An in vitro study of subharmonic emissions from monodisperse lipid-coated microbubbles

Abstract

Subharmonic imaging is an ultrasound imaging method which utilizes the subharmonic response of a contrast agent to ultrasound excitation. It is possible to achieve high agent-to-tissue contrast because tissues do not emit subharmonic signals. In this project, we investigated the relationship between subharmonic emissions from monodisperse lipid-coated microbubbles and acoustic pressure. First, the resonance frequency for monodisperse microbubble suspension was determined from attenuation spectra measured using a through-transmission technique. Next, the microbubbles were excited at the resonance and at twice the resonance frequency. A transducer positioned orthogonal to the excitation transducer was used to detect acoustic emissions from the microbubbles at half the excitation frequency. It was found that the pressure required for subharmonic emissions was lower when monodisperse microbubbles were excited at twice the resonance frequency. For example, 6.5μm diameter microbubbles with a resonance frequency of 1.4 MHz had a pressure threshold for subharmonic emissions of approximately 30 kPa at 2.8 MHz excitation while those excited at 1.4 MHz could not be forced into subharmonic oscillations for the pressure range we used in this study (i.e., below 150 kPa). Implications of these results on the use of monodisperse lipid-coated microbubbles for subharmonic imaging will be discussed.