Neuroimaging Studies in Pediatric Anesthesia Neurotoxicity

小儿麻醉神经毒性的神经影像学研究

• 批准号: 10558691
• 负责人: David O. Warner
• 金额: $ 64万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10558691
• 关键词: 3 year old; 3-Dimensional; Academic skills; Adolescent; Adverse effects; Affect; Age; Anatomy; Anesthesia procedures; Anesthetics; Animals; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Biological Markers; Birth; Brain; Brain imaging; Cause of Death; Child; Child Development; Childhood; Childhood Injury; Cognition; Cognitive; Cognitive deficits; Communication; County; Data; Diagnosis; Diffusion Magnetic Resonance Imaging; Dose; Drug usage; Exposure to; Frequencies; Functional Magnetic Resonance Imaging; Future; General Anesthesia; Human; Image; Injury; Intelligence; Label; Language; Late Effects; Learning; Learning Disabilities; MRI Scans; Magnetic Resonance Imaging; Measurement; Mediating; Medical; Memory; Motor; Motor Skills; Nerve Degeneration; Neuroanatomy; Neurocognitive; Neurons; Neuropsychological Tests; Neuropsychology; Outcome; Parents; Pathogenesis; Pattern; Pharmaceutical Preparations; Phenotype; Pregnant Women; Problem behavior; Procedures; Protocols documentation; Reading; Recording of previous events; Records; Reporting; Research; Rest; Safety; Sampling; Schools; Sedation procedure; Socioeconomic Status; Structure; Test Result; Testing; Third Pregnancy Trimester; United States; United States Food and Drug Administration; Variant; Work; Writing; achievement test; brain abnormalities; brain magnetic resonance imaging; clinically relevant; clinically significant; cohort; executive function; imaging study; insight; juvenile animal; medication safety; nerve injury; neuroimaging; neurotoxicity; nonhuman primate; novel; population based; pre-clinical; processing speed; recruit; sedative; tool; translational potential; virtual; willingness

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.

项目概要/摘要 每年有数百万幼儿接受全身麻醉。 麻醉可能导致神经退行性变化，对学习和行为产生不利影响。 FDA 最近发布的《药物安全》强调了这些观察结果引起的担忧 通信警告：全身麻醉和镇静药物用于 3 岁以下儿童 之前长期或反复接触这些物质“可能会影响儿童大脑的发育”。 在工作中，我们研究了 3 岁之前的麻醉暴露与神经发育之间的关系 表型，通过对 997 名儿童进行详细的神经心理学评估来评估 倾向匹配、基于人口的出生队列（1994-2007 年在明尼苏达州奥姆斯特德县出生的儿童）。 接触多种麻醉剂的儿童在认知处理速度和精细运动方面存在持续缺陷 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 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）和学习的频率增加 多动症等疾病与大脑结构和功能异常有关。 MRI 扫描显示的儿童 我们对之前测试的儿童进行了初步影像学研究 研究发现，多次接受麻醉的儿童也表现出一致的神经解剖学特征 该提案的中心假设是 3 岁之前接受麻醉是相关的。 通过 MRI 评估大脑的特定结构和功能变化。 建议是确定这些儿童的神经发育异常是否与特定的相关 为了实现这一目标，将从奥姆斯特德县招募儿童。 我们之前的工作中已经根据麻醉暴露史对儿童进行了表型分析（未暴露的儿童各 100 名， 他们的大脑将在新型 3T MRI 扫描仪中按照协议进行成像。 包括 3-D T1 加权和 T2 加权解剖序列、静息态功能 MRI 和扩散 我们将确定 MRI 结果、麻醉暴露和麻醉剂量之间的关系。 神经认知发现来评估大脑成像测量介导这种关联的假设 这项研究的预期产品可能是第一个麻醉暴露与神经认知结果的关系。 儿童麻醉相关神经损伤的生物标志物一致的影像学变化（如所示） 我们的初步数据），尽管儿童之间在诸如类型等因素方面存在很大差异 程序和社会经济地位，可以为潜在的负责机制提供重要见解 为了受伤。