Objective Quantification of Detrusor Overactivity Using Spectral Measures of Cystometry Data.

OBJECTIVE: To develop scalable objective methods for differentiating patients with and without detrusor overactivity (DO) using quantitative Fast Fourier Transform (FFT)-based measures and routinely captured cystometry data. METHODS: Retrospective cystometry data were collected as prevoid vesical and abdominal pressure signals from 18 DO and 10 SUI (non-DO) cystometry recordings. Data were filtered and divided into two equal-duration segments, Early and Late Fill, representing the first and second halves of filling. FFT was applied, followed by subtraction of abdominal spectra from vesical spectra. Spectral Power (SP) and Weighted Average Frequency (WAF) measures were calculated for each segment spectra within 1-6 cycles min-1. RESULTS: Compared to non-DO, the mean SP was significantly higher in DO patients for both Early and Late Fill segments. WAF was significantly lower in DO patients for both segments. Changes in spectral pressures appeared to be linked to the presence of detrusor contractions (DCs) and were especially visible when DCs were present in the Early Fill segments of cystometry. CONCLUSION: FFT-based spectral measures derived from routinely captured cystometry data are significantly different between DO and non-DO patients. This preliminary method is clinically scalable and can be further developed to facilitate the detection of DO, classify disease phenotype, and capture therapeutic efficacy.

Measurement and Quantification of Cystometric Bladder Pressure Spectra in an in-vivo Sheep Model: A Feasibility Study.

Cystometry is a standard procedure for the clinical evaluation of lower urinary tract disorders such as detrusor overactivity (DO). The utility of this procedure for DO diagnosis, however, is limited by the use of physician observations of bladder contractions and patient reported filling sensations. Although a number of preclinical and clinical studies have observed and developed methods to characterize bladder pressure dynamics, these techniques have not been scaled for routine clinical application. The goal of this study was to evaluate the feasibility of using an awake large animal model to characterize bladder pressure signals from cystometry as bladder pressure spectra and quantify changes in spectra during bladder filling. Two adult female sheep were trained for quiet catheterization in a minimally supportive sling and underwent multiple awake and limited anesthetized cystometry tests. In each test, bladder pressure was measured during continuous filling or with filling that included periods of no filling (constant volume). A Fast-Fourier Transform (FFT)-based algorithm was then used to quantify changes in pre-voiding bladder pressure spectra. Changes in Spectral Power (SP) and Weighted Average Frequency (WAF) were calculated during filling. To visualize temporal changes in bladder pressure frequencies during filling, Continuous Wavelet Transform (CWT) was also applied to cystometry data. Results showed that a significant increase in SP and decrease in WAF were both associated with bladder filling. However, during awake constant volume tests, SP significantly increased while changes in WAF were nonsignificant. Anesthetized tests demonstrated comparable values to awake tests for WAF while SP was considerably reduced. CWT facilitated visualization of spectral changes associated with SP and WAF as well as apparent non-voiding contractions during awake and anesthetized volume tests.Clinical Relevance-Bladder pressure spectra during cystometry are detectable in sheep and the changes during filling are similar to those observed in human retrospective clinical data. Sheep cystometry may be a valuable testbed for establishing and testing quantitative pressure spectra for use as a clinical diagnostic tool.

An Instrumented Urethral Catheter with a Distributed Array of Iontronic Force Sensors.

This paper develops a novel instrumented urethral catheter with an array of force sensors for measuring the distributed pressure in a human urethra. The catheter and integrated portions of the force sensors are fabricated by the use of 3D printing using a combination of both soft and hard polymer substrates. Other portions of the force sensors consisting of electrodes and electrolytes are fabricated separately and assembled on top of the 3D-printed catheter to create a soft flexible device. The force sensors use a novel supercapacitive (iontronic) sensing mechanism in which the contact area between a pair of electrodes and a paper-based electrolyte changes in response to force. This provides a highly sensitive measure of force that is immune to parasitic noise from liquids. The developed catheter is tested using a force calibration test rig, a cuff-based pressure application device, an extracted bladder and urethra from a sheep and by dipping inside a beaker of water. The force sensors are found to have a sensitivity of 30-50 nF/N, which is 1000 times larger than that of traditional capacitive force sensors. They exhibit negligible capacitance change when dipped completely in water. The pressure cuff tests and the extracted sheep tissue tests also verify the ability of the sensor array to work reliably in providing distributed force measurements. The developed catheter could help diagnose ailments related to urinary incontinence and inadequate urethral closure pressure.

