The frequency spectrum of bladder non-voiding activity as a trigger-event for conditional stimulation: Closed-loop inhibition of bladder contractions in rats.

AIMS: To test the hypothesis that the frequency of bladder non-voiding contractions (NVCs) can be used as a trigger event for closed-loop conditional inhibition of detrusor contractions via tibial nerve (TN) or dorsal penile nerve (DPN) stimulation. METHODS: In urethane anaesthetized male Wistar rats, the bladder was filled continuously with saline to evoke contractions. To test the plausibility of conditional inhibition via the TN, electrical stimulation was switched on manually when the pressure increased above a threshold of 10 cmH2 0 above the baseline. For testing conditional stimulation via the DPN, the pressure signal was continuously stored and a baseline threshold, the area under the curve (AUC) of the amplitude spectrum in the 0.2-20 Hz range of a 5 s window at the beginning of filling was calculated. When the AUC of subsequent pressure windows superseded the baseline threshold, the DPN was automatically stimulated. RESULTS: TN stimulation failed to inhibit evoked voiding contractions. The NVC frequency spectrum based DPN stimulation successfully inhibited 70% of the evoked contractions and resulted in a 45% increase in bladder capacity (BC). CONCLUSIONS: While, conditional TN stimulation failed to suppress bladder contractions, DPN stimulation, automatically triggered by an increased frequency of bladder non-voiding activity, resulted in bladder inhibition, and a consequential increase in BC. This study demonstrates the plausibility of using the frequency of NVCs as a trigger event for conditional inhibition of detrusor contractions.

Urethane anesthesia in acute lower urinary tract studies in the male rat.

Urethane is a widely used anesthetic in animal lower urinary tract research. Our objective was to investigate the quality of anesthesia and the correlation between bladder (voiding) contractions, micturition pressure, bladder capacity and urethane dosage and body weight. Urethane was given subcutaneously and/or intraperitoneally (1.0-1.2 g/kg). The bladder was filled with saline and the bladder pressure was recorded continuously. Animals in which the subcutaneous/intraperitoneal ratio was higher needed less urethane. Heavier animals needed less extra urethane. In animals, in which no bladder contractions could be evoked, the total amount of urethane given was similar to that in those that did show contractions. In the animals that did void, the bladder never emptied completely and residual volumes remained. There was no relationship between animal weight or total amount of urethane and mean capacity. Anesthesia lasted up till 14 h, during which bladder (voiding) contractions could be recorded. Considering all results, we conclude that urethane is a well suited anesthetic for acute lower urinary tract physiological research in the intact rat.

Noninvasive Diagnosis of Bladder Outlet Obstruction in Patients with Lower Urinary Tract Symptoms Using Ultrasound Decorrelation Analysis.

PURPOSE: We developed a noninvasive method to diagnose bladder outlet obstruction. An ultrasound based decorrelation method was applied in male patients with lower urinary tract symptoms. MATERIALS AND METHODS: In 60 patients ultrasound data were acquired transperineally while they were voiding while sitting. Each patient also underwent a standard invasive pressure flow study. RESULTS: High frequent sequential ultrasound images were successfully recorded during voiding in 45 patients. The decorrelation (decrease in correlation) between subsequent ultrasound images was higher in patients with bladder outlet obstruction than in unobstructed patients and healthy volunteers. ROC analysis resulted in an AUC of 0.96, 95% specificity and 88% sensitivity. A linear relationship was fitted to the decorrelation values as a function of the degree of obstruction represented by the bladder outlet obstruction index, measured in the separate pressure flow studies. CONCLUSIONS: It is possible to noninvasively diagnose bladder outlet obstruction using the ultrasound decorrelation technique.

Inhibitory effects of tibial nerve stimulation on bladder neurophysiology in rats.

