Videocystometry, a novel approach to study the murine lower urinary tract

The lower urinary tract consists of the bladder and the urethra and performs dual functions. On the one hand, it stores urine and on the other hand, it empties the bladder at a socially convenient time. Lower urinary tract symptoms is a term used to describe an array of symptoms concerning the urinary tract. These symptoms can be related to the storage function such as urinary incontinence or to the emptying function such as incomplete emptying. Lower urinary tract symptoms can have an important impact on quality of life and current treatments often lack efficacy. To develop new treatment options for lower urinary tract symptoms, research performed on animal models is essential. To this end, mice and rats are typically used as they have useful anatomical and physiological similarities to humans, and as their use is generally cost effective. Several techniques exist for the assessment of lower urinary tract function in these small animal models. Up until now, cystometry was the most commonly used technique for this purpose. Cystometry yields information on bladder pressure, voided volume and voiding frequency during multiple bladder filling and voiding cycles. However, important information on bladder volume, residual volume and urethral flow rate are lost. For this reason we developed a new technique, videocystometry, that combines classic cystometry with continuous, high-speed, x-ray based imaging of the bladder. These images are then converted to bladder volume based on image intensity or bladder border. Videocystometry generates, for the first time, quantitative data on both bladder pressure and bladder volume related parameters. This technique allows unprecedented and detailed information on bladder capacity, residual volume, voiding efficiency, voided volume, urethral flow rate and urethral flow conductance. To validate this new technique we created an acute bladder outlet obstruction model. Using videocystometry we observed a marked obstructive voiding pattern with a decrease in voiding efficiency, an increase in residual volume and voiding frequency and a decrease in urethral flow rate and urethral flow conductance in this model of disease. Next, we show that videocystometry can be performed in awake and non-restrained animals, using an artificial intelligence based protocol to speed up and standardize the analysis of the video output. We then studied the effect of urethane anesthesia, the most commonly used anesthetic during (video)cystometry, on lower urinary tract function. We found that urethane anesthesia had a dose-dependent effect on lower urinary tract function with a 50% decrease in voiding efficiency in mice that received a full dose of urethane. Lastly, we developed a more physiological and non-invasive technique for the assessment of the lower urinary tract by adapting videocystometry. We called this new technique fluoroscopic volumetry as it allows the continuous and non-invasive measurement of bladder volume during multiple filling and voiding cycles based on continuous bladder imaging, albeit without pressure measurements.

Publication year:2022

Accessibility:Open