Proton Magnetic Resonance Spectroscopy of the Developing Human Brain

Neurodevelopmental disorders are pervasive and pose a significant public health problem. Many of these disorders can have a lifelong impact on the quality of life and may affect an individual's ability to function independently. In numerous pediatric and fetal neurological disorders, biochemical alterations precede or mediate structural and functional abnormalities that result in the patient's symptoms. Therefore, the ability of Proton Magnetic Resonance Spectroscopy (¹H-MRS) to characterize these changes offers a valuable complement to neuro-anatomical imaging by allowing for a more timely and specific diagnosis, which may, in turn, enable earlier initiation of therapies and support services. This manuscript discusses the technical foundations of ¹H-MRS and demonstrates its clinical relevance through representative applications in the developing human brain, including the evaluation of neurodevelopmental trajectories, diagnosis of inherited metabolic disorders, assessment of hypoxic-ischemic encephalopathy (HIE), monitoring of brain development in congenital heart disease (CHD), and its role in neuro-oncology. Despite its promise as a valuable tool in neuroradiology, the widespread adoption of ¹H-MRS remains limited by technical constraints and challenges in spectral interpretation. Therefore, this manuscript also outlines the key barriers that hinder its full clinical potential and discusses how targeted technological innovations, along with the development of large-scale reference datasets, can enhance the reliability and diagnostic utility of ¹H-MRS in improving outcomes for neurodevelopmental disorders.