Improved Myocardial Blood Flow Estimation with Residual Activity and Motion Correction in 18F-flurpiridaz PET myocardial perfusion imaging

Background: 18F-flurpiridaz is a promising PET agent for myocardial perfusion imaging (MPI), but with the long half-life attention needs to be paid to the rest/stress imaging due to residual rest activity seen on the stress scans. Additionally, patient motion during the dynamic scan can have also substantial impact on myocardial blood flow (MBF) estimation. We sought to evaluate the diagnostic performance of MBF quantification with 18F-flurpiridaz PET by applying motion correction (MC) and residual activity correction (RAC).

Methods: We retrospectively analyzed a subset of patients from the phase 3 Flurpiridaz trial (NCT01347710) with available dynamic images. Out of 755 patients recruited for the trial, 559 underwent pharmacologic stress PET. Dynamic 18F- Flurpiridaz PET data were available for 276 patients from 43 clinical imaging sites. After excluding corrupted or incorrectly acquired dynamic images (N=44), 232 patients were included in the analysis. PET imaging was performed in 2D or 3D mode with CT attenuation correction within a median of 2 ± 28 days of invasive coronary angiography. Dynamic PET acquisition at rest was initiated with intravenous bolus injection of 18F-flurpiridaz (2.7 ± 0.2 mCi). Pharmacologic stress was performed with adenosine, dipyridamole, or regadenoson according to local practice 53±11minutes after rest study. At peak stress, dynamic PET image acquisition was repeated with intravenous bolus injection of 18F-flurpiridaz (5.9±0.3 mCi). Manual frame-by-frame MC (26 frames (15 x10 seconds, 5x30 seconds, 9x60 seconds, 1x 300 seconds) was performed for the stress and rest images. Subsequently, RAC was accomplished by subtracting the rest polar maps residual counts from the first 10-second frame (before the second 18F-flurpiridaz injection) from the dynamic stress polar maps. Rest and stress myocardial MBF [ml/min/g] were obtained by fitting the corresponding time-activity curves for each polar map region to early kinetics model with spill over correction derived for stress and rest flow [ml/min/g]. MFR was obtained as the ratio of the stress and rest MBF. Global, per-vessel and per-segment, rest/stress MBF and MFR were evaluated using three methods with and without MC and RAC (1:No MC/no RAC, 2:MC/no RAC,3: MC/RAC). For the CAD diagnosis minimal 17-segment MFR and stress MBF was used. Obstructive CAD was defined as ≥70% narrowing of the 3 major coronary arteries and ≥50% for the left main coronary artery on invasive angiography.

Results: Global stress MBF (median [interquartile range]1.7 [1.4, 1.9] vs 2.5 [1.9,2.9]) and MFR(2.4 [1.9, 3.0] vs 3.0 [2.4,3.8]) in patients with CAD were lower compared to patients without CAD (p<0.0001 for all). Stress MBF and MFR were lower for MC/RAC than corresponding values for No MC/No RAC (p<0.0001 for both). The frequency of motion shifts ≥ 5 mm was 27% on x axis, 77% on y axis and 19% on z axis for stress and 8% on x axis, 19% on y axis and 7% on z axis for rest. Spill over fraction (median [interquartile range decreased with MC/RAC (0.21 [0.16,0.28]) compared to No MC/RAC (0.26 [0.21,0.35],p<0.0001) or No MC/ No RAC (0.38 [0.30,0.45],p<0.0001). The area-under the receiver operating characteristics curve (AUC) for the diagnosis of obstructive CAD by segmental stress MBF and MFR were higher with MC and RAC compared to No MC /No RAC (stress MBF: p<0.0001, MFR p<0.0001) (Table 1).

Conclusions: MBF estimation with MC and RAC improves the diagnostic performance of same day rest/stress18F-flurpiridaz PET MPI. RAC and MC seems to be the critical correction in evaluation dynamic rest/stress PET flow obtained with F-18 Flurpiridaz. Table 1. AUC for the detection of obstructive CAD by minimal segmental stress MBF and MFR with and without motion correction and residual activity correction

MC: motion correction, RAC: residual activity correction