Tibial nerve stimulation (TNS) is a form of peripheral neuromodulation which has been found effective in treating overactive bladder symptoms, with lesser side effects than first line pharmacotherapy. Despite its widespread clinical use, the underlying mechanism of action is not fully understood. Our aim was to study its effect on the bladder neurophysiology and the trigger mechanism of voiding in the overactive detrusor, simulated by acetic acid (AA) instillation. In urethane anaesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 µs and amplitude approximately three times the threshold to induce a slight toe movement. The pressure at which a voiding contraction was triggered (pthres) did not change significantly between the pre- and post-TNS measurements in AA induced detrusor overactivity. It was found that TNS significantly reversed the effects of AA irritation by increasing the bladder compliance and the bladder volume at pthres, as well as suppressed the threshold afferent nerve activity. The slope of the linear relationship between pressure and the afferent activity increased after AA instillation and decreased significantly after stimulation. In addition to its well-known central inhibitory mechanisms, this study has demonstrated that TNS improves bladder storage capacity by delaying the onset of voiding, via an inhibitory effect on the bladder afferent signaling at the peripheral level.

Effect of tibial nerve stimulation on bladder afferent nerve activity in a rat detrusor overactivity model.

OBJECTIVES: To study the post-stimulation effect of tibial nerve stimulation on rat bladder afferent activity, and urodynamic parameters in normal and acetic acid-induced detrusor overactivity conditions. METHODS: In urethane anesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 µs and amplitude approximately threefold the threshold to induce a slight toe movement. The post-stimulation effect was studied by measuring afferent nerve activity of postganglionic pelvic nerve branches and various urodynamic parameters under two different conditions: (i) in physiological saline filling experiments (simulating normal bladder condition); and (ii) in acetic acid irritated bladders (simulating detrusor overactivity). RESULTS: After 30 min of tibial nerve stimulation in saline filling experiments, the bladder capacity, threshold pressure and afferent nerve activity were not significantly different from the prestimulation measurements. The instillation of 0.5% acetic acid significantly reduced the bladder capacity and increased the afferent nerve activity. Tibial nerve stimulation significantly improved the bladder capacity and suppressed the afferent nerve activity compared with prestimulation acetic acid measurements. CONCLUSIONS: Tibial nerve stimulation is able to significantly restore the bladder capacity by inhibiting afferent nerve activity in chemically irritated rat bladders. The present study provides important basic electrophysiological evidence to substantiate the clinical use of tibial nerve stimulation for treatment of symptoms related to detrusor overactivity.

Diagnosing Bladder Outlet Obstruction Using Non-invasive Decorrelation-Based Ultrasound Imaging: A Feasibility Study in Healthy Male Volunteers.

A feasibility study on the applicability of an ultrasound decorrelation method to urinary flow imaging was carried out in 20 healthy male volunteers, to provide a basis for a non-invasive approach to diagnose bladder outlet obstruction. Each volunteer voided five times in a flow meter in standing position. During each voiding, ultrasound radiofrequency frames were acquired transperineally at different flow rates. The results indicated that the decrease in correlation (decorrelation) of ultrasound radiofrequency signals had no unique relation with flow rate, but decreased distinctively with urinary flow velocity. In most of the healthy volunteers, the decorrelation was small because of the low flow velocity. However, because of the different flow velocities in volunteers, the variation in slope between volunteers was statistically significant. Therefore, it is probably possible to use the decorrelation method to differentiate between healthy persons and patients with obstruction.

Urinary Bladder Contractility Revisited. Correlation of Noninvasively and Invasively Measured Contractility Parameters in Patients Eligible for Transurethral Resection of the Prostate.

