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症（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个功能磁共振成像研究，并于 2008 年获得了 R01 资格，可以在学龄儿童中使用神经影像学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极其可靠的潜在生物标志物。 R01 还包括资助招募酗酒孕妇和产后 6 个月 EBC 神经行为研究的对照组。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尤为严重。生命最初几周的体积 MRI 测量可以检测区域体积的早期差异，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学结果指标。迄今为止，很少有研究在新生儿中使用 MRI 大脑形态测量分割进行，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。我们建议对产前接触酒精的新生儿进行首次结构 MRI 研究。将招募两组孕妇——35 名重度饮酒者和 35 名未接触酒精的对照者。目的是（1）确定产前大量酒精暴露的新生儿的哪些大脑结构不成比例地较小； (2) 测试特定新生儿大脑区域中与产前暴露相关的体积减少是否可以预测 6 个月时的神经行为表现缺陷； (3) 使用信息论配准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图谱，以验证和完善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、更有效地标记婴儿大脑结构。 公共卫生相关性：胎儿酒精综合症（FAS）和酒精相关疾病是一个重要的全球健康问题，也是南非的一个主要公共卫生问题，其长期影响包括显着的、不可逆转的神经认知和行为障碍。由于 FAS 和酒精相关疾病在婴儿期很难诊断，因此识别新生儿特定大脑区域的形态学影响可以促进对这些疾病病因的了解，改进诊断，并可以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影像数据，用于完善婴儿脑部扫描分割的自动化方法。

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.