Share：
Share this content in WeChat
X
[Chinese] [PDF] 5 1
• Reviews •
Research progress of multimodal magnetic resonance imaging in occupational manganese exposure-induced neurotoxicity
GAO Yuli  WU Jiayu  WU Xiaoping 

Cite this article as: GAO Y L, WU J Y, WU X P. Research progress of multimodal magnetic resonance imaging in occupational manganese exposure-induced neurotoxicity[J]. Chin J Magn Reson Imaging, 2026, 17(3): 161-167. DOI:10.12015/issn.1674-8034.2026.03.023.


[Abstract] Chronic manganese exposure can adversely affect the central nervous system, resulting in motor and cognitive impairments. Advances in neuroimaging have enabled multimodal MRI to sensitively and non-invasively characterize structural, functional, and metabolic brain alterations in manganese-exposed individuals, even at early and subclinical stages. These imaging findings provide critical insights into the neurobiological mechanisms underlying manganese-induced neurotoxicity. This review synthesizes current evidence on the application of multiple MRI modalities in occupational manganese exposure, focusing on their ability to detect microstructural damage, functional network alterations, and potential imaging biomarkers. It also summarizes the current limitations of these studies and outlines future research directions, aiming to support mechanistic interpretation, early identification of manganese-related neural injury, and improved imaging-based risk assessment in occupational settings.
[Keywords] manganese；occupational exposure；neurotoxicity；multimodal magnetic resonance imaging；magnetic resonance imaging

GAO Yuli1, 2   WU Jiayu2   WU Xiaoping2*  

1 Yan'an university, Yan'an 716000, China

2 Department of Radiology, the Affiliated Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an 710000, China

Corresponding author: WU X P, E-mail: szping518@163.com

Conflicts of interest   None.

Received  2025-10-30
Accepted  2026-01-05
DOI: 10.12015/issn.1674-8034.2026.03.023
Cite this article as: GAO Y L, WU J Y, WU X P. Research progress of multimodal magnetic resonance imaging in occupational manganese exposure-induced neurotoxicity[J]. Chin J Magn Reson Imaging, 2026, 17(3): 161-167. DOI:10.12015/issn.1674-8034.2026.03.023.

