MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates

Transgenic mice are increasingly used to probe genetic aspects of cardiovas cular pathophysiology. However, the small size and rapid rates of murine he arts make noninvasive, physiological in vivo studies of cardiac bioenergeti cs and contractility difficult. The aim of this report was to develop an in tegrated, noninvasive means of studying in vivo murine cardiac metabolism, morphology, and function under physiological conditions by adapting and mod ifying noninvasive cardiac magnetic resonance imaging (MRI) with image-guid ed P-31 magnetic resonance spectroscopy techniques used in humans to mice. Using spatially localized, noninvasive P-31 nuclear magnetic resonance spec troscopy and MRI at 4.7 T, we observe mean murine in vivo myocardial phosph ocreatine-to-ATP ratios of 2.0 +/- 0.2 and left ventricular ejection fracti ons of 65 +/- 7% at physiological heart rates (similar to 600 beats/min). T hese values in the smallest species studied to date are similar to those re ported in normal humans. Although these observations do not confirm a degre e of metabolic scaling with body size proposed by prior predictions, they d o suggest that mice can serve, at least at this level, as a model for human cardiovascular physiology. Thus it is now possible to noninvasively study in vivo myocardial bioenergetics, morphology, and contractile function in m ice under physiological conditions.