In Vivo 3D MRI Measurement of Tumour Volume in an Orthotopic Mouse Model of Prostate Cancer

Abstract

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in western countries. Orthotopic implantation is considered as an ideal xenograft model for CaP study, and noninvasive measurement of tumor volume changes is important for monitoring responses to anticancer therapies. In this study, the T2-weighted fast spin echo sequence magnetic resonance imaging (MRI) was performed on a CaP orthotopic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model weekly for 6 weeks post PC-3 CaP cell inoculation, and the fat signal was suppressed using a chemical shift-selective pulse. Subsequently, the MRI data were imported into the image processing software Avizo Standard and stacked into three-dimensional (3D) volumes. Our results demonstrate that MRI, combined with 3D reconstruction, is a feasible and sensitive method to assess tumor growth in a PC-3 orthotopic CaP mouse model and this established monitoring approach is promising for longitudinal observation of CaP xenograft development after anticancer therapy in vivo. Further investigation is needed to validate this protocol in a larger cohort of mice to generate enough statistical power.

Keywords: animal model; magnetic resonance imaging; prostate cancer.

Figure 1.

Representative MRI images of longitudinal tumor growth in the orthotopic mouse model. A-F, Images were acquired at 1,2,3,4,5, and 6 week(s) post CaP cell inoculation, respectively. A-D were acquired from mouse 1, and E, F were acquired from mouse 2. Prostate cancer (CaP) tumorigenesis as early as 1 week after cell inoculation could be detected, and CaP tumor is clearly delineated from surrounding anatomies. Blue line delineates the prostate gland; Yellow arrow indicates prostate tumor boundaries; red star indicates the urinary bladder. CaP, prostate cancer; MRI, magnetic resonance imaging.

Figure 2.

Representative 3D reconstructed MRI images of longitudinal tumor growth in the orthotopic mouse model. A-F, Using Avizo Standard software, MRI scan slices acquired from the same mouse were reconstructed into 3D (outlined by blue surface) at 6 different time points, respectively. 3D, three-dimensional; MRI, magnetic resonance imaging.

Figure 3.

Exponential growth curves for longitudinal 3D volumetric measurements, correlation and agreement of 3D MRI with gross pathology measurements. A, Three-dimensional MRI prostate tumor volumes from the 3 mice were plotted against time, with fitted exponential growth curves, r ² = 0.968, 0.966, and 0.967, respectively. B, Correlation of 3 paired tumor volumes measured by 3D MRI and gross pathology was demonstrated by linear regression. Pearson r = 0.92, P = .24. C, Good agreement between 3D MRI and gross pathology measurements were plotted and analyzed using Bland-Altman analysis. 3D, three-dimensional; MRI, magnetic resonance imaging; SD, standard deviation.