Magnetic resonance imaging and spectroscopy in neonatal encephalopathy: current consensus position and future opportunities

Abstract: Neonatal encephalopathy (NE) is a significant global health concern. It is a leading cause of long-term neurodevelopmental impairment, with hypoxic-ischaemic perinatal brain injury being the most common underlying contributor. Although therapeutic hypothermia has reduced mortality and improved outcomes for some affected infants, many survivors experience neurodevelopmental disability, including cerebral palsy and/or deficits in cognition, behaviour, and executive functioning. Early and accurate prognostication and identification of injury severity remain a challenge due to evolving clinical signs and multiple etiologies. Magnetic resonance imaging (MRI) is the gold standard for characterizing NE-related brain injury. Diffusion-weighted imaging (DWI) enables early detection of injury, and proton magnetic resonance spectroscopy (¹H-MRS), specifically the Lac/NAA peak area ratio from basal ganglia and thalamus, provides robust prognostic indicators of two-year neurodevelopmental outcomes. MRI scoring systems incorporating multiple modalities correlate well with later neurodevelopmental outcomes. Advanced imaging modalities, such as diffusion tensor imaging (DTI), arterial spin labelling (ASL), and blood oxygen level-dependent (BOLD) imaging, offer further insights into microstructural integrity, perfusion, and functional connectivity. By standardizing acquisition protocols and post-processing, MRI biomarkers can serve as reliable, early surrogate endpoints in neuroprotection trials, allowing smaller sample sizes and accelerating clinical translation. MRI and ¹H-MRS integration enhances prognostication, guides clinical management, and supports informed decision-making in NE care. Impact: This article highlights the importance of state-of-the-art MRI and MRS techniques for assessing neonatal encephalopathy (NE), emphasizing optimized protocols, accurate interpretation, and the use of MRI scoring systems to enhance clinical decision-making. It provides a comprehensive guide to advanced MRI/MRS acquisition and interpretation in neonates with NE, addressing current limitations and future directions. By optimizing neonatal MRI/MRS practices, this work aims to improve early diagnosis and prognostication, guide treatment strategies, and ultimately improve the management of neonates with NE.