NEUROIMAGING IN AUTISM

脑解剖学、脑化学和 行为/认知将在儿童中表征， 自闭症与智力迟钝儿童的比较， 来自两个临床组的儿童的正常兄弟姐妹。 这些 将在2个时间点比较关系，以评估 潜在的大脑发育过程被假设为 对自闭症儿童有效。 具体而言，在参考 脑容量增加的影像学表现 在自闭症中，如果大脑肥大反映了 神经元的过度增殖和/或细胞凋亡的破坏 在产前或围产期期间， 脑解剖学/脑化学预计将保持稳定 在两个时间点上。 另一方面，如果结构 异常反映了突触修剪异常， 在学龄前时期，或神经胶质增生， 第二次预计会扩大群体差异 点 对于60名自闭症儿童的样本，40名精神分裂症儿童， 和20名年龄匹配的3-4岁正常同胞 旧的，从二维和三维和三维磁共振成像的大脑解剖测量， 二维质子平面回波局部脑化学 光谱成像（PEPSI）和行为/认知将是 得到了 自闭症儿童和智力迟钝儿童 将纵向跟踪这些措施，并在 6-7岁的 另外一组正常的兄弟姐妹 在6-7岁时进行评估，以提供规范性数据。 的一部分 该提议增加了标准脑体积数据， 由NIMH的Jay Giedd博士提供， 还评估站点之间的测量可靠性。 使用基于强度的分割的形态测量分析 技术、子区域分割和三维表面绘制 技术将被用来表征微妙的差异， 脑解剖学 PEPSI将用于检查区域特定的 脑化学差异;脑解剖区域 表现出结构异常，脑化学模式， N-乙酰基戊酸盐（NIAA），胆碱和乳酸水平将有助于 以区分这种异常是否反映了神经元 而不是神经胶质。 此外，NAA的模式 变化将有助于区分异常突触修剪 发展过程。 我们预测大脑中的化学物质 异常将映射到相应的大脑结构 神经心理任务的异常和损伤 评估这些大脑区域。 结合PEPSI测量 与MRI相比， 划分自闭症儿童的亚群比MRI 仅检测解剖学差异。

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.