[1]
AASETH J O. Toxic and essential metals in human health and disease 2021[J/OL]. Biomolecules, 2022, 12(10): 1375 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36291583/. DOI: 10.3390/biom12101375.
[2]
BAJ J, FLIEGER W, BARBACHOWSKA A, et al. Consequences of disturbing manganese homeostasis[J/OL]. Int J Mol Sci, 2023, 24(19): 14959 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/37834407/. DOI: 10.3390/ijms241914959.
[3]
GONZALEZ-CUYAR L F, NELSON G, NIELSEN S S, et al. Olfactory tract/bulb metal concentration in manganese-exposed mineworkers[J/OL]. Neurotoxicology, 2024, 102: 96-105 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/38582332/. DOI: 10.1016/j.neuro.2024.04.001.
[4]
RACETTE B A, NELSON G, DLAMINI W W, et al. Severity of parkinsonism associated with environmental manganese exposure[J/OL]. Environ Health, 2021, 20(1): 27 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/33722243/. DOI: 10.1186/s12940-021-00712-3.
[5]
SHARMA A, FENG L, MURESANU DF, et al. Manganese nanoparticles induce blood-brain barrier disruption, cerebral blood flow reduction, edema formation and brain pathology associated with cognitive and motor dysfunctions[J]. Prog Brain Res, 2021, 265: 385-406. DOI: 10.1016/bs.pbr.2021.06.015.
[6]
BI Y, HUANG N, XU D, et al. Manganese exposure leads to depressive-like behavior through disruption of the Gln-Glu-GABA metabolic cycle[J/OL]. J Hazard Mater, 2024, 480: 135808 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/39288524/. DOI: 10.1016/j.jhazmat.2024.135808.
[7]
GANDHI D, RUDRASHETTI A P, RAJASEKARAN S. The impact of environmental and occupational exposures of manganese on pulmonary, hepatic, and renal functions[J]. J Appl Toxicol, 2022, 42(1): 103-129. DOI: 10.1002/jat.4214.
[8]
PISHARADY P K, EBERLY L E, ADANYEGUH I M, et al. Multimodal MRI improves diagnostic accuracy and sensitivity to longitudinal change in amyotrophic lateral sclerosis[J]. Commun Med(Lond), 2023, 3(1): 84-98. DOI: 10.1038/s43856-023-00318-5.
[9]
ZHANG L, ROY S, GUO B. The role of manganese-based MRI contrast agents for cancer theranostics: where do we stand in 2025?[J]. Theranostics, 2025, 15(9): 4147-4174. DOI: 10.7150/thno.108705.
[10]
JENSEN N, TERRELL R, RAMOJU S, et al. Magnetic resonance imaging T1 indices of the brain as biomarkers of inhaled manganese exposure[J]. Crit Rev Toxicol, 2022, 52(5): 358-370. DOI: 10.1080/10408444.2022.2128719.
[11]
DAYAN R, ARKADIR D. Manganese accumulation in the brain[J/OL]. N Engl J Med, 2023, 389(14): 1320 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/37792615/. DOI: 10.1056/NEJMicm2301805.
[12]
ALICI N Ş, NADIR ÖZIŞ T, ÇELIKER G, et al. Welder's lung and brain MRI findings in manganese-exposed welders: occupational diseases of welders[J/OL]. Med Lav, 2022, 113(6): e2022049 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36475507/. DOI: 10.23749/mdl.v113i6.13143.
[13]
LEE E Y, FLYNN M R, DU G, et al. Nigral MRI features of asymptomatic welders[J]. Parkinsonism Relat Disord, 2021, 85: 37-43. DOI: 10.1016/j.parkreldis.2021.02.020.
[14]
MONSIVAIS H, YEH C L, EDMONDSON A, et al. Whole-brain mapping of increased manganese levels in welders and its association with exposure and motor function[J/OL]. Neuroimage, 2024, 288: 120523 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/38278427/. DOI: 10.1016/j.neuroimage.2024.120523.
[15]
THUNBERG P, WASTENSSON G, LIDÉN G, et al. Welding techniques and manganese concentrations in blood and brain: Results from the WELDFUMES study[J]. Neurotoxicology, 2024, 105: 121-130. DOI: 10.1016/j.neuro.2024.09.005.
[16]
SCHMIDBAUER V U, YILDIRIM M S, DOVJAK G O, et al. Synthetic MR imaging-based WM signal suppression identifies neonatal brainstem pathways in vivo[J]. AJNR Am J Neuroradiol, 2022, 43(12): 1817-1823. DOI: 10.3174/ajnr.A7710.
