Investigation of Cerebral Hemodynamics and Oxygenation Relationships Under Sedation in Children: ICHOR USC

项目摘要 这项研究的主要目的是利用神经影像学来了解血流动力学反应 麻醉和镇静通常用于儿科患者的麻醉和镇静， 脑血流量和代谢的深刻而迅速的变化。在正常情况下， 在成年人中，这些变化相互紧密耦合，以保护大脑免受缺氧， 缺血然而，在麻醉期间血流和代谢耦合的程度， 儿科患者的镇静作用尚不清楚。本项目的目的是（1）量化 婴儿对麻醉的血流动力学和代谢反应，以及（2）比较这些反应 在对具有不同疾病状态的婴儿施用特定麻醉剂期间， 使它们更容易受到能量流与新陈代谢分离的影响。如果我们的假设成立 婴儿特别容易受到这种分离的影响，我们的研究结果将导致未来 评估血流动力学反应作为预测和介导不良反应的潜在生物标志物的研究 暴露于麻醉的婴儿的结局。因此，该项目与NHLBI的 战略目标是确定导致病理生物学个体差异的因素， 治疗反应。 该项目需要一个机会，使同时流动和代谢测量， 麻醉的婴儿临床MR成像提供了这个机会。因此，我们将报名参加 一项自然队列研究，120名1岁以下需要临床MRI扫描的婴儿， 一半接受麻醉一半不接受入组婴儿将接受MRI序列成像， 测量脑血流量和新陈代谢。此外，我们还将招募30名婴儿， 将相同年龄的婴儿纳入一项初步随机对照试验（RCT）， 随机接受丙泊酚或七氟烷麻醉。随机化将极大地 减少自然主义研究中存在的疾病和麻醉剂的潜在混淆。 学习设计随机对照试验（目标1）是解决与教学法和实习，以提高我的 翻译研究技能。这个项目要求我学习麻醉剂和镇静剂 改变血液动力学和流体动力学（目标2）以及已知和假定的 神经毒性和血流代谢解偶联影响发育中的大脑（目标3）。这个项目和 我的研究生涯将帮助需要麻醉或镇静的婴儿。它创造了一个范例， 可以在儿科重症监护中安全地探索麻醉的血流动力学反应 患者它需要结合MRI和图像处理技术，我已经 具有-对血流动力学改变的病理生理学后果有更深入的了解 婴儿对麻醉的反应。它还要求我提高设计能力， 适合严格且狭窄的临床机会的研究项目--我将掌握的技能 在K25的支持下。

Project Summary The broad objective of this research is to use neuroimaging to understand the hemodynamic responses to anesthesia and sedation. Anesthesia and sedation, commonly used in pediatric patients, cause profound and rapid changes in cerebral blood flow and metabolism. Under normal conditions in adults, these changes are tightly coupled to one another to protect the brain from hypoxia and ischemia. However, the extent to which flow and metabolism are coupled during anesthesia and sedation in pediatric patients is unknown. The aims of this project are (1) to quantify the hemodynamic and metabolic responses to anesthesia in infants, and (2) to compare those responses during the administration of specific anesthetics in infants with differing disease states that may make them more vulnerable to the uncoupling of flow from metabolism. If our hypotheses are borne out and infants are particularly vulnerable to this uncoupling, our findings will lead to future studies to assess hemodynamic responses as potential biomarkers that predict and mediate adverse outcomes in infants exposed to anesthesia. Therefore, this project is relevant to the NHLBI's strategic objective to identify factors that account for individual differences in pathobiology and treatment response. This project requires an opportunity for making simultaneous flow and metabolism measurements in anesthetized infants. Clinical MR imaging provides this opportunity. Therefore, we will enroll into a Naturalistic Cohort Study 120 infants younger than 1 year of age who require a clinical MRI scan, half receiving anesthesia and half not. Enrolled infants will be imaged with MRI sequences that measure cerebral blood flow and metabolism. In addition, we will enroll 30 additional infants of the same age into a Pilot Randomized Comparator Trial (RCT), in which the infants will be randomized to receive either propofol or sevoflurane anesthesia. Randomization will dramatically reduce potential confounding of diseases and anesthetic agents present in the naturalistic study. Learning to design RCTs (Goal 1) is addressed with didactics and a practicum to advance my translational research skills. This project requires my learning how anesthetics and sedatives alter hemodynamics and fluid dynamics (Goal 2) and how the known and putative mechanisms of neurotoxicity and flow-metabolism uncoupling affect the developing brain (Goal 3). This project and my research career will help infants who require anesthesia or sedation. It creates a paradigm in which the hemodynamic response to anesthesia can be explored safely in pediatric critical care patients. It requires the combination of MRI and image processing know-how - skills that I already have - with a deeper understanding of the pathophysiological consequences of altered hemodynamic responses to anesthesia in infants. It also requires that I develop an improved ability to design research projects that fit within a rigorous and narrow clinical opportunity - skills that I will gain with this K25 support.