Alterations of glymphatic transport in hypoxic-ischemic encephalopathy were assessed using dynamic contrast-enhanced MRI.

Motivation: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury. Understanding the effects of HIE on the glymphatic system could inform new therapeutic strategies. Goal(s): This study aims to investigate the glymphatic impairment associated with HIE. Approach: We analyzed diffusion weighted image analysis along the perivascular space (DWI-ALPS) in HIE neonates and conducted qualitative and quantitative assessments of glymphatic transport in an HIE mouse model using DCE-MRI. Results: The ALPS index was significantly lower in neonates with HIE. In HIE mice, delayed gadolinium uptake , reduced transfer constants (Kf and Ks), and increased volume fractions of the perivascular space, indicating impaired glymphatic function. Impact: This study identifies impaired glymphatic transport in neonates with HIE, leading to decreased CSF influx and interstitial fluid stagnation. Understanding these mechanisms may inform therapies to enhance glymphatic clearance and improve long-term neurodevelopmental outcomes for affected neonates.