title: Direct visualization of mouse brain oxygen distribution by electron paramagnetic resonance imaging: application to focal cerebral ischemia.
abstract: Electron paramagnetic resonance imaging (EPRI) is a new modality for visualizing O(2) distribution in tissues, such as the brain after stroke or after administration of drugs of abuse. We have recently shown that 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [1] is a pro-imaging agent that can cross the blood-brain barrier. After hydrolysis by esterases, the anion of 3-carboxy-2,2,5,5-tetramethyl-1-tetramethyl-1-pyrrolidinyloxyl [2] is trapped in brain tissue. In this study, we investigated the feasibility of using this to map the changes of O(2) concentration in mouse brain after focal ischemia. The decrease in tissue O(2) concentration in the ischemic region of mouse brain was clearly visualized by EPRI. The hypoxic zone mapped by EPRI was spatially well correlated with the infarction area in the brain imaged by diffusion-weighted magnetic resonance imaging (MRI). Finally, we observed a decrease in the size of the hypoxic region when the mouse breathed higher levels of O(2). This finding suggests that EPRI with specifically designed nitroxides is a promising imaging modality for visualizing O(2) distribution in brain tissue, especially in an ischemic brain. We believe that this imaging method can be used for monitoring the effects of therapeutic intervention aimed at enhancing brain O(2) supply, which is crucial in minimizing brain injury after stroke.
authors.affiliation: Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
authors.forename: Rohit
authors.initials: R
authors.lastname: Sood
authors.forename: John
authors.initials: J
authors.lastname: Weaver
authors.forename: Graham S
authors.initials: GS
authors.lastname: Timmins
authors.forename: Aaron
authors.initials: A
authors.lastname: Schnell
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyake
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D003952:Diagnostic Imaging / Q000379:methods; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D000860:Hypoxia; D008279:Magnetic Resonance Imaging; D051379:Mice; D010100:Oxygen / Q000032:analysis*
chemical_list: D010100:Oxygen
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