Magnetic resonance imaging T1 indices of the brain as biomarkers of inhaled manganese exposure

Abstract

Excessive exposure to manganese (Mn) is linked to its accumulation in the brain and adverse neurological effects. Paramagnetic properties of Mn allow the use of magnetic resonance imaging (MRI) techniques to identify it in biological tissues. A critical review was conducted to evaluate whether MRI techniques could be used as a diagnostic tool to detect brain Mn accumulation as a quantitative biomarker of inhaled exposure. A comprehensive search was conducted in MEDLINE, EMBASE, and PubMed to identify potentially relevant studies published prior to 9 May 2022. Two reviewers independently screened identified references using a two-stage process. Of the 6452 unique references identified, 36 articles were retained for data abstraction. Eligible studies used T1-weighted MRI techniques and reported direct or indirect T1 measures to characterize Mn accumulation in the brain. Findings demonstrate that, in subjects exposed to high levels of Mn, deposition in the brain is widespread, accumulating both within and outside the basal ganglia. Available evidence indicates that T1 MRI techniques can be used to distinguish Mn-exposed individuals from unexposed. Additionally, T1 MRI may be useful for semi-quantitative evaluation of inhaled Mn exposure, particularly when interpreted along with other exposure indices. T1 MRI measures appear to have a nonlinear relationship to Mn exposure duration, with R1 signal only increasing after critical thresholds. The strength of the association varied depending on the regions of interest imaged and the method of exposure measurement. Overall, available evidence suggests potential for future clinical and risk assessment applications of MRI as a diagnostic tool.

Keywords:

• Manganese
• biomarker
• magnetic resonance imaging
• neuroimaging
• occupational exposure
• pallidal index
• T1 signal intensity
• T1 relaxation rate
• R1
• review

Acknowledgements

The authors would like to thank Dr. Athena Keene from Afton Chemical, a member company of the International Manganese Institute (IMnI), for helpful comments on preliminary drafts of this article; although Dr. Keene also serves as the Afton Chemical representative on the IMnI Health, Safety and Environment Committee, her comments were provided as an independent scientist with expertise in manganese toxicity. The authors gratefully acknowledge the comments of the three external reviewers selected by the editor and anonymous to the authors. As a result of their comments, we limited the scope of the paper and made a number of changes that improved the original draft of this paper.

Declaration of interest

This work was conducted under a research contract to review the recent scientific literature on manganese biomarkers between the International Manganese Institute (IMnI, www.manganese.org), an industry association representing the international manganese industry, and Risk Sciences International (RSI, www.risksciences.com), a Canadian company established in 2006 in partnership with the University of Ottawa. Additional financial support was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC, www.nserc.ca) to D. Krewski, who holds the NSERC Chair in Risk Science at the University of Ottawa. N. Farhat, D. Krewski, N. Karyakina, D. Mattison, F. Momoli, S. Ramoju and N. Shilnikova were compensated by RSI for their contributions to the review. N. Farhat was also supported in part by postdoctoral fellowships from the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa and from Carleton University under the Mitacs Accelerate program (www.mitacs.ca), a peer-reviewed university-industry partnership program with RSI as the industrial partner. B. Cline contributed to this article as a senior scientist at IMnI. The authors, whose affiliations are shown on the title page, had sole responsibility for preparation of this paper, including determining the strategy for reviewing the scientific literature summarized in this article, synthesizing the findings, and drawing conclusions. Although Dr. Cline briefed the IMnI Health, Safety and Environment Committee on the results of the present review, the Committee did not provide input to this work. None of the authors have appeared before regulatory agencies on behalf of the sponsors or appeared as experts in legal proceedings concerning matters reviewed in this paper. The scientific opinions and conclusions expressed in the paper are exclusively those of the authors and are independent of the sources of financial support.

Supplemental material

Supplemental data for this article is available online at https://doi.org/10.1080/10408444.2022.2128719.