In vivo analysis of redox status in organs - from bench to bedside

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, and hydrogen peroxide play an important role in the maintenance of life. However, production of excessive ROS and/or deficiency of the antioxidant system lead to oxidative stress and cause a variety of diseases. In the present study, we used electron spin resonance (ESR) to detect ROS in vivo to clarify its roles in redox dynamics and organ damage. However, the limited permeability of microwaves and low anatomic resolution of ESR equipment made it difficult to apply clinically. Nitroxide is widely used as a sensitive redox sensor for in vivo ESR analysis. The unpaired electrons of nitroxide are known to cause the T1 relaxation time-shortening effect of water protons, creating magnetic resonance imaging (MRI) effects. The remarkable development of MRI has facilitated the spatiotemporal analysis of nitroxide, which was previously impossible. In a rat model, we have been able to image and analyze the process of nitroxide reduction using MRI. MRI using nitroxide as a contrast medium is considered to be clinically applicable for evaluation of organ redox, imaging of ROS (which cause organ damage), and evaluation of therapeutic effects. In this review, we describe current advances in the analysis of in vivo redox capacity in animals using ESR and MRI equipment. We consider that redox evaluation using MRI can contribute to advances in clinical medicine.