Developmental Inflection in Glymphatic System-Related MRI Parameters During Childhood: DTI-ALPS Index and Choroid Plexus Volume Analyses in a Retrospective Clinical Cohort.

Purpose

To delineate pediatric developmental trajectories of glymphatic neuroimaging parameters using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and absolute choroid plexus volume (CPV).

Methods

This retrospective study evaluated a cohort of 537 pediatric participants (271 males, 266 females; aged 7 months to 20 years) without macrostructural imaging pathology. Subjects underwent brain MRI across four 3T scanners to measure the DTI-ALPS index and absolute CPV, with multi-site batch effects corrected via ComBat-generalized additive models (ComBat-GAM) harmonization. Chronological trajectories and developmental inflection points were modeled using GAM and segmented linear regression.

Results

The DTI-ALPS index exhibited a continuous age-related increase, with a significant inflection point at 5.42 years (95% confidence interval [CI]: 3.71, 7.13), transitioning from a rapid initial phase (slope = 0.0023, p < 0.001) to a slower, gradual increase (slope = 0.0004, p < 0.001). CPV demonstrated a prominent, continuous linear contraction after an inflection point at 2.67 years (95% CI: 1.46, 3.87; slope = -2.1040, p < 0.001), running discordant to macroscopic cranial scaling. After adjusting for age and ICV, absolute CPV and the DTI-ALPS index showed no significant residual correlation (ρ = -0.025, p = 0.561).

Interpretation

Initial rapid changes in the DTI-ALPS index stabilize after early childhood, while CPV undergoes continuous contraction independent of head growth. These chronologically decoupled pathways provide noninvasive insights into independent physiological mechanisms governing the pediatric fluid-clearance environment.