NEUROIMAGING IN AUTISM

自闭症的神经影像

基本信息

批准号：
6494817
负责人：
STEPHEN R DAGER
金额：
$ 16.54万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-06-01 至 2002-09-19
项目状态：
已结题

项目摘要

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.

大脑解剖学，大脑化学和行为/认知将在患有自闭症与患有智力低下的儿童相比来自两个临床组的儿童的正常兄弟姐妹。这些将在两个时间点比较关系以评估据称是的基本大脑发育过程自闭症儿童的手术。具体来说，参考到脑量增加的良好复发成像发现在自闭症中，如果脑肥大反映了由神经元的过度溶质和/或凋亡中断在围产期或围产期期间，然后在脑解剖学/脑化学预计将保持稳定在两个时间点上。另一方面，结构异常反映突触修剪异常在学龄前或神经胶质，紧急或预计将第二次放大群体差异观点。对于60名自闭症儿童的样本，有40名精神儿童智障和20岁年龄匹配的正常兄弟姐妹3-4岁旧的，二-D和3-D和3-D MRI的脑解剖结构的量度， 2-D质子回声平面的区域大脑化学光谱成像（百事可乐）和行为/认知将是获得。自闭症儿童和智力低下的孩子将纵向遵循，并将这些措施重新评估 6-7岁。另外一组普通兄弟姐妹将在6-7岁时评估以提供规范性数据。作为该建议，附加规范性的大脑容量数据将由NIMH的Jay Giedd博士提供还可以评估站点之间的测量可靠性。使用基于强度的分割的形态分析技术，子区域分割和3-D表面渲染技术将用于表征微妙的差异大脑解剖学。百事可乐将用于检查区域特定的大脑化学的差异；对于大脑解剖区域表现出结构异常，大脑化学模式 N-乙酰基sparatate（NIAA），胆碱和乳酸水平将有助于区分这种异常是否会反映神经元与神经胶质过程相反。另外，NAA的模式更改将有助于区分异常的突触修剪发展过程。我们预测大脑化学异常将映射到相应的大脑结构神经心理学任务的异常和损害评估那些大脑区域。组合百事可乐测量预计MRI对比MRI划分自闭症儿童的亚群仅检测解剖学差异。