OBJECTIVE: To validate a noninvasively estimated measure of urinary bladder contractility by correlating it with 3 existing invasive contractility parameters and to compare and correlate those invasive parameters. METHODS: A group of 74 patients, recruited in 3 different hospitals, and eligible for transurethral resection of the prostate on clinical grounds, were noninvasively studied preoperatively using the condom catheter method. The maximum condom pressure pcond.max measured during a mechanical interruption of flow rate was considered an estimate of urinary bladder contractility and compared to conventional contractility parameters calculated from preoperative (invasive) pressure-flow studies. RESULTS: The highest correlations were found between the invasive parameters. The correlation between the noninvasive parameter on the one hand and the invasive parameters on the other hand was lower, but mostly significant. In a number of patients, pcond.max underestimated the isovolumetric bladder pressure. The underestimated patients were more obstructed than those who were not underestimated and had a higher (invasively measured) contractility. When the underestimated patients were deselected, the correlation between the noninvasive pcond.max and the invasive parameters in the remaining 52 patients was higher. CONCLUSION: The 4 tested contractility parameters represent different aspects of urinary bladder contractility. Nevertheless, there was a significant correlation among them supporting the concept of a common basis, that is, detrusor contractility. The invasive contractility parameter bladder contractility index overestimated contractility in patients with lower urinary tract symptoms and/or benign prostatic enlargement. A modified parameter is suggested.

Noninvasive estimation of the pressure profile in the male urethra using ultrasound imaging.

PURPOSE: Decreased prostatic compliance as a result of benign prostatic enlargement can result in bladder outlet obstruction. This changes the urethral pressure profile during voiding. In this study, the authors propose noninvasive estimation of this pressure profile. In four soft tissue mimicking models of the urethra with increasing degree of obstruction, the authors measured deformation of the wall during flow, using ultrasound imaging. Combined with estimates of the model compliance, the authors were able to estimate the pressure profile. METHODS: First, the compliances (Young's moduli) of the four models were derived by applying static luminal pressure and measuring the resulting strain of the tissue using an ultrasound imaging system. Next, continuous flow was applied to the models and the strain in the urethral wall was measured similarly. The luminal pressure profile was estimated from the strain (measured under continuous flow conditions) and the derived compliance (measured under static pressure conditions). The estimated pressures up- and downstream of the obstruction were compared with the corresponding measured pressures. In the obstructed region, the strain gradient was estimated using linear regression. RESULTS: The luminal pressure values estimated from the ultrasound data up- and downstream of the obstruction were not significantly different from the corresponding measured pressures. The general pressure profile showed a decrease along the length of the obstruction followed by a small increase after the obstruction. The strain gradient in the obstructed region reflected the decrease in urethral pressure and increased with flow rate and degree of obstruction. CONCLUSIONS: The results from this model study illustrate the feasibility of noninvasive estimation of the urethral pressure profile using ultrasound. This offers the prospect of a noninvasive, ultrasound based diagnostic tool for assessment of bladder outlet obstruction in men with lower urinary tract symptoms.

Neurophysiological modeling of bladder afferent activity in the rat overactive bladder model.

The overactive bladder (OAB) is a syndrome-based urinary dysfunction characterized by "urgency, with or without urge incontinence, usually with frequency and nocturia". Earlier we developed a mathematical model of bladder nerve activity during voiding in anesthetized rats and found that the nerve activity in the relaxation phase of voiding contractions was all afferent. In the present study, we applied this mathematical model to an acetic acid (AA) rat model of bladder overactivity to study the sensitivity of afferent fibers in intact nerves to bladder pressure and volume changes. The afferent activity in the filling phase and the slope, i.e., the sensitivity of the afferent fibers to pressure changes in the post-void relaxation phase, were found to be significantly higher in AA than in saline measurements, while the offset (nerve activity at pressure ~0) and maximum pressure were comparable. We have thus shown, for the first time, that the sensitivity of afferent fibers in the OAB can be studied without cutting nerves or preparation of single fibers. We conclude that bladder overactivity induced by AA in rats is neurogenic in origin and is caused by increased sensitivity of afferent sensors in the bladder wall.

Development of a noninvasive method to diagnose bladder outlet obstruction based on decorrelation of sequential ultrasound images.

