Cardiac magnetic resonance imaging in small animal models of human heart failure
Introduction
There are several well established small animal models in cardiology research, two of them being rats and mice. The rat heart infarct model has been proven to be predictive for cardiac remodeling after myocardial infarction (MI) in patients and for therapy (Pfeffer et al., 1985, Pfeffer et al., 1979). Medication such as ACE inhibitors, which are now in routine use for treatment or prevention of heart failure, were first tested in that model (Pfeffer et al., 1985). The mouse has gained importance due to opportunities for producing transgene models. But in both animals, in vivo assessment of cardiac morphology and function is hindered by the small size of the heart and its rapid action. Depending on the bodyweight, the left ventricle of a rat heart weighs ∼500 mg, while that of a mouse is less than 100 mg. Nevertheless, it is desirable to monitor changes of even a fraction of that weight to characterize the influence of pharmacological interventions or manipulation of genotype. In addition, the heart rate of 300 per minute in the rat and 500 per minute in the mouse is challenging for assessment of cardiac function.
Being non-invasive and exact, magnetic resonance imaging (MRI) can offer new insights allowing serial investigations of rat and mice cardiac morphology and function. The aim of the study was to compare data acquired by MRI and conventional, established methods (Pfeffer and Frohlich, 1972; Pfeffer et al., 1979). After completion of the validation experiments, the technique was used for investigation of cardiac remodeling after induction of ischemia in the mouse and applied to several interventional studies in the rat heart infarction model, such as impact of transmyocardial laser revascularisation on remodeling after MI, and influence of androgene levels and of cerivastatin therapy on left ventricular remodeling.
Section snippets
Cine MRI
Cine MRI was performed on a 7 T-Biospec (Bruker, Germany) using an ECG-triggered FLASH-sequence. For rat imaging, a home-built rat-sized whole body coil was used as transmitter and a surface coil as receiver. An ECG-triggered fast gradient echo (FLASH) cine sequence was used (Haase et al., 1986). Flip angle was 30–40°, echo time was 1.1 ms, and repetition time 3.2 ms. A total of 12 frames per heart cycle were obtained. The total acquisition time (TAT) for one cine sequence was 40–50 s depending
Results of the validation study
As shown in Table 1, good correlation between MRI and invasive techniques was found. Significant differences between methods were detected in infarct size, end-diastolic volume and ejection fraction.
Discussion and application studies
The validation study showed good agreement of MRI-acquired data with established methods for measuring LV mass and stroke volume. Both methods to determine MI-size correlate well, differing only by 5%. The difference with the MRI-method is due to inhomogeneity of shrinkage caused by formalin fixation of the excised hearts. There was good correlation of postmortal determined volume with in vivo measured end-diastolic volume. The significant difference was bigger in the controls than in MI-rats
Conclusion
In the validation study MRI was shown to correlate closely with invasive or ex vivo techniques that are typically used in the rat model of myocardial infarction. Due to its non-invasive character, MRI allows for serial investigations of the same animal. Hence, changes due to therapy or interventions can be monitored closely and more exactly. Small differences can be detected, and the number of animals to be sacrificed for research purposes is reduced.
In conclusion we show that cardiac MRI is a
Acknowledgments
This work was supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich “Pathophysiologie der Herzinsuffizienz” SFB 355/A8.
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