Mapping of redox status in a brain-disease mouse model by three-dimensional EPR imaging

Electron paramagnetic resonance imaging using nitroxides is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. Typically, however, data acquisition times have been too slow to obtain a sufficient number of projections for three-dimensional images, when using continuous wave-electron paramagnetic resonance imager in small rodents, using nitroxides with comparatively short T(2) and a half-life values. Because of improvements in imagers that enable rapid data-acquisition, the feasibility of three-dimensional electron paramagnetic resonance imaging with good quality in mice was tested with nitroxides. Three-dimensional images of mice were obtained at an interval of 15 sec under field scanning of 0.3 sec and with 46 projections in the case of strong electron paramagnetic resonance signals. Three-dimensional electron paramagnetic resonance images of a blood brain barrier-permeable nitroxide, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, in the mouse head clearly showed that 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl was distributed within brain tissues, and this was confirmed by MRI observations. Based on the pharmacokinetics of nitroxides in mice, half-life mapping was demonstrated in an ischemia-reperfusion model mouse brain. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in mouse head under oxidative stress by the improved continuous wave-electron paramagnetic resonance imager noninvasively.