Monitoring Vascular Disrupting Therapy in a Rabbit Liver Tumor Model: Relationship between Tumor Perfusion Parameters at IVIM Diffusion-weighted MR Imaging and Those at Dynamic Contrast-enhanced MR Imaging

Radiology. 2016 Jan;278(1):104-13. doi: 10.1148/radiol.2015141974. Epub 2015 Jul 22.

Abstract

Purpose: To investigate whether perfusion-related intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance (MR) imaging parameters correlate with dynamic contrast material-enhanced MR imaging parameters in between-subject and/or within-subject longitudinal settings for monitoring the therapeutic effects of a vascular disrupting agent (VDA) (CKD-516) in rabbit VX2 liver tumors.

Materials and methods: With institutional Animal Care and Use Committee approval, 21 VX2 liver tumor-bearing rabbits (treated, n = 15; control, n = 6) underwent IVIM DW imaging with 12 b values (0-800 sec/mm(2)) and dynamic contrast-enhanced MR imaging performed before (baseline) CKD-516 administration and 4 hours, 24 hours, and 7 days after administration. Perfusion-related IVIM DW imaging parameters of the tumors, including the pseudodiffusion coefficient (D*) and perfusion fraction (f), as well as dynamic contrast-enhanced MR imaging parameters, including the volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC), were measured. IVIM DW imaging parameters were correlated with dynamic contrast-enhanced MR imaging parameters by using Pearson correlation analysis between subjects at each given time and by using a linear mixed model for within-subject longitudinal data.

Results: In the treated group, D*, f, K(trans), and iAUC significantly decreased (-40.7% to -26.3%) at 4-hour follow-up compared with these values in the control group (-6.9% to +5.9%) (P < .05). For longitudinal monitoring of CKD-516 treatment, D* and f showed significant positive correlations with K(trans) and iAUC (P = .004 and P = .02; P < .001 and P = .006, respectively), while no significant correlations were observed between IVIM DW imaging and dynamic contrast-enhanced MR imaging parameters between subjects at any given time (P > .05).

Conclusion: In a rabbit tumor model, perfusion parameters serially quantified with IVIM DW imaging can be used as alternatives to dynamic contrast-enhanced MR imaging parameters in reflecting the dynamic changes in tumor perfusion during the within-subject longitudinal monitoring of VDA treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzophenones / pharmacology*
  • Biomarkers, Tumor / blood
  • Contrast Media
  • Diffusion Magnetic Resonance Imaging
  • Enzyme-Linked Immunosorbent Assay
  • Image Processing, Computer-Assisted
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / drug therapy*
  • Magnetic Resonance Imaging / methods*
  • Rabbits
  • Tumor Necrosis Factor-alpha / blood
  • Valine / analogs & derivatives*
  • Valine / pharmacology

Substances

  • Benzophenones
  • Biomarkers, Tumor
  • Contrast Media
  • N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide
  • Tumor Necrosis Factor-alpha
  • Valine