Instrumented Urethral Catheter and Its Ex Vivo Validation in a Sheep Urethra.

This paper designs and fabricates an instrumented catheter for instantaneous measurement of distributed urethral pressure profiles. Since the catheter enables a new type of urological measurement, a process for accurate ex-vivo validation of the catheter is developed. A flexible sensor strip is first fabricated with nine pressure sensors and integrated electronic pads for an associated sensor IC chip. The flexible sensor strip and associated IC chip are assembled on a 7 Fr Foley catheter. A sheep bladder and urethra are extracted and used in an ex-vivo set up for verification of the developed instrumented catheter. The bladder-urethra are suspended in a test rig and pressure cuffs placed to apply known static and dynamic pressures around the urethra. A significant challenge in the performance of the sensor system is the presence of parasitics that introduce large bias and drift errors in the capacitive sensor signals. An algorithm based on use of reference parasitic transducers is used to compensate for the parasitics. Extensive experimental results verify that the developed compensation method works effectively. Results on pressure variation profiles circumferentially around the urethra and longitudinally along the urethra are presented. The developed instrumented catheter will be useful in improved urodynamics to more accurately diagnose the source of urinary incontinence in patients.

Pelvic floor dynamics during high-impact athletic activities: A computational modeling study.

BACKGROUND: Stress urinary incontinence is a significant problem in young female athletes, but the pathophysiology remains unclear because of the limited knowledge of the pelvic floor support function and limited capability of currently available assessment tools. The aim of our study is to develop an advanced computer modeling tool to better understand the dynamics of the internal pelvic floor during highly transient athletic activities. METHODS: Apelvic model was developed based on high-resolution MRI scans of a healthy nulliparous young female. A jump-landing process was simulated using realistic boundary conditions captured from jumping experiments. Hypothesized alterations of the function of pelvic floor muscles were simulated by weakening or strengthening the levator ani muscle stiffness at different levels. Intra-abdominal pressures and corresponding deformations of pelvic floor structures were monitored at different levels of weakness or enhancement. FINDINGS: Results show that pelvic floor deformations generated during a jump-landing process differed greatly from those seen in a Valsalva maneuver which is commonly used for diagnosis in clinic. The urethral mobility was only slightly influenced by the alterations of the levator ani muscle stiffness. Implications for risk factors and treatment strategies were also discussed. INTERPRETATION: Results suggest that clinical diagnosis should make allowances for observed differences in pelvic floor deformations between a Valsalva maneuver and a jump-landing process to ensure accuracy. Urethral hypermobility may be a less contributing factor than the intrinsic sphincteric closure system to the incontinence of young female athletes.

Distributed pressure sensors for a urethral catheter.

A flexible strip that incorporates multiple pressure sensors and is capable of being fixed to a urethral catheter is developed. The urethral catheter thus instrumented will be useful for measurement of pressure in a human urethra during urodynamic testing in a clinic. This would help diagnose the causes of urinary incontinence in patients. Capacitive pressure sensors are fabricated on a flexible polyimide-copper substrate using surface micromachining processes and alignment/assembly of the top and bottom portions of the sensor strip. The developed sensor strip is experimentally evaluated in an in vitro test rig using a pressure chamber. The sensor strip is shown to have adequate sensitivity and repeatability. While the calibration factors for the sensors on the strip vary from one sensor to another, even the least sensitive sensor has a resolution better than 0.1 psi.

Flexible Distributed Pressure Sensing Strip for a Urethral Catheter.

