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

Abstract

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 ¹⁵O-H₂O and the blood-borne activity. We propose a noninvasive reference-based hybrid PET/MRI method that uses functional MRI techniques to calibrate ¹⁵O-O₂ 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 ¹⁵O-H₂O PET, and if the PMROx was sensitive to anesthetic-induced changes in metabolism. <b>Methods:</b>¹⁵O-H₂O and ¹⁵O-O₂ PET data were acquired using a hybrid PET/MR scanner, together with simultaneous functional MRI (OxFlow and ASL), from juvenile pigs (<i>n</i> = 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 ¹⁵O-H₂O PET or ASL (PMROx_ASL). Changes in metabolism were investigated by increasing the propofol infusion to 20 mL/kg/h. <b>Results:</b> 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 mL/100 g/min), or between PMROx and PET-only CMRO₂ estimates (1.89 ± 0.16 and 1.81 ± 0.10 mLO₂/100 g/min). Moreover, PMROx and PMROx_ASL were sensitive to propofol-induced reduction in CMRO₂. <b>Conclusion:</b> 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 ¹⁵O-O₂ only; however, future validation involving human participants are required.