X-ray videocystometry for high-speed monitoring of urinary tract function in mice

Abstract

Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Videocystometry substantially outperforms current state-of-the-art methods to monitor the urine storage and voiding process, by enabling quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow, in both anesthetized and awake, nonrestrained mice. Using videocystometry, we identified localized bladder wall micromotions correlated with different states of the filling/voiding cycle, revealed an acute effect of TRPV1 channel activation on voiding efficiency, and pinpointed the effects of urethane anesthesia on urine storage and urethral flow. Videocystometry has broad applications, ranging from the elucidation of molecular mechanisms of bladder control to drug development for LUTd.

Machine learning-assisted fluoroscopy of bladder function in awake mice

“…This approach allowed us to determine time-dependent changes in bladder volume based on the spheroid approximation (fig. 1b), along with other volume-related voiding parameters: bladder capacity (BC), residual volume (RV), and voiding efficiency (E voiding ), as described previously (3).…”

“…Note that animals that were immediately treated with a single 1.2g/kg-dose yielded similar values for BC, RV and E voiding as animals that reached this dose at the end of the stepwise dosing protocol, indicating that the reduced voiding efficiency and increased residual volume are due to the urethane rather than to fatigue (fig. 2c-f, blue) (3). Taken together, our findings indicate that urethane leads to a pronounced and dose-dependent reduction of the ability of the bladder to empty during voiding.…”

“…For comparison. The blue symbols represent data from mice that received a single dose of 1.2 g/kg at the start of the recording (3). One-way repeated measures ANOVA was used to test for statistically significant differences with the 0.0 g/kg condition.…”

“…Videocystometry and suprapubic catheter implantation were performed as described earlier (3,11). In short, a PE-50 catheter was implanted into the bladder dome of five female mice through an abdominal midline incision while under 2% isoflurane anesthesia (Iso-vet, Dechra veterinary products, Bladel, The Netherlands).…”

“…To overcome some of these limitations, we recently introduced videocystometry, a new approach combining cystometry with continuous, fluoroscopy-based bladder imaging. By imaging the contrast-filled bladder at video rate, this approach provides quantitative and time-resolved measurements of bladder volume and urethral flow, along with other relevant aspects of LUT function such as vesicoureteral reflux and micromotions of the bladder wall (3). Notably, the accurate analysis of bladder volume and urethral flow during consecutive filling-voiding cycles relies on the precise delineation of the bladder.…”