In spite of advances in neonatal intensive care, perinatal brain damage remains a major cause of morbidity and mortality. Understanding the developmental changes in cerebral hemodynamics and energy metabolism that occur in human neonates is critical for designing rational treatment strategies that ensure an adequate supply of nutrients critical for brain function and development while minimizing deleterious side effects of therapeutic interventions. The purpose of this project is to refine and apply existing methodology for quantitative measurement of cerebral blood flow (CBF) and glucose metabolism (CMRGlu) to critically ill newborn infants. The hypotheses to be tested are (1) Glucose transport into the brain of newborn infants is not rate limiting for CMRGlu at plasma glucose concentrations above 2 mmol/L (36 mg/dl). (2) Near infrared spectroscopy (NIRS) can be used for quantitative measurement of CBF in newborn infants within plus/minus 10% accuracy.
The specific aims are: 1. Measure blood-to-brain glucose transport and CMRGlu at ambient plasma glucose concentrations in newborn infants of different gestational ages hospitalized in the Neonatal Intensive Care Unit with 1-11C-glucose and positron emission tomography (PET) using a method that we have developed and validated in non-human primates. 2. Collect NIRS data for measurement of CBF from newborn infants at the time that they undergo PET measurements of CBF required for specific aim 1 and determine the effect of different processing algorithms on the accuracy of NIRS measurements as compared with PET. Determination of the plasma glucose concentration at which influx becomes rate limiting for cerebral glucose metabolism in ill newborn human infants will establish a biologically relevant level of hypoglycemia requiring treatment, thus enabling clinicians to reduce the danger of hypoglycemic brain damage and minimize any deleterious effects of unnecessary hyperglycemia. Validation of the accuracy of NIRS for quantitative measurements of CBF at the bedside will establish this technology for rapid and repetitive monitoring of CBF in ill newborn infants for further research and clinical studies.
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