A multi-sensor flexible strip is developed for a urethral catheter to measure distributed pressure in a human urethra. The developed sensor strip has important clinical applications in urodynamic testing for analyzing the causes of urinary incontinence in patients. There are two major challenges in the development of the sensor. First, a highly sensitive sensor strip that is flexible enough for urethral insertion into a human body is required and second, the sensor has to work reliably in a liquid in-vivo environment in the human body. Capacitive force sensors are designed and micro-fabricated using polyimide/PDMS substrates and copper electrodes. To remove the parasitic influence of urethral tissues which create fringe capacitance that can lead to significant errors, a reference fringe capacitance measurement sensor is incorporated on the strip. The sensing strip is embedded on a catheter and experimental in-vitro evaluation is presented using a bench-top pressure chamber. The sensors on the strip are able to provide the required sensitivity and range. Preliminary experimental results also show promise that by using measurements from the reference parasitic sensor on the strip, the influence of parasitics from human tissue on the pressure measurements can be removed.

Novel artificial urinary sphincter in the canine model: the tape mechanical occlusive device.

OBJECTIVES: To assess the functionality, occlusive efficiency, and biocompatibility of a novel artificial urinary sphincter, the tape mechanical occlusive device (TMOD), after implantation in a live canine model, as well as its occlusive efficiency and sizing parameters in human cadavers. METHODS: Three female canines underwent implantation of the TMOD at the level of the bladder neck. Functionality was assessed starting at 2 weeks after implantation and continued for ≤9 weeks. The TMODs were activated at 2 weeks and then deactivated for 3, 30-minute sessions daily to permit voiding. The urethral occlusion pressures and biocompatibility for systemic toxicity and the local tissue response were examined. Additionally, the TMOD was inserted in 3 male cadavers to determine the sizing parameters and to assess the urethral occlusion pressures using pressure profilometry. RESULTS: In the canine model, the urethral occlusion pressures increased from a range of 9-42 cm H(2)O with the TMOD deactivated to a range of 57-82 cm H(2)O with the TMOD activated. Pathologic examination revealed unremarkable pseudocapsular tissues surrounding the device. No histologic or structural evidence of systemic toxicity was observed. Sizing parameters similar to those of other urologic implants were confirmed in the male cadavers, and the urethral occlusion pressures increased from 24 to 30 cm H(2)O with the device deactivated to 61-105 cm H(2)O with the device activated. CONCLUSIONS: The TMOD meets the current standards for an artificial urinary sphincter in terms of functionality, biocompatibility, and achieving desired occlusion pressures following chronic implantation. Additional testing in male canines followed by early human clinical trials is being contemplated.

The biomechanics of erections: two- versus one-compartment pressurized vessel modeling of the penis.

Previous biomechanical models of the penis simulated penile erections utilizing 2D geometry, simplified 3D geometry or made inaccurate assumptions altogether. These models designed the shaft of the penis as a one-compartment pressurized vessel fixed at one end when in reality it is a two-compartment pressurized vessel in which the compartments diverge as they enter the body and are fixed at two separate anatomic sites. This study utilizes the more anatomically correct two-compartment penile model to investigate erectile function. Simplified 2D and 3D models of the erect penis were developed using the finite element method with varying anatomical considerations for analyzing structural stresses, axial buckling, and lateral deformation. This study then validated the results by building and testing corresponding physical models. Finally, a more complex and anatomically accurate model of the penis was designed and analyzed. When subject to a lateral force of 0.5 N, the peak equivalent von Mises (EVM) stress in the two-compartment model increased by about 31.62%, while in the one-compartment model, the peak EVM stress increased by as high as 70.11%. The peak EVM stress was 149 kPa in the more complex and anatomically accurate penile model. When the perforated septum was removed, the peak EVM stress increased to 455 kPa. This study verified that there is significant difference between modeling the penis as a two- versus a one-compartment pressurized vessel. When subjected to external forces, a significant advantage was exhibited by two corporal based cavernosal bodies separated by a perforated septum as opposed to one corporal body. This is due to better structural integrity of the tunica albuginea when subjected to external forces.

