Imaging Biomarkers of the Glymphatic System in the Developing Brain

The glymphatic system is increasingly recognized as a brain-wide pathway that mediates cerebrospinal fluid-interstitial fluid exchange and metabolic waste clearance. However, unlike in adults, its developmental trajectory and clinical relevance during infancy and childhood remain poorly understood. This review summarizes imaging biomarkers of glymphatic structure and function across neurodevelopment, with a particular emphasis on infancy, while also addressing the broader pediatric population. We focus on noninvasive MRI-based measures applicable to pediatric practice, including perivascular space (PVS) grading and volumetry, the diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index, and choroid plexus (CP) volume. Developmental evidence indicates that PVS visibility and volume, the DTI-ALPS index, and CP volume undergo age-related changes during early development. However, age-specific normative data remain limited, particularly between infancy and school age. In pediatric populations, glymphatic-related imaging alterations have been reported in preterm birth, neonatal hypoxic-ischemic injury, and neurodevelopmental disorders such as autism spectrum disorder. Collectively, these findings highlight the potential clinical utility of non-contrast glymphatic imaging biomarkers in children and underscore the need for larger longitudinal and multicenter studies to establish normative reference values and clarify their prognostic significance.