title: CT for evaluation of myocardial cell therapy in heart failure: a comparison with CMR imaging.
abstract: OBJECTIVE
  The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
  
  
  BACKGROUND
  Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
  
  
  METHODS
  Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
  
  
  RESULTS
  MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001).
  
  
  CONCLUSIONS
  This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21205, USA. kschuleri@jhmi.edu
authors.forename: Karl H
authors.initials: KH
authors.lastname: Schuleri
authors.forename: Marco
authors.initials: M
authors.lastname: Centola
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Choi
authors.forename: Kristine S
authors.initials: KS
authors.lastname: Evers
authors.forename: Fady
authors.initials: F
authors.lastname: Dawoud
authors.forename: Richard T
authors.initials: RT
authors.lastname: George
authors.forename: João A C
authors.initials: JA
authors.lastname: Lima
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lardo
mesh_terms: D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D006333:Heart Failure / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016014:Linear Models; D019028:Magnetic Resonance Imaging, Cine; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D015588:Observer Variation; D011237:Predictive Value of Tests; D020127:Recovery of Function; D012038:Regeneration; D015203:Reproducibility of Results; D013318:Stroke Volume; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids; D016277:Ventricular Function, Left
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; C044834:iodixanol; D019786:Gadolinium DTPA