High-definition ultrasound characterization of acute cyclophosphamide-induced cystitis in the mouse

Purpose: To examine associations if any between changes in voiding function, hematuria, and bladder ultrasonography metrics in murine cyclophosphamide-induced chemical cystitis. Materials and Methods: Cystitis was induced in 6 female mice by an intraperitoneal injection of cyclophosphamide (300 mg/ kg). Voiding frequency, void volume, hematuria assessment, and ultrasonographic measurements of the bladder were obtained at baseline, days 1 to 5, and days 9, 11, and 13. Voiding was induced with preferred sweet drinking solution and voiding data collected using an automated data collection system in 135 minute sessions. Bladder wall thickness, lumen volume, and vascular Doppler were acquired using a high definition ultrasound system. Spearman’s correlation was used to analyze the association between the voiding changes, hematuria, and ultrasound findings. Results: Hematuria was present 24 hours after cyclophosphamide injection. All animals displayed increased bladder vascularity, bladder wall thickness, and void frequency that was associated with concurrent decreased total and average void volumes. Increased bladder wall vascularity was correlated with the presence of hematuria (r=0.59, p<0.01) and bladder wall thickness (r=0.79, p<0.01). Hematuria correlated with increased void frequency (r=0.34, p<0.01). Average void volume was negatively correlated with hematuria (r=-0.50, p<0.01) and frequency (r=-0.38, p<0.01). Conclusions: High-definition ultrasound imaging permits in vivo monitoring of changes in bladder morphology associated with voiding function in relation to cyclophosphamide-induced cystitis. Ultrasound imaging of the bladder may assist in differential diagnosis of bladder dysfunction.