Detection and Quantitative Analysis of Early Stage Orthotopic Murine Bladder Tumor Using In Vivo Magnetic Resonance Imaging

Abstract

We evaluated in vivo magnetic resonance imaging (MRI) as a noninvasive method for early detection and quantitative measurements of superficial tumors in an orthotopic murine bladder tumor model. Murine bladder tumor cells were instilled into 25 mouse bladders and subsequently scanned with MRI 10, 14, 17 and 24 days after tumor inoculation. High quality T1-weighted spin-echo transverse images were obtained with 1.5 mm thick slices. Conditions for contrast agent instillation were optimized by evaluating varying concentrations of Gd-diethylenetetramine pentaacetic acid, water and air. Total tumor area in the largest bladder section on MRI was measured and compared quantitatively with actual tumor areas measured in whole mount bladder step sections. Optimal MRI studies were obtained with intravesical instillation of 50 microl Gd-diethylenetetramine pentaacetic acid and 50 microl air. Overall 17 tumors in 11 mice were identified pathologically 10 days after tumor inoculation, of which 14 (82.4%) were identified by MRI with a largest mean diameter of 1.4 +/- 0.1 mm (range 1.0 to 2.2). Mean total tumor area on MRI 10, 14, 17 and 24 days after tumor inoculation was 0.024 +/- 0.005, 0.108 +/- 0.049, 0.165 +/- 0.020 and 0.318 +/- 0.023 cm2, respectively, which correlated well with actual tumor area (r2 = 0.977, p <0.001). MRI is accurate and effective for noninvasively monitoring tumor growth in the orthotopic murine bladder cancer model. The improved resolution that we report compared with previous murine bladder studies highlights its potential for monitoring the therapeutic efficacy of antitumor agents for early superficial bladder tumors.