NEUROIMAGING IN AUTISM

脑解剖、脑化学与脑功能的关系 行为/认知特征将在儿童中表现出来 自闭症与智力低下儿童和 两个临床组儿童的正常兄弟姐妹。这些 关系将在两个时间点进行比较，以评估 潜在的大脑发育过程被假设为 在患有自闭症的儿童中使用。具体而言，在参考文献中 脑体积增大的重复性很好的影像表现 在自闭症中，如果大脑肥大反映了由 神经元过度增殖和/或细胞凋亡中断 在产前或围产期，则组内差异 脑解剖/脑化学预计保持稳定 跨越这两个时间点。另一方面，如果结构 异常反映起病时突触修剪异常 在学龄前时期，或神经胶质增生症，紧急情况或 预计第二次将扩大群体差异 指向。 对于60名自闭症儿童的样本，40名患有精神疾病的儿童 发育迟缓和20名年龄匹配的3-4岁正常兄弟姐妹 旧的，从2-D，3-D和3-D MRI测量大脑解剖， 来自二维质子回波平面的局部脑化学 光谱成像(百事可乐)和行为/认知 获得。自闭症儿童和智力低下儿童 将纵向跟踪，这些措施将重新评估为 6-7岁。另外一组正常的兄弟姐妹将 在6-7岁时进行评估，以提供标准化数据。作为以下内容的一部分 这项建议，额外的规范性脑体积数据将 由Jay Giedd博士在NIMH提供，将用于 也是为了评估站点之间的测量可靠性。 基于灰度分割的形态测量分析 技术、子区域分割和三维面绘制 技术将被用来表征细微的差异 脑部解剖学。百事可乐将被用来检查特定地区 大脑化学的差异；针对大脑解剖区域 表现出结构异常，大脑化学模式 N-乙酰天冬氨酸(NIAA)、胆碱和乳酸水平将有所帮助 以区分这种异常是否会反映神经元 而不是神经胶质突起。此外，NAA的模式 改变将有助于区分异常的突触修剪 发育过程。我们预测大脑中的化学物质 异常会映射到相应的大脑结构 神经心理任务中的异常和损害 评估这些大脑区域。百事可乐的综合测量 对核磁共振检查的敏感性和特异性 比MRI更准确地划分自闭症儿童亚群 仅检测解剖学上的差异。

Relationships between brain anatomy, brain chemistry and behavior/cognition will be characterized among children with autism in comparison to children with mental retardation and normal siblings of children from the two clinical groups. These relationships will be compared at 2 time points to assess underlying brain developmental processes hypothesized to be operative among children with autism. Specifically, in reference to the well-replicated imaging findings of increased brain volum in autism, if brain hypertrophy reflects hyperplasia arising from over-proliferation of neurons and/or disruption of apoptosis during the pre or perinatal periods, then group differences in brain anatomy/brain chemistry are expected to remain stable across the two time points. If, on the other hand, structure abnormalities reflect synaptic pruning abnormalities with onset during the preschool period, or gliosis, emergance or amplification of group differences is expected at the second time point. For samples of 60 children with autism, 40 children with mental retardation, and 20 age-matched normal siblings aged 3-4 years old, measures of brain anatomy from 2-D and 3-D and 3-D MRI, regional brain chemistry from 2-D proton echo-planar spectroscopic imaging (PEPSI) and behavior/cognition will be obtained. Children with autism and those with mental retardation will be followed longitudinally and these measures reassessed at 6-7 years of age. An additional group of normal siblings will be assessed at ages 6-7 to provide normative data. As part of this proposal, addditional normative brain volumetric data will be made available by Dr. Jay Giedd at the NIMH which will be used also to assess measurement reliability between sites. Morphometric analysis using intensity-based segmentation techniques, subregion segmentation and 3-D surface rendering techniques will be used to characterize subtle differences in brain anatomy. PEPSI will be used to examine regionally-specific differences in brain chemistry; for brain anatomical regions exhibiting structural abnormalities, brain chemistry patterns of N-acetyl asparatate (NIAA), choline, and lactate levels will help to distinguish whether such abnormalities will reflect neuronal as opposed to glial processes. Additionally, patterns of NAA change will help to distinguish abnormal synaptic pruning developmental processes. We predict that brain chemical abnormalities will map both to corresponding brain structural abnormalities and impairments on neuropsychological tasks assessing those brain regions. PEPSI measurements in combination with MRI is expected to be more sensitive and specific for demarcating subpopulations of children with autism than MRI detection of anatomical differences alone.