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.

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.

• Authors: Ijin Joo, Jeong Min Lee, Robert Grimm, Joon Koo Han, Byung Ihn Choi
• Journal: Radiology (Radiology) Vol. 278 Issue 1 Pg. 104-13 (Jan 2016) ISSN: 1527-1315 [Electronic] United States
• PMID: 26200601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © RSNA, 2015

Chemical References

• 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

Topics

• 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, drug therapy)
• Magnetic Resonance Imaging (methods)
• Rabbits
• Tumor Necrosis Factor-alpha (blood)
• Valine (analogs & derivatives, pharmacology)