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Assessing neonatal brain glymphatic system development using diffusion tensor imaging along the perivascular space
Ting Peng1,2, Ying Lin2, Xin Xu3
1Department of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.
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.
