Nonlinear dynamics of single freely-floating microbubbles under prolonged insonation

The acoustic nonlinear responses of ultrasound contrast agent microbubbles (MBs) are of great interest for both diagnostic and therapeutic applications. Previously, optical and acoustical methods were developed to characterize single bubbles floating against a rigid wall. However, there is a need to develop an efficient approach for statistical measurement of single freely-floating MBs. Here we combine simultaneous optical sizing and sensitive acoustical characterization measurement to study quantitatively the nonlinear dynamics of single freely-floating bubbles under prolonged ultrasound exposure. The nonlinearity (ε_2f, ε_3f) and asymmetry (i.e., compression-dominant behavior) of bubble vibrations were found to increase with increasing oscillation amplitude, and reach the maximum for bubbles at resonance. Moreover, with the same fundamental response (ε_f), the second harmonic response (ε_2f) of bubbles smaller than the resonance size is ~150% stronger than bubbles bigger than the resonance size. The data showed agreement with numerical simulations based on the shell-buckling model by Marmottant et al. The new system shows its great potential for in vitro characterization of contrast agent MB populations.