title: In vivo proton electron double resonance imaging of the distribution and clearance of nitroxide radicals in mice.
abstract: Proton electron double resonance imaging (PEDRI) is an emerging technique that utilizes the Overhauser effect to enable in vivo and in vitro imaging of free radicals in biological systems. Nitroxide spin probes enable measurement of tissue redox state based on their reduction to diamagnetic hydroxylamines. PEDRI instrumentation at 0.02 T was applied to assess the ability to image the in vivo distribution, clearance, and metabolism of nitroxide radicals in living mice. Using phantoms of 2,2,5,5-tetramethyl-3-carboxylpyrrolidine-N-oxyl (PCA) in normal saline the dependence of the enhancement on RF power and spin probe concentration was determined. Enhancements of up to -23 were obtained in phantoms with 2 mM levels. Maximum enhancement of -7 was observed in vivo. Coronal images of nitroxide-infused mice enabled visualization of the kinetics of spin probe uptake and clearance in different organs including the great vessels, heart, lungs, kidneys, and bladder with an in-plane spatial resolution of 0.6 mm. PEDRI of living mice was also performed using 3-carbamoyl-proxyl and 2,2,6,6-tetramethyl-4-oxopiperidine-N-oxyl to compare the different rate of clearance and metabolism among different nitroxide probes. PCA, due to its intravascular compartmentalization, provided the sharpest contrast for the vascular system and highest enhancement values in the PEDRI images among the three nitroxides.
authors.affiliation: Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio 04210-1252, USA.
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
authors.forename: Yuanmu
authors.initials: Y
authors.lastname: Deng
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009589:Nitrogen Oxides / Q000493:pharmacokinetics*; D019047:Phantoms, Imaging
chemical_list: D005609:Free Radicals; D009589:Nitrogen Oxides; C039900:nitroxyl