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

Abstract

PurposeQuantification 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).MethodsMBF 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 ρc (measuring both precision and accuracy) were used.ResultsOver 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, ρc = 0.88) and MFR (range 1.79–5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = −0.99 to 1.28, ρc = 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).ConclusionQuantification 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.

Coronary Microvascular Dysfunction ― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

“…The myocardium can be divided into segments in order to calculate regional blood flow in addition to global flow. 49 PET measurement of myocardial flow reserve can also be used to predict prognosis. 50 PET also has the advantage of assessing all 3 coronary distributions, thus allowing a more accurate assessment of microvascular dysfunction, as CMD has been shown to have a heterogeneous distribution over the 3 vessels.…”

Variability in normal myocardial blood flow measurements: Physiologic, methodologic, or protocol related?

“…Attractive attributes include throughput efficiency (rest/stress studies can be completed in about 40 minutes), low radiation exposure, 8 peak stress regional and global ventricular function comparisons against rest parameters, 9,10 and flow measurements validated against a variety of different standards. [11][12][13][14][15][16][17][18][19][20] A novel capability of PET is the ability to move beyond spatially relative image interpretation to patientcentric quantitation. In a spatially relative domain, abnormality is defined in one of 3 manners: one or two myocardial regions have less tracer uptake than a best and therefore presumed normal area; the left ventricle function deteriorates with stress (e.g., transient ischemic dilation, changes between rest and stress ejection fraction); or a non-perfusion marker such as lung uptake of Tl-201 or ischemic ECG changes alert to physiologically significant CAD not detected by perfusion defect analysis alone.…”

Basic Premises to Molecular Imaging and Radionuclide Therapy – Part 1

“…Rb is partially counterbalanced by the high cost/effectiveness in the clinical field of the alternative radionuclide study, i.e. gated SPECT with technetium-99m perfusion agents [61].…”