[Novel redox molecular imaging "ReMI" with dual magnetic resonance]

Free radicals, reactive oxygen species (ROS), and redox status are known to be involved in cell signaling, proteomics, etc. in homeostasis and oxidative disease. Electron spin resonance (ESR) spectroscopy is a very sensitive and selective technique for detecting free radicals, and we have developed an in vivo ESR spectroscopy/imaging system combined with a nitroxyl probe for noninvasive assessment of free radical reactions in various disease models such as diabetes, cancer, liver/lung damage, gastric lesions, brain injury, etc. The systematic measurement with probes having different degrees of membrane permeability make it possible to clarify the location of free radical generation in blood vessels, cell membranes, and the cytoplasm. Our findings strongly indicate the great advantage of the in vivo ESR spectroscopy/imaging/nitroxyl probe technique in biomedical sciences. However, the spatial resolution of the ESR spectroscopy imaging system is insufficient due to the short T₂ of probes. Proton magnetic resonance imaging (MRI) has significant clinical utility in the diagnosis of disease. Dynamic nuclear polarization (DNP)-MRI yields highly resolved images of free radical distribution in small animals by enhancing the water proton signal intensity via the Overhauser effect. We developed a new sequence for DNP-MRI and succeeded in obtaining simultaneous dual images using radicals labeled with ¹⁴N and ¹⁵N nuclei. This technique can visualize individual redox processes and the individual redox status of inner and/or outer cells in a dose-dependent manner. More recently, we have developed a novel DNP-MRI scanner and enables the use of DNP-MRI in different disease models.