain Imaging of Newborns with Fetal Alcohol Syndrome

描述(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)，那里的FAS发病率是世界上最高的之一。2005年，我们获得资助，在南非实施了第一批fMRI研究，并在2008年获得了R01，以使用学龄儿童的神经成像来检查与眨眼条件反射(EBC)相关的小脑神经回路，我们最近发现，EBC是Fas和其他酒精相关疾病的一个极其可靠的潜在生物标志物。R01还包括招募大量饮酒的孕妇和对照组的资金，用于产后6个月的EBC神经行为研究。胎儿酒精谱系障碍是一个世界性的公共卫生问题，其长期影响包括严重的神经认知障碍，在婴儿期很难诊断。对成人和儿童的磁共振成像(MRI)研究表明，特定的大脑区域受到的影响不成比例。与标准的新生儿行为或神经学检查相比，出生后头几周的体积MRI测量可能会检测到区域体积的早期差异，并提供一个更敏感的未来神经结局指标。到目前为止，在新生儿中使用MRI脑形态测量分割进行的研究很少，目前需要手工标记，因此对于大型数据集来说，劳动密集度太高。我们建议在产前接触酒精的新生儿中进行第一次结构磁共振研究。将招募两组孕妇-35名酗酒者和35名非接触者。其目的是(1)确定在出生前重度酒精暴露的新生儿中，哪些大脑结构不成比例地变小；(2)测试产前暴露相关的特定新生儿大脑区域的体积减少是否预测6个月后神经行为表现的缺陷；以及(3)使用信息论登记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的数据构建一份图谱，以验证和改进马萨诸塞州总医院目前正在开发的自动分割工具，以便更快、更有效地标记婴儿的大脑结构。 公共卫生相关性：胎儿酒精综合征(FAS)和酒精相关疾病是一个重要的世界性健康问题，也是南非的一个主要公共卫生问题，其长期影响包括严重的、不可逆转的神经认知和行为损害。由于Fas和酒精相关的疾病在婴儿期很难诊断，识别新生儿特定脑区的形态效应可以促进对这些疾病的病因的了解，改善诊断，并允许更早地识别受影响的儿童。这项研究还将提供来自健康新生儿的高质量新生儿神经成像数据，用于改进婴儿大脑扫描的自动分割方法。

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.