[17]
LAVIELLE A, PINAUD N, ZHANG B, et al. Quantitative brain T1 maps derived from T1-weighted MRI acquisitions: a proof-of-concept study[J/OL]. Eur Radiol Exp, 2024, 8(1): 109 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/39377962/. DOI: 10.1186/s41747-024-00517-2.
[18]
MONSIVAIS H, DYDAK U. Subject-specific mapping of excess manganese accumulation in the brain of welders using magnetic resonance imaging relaxometry[J/OL]. Toxics, 2025, 13(3): 157 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/40137484/. DOI: 10.3390/toxics13030157.
[19]
WOO S, NOH Y, KOH S B, et al. Associations of ambient manganese exposure with brain gray matter thickness and white matter hyperintensities[J]. Hypertens Res, 2023, 46(8): 1870-1879. DOI: 10.1038/s41440-023-01291-1.
[20]
COUGHLAN G T, KLINGER H M, BOYLE R, et al. Sex differences in longitudinal Tau-PET in Preclinical Alzheimer Disease: a Meta-Analysis[J]. JAMA Neurol, 2025, 82(4): 364-375. DOI: 10.1001/jamaneurol.2025.0013.
[21]
WU J, ZHANG Q, SUN P, et al. Gray matter microstructural alterations in manganese-exposed welders: A preliminary neuroimaging study[J]. Eur Radiol, 2022, 32(12): 8649-8658. DOI: 10.1007/s00330-023-09895-4.
[22]
WU J, ZHANG Q, MA M, et al. Gray matter morphometric biomarkers for distinguishing manganese-exposed welders from healthy adults revealed by source-based morphometry[J]. Neurotoxicology, 2024, 103: 222-229. DOI: 10.1016/j.neuro.2024.07.002.
[23]
KIM J, KIM B G, HONG Y S, et al. Effects of mixed metal exposure on MRI metrics in basal ganglia[J]. Toxicol Sci, 2024, 202(2): 291-301. DOI: 10.1093/toxsci/kfae117.
[24]
CAI W, YOUNG C B, YUAN R, et al. Subthalamic nucleus–language network connectivity predicts dopaminergic modulation of speech function in Parkinson's disease[J/OL]. Proc Natl Acad Sci U S A, 2024, 121(22): e2316149121 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/38768342/. DOI: 10.1073/pnas.2316149121.
[25]
ZHAO C, HUANG W J, FENG F, et al. Abnormal characterization of dynamic functional connectivity in Alzheimer's disease[J]. Neural Regen Res, 2022, 17(9): 2014-2021. DOI: 10.4103/1673-5374.332161.
[26]
HAN W, SU Y, WANG X, et al. Altered resting-state brain activity in patients with major depression disorder and bipolar disorder: A regional homogeneity analysis[J]. J Affect Disord, 2025, 379: 313-322. DOI: 10.1016/j.jad.2025.03.057.
[27]
HEARNE L J, MILL R D, KEANE B P, et al. Activity flow underlying abnormalities in brain activations and cognition in schizophrenia[J/OL]. Sci Adv, 2021, 7(29): eabf2513 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/34261649/. DOI: 10.1126/sciadv.abf2513
[28]
CHANG Y, SONG H J, LEE J J, et al. Neuroplastic changes within the brains of manganese-exposed welders: recruiting additional neural resources for successful motor performance[J]. Occup Environ Med, 2010, 67(12): 809-815. DOI: 10.1136/oem.2009.052761.
[29]
CHANG Y, LEE J J, SEO J H, et al. Altered working memory process in the manganese-exposed brain[J]. Neuroimage, 2010, 53(4): 1279-1285. DOI: 10.1016/j.neuroimage.2010.07.001.
[30]
SEO J, CHANG Y, JANG K E, et al. Altered executive function in the welders: A functional magnetic resonance imaging study[J]. Neurotoxicol Teratol, 2016, 56: 26-34. DOI: 10.1016/j.ntt.2016.05.003.
[31]
VAN RUITENBEEK P, SANTOS MONTEIRO T, CHALAVI S, et al. Interactions between the aging brain and motor task complexity across the lifespan: balancing brain activity resource demand and supply[J]. Cereb Cortex, 2023, 33(10): 6420-6434. DOI: 10.1093/cercor/bhac514.
[32]
TINKOV A A, PAOLIELLO M M B, MAZILINA A N, et al. Molecular targets of manganese-induced neurotoxicity: a five-year update[J/OL]. Int J Mol Sci, 2021, 22(9): 4646 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/33925013/. DOI: 10.3390/ijms22094646.
