title: Dynamic contrast-enhanced magnetic resonance imaging of tumors: preclinical validation of parametric images.
abstract: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested to be a valuable method for characterizing the physiological microenvironment of tumors and thus a promising method for individualizing cancer treatment. The aim of this study was to test the hypothesis that valid parametric images of the tumor microenvironment can be obtained by pharmacokinetic analysis of DCE-MRI series. Cells of four human melanoma xenograft lines (A-07, D-12, R-18 and T-22) were used as preclinical models of human cancer. DCE-MRI was performed at 1.5 T at a spatial resolution of 0.23 x 0.47 x 2.0 mm(3) and a time resolution of 14 s. Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) was used as contrast agent. The DCE-MRI data were analyzed on a voxel-by-voxel basis by using a pharmacokinetic model recommended for analysis of clinical DCE-MRI series. Parametric DCE-MR images were compared with tumor blood perfusion measured by the (86)Rb uptake method, and fractional volume of the extravascular extracellular space assessed by analysis of histological preparations. Parametric images reflecting tumor blood perfusion and fractional volume of the extravascular extracellular space were obtained. The numerical values of the DCE-MRI-derived parameters were not significantly different from the absolute values of tumor blood perfusion or fractional volume of the extravascular extracellular space in any of the tumor lines. This study shows that DCE-MRI can provide valid quantitative parametric images of the tumor microenvironment in preclinical cancer models and thus supports the suggestion that DCE-MRI may be developed to be a clinically useful method for individualization of microenvironment-based cancer treatment, a possibility that merits increased clinical interest.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
authors.forename: Tormod A M
authors.initials: TA
authors.lastname: Egeland
authors.forename: Trude G
authors.initials: TG
authors.lastname: Simonsen
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Kristine
authors.initials: K
authors.lastname: Gulliksrud
authors.forename: Christine
authors.initials: C
authors.lastname: Ellingsen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA