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
Abstract
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…
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