[33]
LU Y, GAO L, YANG Y, et al. Protective role of mitophagy on microglia-mediated neuroinflammatory injury through mtDNA-STING signaling in manganese-induced parkinsonism[J/OL]. J Neuroinflammation, 2025, 22(1): 55 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/40022162/. DOI: 10.1186/s12974-025-03396-5.
[34]
LI X, ABIKO K, SHERIFF S, et al. The distribution of major brain metabolites in normal adults: short echo time whole-brain MR spectroscopic imaging findings[J/OL]. Metabolites, 2022, 12(6): 543 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/35736476/. DOI: 10.3390/metabo12060543.
[35]
DYDAK U, JIANG Y M, LONG L L, et al. In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese[J]. Environ Health Perspect, 2011, 119(2): 219-224. DOI: 10.1289/ehp.1002192.
[36]
KHAREL P, SINGHAL N K, MAHENDRAN T, et al. NAT8L mRNA oxidation is linked to neurodegeneration in multiple sclerosis[J/OL]. Cell Chem Bio, 2023, 30(3): 308-320.e5 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36882060/. DOI: 10.1016/j.chembiol.2023.02.007.
[37]
CHANG Y, WOO S T, LEE J J, et al. Neurochemical changes in welders revealed by proton magnetic resonance spectroscopy[J]. Neurotoxicology, 2009, 30(6): 950-957. DOI: 10.1016/j.neuro.2009.07.008.
[38]
PAQUETTE A F, CARBONE B E, VOGEL S, et al. The human milk component myo -inositol promotes neuronal connectivity[J/OL]. Proc Natl Acad Sci U S A, 2023, 120(30): e2221413120 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/37433002/. DOI: 10.1073/pnas.2221413120.
[39]
ALI A B, ISLAM A, CONSTANTI A. The fate of interneurons, GABAA receptor sub‐types and perineuronal nets in Alzheimer's disease[J/OL]. Brain Pathol, 2023, 33(1): e13129 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36409151/. DOI: 10.1111/bpa.13129.
[40]
LONG Z, LI X R, XU J, et al. Thalamic GABA predicts fine motor performance in manganese-exposed smelter workers[J/OL]. PLoS One, 2014, 9(2): e88220 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/24505436/. DOI: 10.1371/journal.pone.0088220.
[41]
MA R E, WARD E J, YEH C L, et al. Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI[J/OL]. Neurotoxicology, 2018, 64: 30-42 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/28873337/. DOI: 10.1016/j.neuro.2017.08.013.
[42]
EDMONDSON D A, MA R E, YEH C L, et al. Reversibility of neuroimaging markers influenced by lifetime occupational manganese exposure[J]. Toxicol Sci, 2019, 172(1): 181-190. DOI: 10.1093/toxsci/kfz174.
[43]
WANG G J. Application and progress of magnetic resonance DTI in central nervous system diseases[J]. China Med Devices, 2024, 39(2): 171-178. DOI: 10.10.3969/j.issn.1674-1633.2024.02.029.
[44]
SUN P, HE Z, CHU E, et al. White matter fractional anisotropy decreases precede hyperintensities in Alzheimer's disease[J/OL]. Cell Rep Med, 2025, 6(6): 102138 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/40398415/. DOI: 10.1016/j.xcrm.2025.102138.
[45]
LEWIS M M, LEE E Y, JO H J, et al. Synergy as a new and sensitive marker of basal ganglia dysfunction: a study of asymptomatic welders[J/OL]. Neurotoxicology, 2016, 56: 76-85 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/27373673/. DOI: 10.1016/j.neuro.2016.06.016.
[46]
WANG Y, JIANG Z, CHU C, et al. Push-pull effects of basal ganglia network in Parkinson's disease inferred by functional MRI[J/OL]. NPJ Parkinsons Dis, 2024, 10(1): 224 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/39567536/. DOI: 10.1038/s41531-024-00835-7.
[47]
CHARY K, MANNINEN E, CLAESSENS J, et al. Diffusion MRI approaches for investigating microstructural complexity in a rat model of traumatic brain injury[J/OL]. Sci Rep, 2023, 13(1): 2219 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36755032/. DOI: 10.1038/s41598-023-29010-3.
