Characterizing the FASD cerebral cortex in utero with DTI

用 DTI 表征子宫内 FASD 大脑皮层

• 批准号: 8963409
• 负责人: Christopher D Kroenke
• 金额: $ 40.95万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-20 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8963409
• 关键词: Advocate; Affect; Age; Alcohol consumption; Alcohols; Animals; Anisotropy; Area; Awareness; Behavior; Behavior Control; Behavioral; Biological; Birth; Blood; Brain; Breeding; Caring; Cell Count; Centers for Disease Control and Prevention (U.S.); Cerebral cortex; Cerebrum; Cesarean section; Child; Childhood; Conceptions; Congenital Abnormality; Data; Detection; Development; Dextrins; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Dose; Early Diagnosis; Economics; Ethanol; Exhibits; Experimental Designs; Family; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetus; Fixatives; Gestational Age; Growth; Health; Histologic; Human; Imaging Techniques; Impairment; Individual; Intervention; Life; Macaca mulatta; Magnetic Resonance Imaging; Maltose; Measurement; Measures; Menstrual cycle; Mental Retardation; Methods; Modeling; Monkeys; Motion; Neuraxis; Neurodevelopmental Disorder; Neurologic; Neurons; Neuropil; Odds Ratio; Oral; Outcome; Pattern; Perinatal Exposure; Pregnancy; Prevention strategy; Procedures; Process; Public Health; Quality of life; Recording of previous events; Research Subjects; Resolution; Rodent; Route; Scanning; Self Administration; Source; Surface; Symptoms; Techniques; Testing; Therapeutic Intervention; Thick; Tissues; Training; United States; Variant; Weight; Western World; Work; alcohol abstinence; alcohol effect; alcohol exposure; base; behavioral impairment; cognitive ability; combat; cost effective; diffusion anisotropy; drinking; drinking behavior; fetal; image reconstruction; improved; in utero; indexing; neuroimaging; nonhuman primate; research study; water diffusion

DESCRIPTION (provided by applicant): Fetal exposure to alcohol leads to a wide range of neurological deficits collectively termed fetal alcohol spectrum disorders (FASD). The CDC estimates that FASD currently affects as many as 4.5 out of every 1000 births within the United States. Existing intervention strategies can improve the quality of life in affected individuals, provided they are initiated at the earliest age possible. Unfortunately, early FASD diagnosis is difficult, partly because behavioral manifestations of the disorder are not apparent until childhood. We propose to develop a magnetic resonance imaging (MRI)-based strategy to detect cellular-level morphological alterations in the developing cerebral cortex. Nonhuman primate research subjects will be bred after being trained to drink 1.5 g/kg/day of ethanol, or an isocaloric amount of maltose/dextrin solution. Animals will continue to drink throughout the first 60 days of pregnancy, after which access to ethanol will be terminated. Fetal brain T2-weighted and diffusion tensor imaging (DTI) data will be acquired on 3 groups of ethanol or maltose/dextrin animals: group 1 will be scanned on gestational day (G)85, group 2 on G110, and group 3 on G135. Immediately after MRI, fetuses will be delivered by cesarian section and brains will be prepared for histological processing. The first aim for this experiment is to characterize the effects of early ethanol exposure on cerebral cortical thickness, surface area, and water diffusion anisotropy over the period ranging from G85 to G135. The second aim is to validate the cortical thickness effects of ethanol exposure using unbiased stereological techniques, and to characterize the biological source of the neuroimaging observations. The latter will be accomplished by determining cerebral cortical cell numbers, measuring the volume fraction of the neuropil, and quantifying morphological complexity of cortical neuronal axonal and dendritic arbors. This work will provide an objective strategy for characterizing the effects o early ethanol exposure on subsequent development of the cerebral cortex, which will facilitate earlier detection of FASD that is currently achievable.

描述（由申请人提供）：胎儿接触酒精会导致广泛的神经缺陷，统称为胎儿酒精谱系障碍（FASD）。 CDC 估计，目前美国每 1000 名新生儿中就有 4.5 人患有 FASD。现有的干预策略可以改善受影响个体的生活质量，只要尽可能尽早开始。不幸的是，早期 FASD 诊断很困难，部分原因是这种疾病的行为表现直到儿童时期才明显。我们建议开发一种基于磁共振成像（MRI）的策略来检测发育中的大脑皮层的细胞水平形态变化。非人类灵长类研究对象将在接受每天饮用 1.5 克/公斤乙醇或等热量麦芽糖/糊精溶液的训练后进行繁殖。动物在怀孕的前 60 天将继续饮酒，此后将停止获取乙醇。将在 3 组乙醇或麦芽糖/糊精动物上采集胎儿脑 T2 加权和扩散张量成像 (DTI) 数据：第 1 组将在妊娠日 (G)85 扫描，第 2 组将在 G110 扫描，第 3 组将在 G135 扫描。 MRI 后，胎儿将立即通过剖腹产分娩，并准备大脑进行组织学处理。本实验的第一个目的是表征早期乙醇暴露对 G85 至 G135 期间大脑皮层厚度、表面积和水扩散各向异性的影响。第二个目标是使用无偏立体学技术验证乙醇暴露对皮质厚度的影响，并表征神经影像学观察的生物来源。后者将通过确定大脑皮层细胞数量、测量神经纤维的体积分数以及量化皮层神经元轴突和树突乔木的形态复杂性来完成。这项工作将为表征早期乙醇暴露对大脑皮层后续发育的影响提供一个客观的策略，这将有助于目前可以实现的 FASD 的早期检测。