title: Dynamic contrast-enhanced MRI in mice: an investigation of model parameter uncertainties.
abstract: OBJECTIVE
  To establish the experimental factors that dominate the uncertainty of hemodynamic parameters in commonly used pharmacokinetic models.
  
  
  METHODS
  By fitting simulation results from a multiregion tissue exchange model (Multiple path, Multiple tracer, Indicator Dilution, 4 region), the precision and accuracy of hemodynamic parameters in dynamic contrast-enhanced MRI with four tracer kinetic models is investigated. The impact of various injection rates as well as imprecise knowledge of the arterial input functions is examined.
  
  
  RESULTS
  Fast injections are beneficial for K(trans) precision within the extended Tofts model and within the two-compartment exchange model but do not affect the other models under investigation. Biases from errors in the arterial input functions are mostly consistent in size and direction for the simple and the extended Tofts model, while they are hardly predictable for the other models. Errors in the hematocrit introduce the greatest loss in parameter accuracy, amounting to an average K(trans) bias of 40% for a 30% overestimation throughout all models.
  
  
  CONCLUSIONS
  This simulation study allows the detailed inspection of the isolated impact from various experimental conditions on parameter uncertainty. Because parameter uncertainty comparable to human studies was found, this study represents a validation of preclinical dynamic contrast-enhanced MRI for modeling human tumor physiology.
authors: Department of Physics and Astronomy, University of British Columbia, Vancouver, Canada; Department of Physics, Humboldt University, Berlin, Germany.
authors: Tammo
authors: T
authors: Rukat
authors: Simon
authors: S
authors: Walker-Samuel
authors: Stefan A
authors: SA
authors: Reinsberg
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics*; D006400:Hematocrit; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical
chemical_list: D003287:Contrast Media
keywords: dynamic contrast-enhanced-MRI; perfusion; permeability; pharmacokinetic models; tracer-kinetic models