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.

Ultrasound modalities and quantification: developments of multiparametric ultrasonography, a new modality to detect, localize and target prostatic tumors.

PURPOSE OF REVIEW: An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve the diagnostic pathway with imaging targeted biopsies. This review presents the latest developments in existing and novel ultrasound modalities for the detection and localization of PCa. RECENT FINDINGS: The ultrasound modalities that were very promising on introduction (HistoScanning and Doppler) have shown a wane in performance when tested in larger patient populations. In the meantime, novel ultrasound modalities have emerged in the field of PCa detection. Modalities, such as shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) show very promising results. SWE produces an absolute elasticity measure and removes the need for manual compression of the tissue. The former allows comparison between scans and patients, the latter reduces the interoperator variability. Quantification of CEUS enables easily interpretable and accurate imaging of the microvascular changes associated with clinically significant prostate tumors. SUMMARY: The novel ultrasound modalities of SWE and CEUS imaging open the door for taking targeted biopsies based on the detection and localization of PCa by these novel modalities. This potentially improves PCa detection wherein significantly reducing the number of biopsy cores.

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.

Noninvasive 2-dimensional monitoring of strain in the detrusor muscle in patients with lower urinary tract symptoms using ultrasound strain imaging.

PURPOSE: Pressure flow studies and filling cystometry are currently the standard diagnostic urodynamic tests for lower urinary tract symptoms. A noninvasive ultrasound based method for 2-dimensional monitoring of deformation (or strain) in the detrusor muscle may provide insight into detrusor muscle structural and dynamic properties related to pressure in physiological and disease conditions. MATERIALS AND METHODS: In a male patient population with lower urinary tract symptoms, strain in the detrusor muscle (perpendicular to the bladder wall) was estimated based on 2-dimensional radio frequency ultrasound imaging. The estimated strain was correlated to detrusor pressure and urinary flow rate using Spearman's correlation coefficient. RESULTS: Twenty men (mean ± SD age 66 ± 6 years) with lower urinary tract symptoms were included in the study. Ultrasound data acquisition was successful in 13 patients. In 7 patients data acquisition failed due to out-of-plane motion of the bladder wall during voiding or as a result of patient movement during acquisition. The estimated strain correlated positively with detrusor pressure in the 5 patients with an isovolumetric detrusor contraction (Spearman's 0.70-0.99, p <0.05). Of 8 patients with urinary voiding during detrusor muscle contraction this correlation was significantly positive in 5 patients (Spearman's 0.52-0.81, p <0.05). CONCLUSIONS: In 13 of 20 patients with lower urinary tract symptoms we demonstrated that strain in the detrusor muscle can be estimated using ultrasound imaging. The estimated strain correlated positively with the detrusor pressure. Optimal results were obtained in the pre-voiding phase, suggesting that ultrasound strain imaging can possibly be used to monitor detrusor muscle activity in real time.

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.

Variability and repeatability of perineal sound recording in a population of healthy male volunteers.

OBJECTIVES: In a population of 16 healthy male volunteers we studied the variability and repeatability of perineal sound recording as a non-invasive method for diagnosing bladder outlet obstruction. MATERIALS AND METHODS: The volunteers had a flat age-distribution (22-62 years), a median IPSS-score of 1 (range: 0-18) and voided at least 10 times. From each perineal sound recording the frequency spectrum was calculated and characterized by its weighted average frequency, standard deviation and skewness. We assessed the variability of these parameters using the Kruskal-Wallis test, differences between volunteers using Dunn's test and the repeatability by the normalized standard deviation of the differences between pairs of recordings in each volunteer. RESULTS: For each parameter the variability within volunteers was significantly smaller than the variability between volunteers (Kruskal-Wallis, P < 0.05). For each parameter more than one volunteer was significantly different from three or more volunteers (Dunn's test, P < 0.05). The repeatability of each parameter was comparable to that of the maximum flow rate. CONCLUSION: Perineal sound recording gives repeatable results, which are significantly different between volunteers. In combination with the earlier published results from model-experiments the present results increase the probability that perineal sound recording can be used as a very simple and cheap method to non-invasively diagnose BOO. Clinical testing of this method is therefore strongly indicated.

Toward an acoustic noninvasive diagnosis of urinary bladder outlet obstruction.

On average, in aging males, the prostate enlarges (benign prostatic enlargement or BPE) and may cause bladder outlet obstruction (BOO). The internationally standardized method for diagnosing BOO is based on measurements of urinary flow rate and bladder pressure, using a catheter inserted into the bladder via the urethra. This method is invasive, time-consuming, and uncomfortable for the patient. We are developing a novel diagnostic method based on perineal recording of sound during urinary flow. Although it is known that (some aspects of) the recorded sound are (among others) related to the degree of obstruction, an exact and unique relation allowing derivation of the degree of obstruction from the sound recording is not known. In a biophysical model of the urethra, we found that the weighted average frequency, the standard deviation, and the skewness of the power spectrum are monotonically related to the degree of obstruction. The standard deviation was the most significant predictor of BOO (89% correct). Based on this model study, we are confident that a simple noninvasive acoustic method for diagnosing BOO caused by BPE can be developed. This would lower the threshold for urodynamic testing of patients with lower urinary tract symptoms resulting in higher therapeutic efficacy.

