Kim Annink

19 General introduction biomarkers (S100B) for brain injury, but not in boys whose mothers were treated with allopurinol (60). However, it appeared difficult to antenatally select hypoxic fetuses based on cardiotocography (61) resulting in overtreatment. Therefore, a double- blinded, placebo-controlled RCT “Effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome” (ALBINO) trial is now conducted in Europe. In the ALBINO trial, we investigate the neuroprotective effect of early allopurinol on the resuscitation table in neonates with perinatal asphyxia and early signs of encephalopathy (62,63). The study protocol is further described in chapter eight of this thesis. The pharmacokinetics of allopurinol are well known for infants with HIE that are not treated with therapeutic hypothermia, but this knowledge is not yet available for infants with HIE that are treated with therapeutic hypothermia (64). Therefore, as part of the ALBINO trial a pharmacokinetic sub-study was performed. The results are presented in chapter nine. Innovative neuroimaging methods Add-on neuroprotective therapies will be essential to improve outcome for infants with HIE. However, to evaluate the neuroprotective effect of add-on therapies and to predict long-term outcome, optimization of neuroimaging quality is also important. MRI with a higher field strength can improve neuroimaging quality. Nowadays MRI with a field strength up to 3.0 Tesla (T) is routinely used in infants. The increase of a field strength of 1.5T to 3.0T has improved MRI quality in infants and enabled us to see more details and pathology (65). In adults, 7.0T has shown to further increase diagnostic value and is now frequently used. According to a growing number of studies, 7.0T MRI enables better visualization of micro-bleedings and the microcirculation at SWI, MRA and MRV, detection of additional metabolites at MRS and better quality of T2-weighted imaging that allows to see more details of the anatomy i.e. the different layers of the cortex can be distinguished (66). In infants 7.0T MRI might also be beneficial to optimize MRI quality, but so far this has never been performed. A higher field strength in infants might be accompanied with some safety concerns as discomfort and a rise in temperature of the brain, but also with technical 1

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