Neuroimaging Studies in Pediatric Anesthesia Neurotoxicity

项目摘要/摘要 每年有数以百万计的幼儿接受全身麻醉。幼年动物暴露于 麻醉会导致神经退行性改变，对学习和行为产生不利影响。这个 FDA最近发布了一份药品安全声明，突显了这些观察结果引发的担忧 沟通警示：全身麻醉和镇静药物用于3岁以下儿童 长时间或反复暴露在空气中“可能会影响儿童的大脑发育”。在之前 工作中，我们研究了3岁之前的麻醉暴露与神经发育的关系 表型，通过对997名儿童进行详细的神经心理评估，从一个 倾向匹配、基于人口的出生队列(1994-2007年出生在明尼苏达州奥姆斯特德县的儿童)。 接触多种麻醉剂的儿童在认知处理速度和精细运动方面一直存在缺陷 技能，在一般智力、记忆力和执行力等其他领域没有明显缺陷 功能。据报道，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)和学习频率的增加 残疾人士。ADHD等疾病与脑部结构和功能异常有关 我们对之前测试过的儿童进行了初步的成像研究 研究发现，处于麻醉状态下的多胎儿童也表现出一致的神经解剖学。 改变。这项提议的中心假设是，在3岁之前接触麻醉剂与 核磁共振检查显示脑部结构和功能发生特殊改变。这样做的具体目的是 建议确定这些儿童的神经发育异常是否与特定的 脑部核磁共振的变化。为了实现这一目标，将从奥姆斯特德县招募儿童 儿童已经在我们之前的工作中根据麻醉暴露史进行了表型分析(未暴露者各100人， 单一暴露和多次暴露的儿童)。他们的大脑将在一台新型的3T磁共振扫描仪上进行成像，并制定了一项协议 包括三维T1加权和T2加权解剖序列、静息状态功能磁共振成像和弥散成像 张量成像。我们将确定MRI表现、麻醉暴露和 神经认知研究结果评估脑成像测量调节这种联系的假说 麻醉暴露与神经认知结果之间的关系。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。始终如一的图像更改(如 我们的初步数据)，尽管儿童在诸如类型等因素上存在相当大的差异 程序和社会经济地位，可以为潜在的责任机制提供重要的见解 伤病赔偿。

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.