Prospective MRI Assessment of Early Myelination Over the First Month of Life in Neonates With Neonatal Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia With or Without Sildenafil.

BACKGROUND AND PURPOSE: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of mortality and long-term morbidities, and therapeutic hypothermia (TH), while the standard of care, is not universally effective. The objective of the study was to use T2* values as a surrogate marker of myelination to characterize early myelination after HIE and explore whether sildenafil, used as an adjunct to TH, is associated with improved myelination.

MATERIAL AND

METHODS

This prospective neuroimaging study included neonates with HIE treated with TH; a subset of neonates with MRI-confirmed brain injury received sildenafil in addition to TH. Myelination was assessed using a T2* mapping. T2* values were measured in eight brain regions at three time-points (days 2, 10, and 30). T2* values were compared among neonates without brain injury treated with TH alone (NoBI+TH), neonates with brain injury treated with TH alone (BI+TH), and neonates with brain injury treated with TH plus sildenafil (BI+TH/S).

RESULTS

A total of 167 MRI scans were obtained from 77 neonates: 32 NoBI+TH neonates, 25 BI+TH neonates, and 20 BI+TH/S neonates. On day 2, neonates with brain injury exhibited significantly higher T2* values in the thalamus, posterior limb of the internal capsule [PLIC], anterior white matter [AWM], and anterior corpus callosum [ACC] than the NoBI+TH group. By day 10, elevated T2* values persisted in AWM and ACC in both brain injury groups, and also in PLIC in the BI+TH group. At day 30, T2* values in the BI+TH group remained persistently elevated across these regions, with additional increases in the thalamus, optic radiations [OR], and posterior corpus callosum [PCC]. In contrast, the BI+TH/S group demonstrated significantly lower T2* values in thalamus, PLIC, AWM, OR, ACC, and PCC compared to BI+TH; in several regions (thalamus, PLIC, AWM), T2* values in the BI+TH/S group were no longer different from NoBI+TH.

CONCLUSIONS

T2* values were increased after HIE despite TH, consistent with a possible disruption of early myelination. Sildenafil as an adjunct to TH was associated with lower T2* values over the first month of life, suggesting a potential neurorestorative effect on myelination.