Using a T1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of 17O2 gas. The study was performed by 17O2 inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9% + / - 2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T 1ρ MRI following administration of 17O2 gas. Metabolism was calculated from the change in the T1ρ weighted MRI signal due to H217O generated from 17O2 inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H217O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive 17O2 gas. Given the demonstrated high efficiency in use of 17O2 and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jun 29 2010|
- Cerebral metabolic rate of oxygen consumption
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