Investigation of cerebral energy metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy

Abstract

31P NMR spectroscopy can be safely and successfully used to study cerebral energy metabolism in sick newborn infants, provided a suitable life support and monitoring system is available. Studies of normal infants have shown characteristic spectral peaks assigned to adenosine triphosphate, phosphocreatine, phosphodiesters plus phospholipids, inorganic orthophosphate, and a large peak at the phosphomonoester resonance frequency that is attributable mainly to phosphoethanolamine, a precursor of membrane phospholipids. Both the PCr/Pi and PCr/ATP ratios were lower in normal newborn infants than reported in studies using invasive techniques in adult animals. Tissue hypoxia-ischemia was associated with a fall in PCr levels and a rise in Pi. The PCr/Pi ratio, which is an index of cerebral energy status, was normal during the first day of life in infants who had suffered severe birth asphyxia, but subsequently fell to levels well below the normal range. The presence of this latent period raises the possibility of effective early treatment following birth asphyxia, before irreversible impairment of cellular energy metabolism occurs. Low PCr/Pi ratios have also been demonstrated in infants with idiopathic cerebral infarction, periventricular leukomalacia and inborn errors of metabolism. Preliminary experience suggests that ratios below 0.8 are associated with irrecoverable failure of energy metabolism and cellular necrosis. 31P NMRS and other spectroscopic NMR techniques utilizing, for instance, 1H and 13C nuclei, have exciting potential for exploring the mechanisms and methods of prevention of various forms of cerebral damage in the newborn period.