Proton and phosphorus spectroscopy of hypoxic, ischaemic and haemorrhagic perinatal brain injury
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Peden, Carol J.
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Abstract
Proton magnetic resonance spectroscopy was investigated as a non-invasive technique
to observe biochemical changes in the brains of children who had sustained perinatal
hypoxic, ischaemic and haemorrhagic brain injury.
Methods:
Proton spectra were acquired from the centre of the brain in premature infants, and
from the parieto-occipital region in older children. Phosphorus spectra were also
collected and compared with the proton spectra. Unlocalized phosphorus spectra were
acquired at different repetition times. Some children had localized phosphorus
spectroscopy examinations with two and four dimensional chemical shift imaging. The
children were between 33 weeks post-conceptional age and four years and three months
postnatal age at the time of their initial spectroscopy examination. The ability of early
proton spectroscopy to predict outcome was considered in relation to the clinical
neurological state at eighteen months or more. Because certain assumptions were made
about the proton spectra (e.g. no T2 measurements were made), proton spectra were
acquired from adults with central nervous system tumours. At surgery, biopsies were
taken from the tumours and from normal brain and were analysed with in vitro
spectroscopy, histology and established biochemical techniques. The metabolite ratios
were compared with those from the in vivo spectra. Modifications were made to
commercially available monitoring and ventilation equipment to provide the same
standards of care within the magnetic field for sick patients, as on the neonatal or
intensive care units.
Results:
All the proton spectra had peaks attributable to N-Acetyl aspartate (NAA), choline
containing compounds (Cho) and creatine plus phosphocreatine (Cr). The NAA/Cho
and NAA/Cr peak height ratios increased with age, while the Cho/Cr ratio decreased.
The NAA/Cr ratios were significantly decreased in all children with an abnormal
neurological outcome when compared with the NAA/Cr ratios from children with a
normal outcome. The NAA/Cho ratios were significantly decreased in those children
with a moderate outcome but not in those with a severe neurological outcome. There
were no significant changes in the Cho/Cr ratios.
The phosphorus spectra showed changes; phosphocreatine (PCr) to inorganic
phosphate (Pi) decreased after injury and there was a marked increase in pH in the
children with the poorest outcome. The apparent Tl of Pi was increased in the first
month after birth in the children with a severe outcome. Few changes were seen with
localized phosphorus spectroscopy in children who had focal lesions. Phosphorus
spectra returned to normal within weeks of birth, while the proton spectra remained
abnormal.
The adult tumour proton spectra compared well with the in vitro spectra and histology
of the biopsies. The concentrations changes of metabolites in vivo, were consistent
with the measurements made with established biochemical techniques.
Discussion:
Hypoxic-ischaemic injury produced changes in the proton spectrum from neonatal
brain. These changes persisted with time. Some of these changes correlated with
outcome. Phosphorus spectra showed acute changes in response to injury, but the
changes resolved within weeks. NAA is located in neurons; the decrease in NAA could
be due to failure of neurons to develop normally, or to areas of neuronal loss and
gliosis resulting from hypoxic-ischaemic damage. Phosphorus spectra may return to
normal because neurons and glia have similar phosphorus metabolite ratios. Proton
spectroscopy combined with magnetic resonance imaging, may become a useful
technique for studying the anatomy and biochemistry of the brain in children who have
suffered brain injury.