An acoustic study of disruption of polymer-shelled bubbles [microbubble contrast agents]

The goal of this study was to assess the threshold of disruption and the time-course of the subsequent acoustic response of four agents comprising gas encapsulated within a polymer shell. The four agents shared the same bubble diameter (∼4 μm), contained the same gas (N₂) but had shell thicknesses that varied by a factor of 5. The time-course of the response was assessed by applying a series of pulses to a diluted suspension of these agents. Measurements showed that the pre-disruption response of the agents decreased with increasing shell thickness. Above the disruption threshold for the agents, highly echogenic, nonlinear scatterers were observed and persisted for a mean half-life of about 12 ms, which is consistent with the free diffusion of N₂ in water. This suggests a picture wherein the shell is disrupted, releasing the gas contained within the bubble, generating free gas bubbles. This release is followed by diffusion of the gas into solution and resonant, high amplitude nonlinear scattering. The optimum bubble tested combined a shell thickness which produced a well-defined disruption threshold within the diagnostic range and a gas which dissolved relatively rapidly, thus increasing the decorrelation signal obtainable for disruption diagnostic imaging.