Early brain development after prenatal "Ice" exposure: A Longitudinal MR study

描述（由申请人提供）： 本申请是对RFA DA 05 -007的回应。临床和临床前观察表明，产前甲基苯丙胺（METH）暴露可能会导致异常的大脑结构和神经化学。关于这些大脑变化（结构和化学）与认知发展的关系，我们知之甚少。我们对产前暴露于METH的儿童进行的初步横断面研究提供了强有力的证据，表明这些儿童的皮质下脑结构较小，质子磁共振波谱（1H MRS）显示脑代谢物异常，沿着神经心理学测试表现下降。我们的初步数据还表明，这些儿童并没有表现出适当的年龄相关的增加，在一些皮质下结构（壳核，苍白球，和campi）。 高分辨率MRI结合新的图像处理技术，可以精确地量化脑结构的体积，而1H MRS可以可靠地和非侵入性地量化反映选定脑区域中神经元密度（N-乙酰天冬氨酸或NAA）和其他细胞标记物（胆碱化合物，总肌酸，肌醇，谷氨酸和谷氨酰胺）的神经化学物质。 我们的主要具体目标是：1）评估在子宫内暴露于METH的幼儿（3岁）的脑结构（MRI）和脑代谢物浓度（1H MRS）的变化，并纵向和每年跟踪这些变化，直到7岁。2)在同一时期（3-7岁），每年评估这些儿童的神经心理学表现。3)评价出生前暴露于METH的儿童大脑结构和化学异常（MRI和1H MRS）与认知发育的关系。 我们将在5年的时间内跟踪120名儿童（60名有产前METH暴露，60名无产前METH暴露），以确定儿童早期发育期间脑代谢物水平，形态测量学和神经心理学表现的时间变化。这些儿童中的大多数将被共同招募，并从出生起就在NIDA资助的婴儿发育、环境和生活方式（“IDEAL”）研究中接受随访，该研究评估婴儿神经行为发育。将进行详细的母亲药物使用、心理社会和情绪评估，并将其与这些儿童的生物大脑变化相关联。

DESCRIPTION (provided by applicant): This application is in response to RFA DA05-007. Clinical and preclinical observations suggest that prenatal methamphetamine (METH) exposure may lead to abnormal brain structures and neurochemistry. Little is known about how these brain changes (structural and chemical) relate to cognitive development. Our preliminary cross-sectional studies in children exposed to METH prenatally provide strong evidence that these children have smaller subcortical brain structures and brain metabolite abnormalities on proton MR spectroscopy (1H MRS), along with decreased performance on neuropsychological tests. Our preliminary data also suggest that these children do not show appropriate age-related increases in some subcortical structures (putamen, globus pallidus, and hippocampi). High resolution MRI, coupled with novel image processing technques, can precisely quantify volumes of brain structures while 1H MRS can reliably and non-invasively quantify neurochemicals that reflect neuronal density (N-acetyl aspartate or NAA) and other cellular markers (choline-compounds, total creatine, myoinositol, glutamate plus glutamine) in selected brain regions. Our primary Specific Aims are: 1) To assess changes in brain structure (on MRI) and brain metabolite concentrations (on 1H MRS) in young children (age 3 years) who were exposed to METH in utero, and to follow these changes longitudinally and annually until age 7 years. 2) To evaluate neuropsychological performance in these children on a yearly basis over the same time period (ages 3-7 years). 3) To evaluate how structural and chemical brain abnormalities (on MRI and 1H MRS) are related to cognitive development in children exposed to METH prenatally. We will follow 120 children (60 with and 60 without prenatal METH exposure) over the course of 5 years, to determine temporal changes in brain metabolite levels, morphometry and neuropsychological performance during early childhood development. Most of these children will be co-enrolled and have been followed since birth in the NIDA-funded Infant Development, Environment and Lifestyle ("IDEAL") study, which assesses infant neurobehavioral development. Detailed maternal drug use, psychosocial and mood evaluations will be performed and correlated with biological brain changes in these children.