Enhanced ambient pressure sensitivity of the subharmonic signal from ultrasound contrast microbubbles

Microbubble ultrasound contrast agent (UCA) has been well recognized as a potential noninvasive tool for the blood pressure measurement. A decrease in subharmonic amplitude of 9 to 12 dB has been reported for Levovist, Optison, Definity, Sonazoid, and SonoVue for ambient overpressure values around 180 mmHg. However, a pressure resolution of 3 mmHg is desirable in medical diagnostics, it is still necessary to enhance the pressure sensitivity for the method based on the subharmonic amplitude as a function of local pressure. The purpose of this study was to improve the ambient pressure sensitivity of the subharmonic amplitude by optimizing acoustic parameters in in vitro experiments. The acoustic scattering measurement was carried out at different acoustic parameters, and it was demonstrated for SonoVue by us that the subharmonic amplitude reduced by 10.9 dB at the driving frequency of 4 MHz and the acoustic pressure of 450 kPa (mechanical index MI = 0.225), 19.8 dB at 4 MHz and 500 kPa (MI = 0.25), and 17.6 dB at 1.33 MHz and 350 kPa (MI = 0.3), respectively, when the overpressure increased to 180 mmHg. The results showed the effect of the mechanical index on the ambient pressure sensitivity of subharmonic amplitude, and indicated the existence of a MI threshold ( ≈ 0.23) at which the sensitivity can be enhanced significantly.