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Principal Investigator: Humberto Monsivais
Organization: PURDUE UNIVERSITY
Fiscal Year: 2024
Award: $27,407
Funding agency: National Institute of Environmental Health Sciences
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.
Terms: <AD dementia><Address><Adverse effects><Affect><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Autoregulation><Body Tissues><Brain><Brain Mapping><Brain Nervous System><Brain imaging><Brain region><Chromium><Chronic><Clinical><Cognition><Cognitive><Cognitive deficits><Cr element><Data Set><Degenerative Neurologic Disorders><Deposit><Deposition><Development><Diagnosis><Disease Progression><Early Diagnosis><Elements><Encephalon><Ensure><Environment><Exclusion><Exposure to><Fe element><Gadolinium><Gd element><Goals><Health><Hepatic Cirrhosis><History><Homeostasis><Human><Image><Imaging Device><Imaging Instrument><Imaging Tool><Imaging technology><Individual><Industry><Inhalation Exposure><Intravenous Feeding><Intravenous Hyperalimentation><Ions><Iron><Knowledge><Knowledge acquisition><Liver Cirrhosis><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Manganese><Manganese induced parkinsonism><Manganism><Maps><Measurement><Measures><Mediation><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metal exposure><Metals><Methods><Mn element><Mn-induced Parkinsonism><Modeling><Modern Man><Monitor><Moods><Motor><NMR Imaging><NMR Tomography><Negotiating><Negotiation><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic><Neurologic Degenerative Conditions><Neurologic Dysfunctions><Neurological><Neuropsychologies><Neuropsychology><Nuclear Magnetic Resonance Imaging><Outcome><Oxidative Stress><Paralysis Agitans><Parenteral Feedings><Parenteral Nutrition><Parkinson><Parkinson Disease><Patients><Physiological Homeostasis><Policies><Predisposition><Primary Parkinsonism><Primary Senile Degenerative Dementia><Process><Recording of previous events><Research><Risk><Role><Science><Screening procedure><Spatial Distribution><Statistical Methods><Structure><Susceptibility><Symptoms><Techniques><Technology><Technology Assessment><Testing><Time><Tissues><Toxic effect><Toxicities><Trace metal><Visualization><Visualization software><Welding><Zeugmatography><brain visualization><career><clinical imaging><cognitive defects><cognitive performance><contrast enhanced><contrast imaging><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><developmental><early detection><exposure to metal><farmer><healthy volunteer><histories><human data><hyperalimentation><hyperalimentation therapy><image-based method><imaging><imaging in vivo><imaging method><imaging modality><in vivo><in vivo imaging><innovate><innovation><innovative><interest><motor deficit><motor disease><motor disorder><motor dysfunction><nerve cell death><nerve cell loss><neural imaging><neuro-imaging><neurobehavioral><neurochemical><neurochemistry><neurodegenerative illness><neuroimaging><neurological dysfunction><neurological imaging><neuron cell death><neuron cell loss><neuron death><neuron loss><neuron toxicity><neuronal cell death><neuronal cell loss><neuronal death><neuronal loss><neuronal toxicity><neuropsychologic><neurotoxic><neurotoxicity><novel><particle><prevent><preventing><primary degenerative dementia><psychologic><psychological><response to therapy><response to treatment><screening tools><senile dementia of the Alzheimer type><social role><statistic methods><therapeutic response><therapy response><tool><toxic metal><toxicant><translational impact><treatment response><treatment responsiveness><uptake><visualization tool>