Development of 20 cm sample bore size dynamic nuclear polarization (DNP)-MRI at 16 mT and redox metabolic imaging of acute hepatitis rat model

Abstract

Tissue redox metabolism is involved in various diseases, and an understanding of the spatio-temporal dynamics of tissue redox metabolism could be useful for diagnosis of progression and treatment. In in vivo dynamic nuclear polarization (DNP)-MRI, electron paramagnetic resonance (EPR) irradiation at the resonance frequency of nitroxyl radicals administered as a redox probe for induction of DNP, increases the intensity of MRI signals. For electron spin, it is necessary to apply a resonant frequency 658 times higher than that required for nuclear spin because of the higher magnetic moment of unpaired electrons. Previous studies using a disease model of small animals and in vivo DNP-MRI have revealed that an abnormal redox status is involved in many diseases, and that it could be used to visualize the dynamics of alterations in redox metabolism. To use the current methods in clinical practice, the development of a prototype DNP-MRI system for preclinical examinations of large animals is indispensable for clarifying the problems peculiar to the increase in size of the DNP-MRI device. Therefore, we developed a in vivo DNP-MRI system with a sample bore size of 20 cm and a 16-mT magnetic field using a U-shaped permanent magnet. Because the NMR frequency is very low, we adopted a digital radiofrequency transmission/reception system with excellent filter and dynamic range characteristics and equipped with a digital eddy current compensation system to suppress large eddy currents. The pulse sequence was based on the fast spin-echo sequence, which was improved for low frequency and large-eddy current equipment. The in vivo DNP-MRI system developed was used to non-invasively image the redox reaction of a carbamoyl-PROXYL probe in the livers of large rats weighing 800 g. Furthermore, DNP-MRI analysis was able to capture significant changes in redox metabolism in hepatitis-model rats.