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.

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.

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.

Fast 2-D ultrasound strain imaging: the benefits of using a GPU.

Deformation of tissue can be accurately estimated from radio-frequency ultrasound data using a 2-dimensional normalized cross correlation (NCC)-based algorithm. This procedure, however, is very computationally time-consuming. A major time reduction can be achieved by parallelizing the numerous computations of NCC. In this paper, two approaches for parallelization have been investigated: the OpenMP interface on a multi-CPU system and Compute Unified Device Architecture (CUDA) on a graphics processing unit (GPU). The performance of the OpenMP and GPU approaches were compared with a conventional Matlab implementation of NCC. The OpenMP approach with 8 threads achieved a maximum speed-up factor of 132 on the computing of NCC, whereas the GPU approach on an Nvidia Tesla K20 achieved a maximum speed-up factor of 376. Neither parallelization approach resulted in a significant loss in image quality of the elastograms. Parallelization of the NCC computations using the GPU, therefore, significantly reduces the computation time and increases the frame rate for motion estimation.

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.

Enhancing the performance of lateral shear strain estimation by using 2-D strain imaging.

Radio-frequency (RF) ultrasound can be used to estimate deformation of biological tissue. Decorrelation of sequentially acquired ultrasound signals resulting from the deformation imposes a limitation on the precision (elastographic signal-to-noise ratio; SNRe) of estimating these deformations; this is presented as the lateral shear strain filter. In this paper, we explore the effect of a 2-D-window-based strain estimation approach on the lateral shear strain filter and propose an extension of the 1-D theoretical lateral shear strain filter to 2-D. We compared the performance of the 2-D approach in simulated ultrasound data and a tissue-mimicking phantom with that of the 2-D lateral shear strain filter. In simulations, the 2-D-window-based approach shows an effect in the axial direction similar to the 2-D prediction. In simulations and experiments, increasing the window size in the lateral direction shows an increase in the maximum SNRe of the lateral shear strain filter. Increasing the lateral overlap has no effect on the estimation of lateral shear strain. These results were confirmed in the tissue-mimicking phantom experiments. When compared with the 2-D lateral shear strain filter, the results obtained with the 2-D-window-based approach showed an enhanced performance by incorporating the lateral window size in the lateral shear strain estimation, which was consistent with the proposed theory.

Estimating cyclic shear strain in the common carotid artery using radiofrequency ultrasound.

There is increasing evidence that supports the hypothesis that elevated cyclic shear strain in the adventitia of the common carotid artery promotes plaque progression. In this article, we estimated cyclic shear strain in the carotid arterial wall in 16 asymptomatic human participants using radio-frequency (RF) ultrasound. In each participant, we acquired two separate RF ultrasound recordings. We correlated the cyclic shear strain with the distension waveform (representing the blood pressure waveform) of the carotid artery and the brachial blood pressure. There were no significant differences between the shear strains estimated from the two separate RF ultrasound recordings. The point-in-time of the maximum shear strain showed a significant correlation with that of the dicrotic notch in the distension waveform (Spearman's coefficient = 0.7, p < 0.001). The pulse shear strain (difference between maximum and minimum shear strain) was significantly correlated with the pulse pressure as measured in the brachial artery (Spearman's coefficient = 0.4, p < 0.01). In this study, we show that the cyclic shear strain in the adventitia of the common carotid artery can be estimated using RF ultrasound. We found indications that the estimated cyclic shear strain was induced by the pulsating blood pressure and it was found to be higher in participants with an elevated pulse pressure.

Noninvasive estimation of the blood pressure waveform in the carotid artery using continuous finger blood pressure monitoring.

To noninvasively estimate the blood pressure continuously in the common carotid artery (CCA), we obtained the distension waveform of the CCA from seven healthy volunteers and 20 hypertensive patients using radio-frequency ultrasound. Consequently, it was calibrated by the mean and diastolic pressure measured in the finger artery and compared with applanation tonometry, calibrated using the systolic and diastolic pressure in the brachial artery. The mean difference in estimating the mean blood pressure was 0.3 mm Hg (limits of agreement: -11.7 to 12.3 mm Hg). In estimating the systolic blood pressure, the mean difference was 8.0 mm Hg (limits of agreement: -29.8 to 45.8 mm Hg) and showed increasing variation with blood pressure. The systolic blood pressure values can be expected between 0.83 and 1.35 times the control method. In this study, we obtained proof-of-principle for noninvasively measuring blood pressure in the CCA using continuous finger blood pressure monitoring. This opens the way to estimating location specific arterial stiffness and intra-plaque elasticity.

An angular compounding technique using displacement projection for noninvasive ultrasound strain imaging of vessel cross-sections.