OBJECTIVE: To develop an ultrasound (US)-based method for noninvasive diagnosing of bladder outlet obstruction, and the relationship between decorrelation of sequential US images and the degree of obstruction in a urethra model was studied. MATERIALS AND METHODS: A flexible model of a male urethra was constructed from 15% aqueous solution of polyvinyl alcohol cryogel. To create 4 different degrees of obstruction, polyvinyl alcohol rings representing the prostate were placed around the model. Each model was perfused at different flow rates (1-15 mL/s) with an aqueous solution containing scattering particles mimicking urine. At each flow rate, 10 sequential US images were acquired. The average correlation coefficients between the images were calculated and plotted as a function of the degree of obstruction and the flow rate. RESULTS: The average correlation decreased approximately linearly with an increase in the degree of obstruction. This decrease in correlation (decorrelation) might be due to turbulence caused by the obstruction. A higher degree of obstruction creates more turbulence and results in a higher decorrelation between sequential US images. CONCLUSION: Quantification of the decorrelation between sequential US images may provide us with a new approach to noninvasively diagnose bladder outlet obstruction.

Frequency analysis of urinary bladder pre-voiding activity in normal and overactive rat detrusor.

AIMS: To test the hypothesis that voiding in anesthetized rats is preceded by recurrent changes in the pattern of bladder pressure. To explore the use of frequency analysis as an analytical tool for automatically detecting these changes and to provide quantitative data on bladder pre-voiding activity. METHODS: We developed an algorithm, based on frequency analysis, to study bladder pressure during the filling phase in anesthetized rats. Two applications of the algorithm were tested: (i) as a predictor of a voiding contraction with alarms generated which would make conditional nerve stimulation to prevent incontinence possible; and (ii) as a new index to quantify rapid pressure transients in normal and overactive detrusor conditions (i.e., induced by acetic acid instillation into the bladder). RESULTS: The results show that a very high percentage (∼90%) of the alarms was generated by the algorithm within 100 sec before voiding. The index of rapid transients and the bladder volume before voiding were respectively ∼13% less and ∼42% less in acetic acid. CONCLUSIONS: We have shown that a simple algorithm, based on frequency analysis of bladder pressure, can be used to predict voiding and to provide quantitative data on non-voiding bladder activity and its changes due to pathology. Although the results refer to anesthetized rats, they are promising and warrant further urodynamic investigation to identify if similar patterns occur in non-anesthetized rats and in humans.

Dependence of ultrasound decorrelation on urine scatter particle concentration for a non-invasive diagnosis of bladder outlet obstruction.

AIMS: To develop a non-invasive method to diagnose Bladder Outlet Obstruction (BOO) based on decorrelation of subsequently acquired UltraSound (US) data of urinary flow, we studied the influence of scatter particle concentration on the decorrelation process in urethra models using both aqueous solutions of scattering particles and urine samples. METHODS: A tissue mimicking urethra model made from PolyVinyl Alcohol (PVA) solution was infused with seven aqueous solutions containing different particle concentrations at a constant flow rate value of 10 ml/sec. The average correlation coefficients between subsequent US images were calculated and plotted as a function of particle concentration. This procedure was also applied to stepwise diluted urine samples from nine healthy volunteers. An inversely exponential curve was fitted to the experimental data to estimate the scatter particle concentration in the urine samples. RESULTS: The average correlation values between subsequent US images increased with the particle concentration. The morning urine samples contained an appropriate number of scattering particles to make clinical application of the decorrelation method possible. The fitted correlation curves made an estimation of urine particle concentration possible. CONCLUSION: The results of this study show that morning urine is suitable for US decorrelation without correcting for differences in particle concentration.

Estimation of urinary flow velocity in models of obstructed and unobstructed urethras by decorrelation of ultrasound radiofrequency signals.

The feasibility of estimating urinary flow velocity from the decorrelation of radiofrequency (RF) signals was investigated in soft tissue-mimicking models of obstructed and unobstructed urethras. The decorrelation was studied in the near field, focal zone and far field of the ultrasound beam. Furthermore, the effect of beam width was investigated. The results of this study suggest that it is feasible to estimate flow velocity in models of the urethra by quantifying the decorrelation of RF ultrasound signals. The decorrelation slope increased more rapidly and more linearly with increasing velocity in the focal zone than in the near and far field. A preliminary example of an in vivo measurement in a healthy volunteer illustrated that this method has potential for clinical use in the future.

