Experimental Investigations of Nonlinearities and Destruction Mechanisms of an Experimental Phospholipid-Based Ultrasound Contrast Agent

Objectives:We sought to characterize the acoustical behavior of the experimental ultrasound contrast agent BR14 by determining the acoustic pressure threshold above which nonlinear oscillation becomes significant and investigating microbubble destruction mechanisms. Materials and methods: We used a custom-designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz varying acoustic pressure (range, 50+/-190 kPa). We also performed granulometric analyses on contrast agent solutions to accurately measure microbubble size distribution and to evaluate insoniÞcation effects. Results: Attenuation did not depend on acoustic pressure less than 100 kPa, indicating this pressure as the threshold for the appearance of microbubble nonlinear behavior. At the lowest excitation amplitude, attenuation increased during insonification, while, at higher excitation levels, the attenuation decreased over time, indicating microbubble destruction. The destruction rate changed with pressure amplitude suggesting different destruction mechanisms, as it was confirmed by granulometric analysis. Conclusions: Microbubbles showed a linear behavior until 100 kPa, whereas beyond this value significant nonlinearities occurred. Observed destruction phenomena seem to be mainly due to gas diffusion and bubble fragmentation mechanisms.