SonoVue Microbubbles as Ultrasound Pressure Sensors in a Dynamic Flow Phantom

Abstract

Cardiac catheterization is the gold standard for assessing cardiac pressures. However, this is an invasive and costly procedure. An alternative may be to use the subharmonic signal of microbubble ultrasound contrast agents to estimate pressure using echocardiography. The aim of this work was to investigate the subharmonic response of the ultrasound contrast agent SonoVue (Bracco Spa, Milan, Italy) to dynamic pressures in a flow phantom. SonoVue was circulated through a silicone tube using a peristaltic pump. The ULtrasound Advanced Open Platform (ULA-OP) was used with a cardiac phased array transducer to transmit a pulse-inversion sequence at 2.1 MHz. Radiofrequency data were recorded at five acoustic pressures (71–228 kPa peak-negative) to investigate the effects of pulse length (7-, 12- and 16-cycle pulses) and flow rate (150, 200 and 375 mL/min). The subharmonic (1.05 MHz) amplitude of SonoVue was calculated over a 40% bandwidth. A solid-state catheter recorded ground-truth pressures. Increasing pulse length improved the correlation coefficient between the subharmonic signal of SonoVue and pressure (r = 0.74 ± 0.14, 0.79 ± 0.06 vs. 0.86 ± 0.04 for 7-, 12- and 16-cycle pulses, respectively; <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$n$</tex> = 3 at optimal acoustic pressure). The strong correlations with 16-cycle pulses persisted at different flow rates ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$r &gt; 0.8$</tex> ). This is the first report showing the ability of SonoVue to track pressure cycles five times faster than the average resting heart rate (376 cycles/min at 375 mL/min flow rate). SonoVue may potentially be used to assess diastolic and pulse pressures using ultrasound instead of cardiac catheterization.