Neuroimaging Studies in Pediatric Anesthesia Neurotoxicity

项目总结/摘要 每年有数百万儿童接受全身麻醉。幼龄动物暴露于 麻醉可引起神经退行性变化，对学习和行为产生不利影响。的 FDA最近发布的药物安全性报告强调了这些观察结果引起的担忧。 沟通警告，全身麻醉和镇静药物用于儿童< 3岁， 长期或反复接触“可能会影响儿童大脑的发育”。于过往 在这项工作中，我们研究了3岁之前的麻醉暴露与神经发育之间的关系。 通过对997名儿童进行详细的神经心理学评估， 倾向匹配，基于人口的出生队列（1994-2007年出生于明尼苏达州奥姆斯特德县的儿童）。 暴露于多种麻醉剂的儿童在认知处理速度和精细运动方面存在一致性缺陷 技能，在其他领域没有显着缺陷，包括一般智力，记忆力和执行力 功能这些缺陷与行为问题和学习困难有关， 父母，包括注意力缺陷/多动障碍（ADHD）和学习的频率增加 残疾。ADHD等疾病与大脑结构和功能异常有关， 我们对先前接受测试的儿童进行了初步的成像研究， 研究发现，多次暴露于麻醉的儿童也表现出一致的神经解剖学特征， 变化该建议的中心假设是，3岁之前暴露于麻醉与 通过MRI评估大脑中的特定结构和功能变化。这一具体目标 建议是确定这些儿童的神经发育异常是否与特定的 脑部核磁共振成像的变化为了实现这一目标，儿童将从奥姆斯特德县的那些 在我们先前的工作中，根据麻醉暴露史（每100例未暴露， 单次和多次暴露的儿童）。他们的大脑将在一种新型的3 T MRI扫描仪上成像， 包括三维T1加权和T2加权解剖序列、静息态功能性MRI和弥散 张量成像我们将确定MRI结果、麻醉暴露和 神经认知研究结果评估大脑成像测量介导这种关联的假设 麻醉暴露与神经认知结果的关系。这项研究的预期产品可能是第一个 儿童麻醉相关神经损伤的生物标志物。一致的成像变化（如 我们的初步数据），尽管儿童之间的差异很大，如类型的因素， 程序和社会经济地位，可以提供重要的见解，潜在的机制负责 因为受伤

PROJECT SUMMARY/ABSTRACT Millions of young children are exposed to general anesthesia each year. Exposure of young animals to anesthesia can cause neurodegenerative changes with adverse effects on learning and behavior. The concern generated by these observations is highlighted by the recent FDA issuance of a Drug Safety Communication warning that general anesthesia and sedation drugs used in children < 3 years of age who were undergoing prolonged or repeated exposures “may affect the development of children’s brains.” In prior work, we studied the association between anesthesia exposure prior to age 3 and neurodevelopmental phenotype, as assessed by a detailed neuropsychological assessment of 997 children sampled from a propensity-matched, population-based birth cohort (children born in Olmsted County, MN from 1994-2007). Children exposed to multiple anesthetics had consistent deficits in cognitive processing speed and fine motor skills, without significant deficits in other domains including general intelligence, memory, and executive function. These deficits were associated with behavioral problems and learning difficulties as reported by parents, including an increased frequency of attention-deficit/hyperactivity disorder (ADHD) and learning disabilities. Conditions such as ADHD are associated with structural and functional brain abnormalities in children as revealed by MRI scans We performed preliminary imaging studies in the children tested in the prior studies and found that children multiply-exposed to anesthesia also demonstrate consistent neuroanatomical changes. The central hypothesis of this proposal is that exposure to anesthesia prior to age 3 is associated with specific structural and functional changes in the brain as assessed by MRI. The Specific Aim of this proposal is to determine if the neurodevelopmental abnormalities of these children are associated with specific changes in brain MRIs. To accomplish this aim, children will be recruited from among those Olmsted County children already phenotyped in our prior work, based on anesthesia exposure history (100 each of unexposed, singly-, and multiply-exposed children). Their brains will be imaged in a novel 3T MRI scanner, with a protocol including 3-D T1-weighted and T2-weighted anatomic sequences, resting-state functional MRI, and diffusion tensor imaging. We will determine the relationship between MRI findings, anesthesia exposure, and neurocognitive findings to evaluate the hypothesis that brain imaging measurements mediate the association of anesthesia exposure with neurocognitive outcomes. The expected product of this research could be the first biomarker for anesthesia-associated neural injury in children. Consistent imaging changes (as suggested by our preliminary data), despite the considerable variation between children regarding factors such as type of procedure and socioeconomic status, could provide important insights into potential mechanisms responsible for injury.