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DOI: 10.1055/s-0031-1297411
Assessing LV function in small animal models: Is MRI always superior to echocardiography?
Objective: The preclinical evaluation of novel myocardial regeneration studies relies heavily on reproducible assessment of global and regional cardiac function. Magnetic resonance imaging (MRI) is considered the gold-standard for LV function measurement, but requires complex experimental setup and general anesthesia. We developed a method for 2D speckle tracking echocardiography in mice, and systematically compared its validity with that of MRI data.
Methods: Twenty-six mice underwent permanent LAD ligation for induction of myocardial infarction. Twenty-two of those received cardiac cell therapy (mesenchymal stromal cells or amnion epithelial cells), and 4 injection of medium only (control). For weeks after treatment, all animals first underwent transthoracic 2D speckle tracking echocardiography with longitudinal strain measurement in light sedation, and were later anesthesized and intubated for cardiac MRI in a clinical 1.5 T magnet equipped with a dedicated small animal coil. Global and regional LV function data were analyzed in blinded fashion and compared with infarct size evaluation by histology.
Results: As determined by MRI, LAD ligation led to reduced LVEF (31±6%) and increased LVEDV (0.14±0.5)ml and LVESV (0.98±0.3ml), but cell transplantation did not lead to a change in any of these parameters (LVEF 30±8%, p=0.4; LVEDV 0.15±0.3ml, p=0.2; LVESV 0.95±0.4ml, p=0.6). By echocardiography, however, cell transplantation led to significantly improved global LV function (LVEF 53±10%, p=0.001). Regional contractile function in the area-of-interest (AOI) was also improved, as reflected by greater wall thickening (AOI p=0.01 vs. control) and by 2D longitudinal strain and strain rate (48±12% vs. 21±14%, p=0.001). These correlated with histology findings, that showed reduced infarct size and greater AOI wall thickness in cell-treated hearts. Isoflurane anesthesia led to markedly reduced heart rate during MRI, while light sedation for echocardiography was associated with significantly higher heart rate. Heart rate at the time of investigation was identified as a predictor of change in LV function.
Conclusion: In Cardiac MRI, general anesthesia associated cardiac depression in mice masks cell-therapy induced changes in contractile function. Speckle tracking echocardiography data correlate more closely with changes in histology and may reflect LV function more accurately.