title: Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.
abstract: BACKGROUND
  The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function.
  
  
  METHODS
  Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments.
  
  
  RESULTS
  Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s.
  
  
  CONCLUSIONS
  PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.
authors.affiliation: Department of Anesthesiology and Intensive-Care, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Ingeborg.Herold@cze.nl.
authors.forename: Ingeborg H F
authors.initials: IH
authors.lastname: Herold
authors.affiliation: Department of Electrical Engineering, Signal Processing Systems, Eindhoven University of Technology, De Zaale, 5612 AZ, Eindhoven, The Netherlands. S.Saporito@tue.nl.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saporito
authors.affiliation: Department of Anesthesiology and Intensive-Care, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Arthur.Bouwman@cze.nl.
authors.forename: R Arthur
authors.initials: RA
authors.lastname: Bouwman
authors.affiliation: Department of Cardiology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Patrick.Houthuizen@cze.nl.
authors.forename: Patrick
authors.initials: P
authors.lastname: Houthuizen
authors.affiliation: Department of Electrical Engineering, Signal Processing Systems, Eindhoven University of Technology, De Zaale, 5612 AZ, Eindhoven, The Netherlands. H.C.v.Assen@tue.nl.
authors.forename: Hans C
authors.initials: HC
authors.lastname: van Assen
authors.affiliation: Department of Electrical Engineering, Signal Processing Systems, Eindhoven University of Technology, De Zaale, 5612 AZ, Eindhoven, The Netherlands. M.Mischi@tue.nl.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mischi
authors.affiliation: Department of Anesthesiology and Intensive-Care, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Erik.Korsten@cze.nl.|Department of Electrical Engineering, Signal Processing Systems, Eindhoven University of Technology, De Zaale, 5612 AZ, Eindhoven, The Netherlands. Erik.Korsten@cze.nl.
authors.forename: Hendrikus H M
authors.initials: HH
authors.lastname: Korsten
mesh_terms: D000368:Aged; D001810:Blood Volume; D001811:Blood Volume Determination / Q000379:methods; D003287:Contrast Media / Q000493:pharmacokinetics; D004452:Echocardiography / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D010743:Phospholipids / Q000493:pharmacokinetics*; D063177:Pulse Wave Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013459:Sulfur Hexafluoride / Q000493:pharmacokinetics*
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride