Arrhythmias in Rat Hearts Exposed to Pulsed Ultrasound After Intravenous Injection of a Contrast Agent

Abstract

ot only is the heart a challenging organ to image, with rhythm and motion fundamental to its design, but it lets you know when it is unhappy. Although contrast-enhanced sonographic techniques for vascular definition and for evaluation of perfusion have had an impact in liver and kidney studies,1–4 nonetheless, the heart as a functional organ in view of the wide prevalence of ischemic heart disease can be imaged and its function can be assessed by cardiac sonography. However, a sonographic method for describing myocardial perfusion directly has been lacking. With this “grail” in mind, a number of companies and investigators have actively been involved in the pursuit of agents and methods for imaging myocardial perfusion. There has been extremely clever science, not only from developers of contrast agents but also from scientists, investigators, and ultrasound engineers. The whole field of ultrasound has benefited vastly from the development of harmonic imaging strategies, and broadband, pulse inversion, and coded excitation implementations have yielded new energy delivery schemes almost as complicated as those used in magnetic resonance imaging. The concepts of intermittent imaging, burst imaging, and computation of the slope of the contrast wash-in curve as indicators of regional perfusion, either on gray scale or power mode images, use the indicator dilution theory and explore the difference between intravascular and extravascular contrast agent penetration. The ability to “break” bubbles, although requiring alterations of the indicator dilution theory, led to notable new horizons in the possibilities for targeted delivery of drugs and even genes loaded into bubbles. I remember in the early 1980s, when Doppler echocardiography required high pulse repetition frequencies, with multiple bursts occurring along individual lines of sight, the Bioeffects Committee of the American Institute of Ultrasound in Medicine became active in a dialogue with the Bureau of Radiologic Health and the Food and Drug Administration. Discussions especially related to the possibility of fetal risk occurred at the time. There was little clinical interest in contrast-enhanced echocardiography at the time; although Echovist had been licensed to Schering (Berlin, Germany), Levovist had not yet been developed. Nonetheless, in documents that preceded those referenced in the interesting article by Zachary et al5 in this issue of the Journal of Ultrasound in Medicine, a body of American Institute of Ultrasound in Medicine bioeffects statements,6–9 although emphasizing thermal effects, raised the possibility that mechanical effects could become amplified and consequential in the presence of gas nuclei, such as within