Influence of visual and auditory cues about bladder volume on real-time filling sensation in healthy volunteers.

Auditory/visual (A/V) cues can trigger urgency in some individuals with overactive bladder (OAB), and patient-reported bladder sensation can be characterized during non-invasive oral hydration studies. The aim of this investigation was to test the hypothesis that A/V cues of bladder volume can alter patient-perceived bladder sensation during hydration studies. Healthy volunteers without urinary symptoms based on ICIq-OAB survey scores were recruited for an oral hydration study where they completed two fill/void cycles. The study was repeated twice, one week apart. Throughout bladder filling, participants reported real-time sensation (0-100%) using a Sensation Meter, and bladder volumes were measured at 5 min intervals with both 3D ultrasound and BladderScan®. Participants were divided into a Cues(+) group that was allowed to view their ultrasound images and hear volume measurements of the BladderScan® every 5 min and a Cues(-) group that was not exposed to these A/V cues. The A/V Cues(+) group had 10 participants (5 women and 5 men) and the Cues(-) group had 10 participants (7 women and 3 men). During the second visit, the Cues(+) group demonstrated decreased sensation compared to the Cues(-) group in the slower first fill, but not the faster second fill. The results of this study demonstrate that A/V cues about bladder volume can acutely alter sensation during hydration studies in healthy individuals with normal bladder function.

Regulation of bladder dynamic elasticity: a novel method to increase bladder capacity and reduce pressure using pulsatile external compressive exercises in a porcine model.

PURPOSE: Dynamic elasticity is a biomechanical property of the bladder in which muscle compliance can be acutely adjusted through passive stretches and reversed with active contractions. The aim of this study was to determine if manipulating dynamic elasticity using external compression could be used as a novel method to acutely increase bladder capacity and reduce bladder pressure in a porcine model. METHODS: Ex vivo experiment: bladders underwent continuous or pulsatile compression after establishing a reference pressure at bladder capacity. Bladders were then filled back to the reference pressure to determine if capacity could be acutely increased. In-vivo experiments: bladders underwent five cycles of pulsatile external compression with ultrasound confirmation. Pre and post-compression pressures were measured, and pressure was measured again 10 min post-compression. RESULTS: Ex vivo experiment: pulsatile compression demonstrated increased bladder capacity by 16% (p = 0.01). Continuous compression demonstrated increased capacity by 9% (p < 0.03). Comparison of pulsatile to continuous compression showed that the pulsatile method was superior (p = 0.03). In-vivo experiments: pulsatile external compression reduced bladder pressure by 19% (p < 0.00001) with a return to baseline 10 min post-compression. CONCLUSIONS: These results suggest that regulation of bladder dynamic elasticity achieved with external compression can acutely decrease bladder pressure and increase bladder capacity. Pulsatile compression was found to be more effective as compared to continuous compression. These results highlight the clinical potential for use of non-invasive pulsatile compression as a therapeutic technique to increase bladder capacity, decrease bladder pressure, and reduce the symptoms of urinary urgency.

A preliminary study of bilateral color mapping of pig bladder vasculature demonstrates potential for acute hemi-ischemic events.

BACKGROUND: Chronic ischemia is a known risk factor for the development of lower urinary tract symptoms (LUTS) and bladder hypocontractility. Less is known, however, about the impact of acute ischemia. Classic teaching suggests that collateral circulation is robust in the bladder and, therefore, loss of a single source of blood flow should have no deleterious effect. This study aims to provide visual evidence that segmental vascular supply is critical for maintaining adequate perfusion to the bladder. METHODS: Ex vivo pig bladders were cannulated bilaterally in the superior vesical arteries and perfused using contrasting red and green dye. Images were collected at each step of the perfusion dyeing process and these images were analyzed using a custom program to calculate the average hue of each side. Statistical analysis was performed using Student's t-test. RESULTS: The two halves being perfused by separate arteries showed a statistically significant difference when compared (P<0.05) on both the outer wall (n=9) and in the mucosal layer (n=4). On the outside wall, the average normalized hue of the green halves was 27.5°±14.3°, while the average normalized hue of the red halves was -58.7°±3.1°. In the mucosa, the average normalized hue of the green halves was 34.5°±17.4°, while the average normalized hue of the red halves was -51.5°±3.5°. CONCLUSIONS: This study identified a novel color mapping method to study pig bladder vascular supply. The results demonstrated a lack of collateral blood flow, highlighting the possibly of acute hemi-ischemic event. However, further research in the effect of acute ischemia on bladder function is necessary.

