Peristalsis prevents ureteral dilation.

PURPOSE: The etiology of ureteral dilation in primary nonrefluxing, nonobstructing megaureters is still not well understood. Impaired ureteral peristalsis has been theorized as one of the contributing factors. However, ureteral peristalsis and its "normal" function is not well defined. In this study, using mathematical modeling techniques, we aim to better understand how ureteral peristalsis works. This is the first model to consider clinically observed, back-and-forth, cyclic wall longitudinal motion during peristalsis. We hypothesize that dysfunctional ureteral peristalsis, caused by insufficient peristaltic amplitudes (e.g., circular muscle dysfunction) and/or lack of ureteral wall longitudinal motion (e.g., longitudinal muscle dysfunction), promotes peristaltic reflux (i.e., retrograde flow of urine during an episode of peristalsis) and may result in urinary stasis, urine accumulation, and consequent dilation. METHODS: Based on lubrication theory in fluid mechanics, we developed a two-dimensional (planar) model of ureteral peristalsis. In doing so, we treated ureteral peristalsis as an infinite train of sinusoidal waves. We then analyzed antegrade and retrograde flows in the ureter under different bladder-kidney differential pressure and peristalsis conditions. RESULTS: There is a minimum peristaltic amplitude required to prevent peristaltic reflux. Ureteral wall longitudinal motion decreases this minimum required amplitude, increasing the nonrefluxing range of peristaltic amplitudes. As an example, for a normal bladder-kidney differential pressure of 5 cmH2 O, ureteral wall longitudinal motion increases nonrefluxing range of peristaltic amplitude by 65%. Additionally, ureteral wall longitudinal motion decreases refluxing volumetric flow rates. For a similar normal bladder pressure example of 5 cmH2 O, refluxing volumetric flow rate decreases by a factor of 18. Finally, elevated bladder pressure, not only increases the required peristaltic amplitude for reflux prevention but it increases maximum refluxing volumetric flow rates. For the case without wall longitudinal motion, as bladder-kidney differential pressure increases from 5 to 40 cmH2 O, minimum required peristaltic amplitude to prevent reflux increases by 40% while the maximum refluxing volumetric flow rate increases by approximately 100%. CONCLUSION: The results presented in this study show how abnormal ureteral peristalsis, caused by the absence of wall longitudinal motion and/or lack of sufficient peristaltic amplitudes, facilitates peristaltic reflux and retrograde flow. We theorize that this retrograde flow can lead to urinary stasis and urine accumulation in the ureters, resulting in ureteral dilation seen on imaging studies and elevated infection risk. Our results also show how chronically elevated bladder pressures are more susceptible to such refluxing conditions that could lead to ureteral dilation.

The 5:1 rule overestimates the needed tunnel length during ureteral reimplantation.

AIMS: Paquin asserts that in order for ureterovesical junctions (UVJs) to prevent reflux, the ureteral tunnel length-to-diameter ratio needs to be 5:1. We hypothesize that the surgical implementation of this observation results in an overestimation of the needed length-to-diameter ratio to prevent vesicoureteral reflux. METHODS: With finite elements, we model the urine storage phase of the bladder under nonlinear conditions. In the reference state, the bladder is assumed to be a sphere with an oblique straight elliptical hole as the UVJ. Broad parametric studies on different length-to-diameter ratios are performed as the bladder volume increases from 10% to 110% capacity. RESULTS: The capability of the UVJ to prevent reflux during storage depends on its length-to-diameter ratio. UVJs with larger length-to-diameter ratios lengthen and narrow as the bladder volume increases, causing the closure of the UVJ and rise in its flow resistance. Our model shows that the UVJ length-to-diameter ratio decreases as the bladder volume increases. The 5:1 ratio implemented at 80% capacity-approximate volume or bladder wall stretch during ureteroneocystostomy (UNC)-corresponds to 7:1 at the reference state-used by Paquin. The 5:1 ratio implemented at the reference state corresponds to 3:1 at 80% capacity. CONCLUSIONS: Our modeling results are consistent with Paquin's original observation on the significance of the UVJ length-to-diameter ratio in preventing reflux. They, however, indicate that the surgical implementation of this rule during UNC results in an overestimation of the requisite tunnel length-to-diameter ratio to prevent reflux. They also suggest that the UVJ closure is due to the bladder wall deformation rather than the pressure.

A Non-Linear Model of an All-Elastomer, in-Plane, Capacitive, Tactile Sensor Under the Application of Normal Forces.

