Age-related change of glymphatic function in normative children assessed using diffusion tensor imaging-analysis along the perivascular space.

Background: The glymphatic system, crucial for brain waste removal and homeostasis, has an underexplored developmental trajectory in children. This study describes changes in glymphatic function during childhood via diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS).

Methods: We retrospectively studied DTI MR images of 72 pediatric participants (mean age = 92.37 months; 0-19.8 years; 50 % females), all showing normal MRI findings from 2019 to 2022. Imaging utilized 3 T scanners with a DTI sequence of 21 diffusion-encoded gradients, focusing on the ALPS index to assess glymphatic function. Clinical outcomes were determined using the Pediatric Cerebral Performance Category Scale and medical records within two weeks post-MRI. Regions-of-interest on diffusion maps were selected manually, guided by fractional anisotropy maps, for automatic ALPS computation. Pearson correlation and multiple linear regression analyzed the relationship between ALPS indices, age, and clinical scores, with a paired t-test comparing bilateral ALPS indices. Significance was set at P < 0.05.

Results: Significant positive correlations between age and both left (R = 0.510, P < 0.001) and right (R = 0.688, P < 0.001) DTI-ALPS indices were observed, indicating developmental changes in glymphatic function. Age alone significantly predicted the DTI-ALPS indices (left ALPS: adjusted R2 = 0.235; right ALPS: adjusted R2 = 0.460), underscoring its developmental trajectory. The study found no significant differences between left and right DTI-ALPS indices, suggesting symmetrical glymphatic function during childhood.

Conclusions: This study reveals developmental changes in the glymphatic system across childhood, demonstrating an age-related increase in glymphatic function and bilateral symmetry.