Thursday, November 21, 2024
11/21/2024
Abstract: The welding industry in the US exposes over 600,000 workers to toxic welding fumes, including the neurotoxic metal manganese (Mn), which can cause manganism, a condition with psychological, cognitive, and motor deficits similar to Parkinson's disease. While effects of inhalation exposure to Mn and accumulation of brain Mn in welders have been studied widely, most (if not all) studies tend to exclude the contributions of iron (Fe), which competes with Mn for the same metal transporter for uptake into the brain. Information about the effects of excess exposure to both, Mn and Fe, is still scarce and unclear. Some studies indicate that excess of both metals could enhance metal-associated toxicity, while other evidence suggests that co-exposure to Mn and Fe appears to counteract oxidative stress from each other. Recent advances in magnetic resonance imaging (MRI) allow for the separate visualization of manganese and iron deposition in the human brain. More specifically, multiparametric quantitative MRI (qMRI) techniques surpass the limitations of conventional imaging by determining tissue parameters quantitatively. The advantage of this quantitative approach is the ability to better disentangle Mn and Fe depositions and identify how regions of high Mn or Fe deposition may correlate with specific symptoms of manganese neurotoxicity. To address the current knowledge gap on the relationship between high chronic exposure to Mn and Fe, and the onset of neurologic dysfunction, this research aims to develop methods that combine qMRI and network science to better understand the brain’s mediation mechanism to excess metal accumulation and distribution, and neuropsychological changes associated with these processes. This will ultimately enable non-invasive measurements to support early diagnoses, monitor metal- related disease progression, and assess therapeutic responses. Our long-term goal is to use this newly acquired knowledge to establish feasible clinical screening tools to diagnose and prevent adverse health effects due to exposure to toxicants in the environment. To test the central hypothesis that quantitative MRI (qMRI) can quantify changes in Mn and Fe deposition separately, the specific aims of the proposed study are: 1) To visualize and quantify subject-specific excess brain Mn and Fe deposition using qMRI imaging and 2) To characterize the brain’s mediation mechanism to excess metal accumulation and its association with neuropsychological outcomes. Our project will have a significant translational impact by expanding the scope of innovative imaging technology to other fields interested in assessing the spatial and temporal distribution of MRI contrast-enhancing toxic metals such as chromium and gadolinium. Furthermore, these findings may guide policies on establishing safe exposure limits for airborne particles to ensure safe and healthy working conditions for welders.
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