Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography

Background: Experimental studies have shown that positron emission tomography (PET) with ¹³N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of ¹³N-labeled PET for measurement of MBF and CFR. Methods and Results: Initial and follow-up ¹³N-labeled ammonia PET studies were performed at rest and during adenosine infusion in six normal volunteers and six patients with stable coronary artery disease. Two investigators analyzed dynamically acquired data from the initial studies and one investigator analyzed the follow-up studies. Time-activity curves of tissue tracer activity were derived by a semiautomated sampling routine. A three-compartment model and curve-fitting algorithm were used to determine estimates of MBF in five myocardial regions. The interobserver correlations for MBF and CFR were excellent (r=0.96 and 0.93, respectively). The interstudy correlation was good for rest and stress MBF (r=0.87). The estimates of CFR on the initial and follow-up studies demonstrated a fair correlation (r=0.72). For individual myocardial regions, there was considerable interstudy variability of stress MBF and CFR, with a mean percent difference for CFR of 19%±19% in normal volunteers and 38%±16% in patients with coronary disease. In normal subjects, regional CFR was highly reproducible (95%) when the values were defined as either normal (≥2.5) or reduced (<2.5). Conclusions: The interobserver of reproducibility of ¹³N-labeled ammonia PET estimates of regional MBF was excellent. The temporal reproducibility of MBF and CFR was fair, with individual regions demonstrating substantial interstudy variability.