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

Hinako Eto; Tatuya Naganuma; Motonao Nakao; Masaharu Murata; Abdelazim Elsayed Elhelaly; Yoshifumi Noda; Hiroki Kato; Masayuki Matsuo; Tomohiko Akahoshi; Makoto Hashizume; Fuminori Hyodo

doi:10.1016/j.freeradbiomed.2021.04.017

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

Free Radic Biol Med. 2021 Jun:169:149-157. doi: 10.1016/j.freeradbiomed.2021.04.017. Epub 2021 Apr 15.

Authors

Affiliations

¹ Center for Advanced Medical Open Innovation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
² Japan Redox limited, 4-29-49-805 Chiyo Hakata-ku, Fukuoka, Japan.
³ Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
⁴ Center for Advanced Medical Open Innovation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Advanced Medical Medicine, Disaster and Emergency Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
⁵ Department of Radiology, Frontier Science for Imaging, School of Medicine, Gifu University, Gifu, 1-1 Yanagido, Gifu, 501-1194, Japan; Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.
⁶ Department of Radiology, Gifu University, Gifu, 1-1 Yanagido, Gifu, 501-1194, Japan.
⁷ Department of Radiology, Frontier Science for Imaging, School of Medicine, Gifu University, Gifu, 1-1 Yanagido, Gifu, 501-1194, Japan; Department of Radiology, Gifu University, Gifu, 1-1 Yanagido, Gifu, 501-1194, Japan.
⁸ Kitakyushu Koga Hospital, Fukuoka, Japan.
⁹ Department of Radiology, Frontier Science for Imaging, School of Medicine, Gifu University, Gifu, 1-1 Yanagido, Gifu, 501-1194, Japan. Electronic address: hyodof@gifu-u.ac.jp.

PMID: 33865961
DOI: 10.1016/j.freeradbiomed.2021.04.017

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.

Keywords: Dynamic nuclear polarization magnetic resonance imaging; Large animals; Nitroxyl radical; Redox metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electron Spin Resonance Spectroscopy
Hepatitis*
Magnetic Resonance Imaging*
Magnetic Resonance Spectroscopy
Oxidation-Reduction
Rats