A porcine bladder model of pre-clinical urodynamics demonstrates increased afferent nerve activity during filling.

INTRODUCTION AND OBJECTIVES: Urodynamics are the accepted gold standard for the evaluation of multiple forms of voiding dysfunction. However, the tests are expensive, invasive, poorly reproducible, and often prone to artifacts. Therefore, there is a pressing need to develop next-generation urodynamics. The purpose of this study was to develop a novel ex vivo porcine bladder urodynamics model with afferent pelvic nerve signaling that can be used as a preclinical surrogate for bladder sensation. METHODS: Porcine bladders including the ureters and vascular supply were harvested from local abattoirs using an established protocol in both male and female animals. Ex vivo bladder perfusion was performed using physiologic MOPS (3-(N-morpholino) propanesulfonic acid) buffer solution. The pelvic nerve adjacent to the bladder was grasped with micro-hook electrodes and electroneurogram (ENG) signals recorded at 20 kHz. Bladders were filled with saline at a nonphysiologic rate (100 mL/min) to a volume of 1 L using standard urodynamics equipment to simultaneously record intravesical pressure. ENG amplitude was calculated as the area under the curve for each minute, and ENG firing rate was calculated as number of spikes (above baseline threshold) per minute. At the conclusion of the experiment, representative nerve samples were removed and processed for nerve histology by a pathologist (hematoxylin and eosin and S100 stains). RESULTS: A total of 10 pig bladders were used, and nerve histology confirmed the presence of nerve in all adequately processed samples. Vesical pressure, ENG firing rate, and ENG amplitude all increased as a function of filling. During filling tertiles (low fill: min 1-3, med fill: min 4-6, and high fill: min 7-10), normalized pressures were 0.22 ± 0.04, 0.38 ± 0.05, and 0.72 ± 0.07 (cmH2O). Similarly, normalized ENG firing rates were 0.08 ± 0.03, 0.31 ± 0.06, and 0.43 ± 0.04 spikes/minute, respectively, and normalized nerve amplitudes were 0.11 ± 0.06, 0.39 ± 0.06, and 0.56 ± 0.14) µV, respectively. Strong relationships between average normalized pressure values and averaged normalized ENG firing rate (r2 = 0.66) and average normalized ENG amplitude (r2 = 0.8) were identified. CONCLUSIONS: The ex vivo perfused porcine bladder can be used as a preclinical model for the development of next-generation urodynamics technologies. Importantly, the model includes a reproducible method to measure afferent nerve activity that directly correlates with intravesical pressure during filling and could potentially be used as a surrogate measure of bladder sensation.

Should we be revisiting LUT basic science and clinical measurement of LUT sensation to improve patient care? ICI-RS 2019.

AIMS: This article reviews current knowledge of the underpinning mechanisms of how the bladder senses fullness locally and also revisits clinical measurements of lower urinary tract sensation. The former represents cellular sensing during bladder filling whereas the latter describes the sensations leading to conscious perception of bladder fullness. METHODS: The topic was discussed in a "think tank" session at the 2019 International Consultation on Incontinence-Research Symposium in Bristol, UK; summarized in the present review. RESULTS: Recent advances in the basic science of bladder sensing relating to (a) the bladder wall-urothelial cells, sensory nerves, interstitial cells, and smooth muscle cells and (b) putative chemo/mechanosensors in the urethra-paraneurons or "brush cells" are discussed. Validated clinical measurement of lower urinary tract sensation is reviewed in the context of how this could be better harnessed for patient benefit. We discuss the potential of app/tablet/mobile technology based on triggers and distractors to override aberrant local sensing/higher sensation and how these technologies could be utilized in treatment. CONCLUSIONS: We conclude that a better understanding of bladder sensation is essential to inform clinical management of lower urinary tract symptoms.

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.

Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019.

Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) and detrusor underactivity (DU)/underactive bladder (UAB). The present article addresses proposal 1: "Are oxidative stress and ischemia significant causes of bladder damage leading to LUTD?" from the 2019 International Consultation on Incontinence-Research Society (ICI-RS) meeting. Bladder ischemia in animals and humans is briefly described, along with the proposed progression from ischemia to LUTD. Bladder ischemia is compared with ischemia of other organs, and the ongoing development of pelvic ischemia animal models is discussed. In addition, the distribution of blood within the bladder during filling and voiding and the challenges of quantification of blood flow in vivo are described. Furthermore, oxidative stress, including potential biomarkers and treatments, and challenges regarding antioxidant therapy for the treatment of LUTD are discussed. Finally, seven critical research questions and proposed studies to answer those questions were identified as priorities that would lead to major advances in the understanding and treatment of lower urinary tract symptoms (LUTS)/LUTD associated with pelvic ischemia and oxidative stress.

