Beside Monitor of Cerebral Metabolism in Premature Infants with Intraventricular

早产儿脑室内代谢的旁路监测

• 批准号: 9751359
• 负责人: Pei-Yi Lin
• 金额: $ 24.89万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-14 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751359
• 关键词: 2 year old; Academy; Address; Adult; Age; Anatomy; Award; Beds; Biological Markers; Biomedical Technology; Blood Vessels; Blood flow; Boston; Brain Injuries; Brain imaging; Caring; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Childhood; Childhood Injury; Clinical; Clinical Trials; Clinical assessments; Communities; Complement; Complication; Depressed mood; Development; Devices; Diagnosis; Diagnostic; Diffuse; Drainage procedure; Early Diagnosis; Early treatment; Engineering; Ensure; Environment; Equipment; Evaluation; Exhibits; Extremely Low Birth Weight Infant; Faculty; Family; Funding; Gap Junctions; Goals; Grant; Growth; Health; Healthcare; Hemorrhage; Hospitals; Human; Hydrocephalus; Imaging technology; Impairment; Incidence; Infant; Infant Development; Interdisciplinary Study; Intervention; Intracranial Pressure; Intraventricular; Lead; Learning; Light; Live Birth; Magnetic Resonance Imaging; Measurement; Measures; Medical; Medical center; Medicine; Mentors; Mentorship; Metabolism; Methods; Modeling; Monitor; Near-Infrared Spectroscopy; Neonatal; Neonatal Brain Injury; Neonatal Intensive Care; Neonatal Intensive Care Units; Neonatology; Neurodevelopmental Impairment; Neurologic; Neurological outcome; Neuronal Injury; Neurons; New England; Newborn Infant; Optics; Outcome; Oxygen; Pathogenesis; Pathway interactions; Patients; Pediatric Hospitals; Perfusion; Perinatal Care; Phase; Population; Predictive Value; Premature Birth; Premature Infant; Prevention; Prevention strategy; Principal Investigator; Quality of life; Recovery; Regulation; Research; Research Personnel; Research Project Grants; Resolution; Resources; Risk; Science; Scientist; Severities; Site; Societies; Spectrum Analysis; Survival Rate; Techniques; Technology; Testing; Time; Toddler; Training; Treatment Effectiveness; Treatment outcome; Ultrasonography; United States; Universities; Weight; Woman; Work; base; brain abnormalities; brain health; career; cerebral hemodynamics; cerebrovascular; clinical application; cost; efficacy testing; experience; hemodynamics; improved; infancy; innovation; instrument; interest; intraventricular hemorrhage; member; metabolomics; mortality; multidisciplinary; neonatal brain; neonatal care; neonate; neurodevelopment; neuroimaging; non-invasive monitor; novel; outcome prediction; post intervention; postnatal period; premature; programs; public health relevance; response; routine imaging; skills; success; tenure track; tool; treatment response

 DESCRIPTION (provided by applicant): I am an experimental scientist with a particular interest in understanding the normal and abnormal brain to improve neurological outcomes and quality of life after neonatal brain injuries. My goal in seeking a K99/R00 Pathway to Independence Award is to obtain, through coursework and mentoring, the training in neonatology, pediatric neuroradiology and infant development to establish myself as an independent principal investigator in inter-disciplinary research in newborn medical science. This proposal is driven by my postdoctoral work within the Martinos Center and my identification of a new niche for advanced NIRS techniques in infants diagnosed with GM-IVH. For this project, I will investigate early post-natal cerebral metabolism in premature infants with germinal-matrix intraventricular hemorrhage (GM-IVH) and post-hemorrhagic hydrocephalus (PHH) and the relationship between cerebral metabolism in GMH-IVH and PHH with infants' developmental outcomes. My long-term career goal is to become a tenure-track faculty member at a research university or medical center and lead my own independent research group. Specifically I want to develop a tool to help doctors time their intervention and better select patients for clinical trials. My ultimate aim is to develop an FDA 510(k)- cleared device fo noninvasive monitoring of cerebral health at the bedside. I envision establishing a competitively funded lab and leading interdisciplinary research dedicated to developing and implementing innovative, noninvasive optical-based technologies in monitoring brain health. In particular, I am keen to establish biomarkers for infants to enable early diagnosis and management of various neonatal brain injuries. The biomarkers might shed light on the best ways to predict which infants would experience poor neurodevelopment. The biomarkers related to neonatal neuronal injury would impact every field of brain injury in children and adults. The proposal for this K99/R00 Pathway to Independence Award is the first step to identifying such biomarkers and providing me the opportunity to further expand the use of biomarkers. Twelve percent of live births in the United States are premature, resulting in the need to care for some 500,000 premature infants. The National Academies estimate premature births cost the US in excess of $26 billion every year. Germinal matrix-intraventricular hemorrhage (GM-IVH) is a major complication of prematurity, occurring in about 45% of extremely low birth weight infants (weight <1000 g), and all grades are associated with adverse long-term neurological impairment. Even as improved neonatal intensive care and technological advances have increased the survival rate of extremely premature infants, the high incidence of GM-IVH has remained unchanged over the past decade. This study will investigate the relationship between GM-IVH and cerebral blood flow and metabolism with the long-term goal of developing novel, easy-to-apply diagnostics for GM-IVH risk and progression. We propose innovative non-invasive Near Infrared Spectroscopy (FDNIRS-DCS) methods suitable for monitoring cerebral hemodynamics and metabolism of premature infants directly at the patient bedside. In earlier work, we have already demonstrated the feasibility and utility of performing cerebral metabolism measurements in the neonatal intensive care unit (NICU). Our central hypothesis is that NIRS measures of cerebral perfusion and oxygen metabolism can serve as additional objective criteria for assessing the impact of GM-IVH, the progression of PHH, and the effect of hydrocephalus treatment on cerebral CBF and CMRO2. This work will test the efficacy of NIRS-measured cerebral oxygen metabolism as a biomarker in neonatal neuronal health and perinatal care. My mentor's group at the Martinos Center at MGH is at a nexus of technology, research and clinical applications. This study will be at the Martinos center and sites within Newborn Medicine at Boston Children's Hospital (BCH), and Brigham and Women's Hospital (BWH). The Martinos Center is an ideal environment with a large multidisciplinary community of experts who develop and apply a wide range of innovative new imaging and biomedical technologies. The Optics Division has multiple human-use FDNIRS, CWNIRS and DCS instruments and has pledged the use of the equipment, resources and facilities needed to complete the aims of this proposal. We have long-standing relationships with neonatal intensive care units (NICUs) at BCH and BWH, as exhibited in our preliminary results. With 120 Level II and III neonatal intensive care beds, they are the largest such programs in New England and ideal for this study. I have formed a strong multi-disciplinary mentoring team in optical engineering (Dr. Franceschini), neonatal neuroimaging (Dr. Grant), neonatal hydrocephalus (Dr. Warf), neonatology (Dr. Inder) and infant neurodevelopment (Dr. Nelson). Each mentor provides critical expertise and experience to guide me to successful completion of this multidisciplinary project. In addition to the mentorship and research, I also plan for training through formal coursework in neonatology and infant development to complement my engineering background. The skills and experience garnered from completion of the proposed training and research objective will prepare me to become an independent investigator in the fields of neonatal brain imaging and development.

