title: Noninvasive quantification of regional myocardial metabolic rate of oxygen by 15O2 inhalation and positron emission tomography. Experimental validation.
abstract: BACKGROUND
  The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMRO2, mL.min-1 x 100 g-1) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15O-labeled molecular oxygen gas (15O2).
  
  
  RESULTS
  Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 micrograms.kg-1.min-1), isoproterenol (1 to 10 microgram/min), and propranolol (5 mg botus +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 15O2 emission (OEF and MMRO2), transmission, [15O]CO emission (blood pool), and [15O]CO2 emission (myocardial blood flow: MBF(pets) mL.min-1.g-1) scans. OEF was calculated from the PET data (OEFpet) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBFref) and OEF (OEFref) were obtained during 15O2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMRO2 was calculated from the PET (MMRO2pet) and the reference (MMRO2ref) data as follows: MMRO2 = OEF x MBF x (O2 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 (OEFpet = 1.03 OEFref -0.01, r = .97), as was MMRO2 over the range 2.4 to 27.5 mL.min-1 x 100 g-1 (MMRO2pet = 0.98 MMRO2ref +0.91, r = .94). OEFpet 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 MMRO2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses (P = NS by ANOVA). Regional values of MBFpet, OEFpet, and MMRO2pet 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 MMRO2 is feasible with 15O2 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.
authors.affiliation: Cyclotron Unit, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: R
authors.initials: R
authors.lastname: de Silva
authors.forename: C G
authors.initials: CG
authors.lastname: Rhodes
authors.forename: H
authors.initials: H
authors.lastname: Iida
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Maseri
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide; D002250:Carbon Radioisotopes; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D001239:Inhalation; D007545:Isoproterenol / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010104:Oxygen Radioisotopes; D011433:Propranolol / Q000494:pharmacology; D012044:Regression Analysis; D015203:Reproducibility of Results; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002250:Carbon Radioisotopes; D010104:Oxygen Radioisotopes; D002245:Carbon Dioxide; D009020:Morphine; D011433:Propranolol; D000241:Adenosine; D007545:Isoproterenol