In-vivo trials

Having developed the theory explaining the flow pattern associated with an elliptical orifice, we now examine the real flow pattern for urine exiting the meatus and the changes which occur during a single void. Figure 5(a) shows representative images taken from a video of a complete voiding event for a healthy male volunteer. The characteristic shape of the urine stream matches closely with that predicted by the experimental and computational models. Results show a typical temporal profile, such that the flow rate increases to a maximum value of and then gradually reduces over the course of the void (Fig. 5(b)). This corresponds with a change in the wavelength which reaches a maximum of approximately coinciding with the peak urine flow rate (Fig. 5(b)). There is a clear positive correlation between wavelength ( ) and flow rate ( ) as predicted Fig. 5(d). The relationship is not purely linear, as illustrated by the change in values during the course of the void (Fig. 5(c)). The parameter reflects the orifice dilation, as quantified through the modelling Fig. 5(c), and thus the non-linearity indicates changes in the meatal dilation during the void. Indeed this was confirmed by measuring from the video images, the meatal opening in terms of the minimum diameter of the urine stream at the meatus (Fig. 5(c)). Thus during voiding the meatus opens under the flow pressure so that the aspect ratio reduces and cross sectional area increases, thereby influencing the wavelength ( ) with an associated reduction in the dilation parameter ( ). At the onset of voiding the pressure is sufficient to cause the meatus to rapidly open (Fig. 5(c)). However towards the end of the voiding the pressure drops gradually and the meatus slowly returns to its closed form due to the viscoelastic nature of the urethral tissue. This explains the difference between the descending and ascending curves in (Fig. 5(d)). Future studies may incorporate solid modelling of the urethral tissues to understand the temporal dynamics of meatal dilation during voiding and hence the effect on the flow pattern.

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larger image TIFF original image Download: Figure 5. The human urine flow stream shows a characteristic pattern that is dependent on flow rate and orifice dilation as predicted by the experimental and computational modelling. (a) Selected video images from which the wavelength was measured by calibrating against a rule held alongside the flow stream. (b) Representative plot for an individual void showing the temporal change in instantaneous flow rate, , and wavelength, . The wavelength is a function of both the flow rate and the shape and size of the meatus. (c) The opening of the urethral orifice during voiding was quantified by the minimum diameter of the meatal ellipse ( ) measured from the video images. The size and shape of the orifice is also characterised by the dilation parameter , such that a reduction in corresponds to an increase in opening. (d) The resulting plot of wavelength, , versus flow rate, , shows a clear correlation. Note that the relationship is non-linear due to the changes in the meatal opening. https://doi.org/10.1371/journal.pone.0047133.g005

We then enlisted a group of 60 male patients who had been referred to a urologist due to low urine flow rate and suspected bladder outlet obstruction associated with prostatic enlargement. The patients were asked to record the maximum wavelength whilst voiding into a clinical urine flow meter. The flow meter used was a Smartflow (Albyn Medical). In addition, the same procedure was performed with a sample of 60 healthy male volunteers with no history of urinary flow problems. All participants from both groups reported the same characteristic urine flow pattern which evolved over the course of a single void in line with the flow rate, as shown in Fig. 5(b) (c).

