The aim of this study was to use multi-detector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
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 setting. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n=9) or 200 million mesenchymal stem cells (MSCs, n=13), twelve weeks after myocardial infarction (MI). Cardiac MRI and MDCT acquisitions were performed prior to randomization 12 weeks after MI induction and at the study endpoint 24 week post-MI. 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.
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) while infarct size increased in non-treated 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 MRI acquisitions (r=0.70; r=0.82; r=0.902; respectively, p<0.001).
This study demonstrates 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. (word count 299)
Keywords: MDCT, MRI, Delayed Contrast Enhancement, Göttingen Minipig, Mesenchymal Stem Cell, Myocardial Infarction, Heart failure