 描述（由申请人提供）：我是一名实验科学家，对了解正常和异常大脑以改善新生儿脑损伤后的神经系统结果和生活质量特别感兴趣。我寻求 K99/R00 独立之路奖的目标是：通过课程作业和指导，获得新生儿学、儿科神经放射学和婴儿发育方面的培训，使自己成为新生儿医学跨学科研究的独立首席研究员。该提案是由我在马蒂诺斯中心的博士后工作推动的。我在诊断患有 GM-IVH 的婴儿中确定了先进 NIRS 技术的新利基。在这个项目中，我将研究患有生发基质脑室内出血 (GM-IVH) 和出血后的早产儿的早期产后脑代谢。脑积水 (PHH) 以及 GMH-IVH 和 PHH 的脑代谢与婴儿发育结果之间的关系 我的长期职业目标是成为研究型大学或研究型大学的终身教职人员。我的最终目标是开发一种经 FDA 510(k) 批准的设备，用于无创监测。我设想建立一个竞争性资助的实验室和领先的跨学科研究，致力于开发和实施基于光学的创新技术来监测大脑健康，我特别热衷于为婴儿建立生物标志物，以实现早期诊断和治疗。各种新生儿脑损伤的治疗。生物标志物可能揭示预测哪些婴儿神经发育不良的最佳方法。与新生儿神经元损伤相关的生物标志物将影响儿童和成人脑损伤的各个领域。K99/R00 独立之路奖的提案是。这是识别此类生物标志物的第一步，并为我提供了进一步扩大生物标志物使用的机会。在美国，12% 的活产婴儿是早产儿，导致需要照顾约 500,000 名早产儿。美国国家科学院估计，美国每年因早产造成的损失超过 260 亿美元。生发基质脑室内出血 (GM-IVH) 是早产的主要并发症，约 45% 的极低出生体重婴儿（体重 <1000 克）会发生这种情况。 ，并且所有级别都与不利的长期神经功能障碍有关，即使新生儿重症监护的改善和技术进步提高了极早产儿的存活率，但其高发病率。 GM-IVH 在过去十年中保持不变。本研究将调查 GM-IVH 与脑血流和代谢之间的关系，长期目标是开发新的、易于应用的 GM-IVH 风险和进展诊断方法。我们提出了创新的非侵入性近红外光谱（FDNIRS-DCS）方法，适用于直接在患者床边监测早产儿的脑血流动力学和代谢。在早期的工作中，我们已经证明了在早产儿中进行脑代谢测量的可行性和实用性。我们的中心假设是，脑灌注和氧代谢的 NIRS 测量可以作为评估 GM-IVH 的影响、PHH 的进展以及脑积水治疗对脑 CBF 的影响的附加客观标准。这项工作将测试 NIRS 测量的脑氧代谢作为新生儿神经元健康和围产期护理的生物标志物的功效。这项研究将在马蒂诺斯中心以及波士顿儿童医院 (BCH) 和布莱根妇女医院 (BWH) 的新生儿医学中心进行。马蒂诺斯中心是一个拥有大型多学科社区的理想环境。光学部门拥有多种人类使用的 FDNIRS、CWNIRS 和 DCS 仪器，并承诺使用完成目标所需的设备、资源和设施。正如我们的初步结果所示，我们与 BCH 和 BWH 的新生儿重症监护病房 (NICU) 有着长期的合作关系，它们拥有 120 个二级和三级新生儿重症监护床位，是新英格兰地区最大的此类项目。我在光学工程（Franceschini 博士）、新生儿神经影像学（Grant 博士）、新生儿脑积水（Warf 博士）、新生儿学（Dr. Grant）方面组建了一支强大的多学科指导团队。 Inder）和婴儿神经发育（尼尔森博士）。每位导师都提供了重要的专业知识和经验来指导我成功完成这个多学科项目。除了指导和研究之外，我还计划通过新生儿学和婴儿发育的正式课程进行培训。以补充我的工程背景。完成拟议的培训和研究目标所获得的技能和经验将使我成为新生儿脑成像和发育领域的独立研究者。