Active control of subharmonic response of ultrasound contrast agent microbubbles

The influence of a dynamic variation in the ambient pressure on the subharmonic response of phospholipid-coated microbubbles was investigated. The ambient pressure in water was modulated by a 2.5 kHz acoustic wave with peak amplitude of 15 kPa. We investigated the fundamental and subharmonic emission at two driving frequencies: 5 and 10 MHz. We measured that the variation in the ambient pressure of 15 kPa can modulate the subharmonic amplitude up to 10 dB. We also noticed that the relative subharmonic amplitude modulation as a function of the LF acoustic pressure was symmetrical for the 5 MHz driving frequency but asymmetric for 10 MHz. However the fundamental amplitude was symmetrically modulated during bubble compression and expansion. Numerical simulations showed that these behaviors can be obtained and are depending on the bubbles´ diameter. The highest subharmonic amplitude was measured when microbubbles were insonified at 10 MHz. This fact together with the asymmetry observed in the subharmonic modulation suggests that smaller bubbles with buckling shell are excited at 10 MHz compared to experiments at 5 MHz. These results present new potentials for in vitro characterization of contrast agent microbubbles and possibly a new imaging modality.