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

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. 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. 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). 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.