Comparison, Agreement, and Significance Cutoffs of F-Flurpiridaz PET Myocardial Blood Flow Quantitation Methods and Software Packages.

F-flurpiridaz is a novel PET myocardial perfusion radiotracer with a high myocardial extraction fraction and low positron range, providing high-resolution images. Additionally, the linear relationship between F-flurpiridaz myocardial extraction and myocardial blood flow (MBF) over a wide range of flow values permits accurate MBF measurement. Several groups have developed strategies to quantitate F-flurpiridaz MBF with methodologic differences. These methods have not previously undergone head-to-head comparisons. Three methods of F-flurpiridaz MBF quantitation were compared using Emory Cardiac Toolbox (ECTb; Syntermed), 4DM (INVIA), and Quantitative PET (QPET; Cedars-Sinai) software. All evaluable pharmacologic stress patients from the phase 3 F-flurpiridaz PET trial (NCT03354273) of F-flurpiridaz were included ( = 405). We adopted Bland-Altman plots to determine absolute differences between MBF quantitative methods, Fleiss κ for agreement across software packages, and Cohen κ for agreement of pairwise comparisons. Diagnostic performances of stress MBF and myocardial flow reserve (MFR) were determined by performing receiver-operating-characteristic analysis for areas under the curve (AUCs), using quantitative invasive coronary angiography as the reference standard. Differences in mean stress MBF and MFR between methods across coronary territory distributions ranged from 0.23 to 0.29 mL/min/g and from 0.37 to 0.40 mL/min/g for ECTb and 4DM, respectively; from 0.09 to 0.11 mL/min/g and from 0.36 to 0.38 mL/min/g for ECTb and QPET, respectively; and from 0.25 to 0.26 mL/min/g and from 0.39 to 0.40 mL/min/g for QPET and 4DM, respectively. There was substantial agreement across software packages, with the Fleiss κ ranging from 0.77 to 0.79 and 0.72 to 0.75 for stress MBF and MFR, respectively. Similar results were found in pairwise comparisons. For coronary artery territories with at least 70% stenosis, median stress MBF and MFR AUCs were 0.73-0.74 and 0.71-0.73, respectively, when evaluated on a per-patient basis, and 0.75-0.77 and 0.74-0.75, respectively, in pooled coronary distributions on a per-vessel basis across all methods. All software packages demonstrated high agreement and similar F-flurpiridaz MBF quantitation, paving the way for the interoperability of these platforms in clinical practice.