Manganese Neurotoxicity Of Magnetic Resonance Imaging Study

Objective This cross-sectional study applied magnetic resonance imaging(MRI)technique to detect the alterations of T₁-weighted image(WI) signal caused by brain manganese accumulation in occupational manganese exposure workers.Additionally,concentrations of airborne MnO₂,blood routine test,six metal elements in blood were determined,and the correlation between the alterations of T₁- WI signal and blood manganese level was analyzed,in order to explore the possibility of MRI as a early biomarker of Mn neurotoxicity and offer scientific basis for screening manganism susceptible population and early diagnosis,prevention and cure of subclinical chronic occupational manganism.Methods 18 male occupational manganese exposure workers without manganism symptoms from a ferro alloy factory in Guangxi were selected to be manganese exposure group(Mn-E),13 of them were boiler workers who exposed with high manganese concentration(the average concentration of MnO₂ in this work place was 0.52(0.00～2.04)mg/m³,subgroup of high manganese exposure,Mn-H),the rest 5 workers worked in power distribution control rooms the near the boilers with low manganese concentration in the air (the average concentration of MnO₂ in this work place was 0.11 (0.00～0.38)mg/m³,subgroup of low manganese exposure,Mn-L).9 male rear service workers from the same factory whose ages,work ages and backgrounds of economy and education were closed to those in Mn-E group were chosen to be control group(the average concentration of MnO₂ in the work place was 0.01 (0.00～0.03)mg/m³).4 male workers with chronic manganism from a hospital in Guangxi were selected to be manganism group(Mn-P).Furthermore,a follow-up investigation was put into practice in 8 workers within Mn-H group from 2003 to 2004.A1.5 Tesla Signa superconducting system with a quadrature coil was used to perform brain MRI of the workers with coronal and axial T₁-WI and axial T₂-WI.Then the manipulator selected the regions of interest (ROI)to determine the signal intensities of globus pallidus(GP)and the frontal white matter(FWM)in the same side,then calculate pallidal indexes(PI). Concentrations of MnO₂(CMnO₂)in work places,blood routine test,and concentrations of several elements(such as Mn,Zn,Cu,Fe,Ca,Mg)in blood were respectively determined by using flame atomic absorption spectrometer (AAS),automated hematology analyzer,inductively coupled plasma-atomic emission spectrophotometry(ICP-AES).Clinical examinations were conducted to the workers in control,manganese exposed and manganism group.All the data was analyzed by the statistical software of SPSS/PC+ For Windows v.13.0.Results(1)Compared with control group(102.2±1.48),PI of Mn-E (116.2±8.43),Mn-L(109.8±4.49)and Mn-H(118.7±8.38)groups were significantly increased(P＜0.05);while there was no statistical significance in Mn-P(103.7±2.80,P＞0.05).(2)The results of ANCOVA showed that there were significant differences with the parameters of CMnO₂,SIGP,SIFWM and PI among control,Mn-L and Mn-H groups(P＜0.01).Correlation test revealed that there was noticeable positive correlation between PI value and MnRBC in Mn-E group(r=0.55,P=0.02).Our multiple regression analysis results indicated that PI value had correlations with CMnO₂ and MnRBC(R²=0.409,P=0.002 and 0.007),SIGP(R²=0.868,P=0.000),SIFWM(R²=0.718,P=0.000).(3) Mn-H had low WBC and MCHC when compared to Mn-L(P＜0.05).CuB in Mn-E,CuB and FeP in Mn-L were higher than control group(P＜0.05),while ZnP,CuP,FeP,MgP and FeRBC in Mn-H were conspicuously lower than Mn-L. (4)A follow-up investigation was undertaken within 8 workers from Mn-E group from 2003 to 2004.Compared to 2003,CMnO₂,SIGP,SIFWM,CaB and MgB in 2004 decreased apparently(P＜0.05)while ZnB increased significantly (P＜0.01),however,there was no change in PI.(5)Only 3 Mn-H workers had slight tremor linguae in both control and Mn-E groups.The main clinical manifestations of the 4 workers with manganism were lassitude,heavy feeling in both lower extremities,headache,dizziness,decreased memory,irritability or emotion alteration,limbs anesthesia,eyelids and/or tongue tremors.Conclusion Mn accumulated in the target region(GP)of the target organ (brain)might be the reason that caused hyperintentisties in MRI T₁-WI signals of symptomlessed occupational manganese exposure workers.PI and MnRBC respectively reflected brain manganese accumulation and body manganese level, moreover,there was a positive correlation between them,which illuminated that both parameters may be the exposed biomarkers of early Mn nuerotoxicity. Objective By carrying through Meta-analysis of pallidal indexes(PI) from published or unpublished trials that applied magnetic resonance image (MRI)to detect brain manganese accumulation caused by occupational manganese exposure and chronic liver diseases from 1995 to 2007,in order to explore the possibility of PI as an early biomarker of Mn neurotoxicity and offer scientific basis for the early diagnosis,prevention and cure of manganism.Methods According to the pre-formulated inclusion criteria,we searched related trials which published from 1995 to 2007.The mostly original source of published trials from home and abroad were relatively "Medline data-base", "Cochrane Library" and "Bio-medical documents data-base of China(CBM disc)".The included trials were able to involve unpublished papers.Then we filtrated the trials that measured up the requirements of this Meta-analysis,and then extracted related data such as PI values,blood manganese concentration, etc.The quality evaluation criteria of Cochrane Reviewer Handbook 4.2.3 was used to evaluate the methodological qualities of the included trials.This Meta-analysis was processed with the standardized professional software Review Manager(Revman)v.4.2.8 from the evaluation system of international Cochrane collaboration web.Based on the results of heterogeneity test, weighted mean difference(WMD)of random effect model or fixed effect model were used in the Meta-analysis.Moreover,we tried to collect the original data of PI values and MnB to make a correlation test with the statistical software of SPSS/PC+ for Windows v.13.0.Results Totally,there were 8 trials with 135 occupational workers and 113 patients with chronic liver diseases met the inclusion criteria.The results of heterogeneity test revealed that heterogeneity was existed in the subgroup of occupational manganese exposure,while homogeneity was existed in chronic liver diseases subgroup,therefore,random effect model and fixed effect model were relatively applied to go on Meta-analysis.The Meta-analysis results showed that overall effect tests of the 2 subgroups both have statistical significances(P＜0.01),which illuminated that PI value was a sensitive, credible,effective half-quantity index to evaluate brain manganese accumulation.Correlation tests displayed that threre was significantly positive correlation between partial original data of PI values and MnB in subgroup of chronic liver diseases(r=0.497,P＜0.01).Conclusion Alterations of MRI T₁-WI signals in detecting brain manganese accumulation were sensitive and characteristic,furthermore,PI value was a sensitive,credible,effective half-quantity index to evaluate brain manganese accumulation.According to the correlation between PI value and MnB,it is possible that MnB also redounded to evaluate brain manganese accumulated level in the near future.