Mapping of cerebral oxidative metabolism with MRI

摘要

Using a T_(1ρ) 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-dini-trophenol (DNP) in a large animal model with minimum utilization of ~(17)O_2 gas. The study was performed by ~(17)O_2 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 ~(17)O_2 gas. Metabolism was calculated from the change in the T_(1ρ) weighted MRI signal due to H_2~(17)O generated from ~(17)O_2 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 H_2~(17)O 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 H_2~( 17)O_2 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.