Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures

Abstract

Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg.

Fig. 1.

Ultrasound radio frequency data acquired from the pulsed wave Doppler gate. The pulsed wave gate data acquired during minimum diastolic (A) and peak systolic right ventricular (RV) pressure (B) phases are shown. The Fourier domain representations of the pulses in A and B are shown in C and D, respectively. The bandwidth from which the subharmonic signal was extracted from each pulse is shaded in gray in C and D. The subharmonic signal amplitude decreases from about 56 dB (C) to about 51 dB (D) as the pressure increases during systole. During the systolic pressure rise, there is no change in fundamental signal amplitude confirming that subharmonic signal alone can be calibrated to indicate absolute pressure values, consistent with an inverse relationship between subharmonic signals and ambient pressure values (1, 13, 15, 17, 18, 32).

Fig. 2.

Sample subharmonic signal amplitudes from the aorta and RV of 1 canine. The subharmonic amplitudes corresponding to the peak systolic (closed triangles) and minimum diastolic (closed circles) pressures in the aorta (A) and RV (B) are shown. The distinct phases of subharmonic emissions from microbubbles identified using ANOVA and post hoc comparisons are indicated.

Fig. 3.

RV pressure waveform using subharmonic aided pressure estimation (SHAPE) and the reference standard (manometer catheter). The inverse relationship between the subharmonic signal variation (solid line) and the pressure (dashed line) is shown (A). Sample RV pressure waveforms obtained using SHAPE (solid line) and pressure catheter (dashed line) from 2 canines are depicted in B and C, respectively. The sensitivity of the subharmonic signal (solid line) to changes in the pressure (dashed line) is demonstrated in D; note the decrease in the subharmonic signal amplitude (solid arrows) as the minimum RV diastolic pressure increases (dashed arrows).