Brain Redox Imaging Using In Vivo Electron Paramagnetic Resonance Imaging and Nitroxide Imaging Probes

Hirotada Fujii,Miho Emoto,Hideo Sato-Akaba

doi:10.3390/magnetochemistry5010011

Hirotada Fujii, Miho Emoto + Show 1 more

Open Access

https://doi.org/10.3390/magnetochemistry5010011

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Abstract

Reactive oxygen species (ROS) are produced by living organisms as a result of normal cellular metabolism. Under normal physiological conditions, oxidative damage is prevented by the regulation of ROS by the antioxidant network. However, increased ROS and decreased antioxidant defense may contribute to many brain disorders, such as stroke, Parkinson’s disease, and Alzheimer’s disease. Noninvasive assessment of brain redox status is necessary for monitoring the disease state and the oxidative damage. Continuous-wave electron paramagnetic resonance (CW-EPR) imaging using redox-sensitive imaging probes, such as nitroxides, is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. For conventional CW-EPR imaging, however, poor signal-to-noise ratio, low acquisition efficiency, and lack of anatomic visualization limit its ability to achieve three-dimensional redox mapping of small rodent brains. In this review, we discuss the instrumentation and coregistration of EPR images to anatomical images and appropriate nitroxide imaging probes, all of which are needed for a sophisticated in vivo EPR imager for all rodents. Using new EPR imaging systems, site-specific distribution and kinetics of nitroxide imaging probes in rodent brains can be obtained more accurately, compared to previous EPR imaging systems. We also describe the redox imaging studies of animal models of brain disease using newly developed EPR imaging.

Highlights

Reactive oxygen species (ROS) are recognized to play important roles in both physiological and pathological processes [1,2]
We described redox imaging studies of animal models of brain disease using the newly developed Electron paramagnetic resonance (EPR) imaging system
Brain redox imaging was first demonstrated in a mouse model of ischemia–reperfusion by 3D EPR imaging, and the obtained multislice redox mapping visualized a heterogeneous distribution of the reduction rate constant of nitroxides in the infarcted hemisphere of examined mouse heads [25]

Summary

Introduction

Reactive oxygen species (ROS) are recognized to play important roles in both physiological and pathological processes [1,2]. The only chemical drawback of nitroxides is their susceptibility to reduction to the corresponding diamagnetic hydroxylamine, resulting in loss of paramagnetism [15,16] Their properties allowing them to undergo bioreduction can provide useful information pertaining to biochemical reactions in organisms. As a result, monitoring the rate of transformation of nitroxides to the corresponding diamagnetic species by EPR imaging can provide an in vivo assessment of redox status in animal disease models. Such redox mapping based on redox-sensitive paramagnetic spin probes has been carried out by EPR imaging. We described redox imaging studies of animal models of brain disease using the newly developed EPR imaging system

In Vivo EPR Imaging Instrument for Small Animals

Three-Dimensional EPR Imaging of the Mouse Head

Conclusions