title: 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: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; and Siemens, Healthcare Sector, Erlangen, Germany (R.G.).
authors.forename: Ijin
authors.initials: I
authors.lastname: Joo
authors.affiliation: From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; and Siemens, Healthcare Sector, Erlangen, Germany (R.G.).
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; and Siemens, Healthcare Sector, Erlangen, Germany (R.G.).
authors.forename: Robert
authors.initials: R
authors.lastname: Grimm
authors.affiliation: From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; and Siemens, Healthcare Sector, Erlangen, Germany (R.G.).
authors.forename: Joon Koo
authors.initials: JK
authors.lastname: Han
authors.affiliation: From the Department of Radiology (I.J., J.M.L., J.K.H., B.I.C.) and Institute of Radiation Medicine (J.M.L., J.K.H., B.I.C.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; and Siemens, Healthcare Sector, Erlangen, Germany (R.G.).
authors.forename: Byung Ihn
authors.initials: BI
authors.lastname: Choi
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging; D004797:Enzyme-Linked Immunosorbent Assay; D007091:Image Processing, Computer-Assisted; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001577:Benzophenones; D014408:Biomarkers, Tumor; D003287:Contrast Media; C552333:N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide; D014409:Tumor Necrosis Factor-alpha; D014633:Valine