DIASTOLIC CLOSING MARGIN PREDICTS BRAIN INJURY IN PREMATURE INFANTS

舒张末期可预测早产儿脑损伤

• 批准号: 9032747
• 负责人: Christopher J. Rhee
• 金额: $ 17.37万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9032747
• 关键词: Advisory Committees; Age; Anesthesiology; Animal Experimentation; Animal Model; Basic Science; Birth Weight; Blood Flow Velocity; Blood Pressure; Blood flow; Brain; Brain Injuries; Caring; Cephalic; Cerebral Palsy; Cerebrovascular Circulation; Cerebrum; Childhood; Clinical; Clinical Research; Complex; Core-Binding Factor; Country; Critical Care; Data; Development; Development Plans; Diastolic blood pressure; Diffusion Magnetic Resonance Imaging; Doctor of Medicine; Doctor of Philosophy; Doppler Ultrasound; Ensure; Extremely Low Birth Weight Infant; Future; Gestational Age; Goals; Guidelines; Hemorrhage; Hyperemia; Hypotension; Imaging Techniques; Infant; Infant Development; Injury; Institution; Intellectual functioning disability; Intervention Trial; Investigation; Ischemia; Ischemic Brain Injury; Kidney; Laboratories; Learning; Learning Disabilities; Life; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Medical center; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Monitor; Motor; Neonatal Brain Injury; Neonatal Intensive Care; Neonatal Intensive Care Units; Neonatology; Neurocognitive; Neurologic; Neurology; Outcome; Patient Care; Patients; Pediatric Hospitals; Pediatrics; Perfusion; Periventricular Leukomalacia; Physiologic Monitoring; Physiological; Physiology; Population; Positioning Attribute; Pregnancy; Premature Birth; Premature Infant; Public Health; Publishing; Qualifying; Reading; Reporting; Research; Research Personnel; Research Proposals; Resources; Risk; Role; Scientist; Secondary to; Shock; Societies; Survivors; Techniques; Texas; Time; Translating; Ultrasonography; Work; autism spectrum disorder; base; career; career development; clinical investigation; clinically relevant; cohort; college; cost; design; experience; hemodynamics; high risk; improved; innovation; intraventricular hemorrhage; knowledge base; meetings; middle cerebral artery; multidisciplinary; neuroimaging; novel; pediatric department; premature; pressure; prevent; professor; public health relevance; skills; success; symposium; tool; white matter; white matter injury

 DESCRIPTION (provided by applicant): This is a revised application for a K23 Award for Dr. Christopher Rhee, an assistant professor and board- certified neonatologist in the Department of Pediatrics at Baylor College of Medicine (BCM) and Texas Children's Hospital (TCH). I am well-qualified and highly motivated to pursue a career in academic medicine with a research focus on neonatal brain injury and cerebral hemodynamics. This K23 award will provide the support necessary for me to: (1) become an expert in premature brain injury; (2) conduct clinical investigations to define optimal brain perfusion parameters; (3) relate changes in brain perfusion to outcomes of interventricular hemorrhage (IVH), white matter injury, and neurodevelopmental outcomes; (4) gather data for the purpose of designing an intervention trial to identify and treat patients based on individualized brain perfusion parameters; and (5) develop an independent research career. I will use research and educational resources at the Texas Medical Center to advance my research career development. The neonatal intensive care unit at TCH is one of the largest in the country and offers the opportunity and resources to learn from an especially large population of premature infants. With more than 100 premature infants with birth weight ≤1000 grams born at TCH annually, we have the diversity and number of patients to perform meaningful clinical research and make an impact on patient care. I have assembled a knowledgeable, diverse, and multidisciplinary mentoring group from neonatology, critical care, anesthesiology, neurology, neuroradiology and developmental pediatrics to guide my career and this proposal. I have been working for the past 5 years in the basic science laboratory of Ken Brady, M.D., (secondary mentor) to learn techniques of brain and kidney perfusion monitoring in animal-models of hemorrhagic-induced shock and have translated these applications to premature infants. I have published the results of both animal and clinical research. Over the past 3 years, I have been working with Jeffrey R. Kaiser, M.D., (primary mentor) to further understand the development of premature cerebral hemodynamics, to explore use of magnetic resonance imaging techniques to evaluate white matter brain injury, and to learn the technique of transcranial Doppler ultrasound to evaluate cerebral blood flow clinically in premature infants. In conjunction with the research plan, I intend develop the skill set to become a leader in premature brain injury. To achieve these goals, I will utilize the resources and expertise of my mentors and Advisory Committee. I will formally take didactic courses, perform selected readings, and attend symposiums on brain physiology and neuroimaging to broaden my knowledge base. In addition, I will have hands-on tutorials learning transcranial Doppler from Dr. Kaiser, advanced physiologic waveform analysis from Dr. Brady, and neuroimaging techniques from Drs. Elisabeth Wilde, Ph.D. and Jill Hunter, Ph.D. Finally, I will meet weekly with my primary and secondary mentor and quarterly with my Advisory Committee to evaluate my progress and discuss changes to my career development plan. I have now developed a brain perfusion parameter, the diastolic closing margin (DCM) that offers a novel way to normalize arterial blood pressure to the critical closing pressure (zero-flow pressure) of the brain vasculature. My preliminary findings demonstrate an association of high brain perfusion pressure (high DCM) with IVH, and I have orally presented this data at the 2014 Pediatric Academic Society meeting and have published two manuscripts from this work. Drs. Kaiser and Brady will provide me with the research tools, research space and scientific guidance to help to ensure my success. The objective of this proposal is to assess the ability of the DCM to predict hemorrhagic and ischemic brain injury in premature infants. My central hypothesis is that a high DCM is associated with IVH, indicating a hyperperfusion injury, and a low DCM is associated with white matter injury, indicating an ischemic injury. If this hypothesis is correct, the mechanism and logical care goals for the most common brain injuries in premature infants will be delineated. My long-term goal is to define clinically relevant brain-specific hemodynamic parameters that can be used at the bedside to prevent hemorrhagic and ischemic brain injury and thereby improve neurodevelopmental outcomes. I will gather necessary preliminary data for the design of a future hemodynamic intervention trial aimed at preventing the most common forms of premature brain injury, in a subsequent R01: Aim 1. Prospectively determine whether a high brain perfusion pressure (high DCM) is predictive of interventricular hemorrhage. Aim 2. Prospectively determine whether a low brain perfusion pressure (low DCM) is predictive of white matter injury. Aim 3. Determine whether physiologic measurements of brain perfusion are predictive of neurodevelopmental outcomes. The K23 will allow me the protected time to conduct this research and continue my career development towards my goal of becoming a successful and independent clinical scientist.

