title: Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus.
abstract: BACKGROUND
  Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods.
  
  
  METHODS
  Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05.
  
  
  RESULTS
  Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling.
  
  
  CONCLUSIONS
  Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. G.Papanastasiou@ed.ac.uk.|Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. G.Papanastasiou@ed.ac.uk.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Papanastasiou
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. michelle.williams@ed.ac.uk.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Williams
authors.affiliation: Christie Medical Physics and Engineering, The Christie NHS FT, Manchester, UK. lucy.kershaw@christie.nhs.uk.
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Kershaw
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. marcdweck@hotmail.com.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. shirjel@doctors.org.uk.
authors.forename: Shirjel
authors.initials: S
authors.lastname: Alam
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. smirsadr@staffmail.ed.ac.uk.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mirsadraee
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. M.Connell@ed.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Connell
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. calum.gray@ed.ac.uk.
authors.forename: Calum
authors.initials: C
authors.lastname: Gray
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. T.J.MacGillivray@ed.ac.uk.
authors.forename: Tom
authors.initials: T
authors.lastname: MacGillivray
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. d.e.newby@ed.ac.uk.|Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. d.e.newby@ed.ac.uk.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh,, Edinburgh, UK. scott.semple@ed.ac.uk.|Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. scott.semple@ed.ac.uk.
authors.forename: Scott Ik
authors.initials: SI
authors.lastname: Semple
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D003287:Contrast Media / Q000008:administration & dosage*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008955:Models, Cardiovascular; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D012039:Regional Blood Flow; D015203:Reproducibility of Results; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D014665:Vasodilator Agents; C090600:gadobutrol; D000241:Adenosine