P125 Whole-brain r1 mapping of manganese in welders - visualisation of increased mn levels in the brain

Abstract

ObjectiveAlthough Manganese (Mn) is essential for brain metabolism, excessive exposure to Mn in occupational settings such as in welding can lead to cognitive and motor deficits. To further study the relation between exposure, brain function and brain Mn accumulation, we developed a new 3D whole-brain MRI approach to visualise the distribution of excessive brain Mn in welders.MethodsWe used a voxel-by-voxel analysis of whole-brain R1 relaxation rate mapping as an indicator of Mn deposition in deep brain structures and the cerebral cortex in 30 welders (mean air Mn = 0.18 ± 0.16 mg/m³) and 20 non-exposed controls from the same factory.ResultsA wide-spread accumulation of Mn throughout the brain was discerned in our study. Outside the basal ganglia, significantly higher R1 values, indicative of higher Mn concentration, were found in the inferior parietal cortex and insula in welders (all p < 0.005), consistent with deficits in motor control and emotional instability found in Mn-exposed welders. Mn deposition in the supplementary motor cortex, primary motor cortex and somatosensory cortex point toward an effect on the motor regulation network. Elevated Mn concentrations (p < 0.005) were also found in superior primary visual cortex, secondary visual cortex and inferior temporal lobe, all belonging to visual association areas. An especially significant difference was found in the precuneus (p < 0.005), an area engaged in visuospatial function. Whole-brain voxel-by-voxel correlation maps (p < 0.005) show that R1 in motor cortex and basal ganglia correlates with Mn exposure over the past 3 months prior to the MRI scan.ConclusionsThese findings suggest that Mn exposure leads to increased Mn accumulation in the motor and visuospatial networks, which may be related to reported impaired neurobehavioral effects.

Diagnosis of manganism and manganese neurotoxicity: A workshop report

“…Recent studies from welders have provided evidence that the accumulation of Mn in the human brain is not restricted to the basal ganglia. Significant accumulations have been reported in the frontal cortex, frontal white matter and the hippocampus ( 33 , 34 ) and whole-brain analysis has revealed elevated Mn particularly along white matter tracts ( 35 ). Furthermore, uptake and clearance vary according to the region of the brain ( 33 ).…”

“…MRI research on typically exposed welders in the USA revealed that Mn deposition in the brains of welders, measured by the MRI longitudinal relaxation rate R1, is widespread and follows white matter tracts, likely contributing to the distribution of excess Mn throughout the brain ( 35 ).…”

Whole-brain R1 predicts manganese exposure and biological effects in welders

“…Mn can also travel anterograde along axons, a feature that has been utilized to great effect for neuronal tracing using Mn-enhanced MRI, or MEMRI. Similarly, we can use the MRI relaxation rate R1, which is proportional to Mn in the region, to measure Mn uptake, accumulation, and dispersion in the brain (Yeh et al, 2016). This has been done in studies involving rats (Lehallier et al, 2012), monkeys (Dorman, 2006;Park et al, 2007;Shinotoh et al, 1995), and humans (Edmondson et al, 2019;Lee et al, 2018Lee et al, , 2015Lewis et al, 2016;Long et al, 2015;Ma et al, 2018), but understanding the relationship between exposure and uptake is still ongoing.…”