Assessment of transient myocardial perfusion defects in intact mice using a microbubble contrast destruction/refill approach

The mouse provides a very useful model for human cardiovascular disease. Consequently, there is significant need for noninvasive approaches for assessing left ventricular function in the setting of various cardiovascular pathophysiological conditions induced in normal and genetically-modified mice. In this work, myocardial contrast echocardiography (MCE) was used to identify regions of ischemia within ultrasound images of the left ventricular myocardium in closed-chest, intact mice. Contrast agent was infused at a constant rate and, periodically, high intensity, contrast destructive frames were applied. Thereafter, an exponential refill curve was fitted to the mean gray scale value within the selected region of interest. Perfusion was investigated before, during and immediately after an induced ischemic event. As anticipated, a significantly reduced refill rate was observed during ischemia. The refill exponential rate constant was observed to decline by 35% in the region of myocardium affected by the induced ischemia.