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Updated: Jul 31, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis
Susan R Criswell1, Susan Searles Nielsen2, Irene M Faust1
1Department of Neurology, Barrow Neurological Institute, 2910 N. 3rd Ave, Phoenix, AZ 85013, USA; Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
Objective:
To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure.
Methods:
We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the basal ganglia. We used voxelwise general linear modeling and linear regression to evaluate the association between cumulative Mn exposure, WM or basal ganglia DBSI metrics, and UPDRS3 scores, while adjusting for age.
Results:
Mn-exposed welders had higher DBSI-derived restricted fraction (DBSI-RF), higher DBSI-derived nonrestricted fraction (DBSI-NRF), and lower DBSI-derived fiber fraction (DBSI-FF) in multiple WM tracts (all p < 0.05) in comparison to less-exposed workers and non-exposed participants. Basal ganglia ROI analyses revealed higher average caudate DBSI-NRF and DBSI-derived radial diffusion (DBSI-RD) values in Mn-exposed welders relative to non-exposed participants (p < 0.05). Caudate DBSI-NRF was also associated with greater cumulative Mn exposure and higher UPRDS3 scores.
Conclusions:
Mn-exposed welders demonstrate greater DBSI-derived indicators of neuroinflammation-related cellularity (DBSI-RF), greater extracellular edema (DBSI-NRF), and lower apparent axonal density (DBSI-FF) in multiple WM tracts suggesting a neuroinflammatory component in the pathophysiology of Mn neurotoxicity. Caudate DBSI-NRF was positively associated with both cumulative Mn exposure and clinical parkinsonism, indicating a possible dose-dependent effect on extracellular edema with associated motor effects.
Insights
Occupational manganese (Mn) exposure in welders is linked to neuroinflammation and white matter (WM) damage, indicated by Diffusion Basis Spectrum Imaging (DBSI) metrics. Higher Mn exposure correlates with parkinsonism symptoms, suggesting a dose-dependent effect.
Area of Science:
- Neuroscience
- Occupational Health
- Radiology
Background:
- Occupational manganese (Mn) exposure is a known neurotoxicant.
- Manganese neurotoxicity can lead to parkinsonism.
- The in-vivo effects of Mn exposure on white matter (WM) integrity and neuroinflammation require further investigation.
Purpose of the Study:
- To evaluate in-vivo neuroinflammation and WM microstructural integrity in individuals with occupational Mn exposure.
- To explore the relationship between cumulative Mn exposure, neuroimaging findings, and clinical motor symptoms.
Main Methods:
- Diffusion Basis Spectrum Imaging (DBSI) was used to assess brain inflammation and WM integrity in Mn-exposed welders, Mn-exposed workers, and non-exposed controls.
- Cumulative Mn exposure was estimated, and Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were collected.
- Tract-based Spatial Statistics and region of interest (ROI) analyses were performed, with voxelwise general linear modeling and regression used to assess associations.
Main Results:
- Mn-exposed welders showed higher DBSI-derived restricted fraction (DBSI-RF) and nonrestricted fraction (DBSI-NRF), and lower fiber fraction (DBSI-FF) in WM tracts compared to controls.
- Increased DBSI-NRF and radial diffusion (DBSI-RD) were observed in the caudate nucleus of Mn-exposed welders.
- Caudate DBSI-NRF correlated with cumulative Mn exposure and higher UPDRS3 scores.
Conclusions:
- Occupational Mn exposure in welders is associated with neuroimaging indicators of neuroinflammation and axonal damage in WM.
- Increased extracellular edema in the caudate nucleus (DBSI-NRF) is linked to cumulative Mn exposure and motor deficits.
- These findings suggest a neuroinflammatory component in Mn neurotoxicity with potential dose-dependent motor effects.