Bladder wall micromotion measured by non-invasive ultrasound: initial results in women with and without overactive bladder.

OBJECTIVE: Rhythmic contractions of the bladder wall during filling result from the synchronization of bladder wall micromotion and are often observed in the urodynamic tracings of individuals with urinary overactive bladder (OAB). This study's objective was to develop a novel, non-invasive method to measure bladder wall micromotion and to conduct an initial study to test the hypothesis that elevated micromotion is associated with OAB. METHODS: This prospective study enrolled women with OAB and asymptomatic volunteers as measured by the ICIQ-OAB survey. After filling the bladder to 40% cystometric capacity, 85 second cine-loops were obtained using a GE Voluson E8 ultrasound system with an 8 MHz curved, abdominal probe. A custom correlation-based texture tracking MATLAB algorithm was used to measure changes in the bladder wall thickness over time and correlate with changes in vesical pressure. Significant bladder wall micromotion was defined as changes in wall thickness with amplitudes higher than 0.1 mm in the frequency range of 1.75-6 cycles/minute as calculated from Fast Fourier Transform (FFT) analysis. The micromotion algorithm was tested on 30 women including 17 with OAB and 13 asymptomatic volunteers. RESULTS: Micromotion was identified in 41% of subjects with OAB and 0% of asymptomatic volunteers, indicating a significant association of micromotion with OAB (Fisher's exact test, P=0.010). Micromotion was also found to have a significant association with a clinical diagnosis of detrusor overactivity (Fisher's exact test, P=0.031). Frequencies with elevated micromotion correlated with frequencies of vesical pressure fluctuations. CONCLUSIONS: The feasibility of a non-invasive method to measure bladder wall micromotion was demonstrated using transabdominal anatomical motion mode (M-mode) ultrasound. Presence of micromotion was significantly associated with OAB and with urodynamic-identified rhythm.

Comparison of Sensation Event Descriptors in Participants with Overactive and Normal Bladders during Non-Invasive Hydration Studies.

PURPOSE: Despite the importance of alterations in bladder sensation, objective metrics to characterize sensation outside of urodynamics remain limited. A real-time sensation meter enables recording of sensation event descriptors throughout filling. The purpose of this study was to evaluate the differences in sensation event descriptor patterns between normal participants and those with OAB. METHODS: Normal and OAB participants were enrolled from responses to the ICIq-OAB survey question on urgency (Q5a: 0 vs. ≥ 3). Real-time bladder sensation on a 0%-100% scale was recorded on a validated tablet sensation meter throughout two fill-void cycles. The first and second fills were considered "slow" and "fast" respectively. After each sensation meter change (sensation event), a pop-up screen asked participants to characterize sensation with one or more of these descriptors: "tense," "pressure," "tingling," "painful," and/or "other." Oral hydration was achieved by rapid consumption of 2L G2® Gatorade. RESULTS: Data from 29 participants (12 normal/17 OAB) were analyzed. The rate of filling from bladder volume and fill duration, was greater for the fast fill in both groups. In the slow fill, "tingling" (64 ± 3% OAB vs. 77 ± 3% normal, p=0.008) and "tense" (78 ± 3% OAB vs. 94 ± 1% normal, p<0.001) occurred at lower sensations in OAB participants. CONCLUSION: During only the slow fill, OAB individuals experience the sensation descriptors of "tingling" and "tense" at earlier sensations than normal individuals. Therefore, this non-invasive method to evaluate real-time sensation descriptors during filling may identify important sensation patterns and improve understanding and phenotyping of OAB.

Phases of decompensation during acute ischemia demonstrated in an ex vivo porcine bladder model.

BACKGROUND: The aim of this project was to develop an ex-vivo porcine bladder model to test the effects of increasing durations of acute ischemia on detrusor function. METHODS: Porcine bladders were perfused through bilateral vesical arteries at physiologic flow (4 mL/min) and filled through a urethral catheter. Intravesical pressures were continuously recorded using standard urodynamics equipment. Bladder contractions, with simulated voiding, were induced by arterial infusion of KCl at 250 mL. Total, passive, and active pressures were recorded for each contraction and data were normalized to the control fill. Bladders underwent the following perfusion protocol by adjusting the arterial flow rates: Equilibration (4 mL/min), control (4 mL/min), partial ischemia (2 mL/min), global ischemia (0 mL/min) and reperfusion (4 mL/min). Perfusion periods were held for 15 min for one group and 30 min for another group of bladders. RESULTS: Porcine bladders (N=19) including 8 (15 min group) and 11 (30 min group) were used. With 15 min ischemia, passive pressure increased 39% (P=0.03) and the active pressure decreased 23% (P=0.002). Total pressure remained constant, identifying a compensated phase. Values returned to baseline with reperfusion. With 30 min ischemia, passive pressure remained unchanged. However, there was a decrease in total pressure 34% (P<0.001) and active pressure 61% (P<0.001), which incompletely recovered to baseline values, identifying a decompensated phase with incomplete recovery upon reperfusion. CONCLUSION: In the porcine bladder, 15 min ischemia resulted in a compensated phase and 30 min ischemia resulted in a decompensated phase of detrusor function. This study provides mechanistic insight into the natural history of ischemia-mediated voiding dysfunction.

Comparative-fill urodynamics in individuals with and without detrusor overactivity supports a conceptual model for dynamic elasticity regulation.

AIMS: Dynamic elasticity was previously identified in individuals with overactive bladder (OAB) using comparative-fill urodynamics (UD) and is a biomechanical mechanism for acutely regulating detrusor wall tension. On the basis of this data, a conceptual model of dynamic elasticity regulation mediated through a balance of passive mechanisms and active contractions was constructed. The present study tested this model by determining whether individuals with detrusor overactivity (DO) exhibit less dynamic elasticity than individuals without DO. METHODS: Individuals with and without urgency based on International Consultation on Incontinence Questionnaire-OAB surveys were prospectively enrolled in a comparative-fill UD study. An initial fill defined the presence or absence of DO and determined cystometric capacity. Three additional fills were employed with either passive emptying via a catheter or active voiding. To identify dynamic elasticity, average filling pressures (Pves ) were compared for fill 1 (before strain softening), fill 2 (after strain softening), and fill 3 (after active void). A dynamic elasticity index was defined. RESULTS: From 28 participants, those without DO showed decreased Pves during filling after strain softening and restored Pves during filling following active voiding, revealing dynamic elasticity. Participants with DO did not show dynamic elasticity. A dynamic elasticity index less than 1.0 cmH2 O/40% capacity was identified in 2 out of 13 participants without DO and 9 out of 15 with DO, revealing a significant association between DO and reduced/absent dynamic elasticity (P = .024). CONCLUSIONS: This study supports a conceptual model for dynamic elasticity, a mechanism to acutely regulate detrusor wall tension through a balance of competing active contractile and passive strain mechanisms. Improved understanding of this mechanistic model may help us to identify novel treatment strategies for OAB.

Validation of a real-time bladder sensation meter during oral hydration in healthy adults: Repeatability and effects of fill rate and ultrasound probe pressure.

