{"title":"Longitudinal changes in pallidal index and their associations with urinary manganese and CaNa₂EDTA chelation","authors":"Tuğba Akkale , Nuriye Kayalı Şendur , Süleyman Filiz , Nilüfer Merve Çelik","doi":"10.1016/j.neuro.2026.103397","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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<strong>.</strong> 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.</div></div><div><h3>Results</h3><div>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</div><div>Decreased in parallel with the observed reduction in PI.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103397"},"PeriodicalIF":3.8000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotoxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161813X26000185","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusion
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.
期刊介绍:
NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.