Subharmonic Scattering of Phospholipid-Shell Microbubbles at Low Acoustic Pressure Amplitudes

Subharmonic scattering of phospholipid-shell microbubbles excited at relatively low acoustic pressure amplitudes (<30 kPa) has been associated with echo responses from compression-only bubbles having initial surface tension values close to zero. In this work, the relation between subharmonics and compression-only behavior of phospholipid-shell microbubbles was investigated, experimentally and by simulation, as a function of the initial surface tension by applying ambient overpressures of 0 and 180 mmHg. The microbubbles were excited using a 64-cycle transmit burst with a center frequency of 4 MHz and peak-negative pressure amplitudes ranging from 20 of 150 kPa. In these conditions, an increase in subharmonic response of 28.9 dB (P < 0.05) was measured at 50 kPa after applying an overpressure of 180 mmHg. Simulations using the Marmottant model, taking into account the effect of ambient overpressure on bubble size and initial surface tension, confirmed the relation between subharmonics observed in the pressure-time curves and compression-only behavior observed in the radius-time curves. The trend of an increase in subharmonic response as a function of ambient overpressure, i.e., as a function of the initial surface tension, was predicted by the model. Subharmonics present in the echo responses of phospholipid-shell microbubbles excited at low acoustic pressure amplitudes are indeed related to the echo responses from compression-only bubbles. The increase in subharmonics as a function of ambient overpressure may be exploited for improving methods for noninvasive pressure measurement in heart cavities or big vessels in the human body.