title: Early detection and measurement of urothelial tumors in mice.
abstract: OBJECTIVE
  To establish reliable noninvasive in vivo methods to detect, measure, and monitor experimentally induced urothelial tumors in mice.
  
  
  METHODS
  UPII-SV40T transgenic mice reliably develop bladder tumors by expression of simian virus 40 large T antigen specifically in bladder urothelium through the use of the uroplakin II promoter. Two wild-type and 10 UPII-SV40T transgenic mice were monitored for microhematuria two to three times weekly using dipstick analysis. A unique flat panel detector-based cone beam computed tomography (FPD-CBCT) system imaged the urinary tracts of anesthetized mice after tail vein injection of an iodinated contrast agent (Omnipaque) that is excreted in urine. Within 10 seconds, the FPD-CBCT system acquired 290 two-dimensional images, which produced three-dimensional volumes with true isotropic resolution (180 microm)3 using a filtered back projection-based modified Feldkamp reconstruction algorithm. Amira, version 3.1.1-1, for MacOSX was used for data analysis and advanced visualization of the three-dimensional reconstructed FPD-CBCT images.
  
  
  RESULTS
  Hematuria was present in UPII-SV40T transgenic mice at 32 days of age; the wild-type animals exhibited no hematuria. Filling defects, associated with histologically confirmed tumors, in the bladders of the UPII-SV40T transgenic mice were visualized in the reconstructed FPD-CBCT images 1 to 45 minutes after contrast agent injection. Longitudinal FPD-CBCT imaging sessions showed the tumor position, volume, and growth.
  
  
  CONCLUSIONS
  The combination of early detection of hematuria and high-resolution in vivo FPD-CBCT imaging of murine bladder tumors enabled accurate longitudinal assessment of tumor growth and progression in individual animals. This approach could provide an important alternative to serial sacrifice experimental designs, while refining statistical power and reducing animal use.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Johnson
authors.forename: David L
authors.initials: DL
authors.lastname: Conover
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Edward M
authors.initials: EM
authors.lastname: Messing
authors.forename: Ruola
authors.initials: R
authors.lastname: Ning
authors.forename: Mary J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: M Adrian
authors.initials: MA
authors.lastname: Rossi
authors.forename: Tung-Tien
authors.initials: TT
authors.lastname: Sun
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Wood
authors.forename: Xue-Ru
authors.initials: XR
authors.lastname: Wu
authors.forename: Jay E
authors.initials: JE
authors.lastname: Reeder
mesh_terms: D000818:Animals; D042241:Early Diagnosis; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*; D019459:Urothelium