Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation.
Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation. Female C57/BL6 mice received injections of 0.5% bupivacaine into their gastrocnemius muscles. Plasma biomarkers, myeloperoxidase activity, and histological sections were assessed at 4 and 24h after bupivacaine injection to measure the inflammatory response. In vivo DNP-MRI was performed with the nitroxyl radicals carbamoyl-PROXYL (cell permeable) and carboxy-PROXYL (cell impermeable) as molecular imaging probes at 4 and 24h after bupivacaine administration. The images obtained after carbamoyl-PROXYL administration were confirmed with the results of L-band EPR spectroscopy. The plasma biomarkers, myeloperoxidase activity, and histological findings indicated that bupivacaine injection caused acute muscle damage and inflammation. DNP-MRI images of mice treated with carbamoyl-PROXYL or carboxy-PROXYL at 4 and 24h after bupivacaine injection showed similar increases in image intensity and decay rate was significantly increased at 24h. In addition, reduction rates in individual mice at 4h and 24h showed faster trends with bupivacaine injection than in their contralateral sides by image-based analysis. These findings indicate that in vivo DNP-MRI with nitroxyl radicals can non-invasively detect changes in the focal redox status of muscle resulting from locally-induced inflammation.
Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Hinako
H
Eto
Innovation Center for Medical Redox Navigation, Kyushu University, Japan. Electronic address: hyodof@redoxnavi.med.kyushu-u.ac.jp.
Fuminori
F
Hyodo
Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Nutavutt
N
Kosem
Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Ryoma
R
Kobayashi
Faculty of Pharmaceutical Sciences, Kyushu University, Japan; Drug Innovation Research Center, Daiichi University of Pharmacy, Japan.
Keiji
K
Yasukawa
Medical Institute of Bioregulation, Research Center for Transomics Medicine, Division of Metabolomics, Kyushu University, Japan.
Motonao
M
Nakao
Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Mamoru
M
Kiniwa
Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Hideo
H
Utsumi
D000818:Animals; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005260:Female; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007249:Inflammation / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D018482:Muscle, Skeletal / Q000473:pathology*; D009589:Nitrogen Oxides / Q000737:chemistry; D013113:Spin Labels
D009589:Nitrogen Oxides; D013113:Spin Labels; C039900:nitroxyl
Dynamic nuclear polarization magnetic resonance imaging; Inflammation; Neutrophil activity; Nitroxyl radical; Oxidation reduction; Skeletal muscle