Strain is considered to be a useful indicator of atherosclerotic plaque vulnerability. This study introduces an alternative for a recently introduced strain imaging method that combined beam steered ultrasound acquisitions to construct radial strain images of transverse cross-sections of superficial arteries. In that study, axial strains were projected in the radial direction. Using the alternative method introduced in this study, axial displacements are projected radially, followed by a least squares estimation of radial strains. This enables the use of a larger projection angle. Consequently, fewer acquisitions at smaller beam steering angles are required to construct radial strain images. Simulated and experimentally obtained radio-frequency data of radially expanding vessel phantoms were used to compare the two methods. Using only three beam steering angles (-30°, 0° and 30°), the new method outperformed the older method that used seven different angles and up to 45° of beam steering: the root mean squared error was reduced by 38% and the elastographic signal- and contrast-to-noise ratios increased by 1.8 dB and 4.9 dB, respectively. The new method was also superior for homogeneous and heterogeneous phantoms with eccentric lumens. To conclude, an improved noninvasive method was developed for radial strain imaging in transverse cross-sections of superficial arteries.

Fluid perfused urethral pressure profilometry and Valsalva leak point pressure: a comparative study in a biophysical model of the urethra.

In patient studies the correlation between maximum urethral closure pressure (MUCP) and Valsalva leak point pressure (LPP) is meagre at best (r = 0.22-0.50). We therefore studied the relation between MUCP and LPP in a flexible and extensible model urethra. We applied differently sized pressure zones and different degrees of resistance to a biophysical model urethra by stepwise inflating three types of blood pressure cuff placed around the model. At each degree of resistance we measured detrusor LPP, an in vitro equivalent of Valsalva LPP. Subsequently, we recorded the Urethral Pressure Profile using a water-perfused 5F end-hole catheter at four withdrawal rates and five perfusion rates and calculated MUCP. We tested the dependence of LPP on pressure zone length and MUCP on perfusion rate, withdrawal rate and pressure zone length using analysis of variance. We tested the correlation between LPP and MUCP using Pearson's correlation coefficient and Linear Regression. LPP did not significantly depend on the pressure zone length (P = 0.80) and increased linearly with increasing cuff pressure. MUCP also increased with increasing cuff pressure, however, MUCP significantly depended (P < 0.01) on perfusion rate, withdrawal rate and pressure zone length. MUCP increased with increasing perfusion rate, and decreased with increasing withdrawal rate. In our model urethra MUCP only accurately reflected urethral resistance for a very limited number of combinations of perfusion rate and withdrawal rate. LPP reflected urethral resistance independent of the type of pressure zone.

A biophysical model of the male urethra: comparing viscoelastic properties of polyvinyl alcohol urethras to male pig urethras.

AIMS: We aim at developing a non-invasive method for grading and diagnosing urinary bladder outlet obstruction, based on noise recording with a perineal contact microphone during voiding. We found that the noise production during voiding depends amongst others on the viscoelastic properties of the urethral wall. To further test our method, we need a realistic biophysical model of the male urethra. METHODS: We made various model urethras with different viscoelastic properties from a 10% aqueous solution of polyvinyl alcohol cryogel. We measured the viscoelastic properties of each model and compared them to those of the male pig urethra. The male pig urethra was used, as it is physiologically comparable to the human male urethra. The viscoelastic properties of both model and pig urethras were measured by applying strain to the urethral wall in a stepwise manner and recording the pressure response. We fitted the step-response of a mechanical model to this pressure response and derived the viscoelastic properties from the coefficients of this response. RESULTS: A uniform model urethra that was freeze-thawed three times, with a Y-shaped flow channel was found to best represent the male pig urethra. CONCLUSIONS: We consider the three times freeze-thawed model urethra with a Y-shaped flow channel the best model of the human male urethra. And we therefore use this model urethra for studying the relation between noise recording during urine flow and the degree of bladder outlet obstruction.

Is the impaired flow after hypospadias correction due to increased urethral stiffness?

PURPOSE: A low flow rate without clinical symptoms is commonly found in boys after hypospadias correction. Urethral calibration usually shows no abnormalities. We investigated whether this impairment might be caused by increased neo-urethral wall stiffness. METHODS: From polyvinyl alcohol cryogel two models of the urethra were made, hypospadias and control; both had a constant and equal inner diameter and equal compliance. The hypospadias model had a less compliant distal segment mimicking the distal neo-urethra after hypospadias correction. In both models, flow rate was recorded as a function of bladder pressure. To test whether the length of the less compliant segment had an effect on the flow rate, both models were shortened by cutting off 1-cm segments. RESULTS: In a physiological range of bladder pressures (10-130 cmH(2)O) the mean flow rate (+/-1 SEM) in the hypospadias model was 2.8+/-0.3 ml/s, significantly lower (P<0.05) than in the control model (5.4+/-0.6 ml/s). Shortening of the hypospadias model showed some increase in flow rate, but this was not statistically significant. In the control model there was also no significant variation in flow rate. CONCLUSION: A low-compliant segment of a urethral model reduced the flow rate. Extrapolating these results to asymptomatic boys with a low urinary flow rate after hypospadias repair might justify a watchful waiting policy.