The purpose of this study was to develop and investigate a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles. A Sonix RP ultrasound scanner with PA4-2 phased array transducer was used in pulse inversion grayscale mode. Unprocessed radiofrequency data were obtained for 5 seconds (n=3) with pulsed wave Doppler from the aorta and/or LV of 4 canines during Sonazoid infusion. Simultaneous pressure measurements were obtained using Millar manometer. Subharmonic data (in dB) were extracted and processed. The resulting calibration factor (mmHg/dB), from the aorta, was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mmHg when estimating these pressures using the aortic calibration factor from the respective canines; but were considerably higher (0.64-8.98 mmHg) when a mean aortic calibration factor was used. In conclusion, subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.

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.

This study evaluated the feasibility of noninvasive intracardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This IRB approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity (Lantheus Medical Imaging, N Billerica, MA) was infused intravenously at 4–10 ml/min. Ultrasound scanning was performed with a Sonix RP (BK Ultrasound, Richmond, Canada) using pulse inversion, three incident acoustic output levels, and 2.5 MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. Correlation coefficient between subharmonic signals and pressure catheter data ranged from −0.3 to −0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided.