Dependence of DCE-MRI biomarker values on analysis algorithm

Background: Dynamic contrast-enhanced MRI (DCE-MRI) biomarkers have proven utility in tumors in evaluating microvascular perfusion and permeability, but it is unclear whether measurements made in different centers are comparable due to methodological differences. Purpose: To evaluate how commonly utilized analytical methods for DCE-MRI biomarkers affect both the absolute parameter values and repeatability. Materials and Methods: DCE-MRI was performed on three consecutive days in twelve rats bearing C6 xenografts. Endothelial transfer constant (Ktrans), extracellular extravascular space volume fraction (ve), and contrast agent reflux rate constant (kep) measures were computed using: 2-parameter (“Tofts” or “standard Kety”) vs. 3-parameter (“General Kinetic” or “extended Kety”) compartmental models (including blood plasma volume fraction (vp) with 3-parameter models); individual- vs. population-based vascular input functions (VIFs); and pixel-by-pixel vs. whole tumor-ROI. Variability was evaluated by within-subject coefficient of variation (wCV) and variance components analyses. Results: DCE-MRI absolute parameter values and wCVs varied widely by analytical method. Absolute parameter values ranged, as follows, median Ktrans, 0.09–0.18 min-1; kep, 0.51–0.92 min-1; ve, 0.17–0.23; and vp, 0.02–0.04. wCVs also varied widely by analytical method, as follows: mean Ktrans, 32.9–61.9%; kep, 11.6–41.9%; ve, 16.1–54.9%; and vp, 53.9–77.2%. Ktrans and kep values were lower with 3- than 2-parameter modeling (p