Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine

Despite the importance of metabolic disturbances in many diseases, there are currently no clinically used methods for the detection of oxidative metabolism in vivo. To address this deficiency, 17O MRI techniques are scaled from small animals to swine as a large animal model of human inhalation and circulation. The hemispheric cerebral metabolic rate of oxygen consumption (CMRO2) is estimated in swine by detection of metabolically produced H217O by rapid T1ρ-weighted proton magnetic resonance imaging on a 1.5 T clinical scanner. The 17O is delivered as oxygen gas by a custom, minimal-loss, precision delivery breathing circuit and converted to H217O by oxidative metabolism. A model for gas arterial input is presented for the deeply breathing large animal. The arterial input function for recirculation of metabolic water is measured by arterial blood sampling and high field 17O spectroscopy. It is found that minimal metabolic water “wash-in” occurs before 60 s. A high temporal resolution pulse sequence is employed to measure CMRO2 during those 60 s after delivery begins. Only about one tidal volume of 17O enriched oxygen gas is used per measurement. Proton measurements of signal change due to metabolically produced water are correlated with 17O in vivo spectroscopy. Using these techniques, the hemispheric CMRO2 in swine is estimated to be 1.23 ± .26 μmol/g/min, consistent with existing literature values. All of the technology used to perform these CMRO2 estimates can easily be adapted to clinical MR scanners, and it is hoped that this work will lead to future studies of human disease.