Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles

The purpose of this study was to develop and validate a noninvasive pressure estimation technique based on subharmonic emissions from a commercially available ultrasound contrast agent and scanner, unlike other studies that have either adopted a single-element transducer approach and/ or use of in-house contrast agents. Ambient pressures were varied in a closed-loop flow system between 0 and 120 mmHg and were recorded by a solid-state pressure catheter as the reference standard. Simultaneously, the ultrasound scanner was operated in pulse inversion mode transmitting at 2.5 MHz, and the unprocessed RF data were captured at different incident acoustic pressures (from 76 to 897 kPa). The subharmonic data for each pulse were extracted using band-pass filtering with averaging, and subsequently processed to eliminate noise. The incident acoustic pressure most sensitive to ambient pressure fluctuations was determined, and then the ambient pressure was tracked over 20 s. In vivo validation of this technique was performed in the left ventricle (LV) of 2 canines. In vitro, the subharmonic signal could track ambient pressure values with r(2) = 0.922 (p < 0.001), whereas in vivo, the subharmonic signal tracked the LV pressures with r(2) > 0.790 (p < 0.001) showing a maximum error of 2.84 mmHg compared with the reference standard. In conclusion, a subharmonic ultrasound-based pressure estimation technique, which can accurately track left ventricular pressures, has been established.