Effects of periurethral neuromuscular electrical stimulation on the voiding frequency in rats.

INTRODUCTION AND HYPOTHESIS: This study aims to test the hypothesis that a urethra-to-bladder inhibitory pathway exists through which periurethral neuromuscular electrical stimulation (NMES) inhibits overactive bladder contractions in rats. METHODS: Bladder overactivity was induced in 22 female Sprague Dawley rats by injection of ketamine/xylazine/acepromizine (K/X/A). A bipolar electrode was placed surgically in the periurethral region to deliver NMES. Intravesical pressure, bladder inter-contraction interval (ICI) and voided volume (VV) were monitored while the bladder was continuously infused with saline. RESULTS: K/X/A induced more frequent bladder contractions (ICI = 48.6 +/- 20.1 s, before cutting the pubo-symphasis) compared to a 10-min ICI induced by urethane. NMES significantly increased ICI (63.1 +/- 31.3 s before vs. 97.2 +/- 42.9 s after NMES, p < 0.001) and VV (0.063 = 0.041 ml before vs. 0.088 = 0.044 ml after NMES, p < 0.02). CONCLUSIONS: Injection of K/X/A may potentially be used as a model of bladder overactivity. NMES inhibits bladder contractions in rats with bladder overactivity, which supports the existence of a urethra-to-bladder inhibitory pathway.

Ambulatory device for urinary incontinence detection in females.

This paper describes the design and use of an ambulatory monitoring device for recording urological response to intense physical activities of women. The system integrates a tri-axial accelerometer, a 360 degree biaxial inclinometer and a specially designed urine leakage detector(ULD) for sensing body motion and urine discharge. The device is small, lightweight and battery powered, and can be worn comfortably. All recordings are taken non-invasively and transmitted wirelessly to a receiver for real-time data logging. The experimental results show that the proposed system can record acceleration, inclination efficiently and detect urine leakage of amounts from 0.5ml to 10ml accurately. The unique design of the ULD sensor exempts it from sweating interference during vigorous activities.

Feasibility of using a computer modeling approach to study SUI Induced by landing a jump.

Stress urinary incontinence (SUI) occurs due to anatomic and/or neurologic factors involving connective tissues, muscles and nerves. Although SUI is more common in post-menopausal and multiparous women, studies have also shown a high prevalence of SUI in young, physically fit female athletes. With a goal toward dynamic subject-specific mechanical characterization of the interaction between anatomical structures during physical activities that elicit SUI in females during physical or daily activities, a computer aided design (CAD)-based computer model of the female pelvis has been developed to test the feasibility of the computer modeling approach in understanding the measurable differences between stress-continent and stress-incontinent women. In the present study, a fluid-structure interaction analysis was conducted by using the finite element (FE) analysis technique based on the CAD-based computer model of the female pelvis to investigate the urine leakage in females during jumping. To the best of our knowledge, this is the first application of a fluid-structure interaction FE analysis approach in understanding the mechanisms of SUI in females. Through a series of computer simulations, the effects of varying impact forces determined by jumping height and bladder volume were investigated. The dynamic computer simulation results revealed that jumping heights have a significant influence on the volume of urine leakage caused by the landing impact of jumping. Bladder volume did not have a significant influence on leakage when the jumping heights were smaller than 1 ft, which indicates that normal walking (corresponds to a jumping height smaller than 0.1 ft) is not the primary cause of urine leakage for healthy females. The computer simulation results also showed that the deformation difference between the anterior and posterior portion of the female pelvis causes opening of the urethra and resultant urine leakage. The present study demonstrates the feasibility of using a computer modeling approach to study female SUI during physical and daily activities.

Advanced finite element mesh model of female SUI research during physical and daily activities.

