ASL reveals regional brain perfusion impairment in neonates with mild hypoxic ischemic encephalopathy

There is a lack of neuroimaging data and effective biomarkers in infants with mild hypoxic ischaemic encephalopathy (HIE). Cerebral reperfusion injury has shown potential as marker of neurodevelopmental outcome in moderate and severe HIE. We examined cerebral perfusion by using arterial spin labelling (ASL) in infants with mild HIE and its associations with adverse outcomes. We also studied the presence of any potential regional sensitivity of cerebral blood flow (CBF) on the effects of HIE severity. This prospective cohort study included term and near-term neonates admitted for HIE across 3 neonatal intensive care units in Italy between October 2019-2022. Magnetic resonance imaging (MRI)-ASL was performed between 4 and 10 days after birth. Neurodevelopmental outcome was assessed at 24-28 months. Of the 94 infants included in the analysis, 74 neonates had mild [79%], 15 moderate [16%], 5 severe encephalopathy [5%]. Of the 71 neonates with mild HIE and neurodevelopmental outcome available, 15 (21%) showed mild disability. Basal ganglia CBF was the only region significantly associated with cognitive, motor and language Bayley scores (false-discovery-rate < 0.05). HIE severity had a regional dependent effect with involvement of Heschl, Rolandic operculum, limbic lobe, subcortical gray nuclei followed by frontal lobes. Basal ganglia CBF in infants with mild HIE was associated with adverse outcomes even without any MRI visible deep brain nuclei injury.