NEUROIMAGING IN AUTISM

自闭症的神经影像

• 批准号: 6272415
• 负责人: STEPHEN R DAGER
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272415
• 关键词: aspartate; autism; behavioral /social science research tag; brain imaging /visualization /scanning; child behavior; child behavior disorders; child psychology; choline; clinical research; cognition; human subject; hyperplasia; lactates; longitudinal human study; magnetic resonance imaging; mental retardation; middle childhood (6-11); neuroanatomy; neurochemistry; neuropsychological tests; neuropsychology; nuclear magnetic resonance spectroscopy; preschool child (1-5)

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.

脑解剖学、脑化学和脑化学之间的关系 儿童的行为/认知将被表征 自闭症儿童与智力低下儿童相比 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 假设的潜在大脑发育过程是 对自闭症儿童有效。 具体可以参考 脑容量增加的良好复制成像结果 在自闭症中，如果大脑肥大反映了由以下原因引起的增生 神经元过度增殖和/或细胞凋亡破坏 在产前或围产期，则组间差异 大脑解剖学/大脑化学预计将保持稳定 跨越两个时间点。 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，出现或 预计第二次群体差异会放大 观点。 以 60 名自闭症儿童为样本，40 名患有精神障碍的儿童为样本 发育迟缓，以及20名年龄匹配的3-4岁正常兄弟姐妹 旧的，通过 2-D 和 3-D 以及 3-D MRI 测量大脑解剖结构， 二维质子回波平面的区域脑化学 光谱成像（PEPSI）和行为/认知将 获得。 自闭症儿童和智力低下儿童 将纵向跟踪这些措施，并在 6-7岁。 另一组正常的兄弟姐妹将 在 6-7 岁时进行评估，以提供规范数据。 作为一部分 该提案中，额外的规范性脑体积数据将 由 NIMH 的 Jay Giedd 博士提供，将使用 还可以评估站点之间的测量可靠性。 使用基于强度的分割进行形态测量分析 技术、子区域分割和 3D 表面渲染 技术将用于表征细微的差异 大脑解剖学。 PEPSI 将用于检查特定区域的情况 大脑化学物质的差异；用于大脑解剖区域 表现出结构异常、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 区分这种异常是否反映神经元 与神经胶质过程相反。 此外，NAA 的模式 变化将有助于区分异常的突触修剪 发展过程。 我们预测大脑化学物质 异常会将两者映射到相应的大脑结构 神经心理学任务的异常和损伤 评估这些大脑区域。 PEPSI 测量组合 MRI 有望对以下情况更加敏感和具体 比 MRI 更能区分自闭症儿童亚群 仅检测解剖学差异。