Non-linear scattering from microbubble contrast agents in the 14-40 MHz range

The non-linear scattering properties of microbubble contrast agents in the 14-40 MHz frequency range are investigated. Experiments were conducted as a function of pressure for two agents (Definity/sup TM/ and Optison/sup TM/) and polystyrene microbeads as control scatterers. For Definity/sup TM/, subharmonic (0.5f/sub 0/) and ultraharmonic (1.5f/sub 0/) scattering was substantial and strongly dependent on pressure up to 26 MHz. Optison/sup TM/ also exhibited sub- and ultraharmonic scattering, but these effects were weaker and found to persist up to 22 MHz. Second harmonic (2f/sub 0/) scattering for Definity/sup TM/, Optison/sup TM/ and the microbeads was strong and increased with pressure suggesting a significant component of 2f/sub 0/ agent signal was due to non-linear propagation. However, the ratio of 2f/sub 0/ to f/sub 0/ scattering was higher for agent than for microbeads (20 dB for Definity/sup TM/) after correcting for frequency dependent microbead scattering. A test for bubble destruction at 20 MHz revealed that a significant subpopulation of bubbles could be disrupted. We conclude that non-linear scattering can be produced with high frequency ultrasound technology and currently available agents. This suggests the possibility of implementing non-linear detection and destruction techniques at high frequencies.