Elsevier

Medical Image Analysis

Volume 7, Issue 3, September 2003, Pages 369-375
Medical Image Analysis

Cardiac magnetic resonance imaging in small animal models of human heart failure

https://doi.org/10.1016/S1361-8415(03)00011-2Get rights and content

Abstract

The aim of this study was to test the feasibility of cine magnetic resonance imaging (MRI) for assessment of the infarcted rat and mouse heart and to compare the results with established methods. These models have been proven to predict genesis and prevention of heart failure in patients. The value of cine MRI was tested in studies investigating interventions to change the course of the remodeling process. MRI was performed for determination of left ventricular (LV) volumes and mass, myocardial infarct (MI) size and cardiac output. LV wet weight was determined after MRI. Rats underwent conventional hemodynamic measurements for determination of cardiac output and LV volumes by electromagnetic flowmeter and pressure–volume curves. Infarct size was determined by histology. MRI-acquired MI-size (18.5±2%) was smaller than that found by histology (22.8±2.5%, p<0.05) with close correlation (r=0.97). There was agreement in LV mass between MRI and wet weight (r=0.97, p<0.05) and in the MRI- and flowmeter measurements of cardiac output (r=0.80, p<0.05). Volume by MRI differed from pressure–volume curves with good correlation (r=0.96, p<0.05). In a serial study of mice after coronary ligation, LV hypertrophy at 8 weeks was detected (Sham 105.1±7.9 mg, MI 144.4±11.7 mg, p<0.05). Left ventricles were enlarged in infarcted mice (end-diastolic volume, week 8: Sham 63.5±4 μl, MI 94.2 μl, p<0.05). In conclusion, cine MRI is a valuable diagnostic tool applicable to the rat and mouse model of MI. Being non-invasive and exact it offers new insights into the remodeling process after MI because serial measurements are possible. The technique was applied to study several interventions and proved its usefulness.

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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