Brain injury in premature is an important clinical problem due to the increasing number of surviving premature infants and the high incidence of neurodevelopmental handicaps in this population. Disturbances of cerebral blood flow (CBF) and oxygen delivery are thought to be crucial factors in neonatal brain injury. However, the exact mechanisms and timing of injury are not understood. In vivo Near infrared spectroscopy (NIRS) provides a means of direct and continuous bedside monitoring of neonatal cerebral hemodynamics and oxygenation. NIRS may be able to detect alterations of cerebral oxygenation or hemodynamics before injury from cellular energy depletion of this technology in the prevention of newborn brain injury will required further laboratory based and clinical studies. The goal of this proposal is for the PI to become an independent investigator capable of approaching questions in newborn neurology with both laboratory and clinical research tools. To achieve this goal, the PI has established an in-depth program of didactic and research training. In Phase I, the PI will use the response to hypoxia and ischemia in neonatal piglets 1) to characterize changes in brain Hb02 and Hb concentration, 2) to compare NIRS CBV measurements CBF estimations to microsphere measures of CBF, 3) to determine the correlation of NIRS measures of cerebral hemodynamics to magnetic resonance measures cerebral energy state, and 4) to determine the ability of NIRS cerebral blood volume measurements predict loss of cerebrovascular regulation. In phase II, the findings of the animal studies will be applied i a clinical study of premature neonates to examine in control and critically ill neonates 1) regulations of CBF, 2) presence or absence of NIRS changes associated with cerebral energy failure in phase I studies, and 3) differences in the variability of cerebral hemodynamic parameters. These will determine the physiological significance of NIRS with measurements and whether changes in cerebral oxygenation and blood volume thought to be associated with increased risk of brain injury are present in critically ill neonates. The overall program will provide the necessary baseline data, logistics, and training in state-of-the-art in-vivo spectroscopy for the PI to undertake further studies of the relationship between NIRS measurements of altered cerebral hemodynamics nd subsequent brain injury.
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