<p>Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition leading to significant neonatal mortality and long-term disability. Timely and accurate diagnosis is vital for effective treatment and improved outcomes. Magnetic resonance imaging (MRI) has emerged as a key tool for assessing brain injury in neonates, with advanced techniques such as amide proton transfer imaging providing insights into tissue metabolism and pH. Amide proton transfer imaging detects changes in protein content and pH values, offering a sensitive reflection of metabolic alterations in the brain environment. Studies have shown that amide proton transfer imaging can identify differences in brain regions associated with HIE, even in the absence of conventional MRI abnormalities. Compared to other imaging modalities, amide proton transfer imaging exhibits high sensitivity in detecting protein content changes and pH, providing molecular-level information that aids in early diagnosis and treatment monitoring. Research also suggests that amide proton transfer imaging can predict long-term neurodevelopmental outcomes, supporting the formulation of personalized rehabilitation plans. Despite its advantages, amide proton transfer imaging has limitations and future research should focus on technical optimization, integration with other imaging techniques, and the discovery of new biomarkers. The integration of amide proton transfer imaging with clinical practice has the potential to significantly improve the management of neonatal HIE, leading to better treatment outcomes and quality of life for affected infants.</p> Graphical Abstract <p></p>