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

Manganese (Mn) is a neurotoxicant that, due to its paramagnetic property, also functions as a magnetic resonance imaging (MRI) T1 contrast agent. Previous studies in Mn toxicity have shown that Mn accumulates in the brain, which may lead to parkinsonian symptoms. In this article, we trained support vector machines (SVM) using whole-brain R1 (R1 = 1/T1) maps from 57 welders and 32 controls to classify subjects based on their air Mn concentration ([Mn]Air), Mn brain accumulation (ExMnBrain), gross motor dysfunction (UPDRS), thalamic GABA concentration (GABAThal), and total years welding. R1 was highly predictive of [Mn]Air above a threshold of 0.20 mg/m3 with an accuracy of 88.8% and recall of 88.9%. R1 was also predictive of subjects with GABAThal having less than or equal to 2.6 mM with an accuracy of 82% and recall of 78.9%. Finally, we used an SVM to predict age as a method of verifying that the results could be attributed to Mn exposure. We found that R1 was predictive of age below 48 years of age with accuracies ranging between 75 and 82% with recall between 94.7% and 76.9% but was not predictive above 48 years of age. Together, this suggests that lower levels of exposure (< 0.20 mg/m3 and < 18 years of welding on the job) do not produce discernable signatures, whereas higher air exposures and subjects with more total years welding produce signatures in the brain that are readily identifiable using SVM

Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI)

The ability of manganese ions (Mn ) to enter cells through calcium ion (Ca ) channels has been used for depolarization dependent brain functional imaging with manganese-enhanced MRI (MEMRI). The purpose of this study was to quantify changes to Mn uptake in rat brain using a dynamic manganese-enhanced MRI (dMEMRI) scanning protocol with the Patlak and Logan graphical analysis methods. The graphical analysis was based on a three-compartment model describing the tissue and plasma concentration of Mn. Mn uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (V ) and the unidirectional influx constant of Mn from plasma to tissue (K ). The measurements were performed on the anterior (APit) and posterior (PPit) parts of the pituitary gland, a region with an incomplete blood brain barrier. Modulation of Ca channel activity was performed by administration of the stimulant glutamate and the inhibitor verapamil. It was found that the APit and PPit showed different Mn uptake characteristics. While the influx of Mn into the PPit was reversible, Mn was found to be irreversibly trapped in the APit during the course of the experiment. In the PPit, an increase of Mn uptake led to an increase in V (from 2.8±0.3ml/cm to 4.6±1.2ml/cm ) while a decrease of Mn uptake corresponded to a decrease in V (from 2.8±0.3ml/cm to 1.4±0.3ml/cm ). In the APit, an increase of Mn uptake led to an increase in K (from 0.034±0.009min to 0.049±0.012min ) while a decrease of Mn uptake corresponded to a decrease in K (from 0.034±0.009min to 0.019±0.003min ). This work demonstrates that graphical analysis applied to dMEMRI data can quantitatively measure changes to Mn uptake following modulation of neural activity

Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI)

The ability of manganese ions (Mn2+) to enter cells through calcium ion (Ca2+) channels has been used fordepolarization dependent brain functional imaging with manganese-enhanced MRI (MEMRI). The purpose ofthis study was to quantify changes to Mn2+ uptake in rat brain using a dynamic manganese-enhanced MRI(dMEMRI) scanning protocol with the Patlak and Logan graphical analysis methods. The graphical analysiswas based on a three-compartment model describing the tissue and plasma concentration of Mn. Mn2+uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (VT) and theunidirectional influx constant of Mn2+ from plasma to tissue (Ki). The measurements were performed onthe anterior (APit) and posterior (PPit) parts of the pituitary gland, a region with an incomplete bloodbrain barrier. Modulation of Ca2+ channel activity was performed by administration of the stimulant glutamateand the inhibitor verapamil. It was found that the APit and PPit showed different Mn2+ uptake characteristics.While the influx of Mn2+ into the PPit was reversible, Mn2+ was found to be irreversibly trapped inthe APit during the course of the experiment. In the PPit, an increase of Mn2+ uptake led to an increase inVT (from 2.8+-0.3 ml/cm3 to 4.6+-1.2 ml/cm3) while a decrease of Mn2+ uptake corresponded to a decreasein VT (from 2.8+-0.3 ml/cm3 to 1.4+-0.3 ml/cm3). In the APit, an increase of Mn2+ uptake led to an increasein Ki (from 0.034+-0.009 min&#8722;1 to 0.049+-0.012 min&#8722;1) while a decrease of Mn2+ uptake corresponded to adecrease in Ki (from 0.034+-0.009 min&#8722;1 to 0.019+-0.003 min&#8722;1). This work demonstrates that graphicalanalysis applied to dMEMRI data can quantitatively measure changes to Mn2+ uptake following modulationof neural activity