Acm Chu

CEREBRAL ENERGY METABOLISM STUDIED WITH PHOSPHORUS NMR SPECTROSCOPY IN NORMAL AND BIRTH-ASPHYXIATED INFANTS

Phosphorus (31P) nuclear magnetic resonance spectroscopy was used to study intracellular metabolism in the brains of 6 normal newborn infants and 10 infants who had been asphyxiated during delivery. In the normal infants spectral peaks mainly attributable to adenosine triphosphate, phosphocreatine (PCr), phosphodiesters plus phospholipids, and inorganic orthophosphate (Pi) were always detected, together with an additional large peak in the phosphomonoester region indicating the presence of a metabolite or metabolites (probably largely phosphoethanolamine) which may be involved in rapid growth of the brain. In the asphyxiated infants, data obtained on the first day of life showed no differences from those in normal infants, but by the second to ninth days inverse changes in the concentrations of PCr and Pi had caused a significant reduction in PCr/Pi. This latency suggest the possibility of effective early treatment before irreversible metabolic damage sets in. Mean intracellular pH when PCr/Pi was minimal was 7.17 +/- 0.10. Values for PCr/Pi below 0.80 were associated with a very bad prognosis for survival and early neuro-developmental outcome.

Brain Metabolism and Intracellular pH During Ischaemia and Hypoxia: An In Vivo 31P and 1H Nuclear Magnetic Resonance Study in the Lamb

Abstract: Brain metabolism and intracellular pH were studied during and after episodes of ischaemia and hypoxia‐ischaemia in lambs anaesthetised with sodium pentobarbitone. 31P and 1H magnetic resonance spectroscopy methods were used to monitor brain pHi and brain concentrations of Pi, phosphocreatine (PCr), β‐nucleoside triphosphate (βNTP), and lactate. Simultaneous measurements were made of cerebral blood flow and cerebral oxygen and glucose consumption. Cerebral ischaemia sufficient to reduce oxygen delivery to 75% of control values was associated with a fall in brain pHi and increase in brain Pi. Progressively severe hypoxia‐ischaemia was associated with a progressive fall in brain pHi, PCr, and βNTP and increase in brain pi In two animals the increase in brain lactate during hypoxia‐ischaemia measured by 1H nuclear magnetic resonance (NMR) could be quantitatively accounted for by the increased net uptake of glucose by the brain in relation to oxygen, but was insufficient to account for the concomitant aci‐dosis according to previous estimates of brain buffering capacity. In four animals brain pHi, PCr, pi, and βNTP had returned to normal 1 h after the hypoxic‐ischaemic episode. In one animal brain pHi had reverted to normal at a time when 1H NMR indicated persistent elevation of brain lactate.

Cerebral metabolism in newborn infants studied by phosphorus nuclear magnetic resonance spectroscopy.

Publisher Summary This chapter discusses a study to examine the cerebral metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy. Six normal infants were studied. They were born at 28–40 weeks of gestation and NMR spectra were obtained when they were 16 h to 97 days old: their gestational-equivalent age at this time was 38–42 weeks. Unilateral lesions were detected by ultrasound in four infants born at 34–40 weeks of gestation and aged 1–14 days. In three of them the diagnosis was thought to be early cerebral infarction, and in the fourth, a small hemorrhage into a possibly infarcted area. PCr/Pi was always reduced in the affected hemisphere compared with the normal one. Depletion was far worse than encountered in any of the birth asphyxiated babies, and was accompanied by a profound intracellular acidosis. The infants subsequently died but there was no reason to suppose that the oxygen supply to the brain was seriously inadequate at the time when the studies were done. The metabolic abnormalities in both these illnesses inhibit the tricarboxylic acid cycle. The most likely explanation for the extremely severe disruption of energy status is that insufficient substrate was available for oxidative phosphorylation to occur.

DERANGED ENERGY METABOLISM IN THE BRAIN OF NEWBORN INFANTS WITH INCREASED CEREBRAL ECHCDENSITIES

Increased cerebral echodensities detected by ultrasound scanning of the brain in newborn infants often resolve, but sometimes progress to cystic periventricular leukoencephalopathy or other loss of brain tissue. The purpose of this investigation was to explore whether increased echodensities were associated with evidence of deranged cerebral energy metabolism as determined by phosphorus nuclear magnetic resonance spectroscopy (NMRS), and whether measurement of the energy status of cerebral tissue identified those infants who died or subsequently developed cysts or microcephaly.15 normal infants born between 28 and 40 weeks of gestation were studied as controls at ages between 1 day and 14 weeks, using methods that have previously been described1. The phosphocreatine (PCr)/inorganic orthophosphate (Pi) ratio, which is an index of the energy state of the tissue, increased from 0.77 ± 0.14 (95% confidence limits) at 30 weeks of gestational age plus postnatal age to 1.12 ± 0.14 at 40 weeks.20 infants, born at 29-41 weeks of gestation, with increased echodensities (not apparently due to haemorrhage, and associated with birth asphyxia in 9 infants) were studied by NMRS aged 1day-4weeks. PCr/Pi was below the normal range in all 5 infants who died. Sequential ultrasound scanning in the 15 survivors showed no evidence of loss of brain substance in the 5 infants whose PCr/Pi ratios were within the normal range, whereas cysts or microcephaly developed in 8 of the 10 infants whose ratios were abnormally low (Fishers exact test, p<0.01).We conclude that (1) cerebral energy status was abnormal in some infants with increased cerebral echodensities and (2), the infants with abnormal energy status were much more likely to die or show subsequent loss of brain substance.1. Hope PL et al. Lancet 1984; ii: 336.

Low phosphocreatine |[lpar]|PCr|[rpar]||[sol]|inorganic phosphate |[lpar]|P1|[rpar]| ratio in the brain of newborn infants indicates poor outcome

The PCr/Pi ratio is an index of the energetic status of tissue. To see whether this ratio gave prognostic information, we used phosphorus nuclear magnetic resonance spectroscopy to measure PCr/Pi in the brains of 6 normal infants and on 71 occasions in 30 infants with neonatal neurological abnormalities due, for example, to birth-asphyxia, periventricular haemorrhage and early cerebral infarction. In the normal infants PCr/Pi ranged from 1.10 to 1.71 (mean 1.35). PCr/Pi fell below this range in 24 of the 30 abnormal infants and below 0.8 in 16 of them. 8 of the 16 infants with PCr/Pi ratios below 0.8 died in the neonatal period from predominantly cerebral causes and all 8 survivors were neurodevelopmentally abnormal at a mean age of 7 months. Among the 20 infants whose PCr/Pi ratios were always 0.8 or above, 2 died (one aged 3 weeks with congenital abnormalities including Moebius syndrome and the other, who had Prader-Willi syndrome, as a cot death aged 9 months): 3 infants were neurodevelopmentally abnormal aged 4, 9 and 10 months, and the remaining 15 infants were progressing normally at a mean age of 6 months.We conclude that PCr/Pi ratios below 0.8 were associated with a very poor prognosis, and may indicate irreversibly deranged cerebral metabolism.