What developments are needed to achieve less-invasive urodynamics? ICI-RS 2019.

AIMS: To assess the state of technologies for urodynamics that are less invasive than standard cystometry and pressure-flow studies and to suggest areas needing research to improve this. METHODS: A summary of a Think Tank debate held at the 2019 meeting of the International Consultation on Incontinence Research Society is provided, with subsequent analysis by the authors. Less-invasive techniques were summarized, classified by method, and possible developments considered. Discussions and recommendations were summarized by the co-chairs and edited into the form of this paper by all authors. RESULTS: There is a full spectrum of technologies available for less-invasive assessment, ranging from simple uroflowmetry through imaging techniques to emerging complex technologies. Less-invasive diagnostics will not necessarily need to replace diagnosis by, or even provide the same level of diagnostic accuracy as, invasive urodynamics. Rather than aiming for a technique that is merely less invasive, the priority is to develop methods that are either as accurate as current invasive methods, or spare patients from the necessity of invasive methods by improving early triaging. CONCLUSIONS: Technologies offering less-invasive urodynamic measurement of specific elements of function can be potentially beneficial. Less-invasive techniques may sometimes be useful as an adjunct to invasive urodynamics. The potential for current less-invasive tests to completely replace invasive urodynamic testing is considered, however, to be low. Less-invasive techniques must, therefore, be tested as screening/triaging tools, with the aim to spare some patients from invasive urodynamics early in the treatment pathway.

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.

An innovative, non-invasive sensation meter allows for a more comprehensive understanding of bladder sensation events: A prospective study in participants with normal bladder function.

AIMS: There is currently no standardized method of characterizing changes in bladder sensation during bladder filling outside of the urodynamics laboratory. The purpose of this investigation was to characterize real-time bladder sensation events using a sensation meter during oral hydration in individuals with normal bladder function. METHODS: Participants enrolled in an accelerated hydration study drank 2 L Gatorade-G2® and utilized a sensation meter to record real-time bladder sensation (0-100%), verbal sensory thresholds, and sensation descriptors of "tense," "pressure," "tingling," "painful," and "other" for two consecutive fill-void cycles. RESULTS: Data from 21 participants (12 females/9 males) were obtained and demonstrated an average of 8-9 sensation events (significant changes in sensation) per fill with no differences in the total number of sensation events and volume between sensation events (fill 1 vs fill 2). An increased number of sensation events occurred at higher capacity quartiles. Event descriptors of "pressure" and "tingling" were the most commonly chosen descriptors in both fills. CONCLUSIONS: The innovative sensation meter includes the sensation event descriptors of "tense," "tingling," "pressure," and "painful," to enable a more comprehensive understanding of bladder sensation as well as real-time identification, quantification, and characterization of sensation events. The study demonstrates 8-9 events per fill, acceleration of sensation during filling, and unique sensation event descriptor patterns. This technology may be helpful in the identification of novel sensation patterns associated with overactive bladder (OAB) and aging.

Bladder volume correction factors measured with 3D ultrasound and BladderScan.

INTRODUCTION: The aim of this study was to investigate conventional 3D ultrasound and portable BladderScan volume measurements and implement correction factors to ensure accurate volume metrics. MATERIALS AND METHODS: Healthy participants without urinary urgency were recruited for a prospective hydration study in which three consecutive voids were analyzed for two separate visits. Just before and after voiding, 3D ultrasound and BladderScan volumes were measured. Estimated voided volumes were calculated as the volume immediately prior to void minus any post void residual and were compared to actual voided volumes measured using a graduated container. Percent errors were calculated, and an algebraic method was implemented to create correction factors for 3D ultrasound and BladderScan. RESULTS: Sixteen individuals completed the study, and six voids were recorded for each participant. A total of 96 volume measurements ranging from 0 mL to 1050 mL with an average of 394 +/- 26 mL were analyzed. Both 3D ultrasound and BladderScan significantly underestimated voided volumes with averages of 296 +/- 22 and 362 +/- 27, respectively. Average percent error for the 3D ultrasound group was 30.1% (pre-correction) and 20.7% (post-correction) (p < 0.01) and 22.4% (pre-correction) and 21.8% (post-correction) for the BladderScan group (p = 0.20). The voided volume correction factors for 3D ultrasound and BladderScan were 1.30 and 1.06, respectively. CONCLUSION: BladderScan and 3D ultrasound typically underestimate voided volumes. Correction factors enabled more accurate measurements of voided volumes for both 3D ultrasound and BladderScan. Accurate volume measurements will be valuable for the development of non-invasive urodynamics techniques.

