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Simple and Accurate Assessment of Forward Cardiac Output by Use of 1-¹¹C-Acetate PET Verified in a Pig Model

¹ Clinical Physiology, Department of Medical Sciences, Academic Hospital, Uppsala, Sweden
² Uppsala University PET Centre, Uppsala, Sweden
³ Thoracic Surgery, Department of Medical Sciences, Academic Hospital, Uppsala, Sweden
⁴ Cardiology, Department of Medical Sciences, Academic Hospital, Uppsala, Sweden

Dynamic 1-¹¹C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function. Methods: Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO_thermo) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-¹¹C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time–activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO_PET) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of ¹¹C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, ¹⁵O-carbon monoxide, and AC-PET scans. Results: CO_thermo ranged from 2.1 to 8.2 L/min. CO_PET determined from both LV and RV was linearly related to CO_thermo with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6–14 mm Hg and the lung-uptake %ID was 2.7–8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO_thermo; r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001). Conclusion: Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.

Key Words: cardiac output • acetate • PET • tracer kinetics

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