Development and Clinical Trial of Novel Field-cycling DNP-MRI for Free Radical Imaging

Probe-free imaging of redox intermediate radicals must become a crucial method and diagnosis. DNP (dynamic nuclear polarization)-MRI, a new imaging method for free radical (Lurie, et al. 1988), utilizes Overhauser effect that nuclear spin close to free radical is 300 times higher polarized than that of natural state by inducing the electron spin resonance of free radical. The advantage of DNP-MRI is the high sensitivity and resolution, theoretically similar to that in MRI. We installed the custom-made DNP-MRI from Philips and succeeded in the imaging of redox status in disease models and the spectroscopic imaging of redox intermediate radicals from FMN, FAD, CoQ10, and vitamin E. It has, however, the large disadvantage of poor sensitivity and heating by ESR irradiation, because of its low magnetic field (15mT MRI). Here, we developed the novel field-cycling DNP-MRI system for clinical trial, in which free radicals are visualized with 0.3T MRI as the polarized proton by irradiating the free radicals at 5mT, and demonstrated the clear images of the phantoms containing FAD radical with less than 0.5 mm of the spatial resolution. The image of FAD radical placed under healthy volunteer hand was superimposed on the anatomical MRI image. The intrinsic radical, melanin, could be also visualized. Overhauser effect is known to be occurred in the various kind of free radicals, metal-complex, etc., and also in lipid membranes. The newly developed DNP-MRI could demonstrate the functional/metabolic imaging by visualizing intrinsic radials, redox intermediates and/or metal enzymes in disease models and also in patients.