Pressure Measurement in a Bladder Phantom Using Contrast-Enhanced Ultrasonography—A Path to a Catheter-Free Voiding Cystometrogram

Abstract

ObjectivesThe long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free. This is of importance because the CMG catheter, due to its space-occupying property and non-physiological effects, can undermine the reliability of the test during voiding and cause misdiagnosis. In this study, we tested this hypothesis and optimized the protocol in a controlled benchtop environment.Materials and MethodsA bladder phantom was designed and built, capable of simulating clinically relevant bladder pressures. Laboratory-made lipid-shelled MBs (similar in composition to the commercial agent, DEFINITY) was diluted in 0.9% normal saline and infused into the bladder phantom using the CMG infusion system. A typical simulated CMG consists of 1 filling and 4 post-filling events. During CMG events, the bladder phantom is pressurized multiple times at different clinically relevant levels (small, medium, and large) to simulate bladder pressures. Simultaneous with pressurization, MB subharmonic signal was acquired. For each event, the change in MB subharmonic amplitude was correlated linearly with the change in bladder phantom pressure, and the SHAPE conversion factor (slope of the linear fit) was determined. In doing so, a specific signal processing technique (based on a small temporal window) was used to account for time-decay of MB subharmonic signal during a simulated CMG.ResultsA strong inverse linear relationship was found to exist between SHAPE and bladder phantom pressures for each of the CMG filling and post-filling events (r2 > 0.9, root mean square error <0.3 dB, standard error <0.01 dB, and P < 0.001). SHAPE showed a transient behavior in measuring bladder phantom pressure. The SHAPE conversion factor (in dB/cm H2O) varied between filling and post-filling events, as well as by post-filling time. The magnitude of the SHAPE conversion factor tended to increase immediately after filling and then decreases with time.ConclusionsMicrobubble subharmonic emission is an excellent indicator of bladder phantom pressure variation. The strong correlation between SHAPE signal and bladder phantom pressure is indicative of the applicability of this method in measuring bladder pressure during a CMG. Our results suggest that different SHAPE conversion factors may be needed for different events during a CMG (ie, at different time points of a CMG). These findings will help us better protocolize this method for introduction into human subjects and allow us to take the next step toward developing a catheter-free voiding CMG using SHAPE.

Bubble nucleation and dynamics in acoustic droplet vaporization: a review of concepts, applications, and new directions

“…Similar observations have been reported for other contrast microbubbles both in vitro and in vivo [134] , [135] , [136] . The simplified reasoning behind the reduction in the subharmonic response with increasing ambient pressure is the decrease in microbubble size and oscillation amplitude.…”

Ultra-high-speed dynamics of acoustic droplet vaporization in soft biomaterials: Effects of viscoelasticity, frequency, and bulk boiling point

“…Perfluorocarbons are fluorinated compounds widely used in the past as oxygen carriers due to their inertness and high oxygen solubility [1] . Phase-shift droplets possess distinct advantages compared with conventional contrast microbubbles such as improved stability and longer circulation half-life in vivo [2] , [3] . These liquid droplets maintain their liquid state at physiologic temperature due to a combination of increased Laplace pressure [4] and inhibition of heterogeneous nucleation [5] .…”