Abstract
BACKGROUND: Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in the regulation of brain iron homeostasis in normal brain development, but these imaging profiles remain to be elucidated. We aimed to establish a relationship between brain iron dynamics and BBB function during childhood using a combined quantitative magnetic resonance imaging (MRI) to depict both physiological systems along developmental trajectories. METHODS: In this single-center prospective study, consecutive outpatients, 2-180 months of age, who underwent brain MRI (3.0-T scanner; Ingenia; Philips) between January 2020 and January 2021, were included. Children with histories of preterm birth or birth defects, abnormalities on MRI, and diagnoses that included neurological diseases during follow-up examinations through December 2022 were excluded. In addition to clinical MRI, quantitative susceptibility mapping (QSM; iron deposition measure) and diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; BBB function measure) were acquired. Atlas-based analyses for QSM and DP-pCASL were performed to investigate developmental trajectories of regional brain iron deposition and BBB function and their relationships. RESULTS: A total of 78 children (mean age, 73.8 months ± 61.5 [SD]; 43 boys) were evaluated. Rapid magnetic susceptibility progression in the brain (Δsusceptibility value) was observed during the first two years (globus pallidus, 1.26 ± 0.18 [× 10(- 3) ppm/month]; substantia nigra, 0.68 ± 0.16; thalamus, 0.15 ± 0.04). The scattergram between the Δsusceptibility value and the water exchange rate across the BBB (k(w)) divided by the cerebral blood flow was well fitted to the sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus (globus pallidus, 2.96-3.03 [mL/100 g](-1); substantia nigra, 3.12-3.15; thalamus, 3.64-3.67) in accordance with the regional heterogeneity of brain iron accumulation. CONCLUSIONS: The combined quantitative MRI study of QSM and DP-pCASL for pediatric brains demonstrated the relationship between brain iron dynamics and BBB function during childhood. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000039047, registered January 6, 2020.