title: Quantitative assessment of magnetic resonance derived myocardial perfusion measurements using advanced techniques: microsphere validation in an explanted pig heart system.
abstract: BACKGROUND
  Cardiovascular Magnetic Resonance (CMR) myocardial perfusion imaging has the potential to evolve into a method allowing full quantification of myocardial blood flow (MBF) in clinical routine. Multiple quantification pathways have been proposed. However at present it remains unclear which algorithm is the most accurate. An isolated perfused, magnetic resonance (MR) compatible pig heart model allows very accurate titration of MBF and in combination with high-resolution assessment of fluorescently-labeled microspheres represents a near optimal platform for validation. We sought to investigate which algorithm is most suited to quantify myocardial perfusion by CMR at 1.5 and 3 Tesla using state of the art CMR perfusion techniques and quantification algorithms.
  
  
  METHODS
  First-pass perfusion CMR was performed in an MR compatible blood perfused pig heart model. We acquired perfusion images at physiological flow ("rest"), reduced flow ("ischaemia") and during adenosine-induced hyperaemia ("hyperaemia") as well as during coronary occlusion. Perfusion CMR was performed at 1.5 Tesla (n = 4 animals) and at 3 Tesla (n = 4 animals). Fluorescently-labeled microspheres and externally controlled coronary blood flow served as reference standards for comparison of different quantification strategies, namely Fermi function deconvolution (Fermi), autoregressive moving average modelling (ARMA), exponential basis deconvolution (Exponential) and B-spline basis deconvolution (B-spline).
  
  
  RESULTS
  All CMR derived MBF estimates significantly correlated with microsphere results. The best correlation was achieved with Fermi function deconvolution both at 1.5 Tesla (r = 0.93, p < 0.001) and at 3 Tesla (r = 0.9, p < 0.001). Fermi correlated significantly better with the microspheres than all other methods at 3 Tesla (p < 0.002). B-spline performed worse than Fermi and Exponential at 1.5 Tesla and showed the weakest correlation to microspheres (r = 0.74, p < 0.001). All other comparisons were not significant. At 3 Tesla exponential deconvolution performed worst (r = 0.49, p < 0.001).
  
  
  CONCLUSIONS
  CMR derived quantitative blood flow estimates correlate with true myocardial blood flow in a controlled animal model. Amongst the different techniques, Fermi function deconvolution was the most accurate technique at both field strengths. Perfusion CMR based on Fermi function deconvolution may therefore emerge as a useful clinical tool providing accurate quantitative blood flow assessment.
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. andreas_schuster@gmx.net.|Department of Cardiology and Pneumology and German Centre for Cardiovascular Research (DZHK, Partner Site Göttingen), Georg-August-University, Göttingen, Germany. andreas_schuster@gmx.net.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schuster
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. niloufar.zarinabad@kcl.ac.uk.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Zarinabad
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. ishidamasaki1@gmail.com.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. matthew.sinclair@kcl.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sinclair
authors.affiliation: Department of Biomedical Engineering & Physics, Academic Medical Centre, Amsterdam, The Netherlands. J.P.vandenWijngaard@amc.uva.nl.
authors.forename: Jeroen Phm
authors.initials: JP
authors.lastname: van den Wijngaard
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. geraintmorton@gmail.com.
authors.forename: Geraint
authors.initials: G
authors.lastname: Morton
authors.affiliation: Philips Healthcare, Imaging Systems - MR, Best, The Netherlands. gilion.hautvast@philips.com.
authors.forename: Gilion Ltf
authors.initials: GL
authors.lastname: Hautvast
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. dr.bigalke@gmx.de.|Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Tübingen, Germany. dr.bigalke@gmx.de.
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.affiliation: Department of Biomedical Engineering & Physics, Academic Medical Centre, Amsterdam, The Netherlands. phorssen@gmail.com.
authors.forename: Pepijn
authors.initials: P
authors.lastname: van Horssen
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. nicolas.smith@kcl.ac.uk.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering & Physics, Academic Medical Centre, Amsterdam, The Netherlands. j.a.spaan@amc.uva.nl.
authors.forename: Jos Ae
authors.initials: JA
authors.lastname: Spaan
authors.affiliation: Department of Biomedical Engineering & Physics, Academic Medical Centre, Amsterdam, The Netherlands. m.siebes@amc.uva.nl.
authors.forename: Maria
authors.initials: M
authors.lastname: Siebes
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. amedeo.chiribiri@kcl.ac.uk.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Chiribiri
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering; King's College London British Heart Foundation (BHF) Centre of Excellence; National Institute of Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust; Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) Medical Engineering Centre, The Rayne Institute, St. Thomas´ Hospital, London, UK. eike.nagel@kcl.ac.uk.
authors.forename: Eike
authors.initials: E
authors.lastname: Nagel
mesh_terms: D000465:Algorithms; D000818:Animals; D001783:Blood Flow Velocity; D003287:Contrast Media; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000175:diagnosis / Q000503:physiopathology; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006940:Hyperemia / Q000175:diagnosis / Q000503:physiopathology; D007090:Image Interpretation, Computer-Assisted; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D045423:Microbubbles; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009942:Organometallic Compounds; D010477:Perfusion; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013552:Swine; D013997:Time Factors
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; C090600:gadobutrol