Applying real-time noninvasive pressure estimation obtained from subharmonic contrast microbubble signals

The long term goal of this project is to monitor and quantify intra-cardiac pressures via contrast-enhanced subharmonic imaging (SHI). Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based contrast agent signals for the noninvasive estimation of hydrostatic blood pressures in heart cavities and major blood vessels. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60deg angle to each other. Changes in the first, second, and subharmonic amplitudes of six different ultrasound contrast agents were measured in vitro at hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa and frequencies of 2.5-6.6 MHz. The optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). Over the pressure range studied the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 10-14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r² ges 0.98, p < 0.001). The optimal sensitivity was achieved at a transmit frequency of 2.5 MHz at a 0.35 MPa acoustic pressure using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHI on a convex transducer with a frequency range from 1.5-4.5 MHz. In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressure gradients in the heart to be obtained noninvasively.