Destruction of Contrast Agent Microbubbles in the Ultrasound Field: The Fate of the Microbubble Shell and the Importance of the Bubble Gas Content

Abstract

Disappearance of ultrasound (US) contrast agents (gasfilled microbubbles) after contrast agent administration in the bloodstream occurs by way of several mechanisms. First, microbubbles are filtered and captured by various organs, including uptake by Kupffer cells in the liver (1,2). Second, gas diffuses from the microbubble core and dissolves in the surrounding medium, leaving the nonechogenic shell behind (3). The third process is the most rapid and important for the practice of diagnostic imaging by US. It is the destruction of microbubbles by the acoustic field of the US medical imaging system. It has been shown that the rate of microbubble destruction in the ultrasound field depends on the ultrasound frequency and pressure (4–7). During imaging, the microbubble contrast agent can be destroyed by a single pulse of the ultrasound, if the ultrasound mechanical index (MI) value is high enough (7,8). This phenomenon has been applied successfully for the imaging of tissue perfusion and perfusion defects (8,9). Thus, the mechanisms of microbubble contrast agent disappearance in the ultrasound field are important and need to be investigated in detail. We have previously reported a microbubble destruction/microscopy study performed with an air-filled microbubble agent, sonicated human serum albumin (Albunex; Mallinckrodt, St Louis, Mo) (10). More recent contrast agents filled with insoluble fluorinated gases, such as Optison (Mallinckrodt), demonstrate extended in vivo circulation and stability (11). It is of interest to evaluate the stability of these microbubbles in the field of the US medical imager. The nature of the gas and the gas exchange may play an important role in the bubble destruction. Here, we describe video microscopic studies performed in vitro for immobilized microbubbles during their insonification. Fluorescence microscopy was used to evaluate the behavior of microbubble shells during the destruction of microbubbles.