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.
Intraventricular hemorrhage (IVH) occurs in 45% of extremely low birth weight premature infants and approximately 25% of preterm infants who suffered severe IVH will require permanent cerebrospinal fluid (CSF) drainage to manage subsequent post-hemorrhagic hydrocephalus (PHH). The lack of a bedside tool to assess newborn brain health limits progress in neonatal care that could improve neurodevelopmental outcomes. The overall goal of this proposal is to determine if FDNIRS-DCS can early identify IVH and PHH, assess response to PHH treatment, and predict outcomes in a population of extremely premature infants.
| Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela et al. (2016) Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage. Sci Rep 6:25903 |