With a goal towards dynamic subject-specific mechanical characterization of the etiology of stress urinary incontinence (SUI) in females during physical or daily activities, a finite element (FE) mesh model generation procedure has been developed to build the subject-specific FE model of the female pelvis from multiple high resolution magnetic resonance (MR) acquisitions with varying contrasts. The advanced female pelvis FE model was developed by using this procedure which consisted of over 35 anatomical parts including: 10 pelvic muscles, 10 pelvic ligaments, 6 pelvic bones, skin, fat tissue, bladder, urethra, uterus, vagina, colon, rectum, anus etc. basically all the major parts of the female pelvis. This comprehensive pelvis model is ready to be used to characterize relative relationships and structures during the physical activities that elicit SUI during activities of daily living.

Biomechanical analysis of penile erections: penile buckling behaviour under axial loading and radial compression.

OBJECTIVE: To characterize the biomechanics of erectile function, as contrary reports have modelled the penis as an isotropic material and state that only axial buckling tests can effectively predict penile rigidity; that assumption is questioned and an alternative structure proposed and validated. METHODS: Three experimental physical cylindrical models of diameters 1.9, 2.54 and 3.81 cm were fabricated and the relationship between axial loading and radial compression was measured for cylindrical pressures of 8-20 kPa. A finite element analysis (FEA) computer model of the penis was constructed to simulate the response of the corpora cavernosa to axial and radial loading for differing diameters and lengths of the penile shaft. The stresses developed in the tunica albuginea of the corporal bodies of the penis during buckling were assessed using a mathematical analysis. RESULTS: From the analysis of surface stresses under variable axial loading, as the angle of an applied load changes on an isotropic shaft, the magnitude of surface stresses varies up to 50 kPa, and for a pressure vessel the magnitude of surface stresses varies up to 100 kPa. The FEA model showed that nodal displacements were greatest around a ring under radial compression, and for the axially loaded model displacements were greatest at the vessel tip under the force gauge. All displacements were 0.1-1.0 mm. There was an exponential relationship between internal pressure and the axial force required to cause buckling in a thin-walled pressure vessel. There was a nearly constant relationship between circumferential displacement and internal pressure under uniform radial compression. The displacement values on the FEA analysis were approximately equal outside of the areas of high stress which were under the load of the external device (compressive ring or force gauge) in both cases. Physical modelling shows that when a pressurized vessel is under either axial or radial load the internal pressure increases. Vessels at high internal pressure require more force to cause buckling than vessels at lower internal pressure. The circumferential displacement of a vessel under radial compression is higher in vessels of lower internal pressure and less in vessels of high internal pressure. The size of a vessel also contributes to its ability to be buckled. Smaller vessels buckle under smaller load, but the ratio of force required to buckle vs. diameter of the cylinder remained constant. CONCLUSIONS: The computer simulations show that with slight deviations from perfectly aligned axial loading the stresses felt on the walls of cylindrical columns vary considerably, whether they are isotropic beams or pressurized vessels. The material properties of the tissues within the corpora cause it to behave as a thin-walled pressurized vessel, in which the hoop stress and axial stress have a constant relationship independent of the length to diameter ratio rather than as an isotropic beam where this relationship varies. Patient discomfort and high operator dependency further contribute to the inconsistencies of axial loading methods to determine penile buckling. Based on the constant relationship between hoop stress and axial stress in thin-walled pressurized vessels this study confirms the validity and desirability of using radial compression methods to assess penile rigidity in lieu of axial loading methods.

William E. Bradley and his contributions to urology.

PURPOSE: We review the myriad contributions to urological science by neurologist and engineer, William E. Bradley. MATERIALS AND METHODS: Remembrances and personal interviews were collated for this article. RESULTS: Doctor Bradley was a pioneer in neurourology. He described a neurophysiological paradigm for micturition, devised urodynamic and electrophysiological techniques, and contributed to the development of genitourinary prosthetic devices. CONCLUSIONS: Doctor Bradley made notable and groundbreaking contributions to urology, many of which are still in use today.

Tissue characterization for improved external penile occlusive device design.

This study is motivated by the need for quantitative data on the material properties of the penis in order to develop an optimal design for an external penile occlusive device (EPOD) for the treatment of urinary incontinence.