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Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Lewis, Mechelle M.; Fry, Rebecca C.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Smeester, Lisa; & Kong, Lan, et al. (2015). T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of Welders with Low-Level Exposure. Toxicological Sciences, 146(2), 281-289. PMCID: PMC4607746


Objectives: Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) vs. frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: 1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and 2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1).
Methods: Thirty five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs).
Results: PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a non-linear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either to controls or to welders with lower exposure.
Discussion: Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the non-linear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies.


Reference Type

Journal Article

Year Published


Journal Title

Toxicological Sciences


Lee, Eun-Young
Flynn, Michael R.
Du, Guangwei
Lewis, Mechelle M.
Fry, Rebecca C.
Herring, Amy H.
Van Buren, Eric
Van Buren, Scott
Smeester, Lisa
Kong, Lan
Yang, Qing
Mailman, Richard B.
Huang, Xuemei