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 (K_trans), extracellular extravascular space volume fraction (v_e), and contrast agent reflux rate constant (k_ep) 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 (v_p) 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 analyticalmethod. Absolute parameter values ranged, as follows, median K_trans, 0.09-0.18 min^-1; k_ep, 0.51-0.92 min^-1; v_e, 0.17-0.23; and v_p, 0.02-0.04. wCVs also varied widely by analytical method, as follows: mean K_trans, 32.9-61.9%; k_ep, 11.6-41.9%; v_e, 16.1-54.9%; and v_p, 53.9-77.2%. K_trans and kep values were lower with 3- than 2-parameter modeling (p<0.0001); k_ep and v_p were lower with pixel- than whole-ROI analyses (p<0.0006). wCVs were significantly smaller for v_e, and larger for k_ep, with individual- than population-based VIFs. Conclusions DCE-MRI parameter values and repeatability can vary widely by analytical methodology. Absolute values of DCE-MRI biomarkers are unlikely to be comparable between different studies unless analyses are carefully standardized.