title: Interrupted infusion of echocardiographic contrast as a basis for accurate measurement of myocardial perfusion: ex vivo validation and analysis procedures.
abstract: BACKGROUND
  Echocardiographic quantification of myocardial perfusion is based on analysis of contrast replenishment after destructive high-energy ultrasound impulses (flash-echo). This technique is limited by nonuniform microbubble destruction and the dependency on exponential fitting of a small number of noisy time points. We hypothesized that brief interruptions of contrast infusion (ICI) would result in uniform contrast clearance followed by slow replenishment and, thus, would allow analysis from multiple data points without exponential fitting.
  
  
  METHODS
  Electrocardiographic-triggered images were acquired in 14 isolated rabbit hearts (Langendorff) at 3 levels of coronary flow (baseline, 50%, and 15%) during contrast infusion (Definity) with flash-echo and with a 20-second infusion interruption. Myocardial videointensity was measured over time from flash-echo sequences, from which characteristic constant beta was calculated using an exponential fit. Peak contrast inflow rate was calculated from ICI data using analysis of local time derivatives. Computer simulations were used to investigate the effects of noise on the accuracy of peak contrast inflow rate and beta calculations.
  
  
  RESULTS
  ICI resulted in uniform contrast clearance and baseline replenishment times of 15 to 25 cardiac cycles. Calculated peak contrast inflow rate followed the changes in coronary flow in all hearts at both levels of reduced flow (P < .05) and had a low intermeasurement variability of 7 +/- 6%. With flash-echo, contrast clearance was less uniform and baseline replenishment times were only 4 to 6 cardiac cycles. beta Decreased significantly only at 15% flow, and had intermeasurement variability of 42 +/- 33%. Computer simulations showed that measurement errors in both perfusion indices increased with noise, but beta had larger errors at higher rates of contrast inflow.
  
  
  CONCLUSIONS
  ICI provides the basis for accurate and reproducible quantification of myocardial perfusion using fast and robust numeric analysis, and may constitute an alternative to the currently used techniques.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Toledo
authors.forename: Keith A
authors.initials: KA
authors.lastname: Collins
authors.forename: Ursula
authors.initials: U
authors.lastname: Williams
authors.forename: Georgeanne
authors.initials: G
authors.lastname: Lammertin
authors.forename: Gil
authors.initials: G
authors.lastname: Bolotin
authors.forename: Jai
authors.initials: J
authors.lastname: Raman
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
authors.forename: Victor
authors.initials: V
authors.lastname: Mor-Avi
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D003326:Coronary Circulation; D004452:Echocardiography / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage*; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; C042852:perflutren