Colon Tumor Growth and Antivascular Treatment in Mice: Complementary Assessment With MR Elastography and Diffusion-Weighted MR Imaging

Radiology. 2012 Aug;264(2):436-44. doi: 10.1148/radiol.12111548. Epub 2012 Jun 12.

Abstract

Purpose: To investigate the potential value of magnetic resonance (MR) elastography and diffusion-weighted (DW) MR imaging in the detection of microstructural changes of murine colon tumors during growth and antivascular treatment.

Materials and methods: The study was approved by the regional ethics committee for animal care. Sixty Balb-C mice, bearing ectopic and orthotopic colon tumors, were monitored for 3 weeks with high-resolution T2-weighted MR imaging, three-dimensional steady-state MR elastography, and DW MR imaging at 7 T. The same imaging protocol was performed 24 hours after injection of combretastatin A4 phosphate (CA4P) in 12 mice. The absolute value of the complex shear modulus (|G*|) and the apparent diffusion coefficient (ADC) were measured in the viable zones of tumors and compared with microvessel density (MVD), cellularity, and micronecrosis by using the Pearson correlation coefficient.

Results: During tumor growth, |G*| increase was correlated with MVD (r = 0.70 [P = .08] and r = 0.78 [P = .002], for both the ectopic and orthotopic models, respectively). Moreover, the ectopic tumors displayed decreased ADC, which correlated with increased cellularity (r = 0.77, P = .04), whereas no changes in ADC and cellularity were observed in orthotopic tumors. After CA4P administration, |G*| decreased in the ectopic model (P < .0001), similar to the MVD evolution (P = .03), whereas no significant changes in |G*| (P = .7) and MVD (P = .6) were observed in the orthotopic model. ADC increased in both models (P = .047 and P = .01 for the ectopic and the orthotopic models, respectively) in relation to increased micronecrosis.

Conclusion: Imaging of mechanical properties and diffusivity provide complementary information during tumor growth and regression that are respectively linked to vascularity and tumor cell alterations, including cellularity and micronecrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology*
  • Diffusion Magnetic Resonance Imaging / methods*
  • Elasticity Imaging Techniques / methods*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Microcirculation / drug effects
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology*
  • Stilbenes / pharmacology*

Substances

  • Stilbenes
  • fosbretabulin