Effects of vesical and perfusion pressure on perfusate flow, and flow on vesical pressure, in the isolated perfused working pig bladder reveal a potential mechanism for the regulation of detrusor compliance.

AIMS: Although there is evidence that deficits in bladder blood flow negatively impact bladder function, the effects of vesical, and perfusion pressures on bladder perfusion (perfusate flow), and of perfusate flow on vesical pressure, remain poorly understood. The present study used the isolated perfused working pig bladder model to examine the relationships between blood flow, and vesical and perfusion pressures. METHODS: Vesical arteries of pig bladders obtained from a local slaughterhouse were cannulated and perfused with Krebs-Henseleit solution at different pressures, and with carbachol to cause bladder contraction. The urethra of each bladder was cannulated to permit filling (10 mL/min), isovolumetric contraction and emptying. A ureter was cannulated with a pressure sensor to monitor vesical pressure. RESULTS: When at rest (50 mL vesical volume), bladder vesical pressure was 8.06 ± 1.5 mmHg and perfusate flow driven by a pressure gradient of 105 mmHg was 22.5 ± 2 mL/min (58.9 ± 7.8 mL/min-100 g). During filling, vesical pressure increased and flow decreased, but not necessarily in-parallel. Perfusate flow decreased transiently during isovolumetric contraction, and flow increased during emptying. A reduction in perfusion pressure from ∼105 to ∼40 mmHg reduced flow from ∼70 to ∼20 mL/min-100g, and reduced flow correlated with reduced vesical pressure. CONCLUSION: Perfusate flow is dependent on bladder perfusion pressure, and not necessarily reciprocally dependent on vesical pressure. Vesical pressure is highly sensitive to the level of perfusate flow, which supports the hypothesis that vesical pressure is dependent on the level of detrusor smooth muscle contractile activity (tone), and that compliance is dependent on bladder perfusion.

Potential vascular mechanisms in an ex vivo functional pig bladder model.

AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.

What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017.

INTRODUCTION: Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. METHODS: A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. RESULTS: The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. CONCLUSIONS: Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology.

Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle.

Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

PURPOSE: Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves) waves during urodynamics (UD). METHODS: After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (<2 g) and analyzed by fast Fourier transform (FFT) to identify LARC signal frequencies. Blinded UD tracings were retrospectively reviewed for signs of LARC on the p ves tracing during filling and were analyzed via FFT. RESULTS: Distinct LARC frequencies were identified in 100% of tissue strips (n = 9) obtained with a mean frequency of 1.97 ± 0.47 cycles/min (33 ± 8 mHz). Out of 100 consecutive UD studies reviewed, 35 visually displayed phasic p ves waves. In 12/35 (34%), real p ves signals were present that were independent of abdominal activity. Average UD LARC frequency was 2.34 ± 0.36 cycles/min (39 ± 6 mHz) which was similar to tissue LARC frequencies (p = 0.50). A majority (83%) of the UD cohort with LARC signals also demonstrated detrusor overactivity. CONCLUSIONS: During UD, a subset of patients displayed phasic p ves waves with a distinct rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

A pilot study to measure dynamic elasticity of the bladder during urodynamics.

AIMS: Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics. METHODS: Patients reporting urgency most or all of the time based on ICIq-OAB survey scores were prospectively enrolled in an extended repeat fill-and-empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call "dynamic elasticity." Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening. RESULTS: Five patients completed the extended urodynamics study. Intravesical pressure (pves ) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P = 0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with pves in Fill 4 returning to the baseline measured during Fill 1 (P = 0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per %capacity (Δaverage pves between fills/Δ%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal). CONCLUSIONS: Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub-typing and novel treatments of overactive bladder. Neurourol. Urodynam. 36:1086-1090, 2017. © 2016 Wiley Periodicals, Inc.