International Continence Society guidelines on urodynamic equipment performance.

These guidelines provide benchmarks for the performance of urodynamic equipment, and have been developed by the International Continence Society to assist purchasing decisions, design requirements, and performance checks. The guidelines suggest ranges of specification for uroflowmetry, volume, pressure, and EMG measurement, along with recommendations for user interfaces and performance tests. Factors affecting measurement relating to the different technologies used are also described. Summary tables of essential and desirable features are included for ease of reference. It is emphasized that these guidelines can only contribute to good urodynamics if equipment is used properly, in accordance with good practice.

Diagnostic power of the noninvasive condom catheter method in patients eligible for transurethral resection of the prostate.

AIMS: The aim of this study was to determine the accuracy of the non-invasive condom catheter method for diagnosing B(ladder) O(utlet) O(bstruction) in patients eligible for T(rans)U(rethral) R(esection) of the P(rostate). METHODS: A group of 71 patients eligible for TURP on clinical grounds were invasively and non-invasively studied. On the basis of invasive pressure-flow studies they were stratified into obstructed, equivocal or unobstructed, according to the International Continence Society standard. Subsequently they were diagnosed non-invasively on the basis of a free flowrate measurement, or on the basis of the free flowrate measurement plus the isovolumetric bladder pressure measured with the condom catheter method. R(eceiver) O(perating) C(haracteristic)s were calculated. RESULTS: The A(rea) U(nder) the (RO)C for discriminating unobstructed/equivocal patients from obstructed patients was 0.68 in our population. This improved to 0.84 for the 50 patients in whom the isovolumetric bladder pressure was not underestimated by the non-invasive method. CONCLUSIONS: In our population of TURP patients, the low flowrates affected the accuracy of the condom method to a degree that it did not perform better than a free flowrate measurement, which performed remarkably well. By excluding measurements in which the condom pressure underestimated the isovolumetric bladder pressure this method may contribute to a more accurate, patient friendly diagnosis of BOO in these patients. In the present study this exclusion was done by comparison with an invasive pressure measurement. A practical non-invasive test would necessitate a non-invasive exclusion criterion, which might be based on the risetime of the condom pressure.

Longitudinal changes in isovolumetric bladder pressure in response to age-related prostate growth in 1,020 healthy male volunteers.

AIM: To non-invasively study if compensation and decompensation occurs in the urinary bladder of healthy male volunteers in response to benign prostatic enlargement (BPE) using the condom catheter method. METHODS: Between 2001 and 2010, 1,020 healthy male volunteers were included in a longitudinal study based on three non-invasive urodynamic examinations during a 5-year follow-up. Inclusion criteria were an informed consent, the ability to void in a normal standing position and a minimum free flow rate of 5.4 ml/sec. Study parameters were prostate volume (PV), maximum free urinary flow rate (Q(max)) and bladder contractility, quantified by the maximum isovolumetric bladder pressure, measured in the condom (P(cond.max)). Volunteers also completed the International Prostate Symptom Score Form (IPSS). RESULTS: Within limitations, the included volunteers had a flat age distribution between 38 and 72 years. This made it possible to combine longitudinal analysis in a 5-year observation interval, with cross sectional analysis in a 35-year age range. Longitudinal analysis showed that with increasing age, PV increased with 1.9% per year, whereas Qmax decreased with 1.1% per year. IPSS increased with 1.1% per year when volunteers were older than 55 years. P(cond.max) increased during the 5-year longitudinal follow-up, but not in the cross sectional analysis. CONCLUSIONS: The difference between cross sectional and longitudinal results of the P(cond.max) may have been caused by compensation of the urinary bladder resulting in a selection effect. This would imply that compensation is a relatively fast process, taking approximately 5 years.

Longitudinal leak point pressure measurements in rats using a modified port à cath system.

