Longitudinal changes in pallidal index and their associations with urinary manganese and CaNa₂EDTA chelation

In this study, the evaluation of the change in pallidal index (PI) (ΔPI) between baseline and follow-up magnetic resonance imaging; the examination of the relationship between ΔPI and spot urine manganese (Mn) levels and baseline PI values; and the investigation of the possible effect of CaNa₂EDTA chelation therapy administered during the follow-up period on pallidal Mn accumulation were aimed.

In 27 participants monitored due to occupational Mn exposure, right and left PI were measured from T1-weighted images using standard protocols. ΔPI was calculated as the difference between the baseline and follow-up measurements. During CaNa₂EDTA treatment, whole blood and spot urine Mn levels were measured on the first day of each treatment course and on rest days, while 24-hour urinary Mn levels were assessed on the third day of treatment. In individuals treated with CaNa₂EDTA, the pre- and post-treatment change in PI was evaluated as a secondary analysis. Associations between ΔPI and Mn biomarkers were analyzed using the Spearman rho coefficient.

It was determined that both right and left PI significantly decreased during the follow-up period. A negative correlation was found between spot urine Mn levels and ΔPI (right: ρ = -0.59; left: ρ = -0.45; p < 0.05), indicating that the reduction in PI is more limited in individuals with higher current exposure. The positive correlation of ΔPI with the initial PI (right: ρ = 0.51; left: ρ = 0.74; p < 0.05) suggests that the initial accumulation level is a determining factor in the amount of reduction. Following CaNa₂EDTA treatment, blood Mn levels significantly Decreased in parallel with the observed reduction in PI.

PI is a dynamic imaging biomarker sensitive to changes in Mn accumulation, reflecting both the exposure level and the response to chelation therapy. The integration of MRI-based measurements with biological exposure markers can provide significant contributions to the monitoring and evaluation of treatment efficacy in populations exposed to Mn.