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience.

AIMS: The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS: Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS: Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS: This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way.

Acute length adaptation and adjustable preload in the human detrusor.

AIMS: The biomechanical properties of length adaptation and adjustable preload have been previously identified in detrusor smooth muscle in animal models. This in vitro study aims to show that human detrusor smooth muscle exhibits length adaptation and adjustable preload tension which could play an important role in both overactive bladder and detrusor underactivity. METHODS: In order to demonstrate length adaptation, human detrusor smooth muscle strips are stretched and contracted beyond an optimum length and then contracted three times at the previous optimum length to determine if maximum active tension could be re-established. To demonstrate adjustable preload (Tap ), human detrusor smooth muscle strips are subjected to a pre-defined loading-unloading (strain softening) sequence to reduce preload. Then, tissues are contracted and the sequence is repeated to determine if this active process restored preload. RESULTS: Nine patients (average age, 62) provide tissue: 89% are men with urothelial carcinoma and a minority (22%) also have neurogenic bladder dysfunction. In the length adaptation protocol, contractions show progressive increases in active tension (P < 0.05). In the Tap protocol, a significant amount of preload is lost to strain softening (P < 0.05) and is restored after active contraction (P = 0.50). Exposure to the rho-kinase inhibitor, H-1152, prevents the restoration of preload (P < 0.05). CONCLUSIONS: This study demonstrates that human detrusor smooth muscle displays both length adaptation and Tap . Furthermore, Tap may be regulatable through a rho-kinase pathway. These biomechanical processes may be important in the pathophysiology of both overactive bladder and detrusor underactivity. Neurourol. Urodynam. 35:792-797, 2016. © 2015 Wiley Periodicals, Inc.

Fetal membrane imaging and the prediction of preterm birth: a systematic review, current issues, and future directions.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is the largest identifiable cause of preterm birth. There is currently no good screening test for PPROM in low-risk asymptomatic patients. Our goal was to identify how imaging methods can be utilized for examining the risks for PPROM in asymptomatic patients. METHODS: This paper is a systematic review of the literature on fetal membrane thickness and its use for the prediction of PPROM. Four key studies are identified and reviewed; two in vitro studies and two in vivo ultrasound studies each using differing methodologies. Additionally reviewed is a study using Optical Coherence Tomography, an emerging technique using near-infrared technology to produce high-resolution images. RESULTS: There is currently insufficient data to determine the association between fetal membrane thickness and PPROM by ultrasound. CONCLUSIONS: Fetal membrane thickness could have relevant clinical ramifications for the prediction of PPROM. Suggested improvements in study methodology and design will lead to progress in this area of research, as well as the use of newer technologies. Larger sample sizes, histological comparison, uniform methodologies for data collection, longitudinal study design and expanding data analysis beyond fetal membrane thickness to other properties would expand our knowledge in this field. In addition, transvaginal ultrasound should be utilized to improve resolution, as well as emerging methodologies such as MRI fusion imaging using ultrasound and Shear Wave Elastography.

A new and automated method for objective analysis of detrusor rhythm during the filling phase.

INTRODUCTION: There is growing acceptance that the detrusor muscle is not silent during the filling phase of the micturition cycle but displays low-amplitude phasic contractions that have been associated with urinary urgency. Unfortunately, there is currently no standardized methodology to quantify detrusor rhythm during the filling phase. Therefore, the purpose of this study was to develop an automated computer algorithm to analyze rat detrusor rhythm in a quick, accurate, and reproducible manner. MATERIALS AND METHODS: Strips of detrusor smooth muscle from rats (n = 17) were placed on force transducers and subjected to escalating doses of PGE2 to generate contractile rhythm tracings. An automated computer algorithm was developed to analyze contractile frequency, amplitude, and tone on the generated rhythm tracings. Results of the automated computerized analysis were compared to human (n = 3) interpretations. Human interpreters manually counted contractions and then recounted the same data two weeks later. Intra-observer, inter-observer, and human-to-computer comparisons were performed. RESULTS: The computer algorithm quantified concentration-dependent changes in contractile frequency, amplitude, and tone after administration of PGE2 (10(-9)-10(-6)M). Concentration-response curves were similar for all contractile components with increases in frequency identified mainly at physiologic concentrations of PGE2 and increases in amplitude at supra-physiologic concentrations. The computer algorithm consistently over-counted the human interpreters, but with less variability. Differences in inter-observer consistency were statistically significant. CONCLUSIONS: Our computerized algorithm accurately and consistently identified changes in detrusor muscle contractile frequency, amplitude, and tone with varying doses of PGE2. Frequency counts were consistently higher than those obtained by human interpreters but without variability or bias. Refinements of this method may allow for more standardized approach in the study of pharmacologic agents on filling phase rhythmic activity.