 描述（由申请人提供）：这是 Christopher Rhee 博士的 K23 奖修订申请，Christopher Rhee 博士是贝勒医学院 (BCM) 和德克萨斯儿童医院 (TCH) 儿科的助理教授和委员会认证的新生儿科医生我有足够的资格和强烈的动力从事学术医学事业，重点研究新生儿脑损伤和脑血流动力学，该 K23 奖项将为我提供必要的支持： (1) 成为过早脑损伤方面的专家；(2) 进行临床研究以确定最佳脑灌注参数；(3) 将脑灌注变化与脑室出血 (IVH)、白质损伤和神经发育结果联系起来； ）收集数据，以便设计一项干预试验，以根据个性化的脑灌注参数识别和治疗患者；（5）发展独立的研究生涯，我将利用德克萨斯医学中心的研究和教育资源来推进我的研究生涯。发展。 TCH 的新生儿重症监护病房是全国最大的新生儿重症监护病房之一，为大量早产儿提供学习机会和资源。TCH 每年出生的早产儿超过 100 名，出生体重≤1000 克。患者的多样性和数量，以进行有意义的临床研究并对患者护理产生影响，我组建了一个知识渊博、多元化、多学科的指导小组，成员包括新生儿科、重症监护科、麻醉科、神经科、神经放射科和临床科。过去 5 年，我一直在医学博士 Ken Brady（二级导师）的基础科学实验室工作，学习出血动物模型中的脑和肾灌注监测技术。在过去的三年里，我一直与医学博士 Jeffrey R. Kaiser（主要导师）合作，以进一步了解这一现象。结合研究计划，探索利用磁共振成像技术评估早产儿脑白质损伤，学习经颅多普勒超声技术评估早产儿脑血流动力学。为了实现这些目标，我将利用我的导师和咨询委员会的资源和专业知识，我将正式参加教学课程，进行选定的阅读，并参加有关脑生理学和脑损伤的研讨会。此外，我还将学习 Kaiser 博士的经颅多普勒实践教程、Brady 博士的高级生理波形分析以及 Elisabeth Wilde 博士和 Jill Hunter 博士的神经影像技术。最后，我将每周与我的初级和二级导师会面，每季度与我的咨询委员会会面，评估我的进展并讨论我的职业发展计划的变化，我现在已经制定了一个大脑灌注参数。舒张期闭合边缘 (DCM) 提供了一种将动脉血压正常化至脑血管系统临界闭合压（零流量压力）的新方法。我的初步研究结果表明，高脑灌注压（高 DCM）与 IVH 存在关联。我在 2014 年儿科学会会议上口头介绍了这些数据，并发表了这项工作的两篇手稿，Kaiser 和 Brady 博士将为我提供研究工具、研究空间和科学指导，以帮助我完成这项工作。确保我的成功。该提案的目的是评估 DCM 预测早产儿出血性和缺血性脑损伤的能力。我的中心假设是，高 DCM 与 IVH 相关，表明存在过度灌注损伤，而低 DCM 与 IVH 相关。与白质损伤有关，表明缺血性损伤如果这个假设是正确的，那么早产儿最常见的脑损伤的机制和逻辑护理目标将被描述出来。我的长期目标是定义临床相关的。我将收集必要的初步数据，用于设计未来的血流动力学干预试验，旨在预防最常见的早产儿形式。目标 1. 前瞻性确定高脑灌注压（高 DCM）是否预示脑室出血。 目标 2. 前瞻性确定低脑灌注压是否预示脑室出血。灌注压（低 DCM）可预测白质损伤。 目标 3. 确定脑灌注的生理测量是否可预测神经发育结果。 K23 将为我提供受保护的时间来进行这项研究并继续我的职业发展，以实现我的目标。成为一名成功且独立的临床科学家。