title: Translation of Methodology Used In Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction.
abstract: BACKGROUND
  Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention.
  
  
  METHODS
  Eighteen sheep were enrolled in a pilot study to evaluate [(99m)Tc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement was measured using Kappa (κ). Power determined the sample sizes needed to show statistically significant changes due to intervention.
  
  
  RESULTS
  Ten sheep completed the full protocol. Data processed was performed with pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15%-35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89). Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion.
  
  
  CONCLUSIONS
  This study demonstrates the suitability of large animal models for imaging with standard MPI protocols and its feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair.
authors.affiliation: Department of Nuclear Medicine, Royal North Shore Hospital, Australia; Discipline of Medical Radiation Sciences, University of Sydney, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bailey
authors.affiliation: Department of Nuclear Medicine, Royal North Shore Hospital, Australia; Discipline of Medical Radiation Sciences, University of Sydney, Australia; Sydney Medical School, University of Sydney, Australia.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Bailey
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Australia; Sydney Medical School, University of Sydney, Australia; Cardiac Technology Centre, North Shore Heart Research Group, Kolling Institute, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hunyor
authors.affiliation: Cardiac Technology Centre, North Shore Heart Research Group, Kolling Institute, Australia; Charles Sturt University, Wagga Wagga, Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Ladd
authors.affiliation: Department of Nuclear Medicine, Royal North Shore Hospital, Australia.
authors.forename: George J
authors.initials: GJ
authors.lastname: Bautovich
keywords: Mesenchymal stem Cells; Myocardial perfusion Imaging; Ovine model; SPECT/CT