Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI).
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.
Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
Christoph
C
Leuze
Yuichi
Y
Kimura
Jeff
J
Kershaw
Sayaka
S
Shibata
Tsuneo
T
Saga
Kai-Hsiang
KH
Chuang
Ichiro
I
Shimoyama
Ichio
I
Aoki
D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D015220:Calcium Channels / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000378:metabolism*; D010902:Pituitary Gland / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D008345:Manganese