title: Dependence of DCE-MRI biomarker values on analysis algorithm.
abstract: 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.
  
  
  OBJECTIVE
  To evaluate how commonly utilized analytical methods for DCE-MRI biomarkers affect both the absolute parameter values and repeatability.
  
  
  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<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.
  
  
  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.
authors.affiliation: Department of Radiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Chaan S
authors.initials: CS
authors.lastname: Ng
authors.affiliation: Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Biostatistics Imaging Physics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: Bankson
authors.affiliation: Department of Radiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Murali K
authors.initials: MK
authors.lastname: Ravoori
authors.affiliation: Department of Radiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biostatistics Veterinary Medicine and Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Brammer
authors.affiliation: Department of Biostatistics Veterinary Medicine and Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Sherry
authors.initials: S
authors.lastname: Klumpp
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Cheshire, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison, WI, United States of America.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Jackson
mesh_terms: D000465:Algorithms; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D045744:Cell Line, Tumor; D003287:Contrast Media; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000000981:diagnostic imaging; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D003287:Contrast Media