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

In this work, the development of subharmonic emission based noninvasive pressure estimation technique is presented. In vitro, ambient pressures were varied (between 0 and 120 mmHg) in a closed-loop flow system circulating 0.2 ml Sonazoid microbubbles (GE Healthcare, Oslo, Norway) suspended in 750 ml of isotonic diluent and recorded by a Millar pressure catheter as the reference standard. Simultaneously, a SonixRP ultrasound scanner (Ultrasonix Medical Corp., Richmond, BC, Canada) operating in pulse inversion mode (f_transmit: 2.5 MHz) was used to acquire unprocessed RF data at five different incident acoustic pressures (from 76 kPa to 897 kPa; n=3). The subharmonic data for each pulse was 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; then the ambient pressure was tracked over 20 seconds. Regression analysis compared subharmonic and catheter pressure values. In vivo validation of this technique was performed noninvasively for tracking left ventricular (LV) pressures of two canines using similar post processing as in vitro. The subharmonic signal tracked ambient pressures with r² = 0.922 for 20 seconds in vitro. In vivo the subharmonic signal tracked the LV pressures with r² >; 0.7P90. Maximum errors in estimating clinically relevant systolic and diastolic pressures ranged from 0.22 to 2.84 mmHg using this subharmonic technique relative to Millar catheter pressures. Clinical validation and real time implementation of this technique may ultimately lead to the first noninvasive cardiac pressure monitoring tool.