Quantitative measurement of changes in calcium channel activityin vivoutilizing dynamic manganese-enhanced MRI (dMEMRI)

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Abstract

The ability of manganese ions (Mn2+) to enter cells through calcium ion (Ca2+) 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 Mn2+ 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. Mn2+ uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (VT) and the unidirectional influx constant of Mn2+ from plasma to tissue (Ki). 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 Ca2+ channel activity was performed by administration of the stimulant glutamate and 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 in the APit during the course of the experiment. In the PPit, an increase of Mn2+ uptake led to an increase in VT (from 2.8 ± 0.3 ml/cm3 to 4.6 ± 1.2 ml/cm3) while a decrease of Mn2+ uptake corresponded to a decrease in 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 increase in Ki (from 0.034 ± 0.009 min− 1 to 0.049 ± 0.012 min− 1) while a decrease of Mn2+ uptake corresponded to a decrease in Ki (from 0.034 ± 0.009 min− 1 to 0.019 ± 0.003 min− 1). This work demonstrates that graphical analysis applied to dMEMRI data can quantitatively measure changes to Mn2+ uptake following modulation of neural activity.

Highlights

□ Present a quantitative functional brain mapping method using manganese-enhanced MRI. □ Dynamic T1 mapping and graphical analysis used to evaluate Ca2 + channel activity. □ Distribution volume (VT) in the posterior pituitary was estimated with a Logan plot. □ The influx constant (Ki) in the anterior pituitary was estimated with a Patlak plot. □ This is the first report of changes to VT and Ki after Ca2 + channel modulation.

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