Molecular Neurodevelopment: An In Vivo 31P-1H MRSI Study

该项目的目标是从6-18岁正常儿童和青少年的代表性人群中获得性别平衡、神经发育的31P和1H磁共振波谱成像(31P-1H MRSI)分子和代谢规范数据库。每个感兴趣体积(体素)的分子/代谢值将与同一体素中灰质、白质和脑脊液(CSF)的百分比相关。个体体素将包括(右和左)前额叶皮质、上颞叶皮质、下顶叶皮质、枕叶皮质、基底节、半卵圆中心和丘脑。选择这些区域是为了包括初级感觉(枕叶和部分上颞叶皮质)、异形联结区(前额叶、下顶叶和部分颞叶上皮层)、皮质下灰质(基底节和丘脑)和白质(半卵圆中心)。研究这些区域作为年龄和性别的函数，将使我们能够确定正常神经发育对具有不同功能的大脑区域的分子/代谢测量的影响。31P MRS提供了膜磷脂和高能磷酸盐代谢的指标，1H MRS提供了谷氨酸、谷氨酰胺、牛磺酸、N-乙酰天冬氨酸(NAA)的额外指标，N-乙酰天冬氨酸(NAA)是神经元功能完整性的潜在标志，肌醇是潜在的神经胶质标志。受试者将接受标准化的神经发育测试，以确保队列代表正常的认知发展，并将每年进行儿科体检，包括Tanner分期。标准化神经发育测试组合将在入学、2年和4年完成。研究开始后，每年对受试者进行纵向31P-1HMRSI和单体素1HMRS随访，为期4年，以生成大脑/代谢测量的神经发育曲线。

The goal of this project is to acquire a gender- balanced, neurodevelopmental 31P and 1H magnetic resonance spectroscopic imaging (31P-1H MRSI) molecular and metabolic normative database from a representative population of normal children and adolescents ages 6-18 years. The molecular/metabolic values for each volume of interest (voxel) will be correlated with the percent grey matter, white matter and cerebral spinal fluid (CSF) in the same voxel. The individual voxels will include the (right and left) prefrontal cortex, superior temporal cortex, inferior parietal cortex, occipital cortex, basal ganglia, centrum semiovale and thalamus. These areas are chosen so as to include areas of primary sensory (occipital and part of superior temporal cortices), heteromodal association (prefrontal, inferior parietal, and part of superior temporal cortices), subcortical grey (basal ganglia and thalamus) and white matter (centrum semiovale). Examining these areas as a function of age and gender will enable us to determine the effects of normal neurodevelopment on the molecular/metabolic measures of brain areas with different functions. 31P MRS provides measures of membrane phospholipid and high-energy phosphate metabolism and 1H MRS provides additional measures of glutamate, glutamine, taurine, N-acetylaspartate (NAA), a potential marker of neuronal functional integrity, and myo- inositol, a potential glial marker. Subjects will have a standardized neurodevelopmental test battery to assure the cohort is representative of normal cognitive development, and will have yearly pediatric physical examinations, including Tanner staging. The standardized neurodevelopmental test battery will be completed at entry, 2, and 4 years. Longitudinal 31P-1H MRSI and single voxel 1H MRS follow-up of the subjects yearly for 4 years after entry into study will be used to generate neurodevelopmental curves for brain/metabolic measures.