Subharmonic response of lipid-coated monodisperse microbubbles

Abstract

Subharmonic emissions from lipid-coated microbubbles, which is not radiated by tissues, can be leveraged to improve contrast-enhanced diagnostic ultrasound. In our work, we investigated subharmonic emissions from monodisperse lipid-coated microbubbles under different acoustic pressure and frequencies. First, the resonance frequency of microbubble monodispersion was determined from measured attenuation spectrum. Next, acoustic emissions from the microbubbles were detected by a transducer positioned orthogonal to the excitation transducer. Our study showed that subharmonic emissions were maximized when bubbles were driven at nearly twice the pressure-dependent resonance frequency rather than the linear resonance frequency. We also observed subharmonic emission at low excitation acoustic pressure (< = 30 kPa) for microbubbles coated with densely packed lipid shells, which suggests that minimizing the initial surface tension can enable subharmonic emissions at very low excitation pressures. Further studies were conducted with shells composed of varying lipids to test the influence of shell composition on the initial surface tension and subharmonic emissions. Theoretical simulations were carried out and agreed with the experimental trends. Implications of these results on the use of monodisperse lipid-coated microbubbles for subharmonic imaging will be discussed.