In this work, a large deformation, non-linear semi-analytical model for an all-elastomer, capacitive tactile unit-sensor is developed. The model is capable of predicting the response of such sensors over their entire sensing range under the application of normal forces. In doing so the finite flat punch indentation model developed earlier is integrated with a capacitance model to predict the change-in-capacitance as a function of applied normal forces. The empirical change-in-capacitance expression, based on the parallel plate capacitance model, is developed to account for the fringe field and saturation effects. The elastomeric layer used as a substrate in these sensors is modeled as an incompressible, non-linear, hyperelastic material. More specifically, the two term Mooney-Rivlin strain energy function is used as a constitutive response to relate the stresses and strains. The developed model assumes both geometrical as well as material non-linearity. Based on the related experimental work presented elsewhere, the inverse analysis, combining finite element (FE) modeling and non-linear optimization, is used to obtain the Mooney-Rivlin material parameters. Finally, to validate the model developed herein the model predictions are compared to the experimental results obtained elsewhere for four different tactile sensors. Great agreements are found to exist between the two which shows the model capabilities in capturing the response of these sensors. The model and methodologies developed in this work, may also help advancing bio-material studies in the determination of biological tissue properties.

Urethral tissue characterization using multiparametric ultrasound imaging.

A decrease in urethral closure pressure is one of the primary causes of stress urinary incontinence in women. Atrophy of the urethral muscles is a primary factor in the 15 % age-related decline in urethral closure pressure per decade. Incontinence not only affects the well-being of women but is also a leading cause of nursing home admission. The objective of this research was to develop a noninvasive test to assess urethral tissue microenvironmental changes using multiparametric ultrasound (mpUS) imaging technique. Transperineal B-scan ultrasound (US) data were captured using clinical scanners equipped with curvilinear or linear transducers. Imaging was performed on volunteers from our institution medical center (n = 15, 22 to 76 y.o.) during Valsalva maneuvers. After expert delineation of the region of interest in each frame, the central axis of the urethra was automatically defined to determine the angle between the urethra and the US beam for further analysis. By integrating angle-dependent backscatter with radiomic texture feature analysis, a mpUS technique was developed to identify biomarkers that reflect subtle microstructural changes expected within the urethral tissue. The process was repeated when the urethra and US beam were at a fixed angle. Texture selection was conducted for both angle-dependent and angle-independent results to remove redundancies. Ultimately, a distinct biomarker was derived using a random forest regression model to compute the urethra score based on features selected from both processes. Angle-dependent backscatter analysis shows that the calculated slope of US mean image intensity decreased by 0.89 (±0.31) % annually, consistent with the expected atrophic disorganization of urethral tissue structure and the associated reduction in urethral closure pressure with age. Additionally, textural analysis performed at a specific angle (i.e., 40 degrees) revealed changes in gray level nonuniformity, skewness, and correlation by 0.08 (±0.04) %, -2.16 (±1.14) %, and -0.32 (±0.35) % per year, respectively. The urethra score was ultimately determined by combining data selected from both angle-dependent and angle-independent analysis strategies using a random forest regression model with age, yielding an R2 value of 0.96 and a p-value less than 0.001. The proposed mpUS tissue characterization technique not only holds promise for guiding future urethral tissue characterization studies without the need for tissue biopsies or invasive functional testing but also aims to minimize observer-induced variability. By leveraging mpUS imaging strategies that account for angle dependence, it provides more accurate assessments. Notably, the urethra score, calculated from US images that reflect tissue microstructural changes, serves as a potential biomarker providing clinicians with deeper insight into urethral tissue function and may aid in diagnosing and managing related conditions while helping to determine the causes of incontinence.

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.

Ureterovesical junction deformation during urine storage in the bladder and the effect on vesicoureteral reflux.

The motivation behind this study is to understand how ureterovesical junction (UVJ) deformation during urine storage in the bladder affects vesicoureteral reflux (VUR), when urine flows backward from the bladder toward the kidneys. Using nonlinear, large deformation finite element simulations, the deformation of the bladder wall during urine storage is modeled in this study. The bladder wall is assumed to be a homogeneous, isotropic, hyperelastic spherical shell with a finite thickness. The UVJ is defined as a straight elliptical cylindrical hole through the bladder wall at the reference configuration before inflation. Broad parametric studies on different UVJ configurations are performed as the bladder inner surface stretches by a factor of 2.2 from an initial radius corresponding to bladder volumes of 10% to slightly over physiologic capacity. For each considered UVJ configuration, a simple fluid analysis of the tunnel flow resistance compares different bladder inner surface stretch ratios. Our model shows that the deformation of the UVJ depends on its orientation with respect to the bladder wall radial and circumferential directions. We show that as the UVJ insertion angle increases, the UVJ cross section decreases and its tunnel length increases during urine storage causing the closure of the UVJ and a rise in its flow resistance. The modeling results indicate that UVJ closure could be explained by bladder wall deformation rather than the local differential pressure. Our findings are consistent with the accepted primary anti-reflux mechanism of the UVJ being dependent on the tunnel length-to-diameter ratio and consequently the UVJ insertion angle.