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^TM and Optison^TM) and polystyrene microbeads as control scatterers. For Definity^TM, subharmonic (0.5f₀) and ultraharmonic (1.5f₀) scattering was substantial and strongly dependent on pressure up to 26 MHz. Optison^TM also exhibited sub- and ultraharmonic scattering, but these effects were weaker and found to persist up to 22 MHz. Second harmonic (2f₀) scattering for Definity^TM, Optison^TM and the microbeads was strong and increased with pressure suggesting a significant component of 2f₀ agent signal was due to non-linear propagation. However, the ratio of 2f₀ to f ₀ scattering was higher for agent than for microbeads (20 dB for Definity^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