Frequency relationships for ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled...

The ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled micropores was explored using available linear theory. Encapsulated microbubbles, used in contrast agents for diagnostic ultrasound, have relatively high resonance frequencies and damping. At 2 MHz the resonance radii are 1.75 microns for free microbubbles, 4.0 microns for encapsulated microbubbles, and 1.84 microns for gas-filled micropores. Higher-pressure amplitudes are needed to elicit equivalent subharmonic, fundamental, or second-harmonic responses from the encapsulated microbubbles, and this behavior increases for higher frequencies. If an encapsulated microbubble becomes destabilized during exposure,the resulting liberated microbubble would be about twice the linear resonance size, which would be likely to produce subharmonic signals. Scattered signals used for medical imaging purposes may be indicative of bioeffects potential: The second harmonic signal is proportional to local shear stress for a microbubble on a boundary, and a strong subharmonic signal may imply destabilization and nucleation of free-microbubble cavitation activity. The potential for bioeffects from contrast agent gas bodies decreases rapidly with increasing frequency. This information should be valuable for understanding of the etiology of bioeffects related to contrast agents and for developing exposure indices and risk management strategies for their use in diagnostic ultrasound.