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

Christoph Leuze, Yuichi Kimura, Jeff Kershaw, Sayaka Shibata, Tsuneo Saga, Kai-Hsiang Chuang, Ichiro Shimoyama, Ichio Aoki

Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.

NeuroImage 2012 Mar

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The ability of manganese ions (Mn(2+)) to enter cells through calcium ion (Ca(2+)) 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(2+) 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(2+) uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (V(T)) and the unidirectional influx constant of Mn(2+) from plasma to tissue (K(i)). 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(2+) 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(2+) uptake characteristics. While the influx of Mn(2+) into the PPit was reversible, Mn(2+) was found to be irreversibly trapped in the APit during the course of the experiment. In the PPit, an increase of Mn(2+) uptake led to an increase in V(T) (from 2.8±0.3 ml/cm(3) to 4.6±1.2 ml/cm(3)) while a decrease of Mn(2+) uptake corresponded to a decrease in V(T) (from 2.8±0.3 ml/cm(3) to 1.4±0.3 ml/cm(3)). In the APit, an increase of Mn(2+) uptake led to an increase in K(i) (from 0.034±0.009 min(-1) to 0.049±0.012 min(-1)) while a decrease of Mn(2+) uptake corresponded to a decrease in K(i) (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 Mn(2+) uptake following modulation of neural activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Christoph Leuze, Yuichi Kimura, Jeff Kershaw, Sayaka Shibata, Tsuneo Saga, Kai-Hsiang Chuang, Ichiro Shimoyama, Ichio Aoki. Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI). NeuroImage. 2012 Mar;60(1):392-9