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Updated: Aug 13, 2026
In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography
Published on: February 16, 2016
Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial
Matthias Nahrendorf1, Jörg U Streif, Karl-Heinz Hiller
1Medizinische Klinik und Poliklinik 1, Universität Würzburg, Josef Schneider-Strasse 2, 97080 Würzburg, Germany.
Insights
Mice lacking the creatine kinase (CK) system show normal ejection fraction but reduced maximal contraction velocity and myocardial perfusion. These findings suggest CK deficiency impairs heart function, even when gross measures appear normal.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Decreased ATP supply from the creatine kinase (CK) system is implicated in heart failure development.
- Previous studies on CK-deficient mice (CK(-/-)) did not reveal significant left ventricular dysfunction.
Purpose of the Study:
- To investigate myocardial phenotype abnormalities in CK(-/-) mice using novel MRI techniques.
- To assess maximal myocardial velocity (V(max)) and myocardial perfusion at baseline and post-myocardial infarction (MI).
Main Methods:
- Utilized novel magnetic resonance imaging (MRI) to measure V(max) and myocardial perfusion.
- Evaluated CK(-/-) mice and wild-type controls at baseline and 4 weeks after induced myocardial infarction (MI).
- Assessed myocardial hypertrophy, ejection fraction (EF), and capillary density via histology.
Main Results:
- CK(-/-) mice exhibited myocardial hypertrophy but maintained normal ejection fraction.
- Significantly reduced V(max) and myocardial perfusion were observed in CK(-/-) mice compared to wild-type.
- Reduced capillary density in CK(-/-) mice paralleled the observed decrease in perfusion.
Conclusions:
- Standard measures like ejection fraction may mask underlying cardiac dysfunction in CK-deficient mice.
- Novel MRI techniques revealed reduced perfusion and maximal contraction velocity in CK(-/-) mice.
- Myocardial hypertrophy in CK-deficient mice does not fully compensate for the absence of the CK system.
Abstract:
A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.
