Investigating the significance of multiple scattering in ultrasound contrast agent particle populations

The majority of the existing models describing the behavior of microbubble ultrasound contrast agents consider single, isolated microbubbles suspended in infinite media. The behavior of a microbubble population is predicted by summing the results for single microbubbles and ignoring multiple scattering effects. The aim of this investigation is to determine the significance of multiple scattering in microbubble populations and establish whether an alternative approach is required. In the first part of the work, linear models are derived to identify approximately the conditions under which multiple scattering may be expected. A nonlinear model for sound propagation in a microbubble suspension then is developed and used to examine multiple scattering at higher insonation pressures. Broadband attenuation measurements are described for two different types of microbubble suspension (albumin encapsulated octofluropropane and copolymer encapsulated isobutane) to ascertain whether or not multiple scattering may be observed experimentally. The results from the simulation work indicate that multiple scattering effects would be discernible at moderate concentrations (106 microbubbles/ml) such as may be present in vivo. The effect upon attenuation in the suspension would be pronounced, however, only if the population contained a sufficient proportion of relatively large (> 4 mu m radius) microbubbles excited at their resonance frequency. This also is found to be the case experimentally. These findings may have important implications for the characterization of ultrasound contrast agents and their use in quantitative diagnostic techniques.