Noninvasive Quantification of Regional Myocardial Metabolic Rate of Oxygen by 15 O 2 Inhalation and Positron Emission Tomography

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Abstract
Background The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMR o 2 , mL·min −1 ·100 g −1 ) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15 O-labeled molecular oxygen gas ( 15 O 2 ). Methods and Results Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 μg·kg −1 ·min −1 ), isoproterenol (1 to 10 μg/min), and propranolol (5 mg bolus+0.2 to 1 mg/min) with morphine (5 mg slow infusion+0.2 to 0.5 mg/min) to obtain a wide range of oxidative metabolism. The PET imaging protocol consisted of 15 O 2 emission (OEF and MMR o 2 ), transmission, [ 15 O]CO emission (blood pool), and [ 15 O]CO 2 emission (myocardial blood flow: MBF pet , mL·min −1 ·g −1 ) scans. OEF was calculated from the PET data (OEF pet ) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBF ref ) and OEF (OEF ref ) were obtained during 15 O 2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMR o 2 was calculated from the PET (MMR o 2pet ) and the reference (MMR o 2ref ) data as follows: MMR o 2 =OEF×MBF×(O 2 content of arterial blood). OEF measured by the steady-state PET method was well correlated with the reference data over the range 0.16 to 0.73 (OEF pet =1.03 OEF ref −0.01, r =.97), as was MMR o 2 over the range 2.4 to 27.5 mL·min −1 ·100 g −1 (MMR o 2pet =0.98 MMR o 2ref +0.91, r =.94). OEF pet calculated by use of the 5-minute and 8-minute autoradiographic analyses were equally well correlated with the reference measurements ( r =.95 and r =.97, respectively). There were no significant differences between values of MMR o 2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses ( P =NS by ANOVA). Regional values of MBF pet , OEF pet , and MMR o 2pet were homogeneously distributed and similar to the whole-heart values both at baseline and during the various pharmacological interventions. Conclusions Accurate quantification of OEF and MMR o 2 is feasible with 15 O 2 inhalation and PET imaging using both the steady-state and autoradiographic analytical approaches. These studies suggest the applicability of this method for quantitative assessments of regional cardiac oxidative metabolism in clinical studies.