Baby Brain Study

Near infrared monitoring and 3T MRI/MRS in Babies with Acute Brain Injury (Ethics 13/LO/0225)

As adjunct neuroprotective therapies evolve, we need more accurate MR biomarkers that can detect earlier and more subtle changes in brain structure and function than before. We believe that phosphorus MR spectroscopy (31P MRS) combined with the other state-of the art imaging techniques (e.g. Chemical Exchange Saturation Transfer (CEST) imaging and brain perfusion) developed by Prof Golay will provide the detail needed to enhance our care of infants undergoing neuroprotection.

Brain intracellular pH

In 2002, Robertson et al., demonstrated that brain intracellular pH (pHi) was alkaline following perinatal hypoxia-ischaemia and the extent of the alkalosis was associated with neurodevelopmental outcome and brain injury severity on conventional MR imaging (MRI) (Robertson et al., 2002). Dr Kendall demonstrated the importance of brain pHi in the rodent brain (Kendall et al., ) and Prof Robertson has shown that manipulation of brain pHi with amiloride is neuroprotective in an asphyxia model (Robertson et al., 2013). Brain pHi is thus likely to be an important marker of injury, but no studies have been done with the MR spectroscopy resolution we have available today nor in babies who have undergone therapeutic hypothermia

Aim of study

To assess the relation between brain pHi, brain perfusion and near Infrared spectroscopy (NIRS) derived measurement of cytochrome oxidase in infants with acute brain injury, in particular those with neonatal encephalopathy at term.

References

Kendall GS, Robertson NJ, Iwata O, Peebles D, Raivich G. N-methyl-isobutyl-amiloride Ameliorates Brain Injury when Commenced Prior to Hypoxia Ischemia in Neonatal Mice. Pediatr Res 2006;59:227-231
Kendall GS, Melbourne A, Johnson S, Price D, Bainbridge A, Gunny R, Huertas-Ceballos A, Cady EB, Ourselin S, Marlow N, Robertson NJ. White matter NAA/Cho and Cho/Cr on MRS Predict Motor Outcome in Preterm Infants. Radiology (in press)
Robertson NJ, Cowan FM, Cox IJ, Edwards AD. Brain alkaline intracellular pH after neonatal encephalopathy. Ann Neurol. 2002 Dec;52(6):732-42.
Robertson NJ, Kato T, Bainbridge A, Chandrasekaran M, Iwata O, Kapetanakis A, Faulkner S, Cheong J, Iwata S, Hristova M, Cady E, Raivich G. Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model. J Neurochem. 2013 Mar;124(5):645-57.