Fourier transform analysis of rabbit detrusor autonomous contractions reveals length dependent increases in tone and slow wave development at long lengths.

PURPOSE: Bladder wall muscle (detrusor) develops low amplitude rhythmic contractions. Low amplitude rhythmic contraction activity is increased in detrusor from patients with overactive bladder. In this in vitro study we used fast Fourier transforms to assess the length dependence of low amplitude rhythmic contraction components. MATERIALS AND METHODS: Rabbit detrusor strips were placed in a muscle bath between 2 clips to adjust length and record isometric tension. Tissues stretched from 70% to 130% of a reference muscle length at 10% increments were allowed to develop low amplitude rhythmic contractions at each length for 20 minutes. Low amplitude rhythmic contraction data were analyzed using fast Fourier transforms and represented by a frequency rather than a time spectrum. RESULTS: Based on fast Fourier transform analysis summarized by signal peaks within specific frequency ranges, rabbit low amplitude rhythmic contraction waveforms were divided into 1 tonic and 2 phasic components, defined as A0 + A1F1 + A2F2, where A0 is a length dependent basal tonic component that increases linearly, A1F1 is a slow wave with a length dependent specific amplitude (A1) and a length independent constant frequency (F1) of approximately 11.2 Hz, and A2F2 is a fast wave with a length dependent amplitude (A2) and frequency (F2) of approximately 0.03 Hz. CONCLUSIONS: Fast Fourier transform analysis revealed that rabbit low amplitude rhythmic contractions consist of a basal tonic component plus 2 phasic components. The amplitude of all 3 components was length dependent. The frequency of the fast component was not length dependent and the slow component was absent at short muscle lengths, developing only at muscle lengths beyond that producing a maximum active contraction.

A stepwise approach for functional near infrared spectroscopy measurement during natural bladder filling.

Background: Functional near infrared spectroscopy (fNIRS) is a versatile, noninvasive, and inexpensive tool that can be used to measure oxyhemoglobin (O2Hb) changes in the cortical brain caused by increasing bladder sensation during filling in upright posture. This study's purpose is to provide a rigorous methodologic template that can be implemented for comparative studies of fNIRS in the diagnosis and management of lower urinary tract symptoms including overactive bladder (OAB) and other forms of lower urinary tract dysfunction. Methods: Participants without any urologic conditions completed a validated oral hydration protocol facilitating and equilibrating natural bladder filling. First desire to void and real time bladder sensation (0-100%) were recorded using a Sensation Meter. A 24-channel fNIRS template simultaneously recorded prefrontal cortical O2Hb. Each channel was analyzed between "first desire" to void and 100% sensation, defined in this study as the period of "high sensation". Channels were sub-divided by cortical regions: right (nine channels), left (nine channels), middle (six channels). Results: A total of eight participants (male: n=4, female: n=4) were enrolled with mean age 39±19.9 years and body mass index (BMI) of 25±3.93 kg/m2. There were no differences in age, BMI, race, or OAB survey scores based on biological sex. Signal acquisition improved with power bank use, postural head support for motion reduction, and head cap optimization. Acceleration-based concurrent motion measurement was effectively utilized to remove motion artifacts. O2Hb concentration patterns appeared irregular during low sensation and increased during high sensation after first desire across the frontal cortex. Conclusions: Employing a stepwise approach, this study defined a methodological guide for improved prefrontal fNIRS signal acquisition and analysis during bladder filling. The technique demonstrated that prefrontal fNIRS cortical O2Hb increases with elevated bladder sensation in normal subjects and sets the stage for comparative studies in individuals with OAB and other forms of lower urinary tract dysfunction.