Assessing neonatal brain glymphatic system development using diffusion tensor imaging along the perivascular space and choroid plexus volume

Abstract

Purpose

Neonatal brain development constitutes a critical period of structural and functional maturation underpinning sensory, motor, and cognitive capacities. The glymphatic system—a cerebral waste clearance network—remains poorly understood in neonates. We investigated non-invasive magnetic resonance imaging (MRI) biomarkers of glymphatic system and their developmental correlates in neonates.

Methods

In 117 neonates undergoing high-resolution T1-weighted and diffusion MRI, we quantified two glymphatic metrics: (1) diffusion tensor imaging along the perivascular space (DTI-ALPS) index, reflecting perivascular fluid dynamics; (2) choroid plexus (CP) volume, a cerebrospinal fluid (CSF) production marker. Associations with postmenstrual age (PMA) at MRI scan, gestational age (GA), birth weight (BW), and sex were analyzed using covariate-adjusted models.

Results

Preterm neonates displayed significantly reduced DTI-ALPS indices versus term neonates (total index: 1.01 vs. 1.05, P = 0.002), with reductions persisting after adjustment (P < 0.05). CP volumes showed right-dominant pre-adjustment differences (preterm: 0.33 vs. term: 0.39, P = 0.039) that attenuated post-adjustment (P = 0.348). DTI-ALPS indices demonstrated transient correlations with PMA/GA/BW in unadjusted analyses (P < 0.05), whereas CP volumes maintained robust PMA associations post-adjustment in all neonates (P = 0.037) and term subgroup (P = 0.013). No significant effects of sex on both metrics were observed.

Conclusion

Our findings reveal prematurity-associated delays in glymphatic maturation, rather than biological sex. The persistent PMA-CP volume relationship suggests developmental regulation of CSF production, while attenuated DTI-ALPS correlations highlight covariate-mediated effects. These glymphatic metrics show potential for monitoring neurodevelopmental trajectories, though longitudinal validation is required to establish their clinical utility in neonatal care.

Clinical trial number

Not applicable.