A Comparative Study of Commercially Available Ultrasound Contrast Agents for Sub-harmonic-Aided Pressure Estimation (SHAPE) in a Bladder Phantom.

OBJECTIVE: The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. METHODS: Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB-saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. RESULTS: All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. CONCLUSION: Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE.

Ultrasound Contrast Stability for Urinary Bladder Pressure Measurement.

The goal of this study was to evaluate ultrasound contrast microbubbles (MB) stability during a typical cystometrogram (CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated. The results verified that air volume in intravenous (IV) bag headspace was not enough to have a significant effect on MB stability during a CMG. We also showed that higher MB dosage results in a more stable condition. Finally, the results indicated that the CMG infusion system adversely affects MB stability. In summary, to ensure MB stability during the entire duration of a CMG, lower filling rates (limited by estimated bladder capacity in clinical applications) and/or higher MB dosage (limited by FDA regulations and shadowing artifact) and/or the consideration of alternative catheter design may be needed.

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

OBJECTIVES: The 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 METHODS: A 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. RESULTS: A 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 H 2 O) 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. CONCLUSIONS: Microbubble 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.