title: Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water.
abstract: OBJECTIVE
  Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-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 (82)Rb and (15)O-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 (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-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, [(82)Rb-(15)O-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 (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). 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).
  
  
  CONCLUSIONS
  Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.
authors.affiliation: Nuclear Medicine Department, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. john.prior@chuv.ch
authors.forename: John O
authors.initials: JO
authors.lastname: Prior
authors.forename: Gilles
authors.initials: G
authors.lastname: Allenbach
authors.forename: Ines
authors.initials: I
authors.lastname: Valenta
authors.forename: Marek
authors.initials: M
authors.lastname: Kosinski
authors.forename: Cyrill
authors.initials: C
authors.lastname: Burger
authors.forename: Francis R
authors.initials: FR
authors.lastname: Verdun
authors.forename: Angelika
authors.initials: A
authors.lastname: Bischof Delaloye
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology; D003326:Coronary Circulation; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D012414:Rubidium Radioisotopes; D014867:Water
chemical_list: D010104:Oxygen Radioisotopes; D012414:Rubidium Radioisotopes; D014867:Water