A Noninvasive Method for Quantifying Cerebral Metabolic Rate of Oxygen by Hybrid PET/MRI: Validation in a Porcine Model

The gold standard for imaging the cerebral metabolic rate of oxygen (CMRO2) is PET; however, it is an invasive and complex procedure that also requires correction for recirculating O-15-H2O and the blood-borne activity. We propose a noninvasive reference-based hybrid PET/MRI method that uses functional MRI techniques to calibrate O-15-O-2 PET data. Here, PET/MRI of oxidative metabolism (PMROx) was validated in an animal model by comparison to PET-alone measurements. Additionally, we investigated if the MRI perfusion technique arterial spin labeling (ASL) could be used to further simplify PMROx by replacing O-15-H2O PET, and if the PMROx was sensitive to anesthetic-induced changes in metabolism. Methods: O-15-H2O and O-15-O-2 PET data were acquired using a hybrid PET/MR scanner, together with simultaneous functional MRI (OxFlow and ASL), from juvenile pigs (n = 9). Animals were anesthetized with 3% isoflurane and 6 mL/kg/h propofol for the validation experiments, and arterial sampling was performed for PET-alone measurements. PMROx estimates were obtained using whole-brain (WB) CMRO2 from OxFlow and local cerebral blood flow (CBF) from either noninvasive O-15-H2O PET or ASL (PMROx(ASL)). Changes in metabolism were investigated by increasing the propofol infusion to 20 mL/kg/h. Results: Good agreement and correlation were observed between regional CMRO2 measurements from PMROx and PET alone. No significant differences were found between OxFlow and PET-only measurements of WB oxygen extraction fraction (0.30 + 0.09 and 0.31 + 0.09)and CBF (54.1 +/- 16.7 and 56.6 +/- 21.0 mLO(2)/100 g/min), or between PMROx and PET-only CMRO2 estimates (1.89 +/- 0.16 and 1.81 +/- 0.10 mLO(2)/100 g/min). Moreover, PMROx and PMROx(ASL )were sensitive to propofol-induced reduction in CMRO2. Conclusion: This study provides initial validation of a noninvasive PET/MRI technique that circumvents many of the complexities of PET CMRO2 imaging. PMROx does not require arterial sampling and has the potential to reduce PET imaging to O-15-O-2 only; however, future validation involving human participants are required.