Presented at the Neonatal Society 2004 Spring Meeting.
Cheong JLY1, Bainbridge A2, Cady EB2, Wyatt JS1, Robertson NJ1
1 Department of Paediatrics and Child Health, University College London, UK
2 Department of Medical Physics and Bioengineering, University College London, UK
Background: Small shifts in brain intracellular pH (pHi) influence diverse cellular functions. Phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) provides a non-invasive measurement of brain pHi from the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine (PCr). Using 31P MRS, at 1.5T an alkaline shift in brain pHi has been observed in term infants with neonatal encephalopathy (NE) during the period of secondary energy failure following perinatal hypoxia-ischaemia (HI) (1). The extent of brain alkalosis was related to the severity of brain injury on magnetic resonance (MR) imaging, neurodevelopmental outcome at one year and brain lactate/creatine, suggesting that brain pHi may be a marker or mechanism of brain injury. Experimental data suggest that brain alkalosis after HI is deleterious to cell survival and that a delay in the rapid return of pHi to normal or prevention of the alkaline overshoot are neuroprotective (2).
At high field (7T), newborn experimental models of HI suggest brain pHi heterogeneity due to more than one visible component of the Pi peak. Precise characterisation of pHi shifts in particular compartments may be useful in targeting neuroprotective strategies.
Objective: To assess brain pHi changes and heterogeneity using high field 31P MRS before, during and after an acute HI cerebral insult in a newborn piglet model of SEF.
Design/Methods: 27 newborn piglets with HI (carotid occlusion and FiO2 12-16% for 1 hr) and 6 controls were studied. Anaesthesia was induced by 5% isoflurane and maintained with isoflurane (<1.5%), nitrous oxide and oxygen. Tracheostomy, umbilical vessel catheterisation and placement of bilateral carotid occluders were performed on all piglets. 31P spectra were acquired over 48 hours (7T Bruker Biospec); [total Pi (Pitotal)]:[exchangeable phosphate pool (epp)] ratio was calculated . Two Pi peaks (Pi1 and 2) were defined based on the Pi lineshape. Brain pHi values 1 and 2 were calculated from the chemical shifts of Pi relative to PCr. Data comparison was by t-test or Mann-Whitney rank sum test as appropriate.
Results: Pi1 and 2 corresponding to pHi1 and 2 at baseline and during SEF are shown (Figure 1). At 42-48 hrs, pHi1 in the insulted group decreased (p<0.01) but all other pHi values were unchanged. At 42-48 hrs, controls showed slightly increased Pitotal/epp (p<0.05); the insulted group showed significantly increased Pitotal/epp, Pi1/epp and Pi2/epp (all p<0.001) characteristic of SEF. At 42-48 hrs, the amplitude of the more alkaline Pi component, Pi1 was double that of Pi2 (p<0.001) (Figure 2).
Conclusion: Two main brain pHi values can be observed at 7T in this newborn model. During SEF, the actual pHi values themselves did not undergo an alkaline shift; rather there was a dramatic increase in the Pi concentration in the upfield or more alkaline component. At low field this may give the impression that the overall pHi has become alkaline and explains the previous findings in infants with NE studied at 1.5T. These data at high field characterize the pHi shift during SEF with more precision reflecting a possible vulnerability of one brain compartment.
References
1. Robertson NJ et al. Ann Neurol 2002; 52:732-42.
2. Vornov JJ et al. J Neurochem 1996;67:2379-2389.