Characterizing the FASD cerebral cortex in utero with DTI

用 DTI 表征子宫内 FASD 大脑皮层

• 批准号: 8598852
• 负责人: Christopher D Kroenke
• 金额: $ 51.97万
• 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/8598852
• 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; Cognitive; 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; 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; Relative (related person); Research Subjects; Resolution; Rodent; Route; Scanning; Self Administration; Solutions; 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; combat; cost effective; dextrin; diffusion anisotropy; drinking; drinking behavior; fetal; image reconstruction; improved; in utero; indexing; neuroimaging; nonhuman primate; public health relevance; 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）：胎儿暴露于酒精会导致广泛的神经缺陷统称为胎儿酒精疾病（FASD）。疾病预防控制中心估计，FASD目前影响美国境内每1000个出生中的4.5个。现有的干预策略可以提高受影响个体的生活质量，只要它们是最早的年龄开始的即可。不幸的是，早期的FASD诊断很困难，部分原因是该疾病的行为表现直到童年才明显。我们建议开发基于磁共振成像（MRI）的策略，以检测发育中的大脑皮层中的细胞水平形态学改变。在接受培训以喝1.5 g/kg/天的乙醇或等量平衡量的麦芽糖/右旋糖解决方案后，非人类灵长类动物研究对象将被育成。在怀孕的前60天，动物将继续喝酒，然后将终止乙醇。胎儿脑T2加权和扩散张量成像（DTI）数据将在3组乙醇或麦芽糖/脱氧动物上获取：第1组将在妊娠日（G）85，G110上的第2组和G135组3组进行扫描。 MRI之后，胎儿将立即由剖腹产分配，并准备大脑进行组织学处理。该实验的第一个目的是表征早期乙醇对脑皮质厚度，表面积和水扩散各向异性的影响，范围从G85到G135。第二个目的是使用公正的立体技术来验证乙醇暴露的皮质厚度影响，并表征神经影像观测的生物学来源。后者将通过确定脑皮质细胞数，测量神经胶质的体积分数，并量化皮质神经元轴突和树突状乔木的形态复杂性来实现。这项工作将提供一个客观的策略，以表征早期乙醇暴露对随后的大脑皮层发展的影响，这将有助于早期发现目前可实现的FASD。