Novel methods for brain injury detection and outcome prediction in pediatric ECMO

描述(由申请人提供)：候选人梅拉尼娅·M·本比亚是约翰·霍普金斯大学麻醉学和重症监护医学系的教员。她的目标是成为一名独立的临床科学家，专注于将严格的研究设计应用于儿科重症监护病房的质量改进，重点是评估与危重新生儿使用体外生命支持技术相关的并发症和结果。为了实现这一目标，她正在攻读博士学位 她是约翰·霍普金斯大学临床研究专业研究生培训计划的毕业生，她将接受高级调查人员的结构化指导，以进行有监督的创新研究。这项研究的具体目的和相关假设是：[目的1.确定新生儿在ECMO期间失去脑血管自我调节的时间是否与脑损伤的血浆生物标志物(如GFAP)升高的时间相关。假设：婴儿在体外循环术中经常出现脑血管自我调节丧失的时期，这些时期使大脑暴露在缺血中，从而导致蛋白质生物标志物释放到体循环中。目的2.确定体外反搏过程中脑损伤生物标志物自动调节功能丧失和脑损伤蛋白生物标志物释放到体循环的时间是否与常规的颅脑超声和磁共振成像(MRI)等神经影像标志物相关。假设：脑血管自动调节功能丧失的时间长短和严重程度以及脑损伤后蛋白质生物标志物释放到体循环的时间长短将与损伤的神经影像标志物的升高相关，并将发生在神经影像改变之前。目的3.确定ECMO期间血浆脑损伤生物标志物浓度升高、自动调节丧失以及脑损伤的神经影像标志物是否独立预测患者出院时、ECMO后6个月和1年的生存和神经预后。假设：脑损伤生物标记物的升高和脑血管自我调节丧失的时间以及脑损伤的神经成像标记物(头部超声和核磁共振)将预测以后的神经功能障碍，但生物标记物和自动调节的变化将提供损伤的早期相关性。]拟议研究的完成将极大地提高我们的知识，了解如何在ECMO期间最好地监测和诊断即将发生或发生的脑损伤，并计划在未来的试验中进行神经保护干预[例如，在ECMO期间将血压控制在高于个体较低脑血流自动调节阈值的水平，而不是标准血压管理]。这些项目和所述的职业发展计划将为独立调查员的成功职业生涯奠定基础。

DESCRIPTION (provided by applicant): The candidate, Melania M. Bembea, is on faculty at the Johns Hopkins University, in the Department of Anesthesiology and Critical Care Medicine. Her goal is to become an independent clinician scientist focused on applying rigorous research design to quality improvement in the pediatric intensive care unit, with an emphasis on evaluating complications and outcomes associated with the use of extracorporeal life support technologies in critically-ill newborns. To realize this goal, she is on course to complete the PhD track of the Johns Hopkins Graduate Training Program in Clinical Investigation, and she will receive structured mentoring by senior investigators for the conduct of supervised, innovative research. The specific aims and related hypotheses of the proposed research are: [Aim 1. Determine if periods of lost cerebrovascular auto regulation during ECMO in neonates are correlated with periods of elevations in plasma biomarkers for brain injury (e.g. GFAP). Hypothesis: Periods of loss of cerebrovascular auto regulation occur frequently during ECMO in infants, and these periods expose the brain to ischemia which leads to the release of protein biomarkers into the systemic circulation. Aim 2. Determine if periods of loss of auto regulation and release of protein biomarkers for brain injury into the systemic circulatio during ECMO are correlated with conventional neuroimaging markers for injury including cranial ultrasound and magnetic resonance imaging (MRI). Hypothesis: The length and severity of periods of loss of cerebrovascular auto regulation and the release of protein biomarkers from brain injury into the systemic circulation will correlate with elevations in neuroimaging markers for injury and will occur before changes in neuroimaging. Aim 3. Determine if elevated plasma brain injury biomarker concentrations and loss of auto regulation during ECMO as well as neuroimaging markers of brain injury are independent predictors of survival and neurologic outcomes at hospital discharge, and at 6 months and 1 year post-ECMO. Hypothesis: Elevations in brain injury biomarkers and periods of loss of cerebrovascular auto regulation as well as neuroimaging markers for brain injury (head ultrasound and MRI) will predict later neurological disability, but changes in biomarkers and auto regulation will provide an earlier correlate of injury.] Completion of the proposed research will significantly advance our knowledge of how best to monitor for and diagnose impending or incident brain injury during ECMO and plan for neuroprotective interventions in future trials [(e.g., targeting blood pressure to a level above an individual's lower cerebral blod flow auto regulatory threshold during ECMO vs. standard blood pressure management)]. These projects and the career development plan described will build a foundation for a successful career as an independent investigator.