Dependence of DCE-MRI biomarker values on analysis algorithm

• Published in: PloS one Vol. 10; no. 7; p. e0130168
• Main Authors: Ng, Chaan S., Wei, Wei, Bankson, James A., Ravoori, Murali K., Han, Lin, Brammer, David W., Klumpp, Sherry, Waterton, John C., Jackson, Edward F.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.07.2015; Public Library of Science (PLoS)
• Subjects: Algorithms; Analytical methods; Animals; Biomarkers; Biomarkers - analysis; Blood plasma; Cancer; Cell Line, Tumor; Coefficient of variation; Concentration (composition); Contrast Media; Coronary vessels; Glioma - diagnosis; Glioma - diagnostic imaging; Image Enhancement - methods; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Mathematical models; Microvasculature; Neoplasms, Experimental - diagnosis; Neoplasms, Experimental - diagnostic imaging; NMR; Nuclear magnetic resonance; Perfusion; Permeability; Pixels; Population; Radiography; Rats; Rats, Nude; Reproducibility; Reproducibility of Results; Sensitivity and Specificity; Studies; Tumors; Values; Variance analysis; Veterinary medicine; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130168

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. To evaluate how commonly utilized analytical methods for DCE-MRI biomarkers affect both the absolute parameter values and repeatability. 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. 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<0.0001); kep and vp were lower with pixel- than whole-ROI analyses (p<0.0006). wCVs were significantly smaller for ve, and larger for kep, with individual- than population-based VIFs. 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.