MRI and proton MR spectroscopy in neonatal hypoxic-ischemic encephalopathy: a comprehensive imaging review

Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and long-term neurodevelopmental disability. Although cranial ultrasound is widely used as a bedside screening tool, brain MRI has become central to diagnosis, injury pattern classification, timing estimation, and outcome prediction. Furthermore, proton MR spectroscopy (¹H-MRS) provides complementary metabolic biomarkers that enhance prognostication. This review focuses on MRI and ¹H-MRS in neonatal encephalopathy due to hypoxic-ischemic injury, addressing both term and preterm infants. The pathophysiologic determinants of injury distribution are summarized, the optimal timing of imaging and diffusion evolution is discussed, and practical acquisition protocols including recommended sequences and ¹H-MRS parameters are proposed. Key MRI phenotypes in term infants-basal ganglia-thalamus injury, watershed/parasagittal cortical-subcortical injury, and global or near-total injury patterns are reviewed with attention to common pitfalls such as diffusion pseudonormalization and evolving T1/T2 signal changes. For preterm infants, this review highlights distinctive vulnerabilities of the germinal matrix and periventricular white matter, emphasizing the spectrum from punctate white matter injury (WMI) to cystic periventricular leukomalacia (PVL). For ¹H-MRS, voxel selection, echo time considerations, and interpretation of lactate, N-acetylaspartate (NAA), choline, creatine, and myo-inositol are detailed. Evidence suggests that deep gray matter lactate/NAA or NAA-based metrics serve as reliable and robust outcome biomarkers. Emerging directions including arterial spin labeling (ASL) perfusion are also discussed.