Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging

Authors

Susan R. Criswell, Department 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. Electronic address: susan.criswell@barrowneuro.org.Follow
Susan Searles Nielsen, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
Irene M. Faust, Department 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.
Joshua S. Shimony, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, USA.
Robert L. White, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA; John Cochran Division, St. Louis VA Medical Center, Neurology Section, 915 N. Grand Blvd, St. Louis, MO 63106, USA.
Jason Lenox-Krug, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
Brad A. Racette, Department 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; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 Andrews Rd, Parktown 2193, South Africa.Follow

Document Type

Article

Abstract

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.

Publication Date

4-29-2023

Publication Title

Neurotoxicology

E-ISSN

1872-9711

Volume

97

First Page

25

Last Page

33

PubMed ID

37127223

Digital Object Identifier (DOI)

10.1016/j.neuro.2023.04.013

Recommended Citation

Criswell, Susan R.; Nielsen, Susan Searles; Faust, Irene M.; Shimony, Joshua S.; White, Robert L.; Lenox-Krug, Jason; and Racette, Brad A., "Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging" (2023). Neurology. 1484.
https://scholar.barrowneuro.org/neurology/1484