Beside Monitor of Cerebral Metabolism in Premature Infants with Intraventricular

 描述(申请人提供)：我是一名实验科学家，对了解正常和异常的大脑以改善新生儿脑损伤后的神经学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，以确立我作为新生儿医学跨学科研究的独立首席研究员的地位。这一建议是由我在Martinos中心的博士后工作和我为被诊断为GM-IVH的婴儿确定了先进的近红外光谱技术的新利基所推动的。在这个项目中，我将研究生发基质脑室出血(GM-IVH)和出血后脑积水(PHH)早产儿的出生后早期脑代谢，以及GMH-IVH和PHH的脑代谢与婴儿发育结局的关系。我的长期职业目标是成为研究型大学或医学中心的终身教员，并领导我自己的独立研究小组。具体地说，我想开发一个工具，帮助医生确定干预的时间，并更好地选择患者进行临床试验。我的最终目标是开发一种通过FDA 510(K)认证的设备，用于床边脑健康的非侵入性监测。我设想建立一个由竞争对手资助的实验室，并领导跨学科研究，致力于开发和实施创新的、基于光学的非侵入性技术来监测大脑健康。特别是，我热衷于为婴儿建立生物标记物，以便能够早期诊断和处理各种新生儿脑损伤。这些生物标志物可能会揭示预测哪些婴儿将经历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到儿童和成人脑损伤的各个领域。K99/R00独立之路奖的提议是识别此类生物标记物的第一步，并为我提供了进一步扩大生物标记物使用的机会。在美国，12%的活产是早产，因此需要照顾大约50万早产儿。美国国家科学院估计，早产每年给美国造成的损失超过260亿美元。生发基质-脑室出血(GM-IVH)是早产儿的主要并发症，约45%的极低出生体重儿(体重和体重1000克)发生，所有级别都与不良的长期神经功能损害有关。尽管改进的新生儿重症监护和技术进步提高了极早产儿的存活率，但GM-IVH的高发病率在过去十年中保持不变。这项研究将探讨GM-IVH与脑血流和代谢的关系，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。我们提出了创新的无创近红外光谱(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，我们已经证明了在新生儿重症监护病房(NICU)进行脑代谢测量的可行性和实用性。我们的中心假设是，脑血流和氧代谢的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和CMRO2的影响的额外客观标准。这项工作将测试NIRS测量的脑氧代谢作为生物标记物在新生儿神经元健康和围产期护理中的有效性。我在麻省理工学院马蒂诺斯中心的导师团队是一家集技术、研究和临床应用于一体的团队。这项研究将在波士顿儿童医院(BCH)和布里格姆妇女医院(BWH)的Martinos中心和新生儿医学网站进行。马蒂诺斯中心是一个理想的环境，拥有一个庞大的多学科专家社区，他们开发和应用各种创新的新成像和生物医学技术。光学司拥有多台人用FDNIRS、CWNIRS和分布式控制系统仪器，并已承诺使用完成本提案目标所需的设备、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。拥有120张二级和三级新生儿重症监护床位，这是新英格兰最大的此类项目，是本研究的理想选择。我在光学工程(Franceschini博士)、新生儿神经成像(Grant博士)、新生儿脑积水(Warf博士)、新生儿学(Inder博士)和婴儿神经发育(Nelson博士)方面组建了一支强大的多学科指导团队。每一位导师都提供重要的专业知识和经验，指导我成功完成这个多学科项目。除了指导和研究，我还计划通过正规的新生儿学和婴儿发育课程进行培训，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为成为新生儿脑成像和发育领域的独立研究员做好准备。

 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.