Mapping of cerebral oxidative metabolism with MRI.
Using a T(1rho) 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 gas. The study was performed by 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% + or - 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(1rho) MRI following administration of gas. Metabolism was calculated from the change in the T(1rho) weighted MRI signal due to H(2)(17)O generated from 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 gas. Given the demonstrated high efficiency in use of 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.
Mellon
Eric A
EA
Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Beesam
R Shashank
RS
Elliott
Mark A
MA
Reddy
Ravinder
R
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D023421:Models, Animal; D010101:Oxygen Consumption / Q000187:drug effects; D010103:Oxygen Isotopes; D013552:Swine; D014475:Uncoupling Agents / Q000494:pharmacology
D010103:Oxygen Isotopes; D014475:Uncoupling Agents; D019297:2,4-Dinitrophenol