Stress urinary incontinence, defined as involuntary loss of urine secondary to an increase in abdominal pressure, represents one of the most significant urological problems. Several animal models to simulate stress urinary incontinence have been presented, including methods to quantify leak point pressure. We have modified an existing leak point pressure procedure to longitudinally quantify stress urinary incontinence in rats by introducing the port à cath system. Reproducible leak point pressure measurements were carried out over a period of more than 40 days at different bladder volumes. Leak point pressure neither showed a significant relationship with the number of times anesthesia was applied nor a significant change over time. The port à cath system provided a reliable, sensitive device for longitudinal urinary bladder pressure measurements in animals with an implanted bladder catheter. This set-up therefore enables the evaluation of bladder pressure in different models for stress urinary incontinence, such as vaginal distention or pudendal transection over long periods of time within the same animal.

Urodynamic effects of volume-adjustable balloons for treatment of postprostatectomy urinary incontinence.

OBJECTIVE: To evaluate the urodynamic changes in patients treated with Adjustable Continence Therapy for men (ProACT) for postprostatectomy incontinence and to explore the clinical and urodynamic preimplantation parameters as predictors of clinical outcome. MATERIALS AND METHODS: Patients underwent urodynamic studies before and after ProACT implantation. ProACT was considered successful if patients used none or 1 dry precautionary pad and nonsuccessful if the patient reported ≥1 wet pad/d. The pre- and postimplantation assessments were retrospectively compared within and between the success and nonsuccess groups. Multivariate logistic regression analysis was performed to investigate the association between the preimplantation variables and the clinical outcomes of ProACT implantation. RESULTS: A total of 49 patients were included, 37 with successful and 12 with nonsuccessful clinical outcome. Postimplantation urodynamic studies were performed a median of 9 months after ProACT implantation. In the successfully treated patients, maximum free flow rate, bladder contractility index, maximum of bladder contractility parameter W, and bladder voiding efficiency were significantly lower after implantation. The detrusor pressure at maximum flow rate, postvoid residual urine volume, and bladder outlet obstruction index were significantly higher. A longer duration of urinary incontinence, the use of >5 pads daily, and a smaller cystometric bladder capacity were all independently associated with nonsuccessful clinical outcome after ProACT implantation. CONCLUSION: ProACT implantation with successful clinical outcome resulted in greater urethral resistance during voiding and reduced bladder contraction strength. A longer duration of incontinence, the use of >5 pads daily, and a smaller cystometric bladder capacity were independent predictors of unsuccessful clinical outcomes, suggesting ProACT implantation should be considered sooner, rather than later, after conservative treatment of postprostatectomy incontinence has failed.

Perineal sound recording for diagnosis of bladder outlet obstruction.

OBJECTIVES: Elderly men are prone to developing lower urinary tract symptoms (LUTS) possibly caused by bladder outlet obstruction (BOO). The most frequently used method to diagnose this condition is an invasive and time-consuming pressure-flow study. We are developing a novel non-invasive method to diagnose BOO in men with LUTS based on perineal sound recording. METHODS: A biophysical model urethra was made from polyvinyl alcohol (PVA) cryogel with viscoelastic properties comparable to those of the male pig urethra. To this model different degrees of obstruction were applied and sound was recorded at different positions downstream of the obstruction. In a study in 16 healthy male volunteers the variability and repeatability of perineal sound recording was tested. RESULTS: In the model three parameters, derived from the frequency spectrum of the recorded sound (i.e., weighted average frequency, standard deviation and skewness) are uniquely related to the degree of obstruction (linear regression, P<0.001). The variability of perineal sound recording in healthy male volunteers was found to be smaller within volunteers than between volunteers (Kruskal-Wallis, P<0.001) and the repeatability was comparable to that of the maximum flow rate. CONCLUSIONS: We conclude that perineal sound recordings are significantly different between volunteers. In combination with the unique relations found in the model-experiments these results increase the probability that perineal sound recording can be used as a simple and cheap non-invasive method to diagnose BOO. Clinical testing of this method is therefore strongly indicated.