[48]
HU Z, SUN P, GEORGE A, et al. Diffusion basis spectrum imaging detects pathological alterations in substantia nigra and white matter tracts with early-stage Parkinson's disease[J]. Eur Radiol, 2023, 33(12): 9109-9119. DOI: 10.1007/s00330-023-09780-0.
[49]
CRISWELL S R, NIELSEN S S, FAUST I M, et al. Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging[J]. Neurotoxicology, 2023, 97: 25-33. DOI: 10.1016/j.neuro.2023.04.013.
[50]
TANG Y, YAN Y, MAO J, et al. The hippocampus associated GABAergic neural network impairment in early-stage of Alzheimer's disease[J/OL]. Ageing Res Rev, 2023, 86: 101865 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36716975/. DOI: 10.1016/j.arr.2023.101865.
[51]
RAO Y L, GANARAJA B, MURLIMANJU B V, et al. Hippocampus and its involvement in Alzheimer's disease: A review[J/OL]. 3 Biotech, 2022, 12(2): 55 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/35116217/. DOI: 10.1007/s13205-022-03123-4.
[52]
LEE E Y, FLYNN M R, DU G, et al. Higher hippocampal mean diffusivity values in asymptomatic welders[J]. Toxicol Sci, 2019, 168(2): 486-496. DOI: 10.1093/toxsci/kfz011.
[53]
YU P, SHEN L, TANG L. Multimodal DTI-ALPS and hippocampal microstructural signatures unveil stage-specific pathways in Alzheimer's disease progression[J/OL]. Front Aging Neurosci, 2025, 17: 1609793 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/40791246/. DOI: 10.3389/fnagi.2025.1609793.
[54]
SAWAMOTO N, DOI D, NAKANISHI E, et al. Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease[J]. Nature, 2025, 641(8064): 971-977. DOI: 10.1038/s41586-025-08700-0.
[55]
MADELUNG C F, LØKKEGAARD A, FUGLSANG S A, et al. High-resolution mapping of substantia nigra in Parkinson's disease using 7 tesla magnetic resonance imaging[J/OL]. NPJ Parkinsons Dis, 2025, 11(1): 113 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/40328786/. DOI: 10.1038/s41531-025-00972-7.
[56]
PAJARILLO E, KIM S, DIGMAN A, et al. The role of microglial LRRK2 kinase in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction[J/OL]. J Biol Chem, 2023, 299(7): 104879 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/37066140/. DOI: 10.1016/j.jbc.2023.104879.
[57]
PAJARILLO E, NYARKO-DANQUAH I, DIGMAN A, et al. Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies[J/OL]. Front Pharmacol, 2022, 13: 1011947 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/36605395/. DOI: 10.3389/fphar.2022.1011947.
[58]
CRISWELL S R, PERLMUTTER J S, HUANG J L, et al. Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders[J]. Occup Environ Med, 2012, 69(6): 437-443. DOI: 10.1136/oemed-2011-100119.
[59]
ZHANG J K, YAKDAN S, KALEEM M I, et al. Spinal cord metrics derived from diffusion MRI: improvement in prognostication in cervical spondylotic myelopathy compared with conventional MRI[J]. J Neurosurg Spine, 2024, 41(5): 639-647. DOI: 10.3171/2024.4.SPINE24107.
[60]
WOOLISCROFT L, SALTER A, ADUSUMILLI G, et al. Diffusion basis spectrum imaging and diffusion tensor imaging predict persistent black hole formation in multiple sclerosis[J/OL]. Mult Scler Relat Disord, 2024, 84: 105494 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/38359694/. DOI: 10.1016/j.msard.2024.105494.
[61]
MAJEWSKI M, PIWKO K, ORDAK M, et al. Magnetic Resonance Imaging and Manganism: A Narrative Review and Laboratory Recommendations[J/OL]. J Clin Med, 2024, 13(10): 2823 [2025-10-30]. https://pubmed.ncbi.nlm.nih.gov/38792364/. DOI: 10.3390/jcm13102823.

PREV Application and progress of nigral imaging in the early diagnosis of Parkinson<sup><sup>,</sup></sup>s disease
NEXT Research progress of MRI radiomics in differential diagnosis and prognostic evaluation of primary central nervous system lymphoma
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn