Imaging Biomarkers of Mn Associated Neurotoxicity in Shipyard Workers

Introduction:  Welding exposes workers to manganese (Mn) fumes, but the impact on the dopaminergic system in the brain remains controversial.   PET imaging with 6-[18F]fluoro-L-DOPA (FDOPA) is a non-invasive measure of nigrostriatal dopaminergic neuron integrity. Functional connectivity and diffusion weighted MRI of the brain provide a non-invasive method of assessing the effects of Mn on basal ganglia connectivity and neurotoxic brain injury.    

Methods:  We imaged 20 asymptomatic welders exposed to Mn fumes, and 20 normal controls using FDOPA PET and structural/diffusion/resting state functional connectivity (rs-fc) MRI. The uptake of FDOPA, Ki, T1-weighted intensity indices, apparent diffusion coefficients (ADC) were generated for each basal ganglia region of interest.   The rs-fcMRI group comparisons were created using random effects analysis of individual Z-transformed correlation images with Monte Carlo randomization applied to correct for multiple comparisons.  

Results:  Caudate Kis were significantly lower in asymptomatic welders (0.0098 + 0.0013 min-1) compared to control subjects (0.0111 + 0.0012 min-1, p = 0.002). The regional pattern of FDOPA uptake in welders was most affected in the caudate > anterior putamen > posterior putamen.  T1-Intensity indices for all regions were significantly higher in welders than controls. Welder diffusion ADC values were significantly lower than controls for globus pallidus and anterior putamen.  Welders demonstrated significantly greater coupling between the right putamen and the right superior and middle temporal lobes and decreased coupling between the right caudate and cerebellum on rs-fcMRI imaging.  

Discussion:  These studies demonstrate that Mn exposed welders have dysfunction in the nigrostriatal dopamine system, DW abnormalities in the globus pallidus and anterior putamen, and altered functional connectivity suggesting neurotoxicity in these regions.