This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Differences in the cerebral metabolic rate of oxygen consumption (CMRO2) within the central nervous system (CNS) in vivo are noted both in normal and pathologic physiology as a marker of cellular metabolism. In the normal CNS, for example, stimulation by sensory or cognitive processes can be specific to regions of activation, giving clues to brain function. Similarly, stroke, many tumors, and degenerative disorders, such as Alzheimer's Disease (AD), cause local changes in metabolism that could be measured by various techniques to provide diagnostic and prognostic information. Despite the importance of measuring CMRO2, there are currently no routinely used clinical techniques that directly assess changes in oxygen metabolism due to the drawbacks in existing technologies. When administered in the form of molecular oxygen, enriched oxygen-17 gas is inhaled through the lungs of the organism under study and is thought to be used by the body analogously to regular oxygen. In this process, oxidative phosphorylation during cellular respiration reduces the oxygen-17 to produce oxygen-17 water which generates MR contrast. Techniques using oxygen-17 are applied to the in vivo quantification of cerebral metabolism in a large animal in order to ready them for human use. As a crucial step to imaging of metabolic changes in humans with oxygen-17, we demonstrate the detection of oxidative metabolic stimulation by the stimulant 2,4-dinitrophenol (DNP) in a large animal model. The long-term objective of this research is to prepare oxygen-17 imaging for clinical trials in the diagnosis of a variety of neurodegenerative diseases and in post-stroke brain assessment. We also hope that oxygen-17 imaging will be applied to investigations of metabolism in virtually any organ in vivo.
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