Noninvasive cardiovascular phenotyping in mice

With the growth of genetic engineering, mice have become common as models of human diseases, which in turn has stimulated the development of techniques to monitor and image the murine cardiovascular system. Invasive methods are often more quantitative, but noninvasive methods are preferred when measurements must be repeated serially on living animals during development or in response to pharmacological or surgical interventions. Because of the small size and high heart rates in mice, high spatial and temporal resolutions are required to preserve signal fidelity. Monitoring of body temperature and the electrocardiogram is essential when animals must be anesthetized for a measurement or other procedure. Several other groups have developed cardiovascular imaging modalities suitable for murine applications, and ultrasound is the most widely used. Our group has developed and applied high-resolution Doppler probes and signal processing for measuring blood velocity in the heart and peripheral vessels of anesthetized mice noninvasively. We can measure cardiac filling and ejection velocities as indices of systolic and diastolic ventricular function and for timing of cardiac events; velocity pulse arrival times for determining pulse-wave velocity and arterial stiffness; peripheral velocity waveforms as indices of arterial resistance, compliance, and wave reflections; stenotic velocities for estimation of pressure drop and detection of vorticity; and tail artery velocity for determining systolic and diastolic blood pressure using a pressure cuff. These noninvasive methods are convenient and easy to apply and have been used to detect and evaluate numerous cardiovascular phenotypes in mutant mice.