Severe congenital heart disease (CHD) remains a common cause of infant morbidity, occurring in 6-8 per 1,000 live births per year. Up to 50% of neonates presenting with CHD will require open-heart surgery in the first few weeks of life. Although survival has increased due to progress in surgical repair, up to 50% have impaired neurodevelopmental outcomes. The persistently high rates of impaired neurodevelopmental outcomes may be due to pre-existing impairments in intrauterine cerebral development and/or brain injury that occurs in the early postoperative time period due to hemodynamic instability. In fact, preoperative neonatal and fetal magnetic resonance imaging (MRI) studies of subjects with CHD provide evidence that in utero brain development is compromised, particularly when the CHD results in poor brain perfusion. Intra-operatively, hypothermia is used to protect the brain during the low flow state required for open-heart surgical repair as hypothermia decreases neuronal activity, and therefore oxygen demand. However, post-operatively, as rewarming occurs and the heart recovers, the brain remains particularly vulnerable. Currently, preoperative brain health is assessed and post-surgical monitoring for acute hypoxic ischemic brain injury is performed with bedside continuous wave near infrared spectroscopy (CWNIRS) measures of frontal brain relative tissue oxygen saturation (rStO2). These rStO2 measures are used to guide treatment decisions, but we have shown that StO2 is insensitive to brain growth in normal preterm and term children, and is insensitive to acute hypoxic ischemic brain injury in neonates. Although oxygen is the primary fuel for neurons, rStO2 does not reflect the amount of oxygen consumed by neurons, and is affected by multiple non-neuronal factors such as blood flow and hematocrit. In contrast, bedside frequency domain NIRS (FDNIRS) combined with diffuse correlation spectroscopy (DCS) provide direct measures of neuronal health by providing absolute measures of neuronal relative cerebral oxygen consumption (rCMRO2). We have shown that FDNIRS-DCS rCMRO2 is sensitive to brain development and to acute hypoxic ischemic brain injury. We propose to use bedside FDNIRS-DCS measures of CMRO2i to assess preoperative brain health and monitor for postoperative hypoxic ischemic brain injury. Our goal is to establish bedside FDNIRS-DCS as an informative bedside tool for assessing and monitoring brain health in neonates undergoing open-heart surgery for CHD. If successful, this project may have a direct and immediate clinical impact.

Public Health Relevance

The lack of a bedside monitor to detect and differentiate pre-existing brain abnormalities from potentially preventable perioperative brain injury severely limit improvements in perioperative management of congenital heart disease. The overall goal of this project is to determine the potential of a novel near infrared spectroscopy system that provides bedside measures of cerebral oxygen consumption to serve as such a bedside monitor.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-V (82))
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Raju, Tonse N
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Children's Hospital Boston
United States
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