OBJECTIVES: A non-invasive protocol was previously developed using three-dimensional ultrasound and a sensation meter to characterize real-time bladder sensation. This study the protocol by measuring the effects of fill rateand ultrasound probe pressure during oral hydration. METHODS: Healthy volunteers with no urinary symptoms (based on International Consultation on Incontinence Questionnaire on Overactive Bladder surveys) were recruited into an oral hydration study. Throughout two complete fill-void cycles, participants drank 2 L Gatorade G2 (The Gatorade Company, Inc., Chicago, Illinois) and used a touch-screen sensation meter to record real-time bladder sensation (0%-100%). The study was repeated three times, once per week (Visits A, B, and C). In Visits A and B, ultrasound was used to measure bladder volume every 5 minutes. Ultrasound was not used in Visit C except at 100% capacity. Volume data from Visit B were used to estimate volumes throughout the fills in Visit C. Sensation-capacity curves were generated for each fill for comparative analysis. RESULTS: Ten participants completed three visits (60 total fills). Increased fill rate led to decreased sensation throughout filling, andultrasound probe pressure led to increased sensation. Participants reported higher sensation at low volumes during Fill 1 of Visit A before training with the sensation meter. Sensation curves with intermittent ultrasound showed repeatability for Fill 2 in Visits A and B. Fill rate and ultrasound probe pressure affect real-time bladder sensation during oral hydration. CONCLUSIONS: This study demonstrated repeatability of real-time bladder sensation during a two-fill oral hydration protocol with ultrasound.

An external compress-release protocol induces dynamic elasticity in the porcine bladder: A novel technique for the treatment of overactive bladder?

INTRODUCTION: Dynamic elasticity is an acutely regulated bladder material property through which filling and passive emptying produce strain softening, and active voiding restores baseline pressure. The aim of this study was to test the hypothesis that strain softening produced by filling-passive emptying is equivalent to that produced by compression-release in a porcine bladder model. METHODS/MATERIALS: Latex balloons and ex vivo perfused pig bladders were used for a series of alternating fill-passive emptying ("Fill") and external compress-release ("Press") protocols. For the Fill protocol balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) filled to capacity to strain soften (reference), and (3) passively emptied to the original volume (poststrain softening). For the Press protocol, balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) externally compressed to reference pressure and then released for five cycles (poststrain softening). After each protocol, bladders were voided with high-KCl buffer to induce "active" voiding. RESULTS: In both balloons and porcine bladder, both the Fill and Press protocols produced significant strain softening (P < 0.05) and poststrain softening pressures were not different for Fill and Press protocols (P > 0.05), indicating a similar degree of strain softening with both methods. CONCLUSIONS: Repeated external compression can induce bladder strain softening similar to filling and passive emptying. This technique may represent a means to acutely regulate bladder compliance and potentially be used as a mechanical treatment for urinary urgency.

Automated quantification of low amplitude rhythmic contractions (LARC) during real-world urodynamics identifies a potential detrusor overactivity subgroup.

OBJECTIVES: Detrusor overactivity (DO) is characterized by non-voiding detrusor smooth muscle contractions during the bladder filling phase and often contributes to overactive bladder. In some patients DO is observed as isolated or sporadic contractions, while in others DO is manifested as low amplitude rhythmic contractions (LARC). The aim of this study was to develop an objective method to quantify LARC frequencies and amplitudes in urodynamic studies (UDS) and identify a subgroup DO of patients with LARC. METHODS: An automated Fast Fourier Transform (FFT) algorithm was developed to analyze a 205-second region of interest of retrospectively collected "real-world" UDS ending 30 seconds before voiding. The algorithm was designed to identify the three largest rhythmic amplitude peaks in vesical pressure (Pves) in the 1.75-6 cycle/minute frequency range. These peak Pves amplitudes were analyzed to determine whether they were 1) significant (above baseline Pves activity) and 2) independent (distinct from any in abdominal pressure (Pabd) rhythm). RESULTS: 95 UDS met criteria for inclusion and were analyzed with the FFT algorithm. During a blinded visual analysis, a neurourologist/urodynamicist identified 52/95 (55%) patients as having DO. The FFT algorithm identified significant and independent (S&I) LARC in 14/52 (27%) patients with DO and 0/43 patients (0%) without DO, resulting in 100% specificity and a significant association (Fischer's exact test, p<0.0001). The average slowest S&I LARC frequency in this DO subgroup was 3.20±0.34 cycles/min with an amplitude of 8.40±1.30 cm-H2O. This algorithm can analyze individual UDS in under 5 seconds, allowing real-time interpretation. CONCLUSIONS: An FFT algorithm can be applied to "real-world" UDS to automatically characterize the frequency and amplitude of underlying LARC. This algorithm identified a potential subgroup of DO patients with LARC.