Quantification of myocardial blood flow with 82Rb positron emission tomography: Clinical validation with 15O-water

Abstract

Purpose: Quantification of myocardial blood flow (MBF) with generator-produced 82Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate 82Rb-measured MBF in relation to that measured using 15O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). Methods: MBF was measured at rest and during adenosine-induced hyperaemia with 82Rb and 15O-water PET in 33 participants (22 control subjects, aged 30±13 years; 11 CAD patients without transmural infarction, aged 60±13 years). A one-tissue compartment 82Rb model with ventricular spillover correction was used. The 82Rb flow-dependent extraction rate was derived from 15O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ c (measuring both precision and accuracy) were used. Results: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r=0.90, [ 82Rb- 15O-water] mean difference±SD=0. 04±0.66 ml/min/g, LoA=-1.26 to 1.33 ml/min/g, ρ c=0.88) and MFR (range 1.79-5.81, r=0.83, mean difference=0.14±0.58, LoA=-0.99 to 1.28, ρ c=0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53±0.74 vs. 3.62±0.68 ml/min/g, p=0.002, for 15O-water; 2.53±1.01 vs. 3.82±1.21 ml/min/g, p=0.013, for 82Rb) and this was paralleled by a lower MFR (2.65±0.62 vs. 3.79±0.98, p=0.004, for 15O-water; 2.85±0.91 vs. 3.88±0.91, p=0.012, for 82Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p>0.31). Conclusion: Quantification of MBF with 82Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using 15O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. 82Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine. © The Author(s) 2012.