For the group of healthy volunteers there was a statistically significant ( ) positive correlation (correlation coefficient ) between peak flow rate ( ) and maximum wavelength ( )(Fig. 6(a)). The patient group showed no statistically significant correlation between and in contrast to the positive correlation for healthy volunteers (Fig. 6(a)). For the patient group, the dilation parameter ( ) was statistically different ( ) and exhibited greater variability than that for healthy men (Fig. 6(b)). Notably some patients with low peak flow rates showed higher values of the dilation parameter indicative of a reduced meatal opening. A reduction in a patient's meatal opening might be expected at very low flow rates where there is insufficient flow to fully open the meatus (Fig. 6, red region). Nonetheless, meatal dilation also appeared to be reduced in patients that have regained a more normal flow rate (Fig. 6, yellow region). It is possible that the reduced urethral opening reflects the greater average age of the patient cohort and associated age-related urethral stiffening [14]. However there was no correlation between age and dilation parameter with younger patients also showing high values. Thus an alternative explanation is that the chronic low flow rates in these patients may lead to urethra atrophy or constriction and that this persists even after the prostatic urethral obstruction causing the low flow rate is reduced. Although it is unclear for how long such an effect might persist, our data is supported by clinical experience which suggests that certain patients may benefit from surgical dilation of the urethra in order to regain a normal flow rate [15]. Thus, our data and the resulting nomogram shown in Fig. 6(a), helps to identify this subset of patients as those for whom is greater than the confidence limit of , determined for healthy volunteers [16].

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larger image TIFF original image Download: Figure 6. Self measurement of the maximum wavelength provides an estimate of the peak urine flow rate for healthy males, but requires individual calibration for patients undergoing treatment for urethral obstruction. (a) Plot of versus showing a statistically significant positive correlation for healthy men ( , solid line) but not for the patient cohort (dashed line). A peak flow rate was considered as abnormally low (red region). The green region represents the confidence envelope for values based on data from the normal group. Individuals with and values within the yellow region have a normal flow rate but reduced urethral dilation. (b) Frequency distributions for the dilation parameter, , for the healthy and patient groups showing a statistically significant difference suggesting that the latter have reduced urethral opening. https://doi.org/10.1371/journal.pone.0047133.g006

Accurate estimation of an individual's peak urine flow rate based on measurements of maximum wavelength can be performed if an individual's meatal dilation is calibrated for. Self measurement of an individual's urine flow pattern and maximum wavelength can provide a simple non-invasive method for monitoring peak urine flow rate as part of the recommended practise of watchful waiting for patients with benign prostatic hyperplasia [17]–[20]. This has advantages over existing uroflowmetry techniques in that it is completely non-invasive, simple and cheap to implement and avoids inaccuracies associated with voiding in a clinical setting and obtaining data from a single void [7], [21]–[24]. For the group of healthy volunteers the statistically significant ( ) positive correlation gave the following relationship between and (10)where is found to be . The accuracy of this estimate of is (2 standard deviations). However this can be greatly improved by precalibrating for an individual's meatal geometry. This could simply be achieved by requesting the patient to void into a standard urine flow meter to obtain the relationship between and . This approach would also provide a non-invasive measurement of an individual's meatal dilation during voiding. This is demonstrated in Fig. 7, which shows the predicted versus measured flow-rate for an individual, where the individual's dilation parameter has been calculated at one point, and used to predict the peak flow-rate at several other voiding events, using the individual's self measurement of . The figure shows the uncertainty in the estimate of was improved to (2 standard deviations).

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larger image TIFF original image Download: Figure 7. Flow rate measurement accuracy can be improved if an individual's dilation parameter is calibrated for. The open symbols show the predicted based on multiplied by the sample mean value of / . The closed symbols show the predicted based on an individual's measured at the first recorded voiding event. The open symbols show the increased scatter if the sample mean value is used rather than the individual's . https://doi.org/10.1371/journal.pone.0047133.g007

In this report we have applied an understanding of capillary wave phenomena in liquid jets to reveal the biophysics behind the characteristic shape of the urine flow stream and how this can be used as a simple non invasive means of measuring urethral opening and urine flow rate. The data obtained in the present study included inaccuracies caused by poor estimates of which are likely to be exacerbated by obesity, poor eye sight, or lack of manual dexterity. However despite the associated scatter there was still a statistically significant correlation between and for healthy volunteers, showing that an individual's peak urine flow rate can be estimated from self measurement of maximum wavelength. Thus this technique can provide a simple non-invasive method for monitoring peak urine flow rate as part of the recommended practise of watchful waiting for patients with benign prostatic hyperplasia [17]–[20]