title: Noncompartmental kinetic analysis of DCE-MRI data from malignant tumors: Application to glioblastoma treated with bevacizumab.
abstract: Dynamic contrast enhanced MRI contrast agent kinetics in malignant tumors are typically complex, requiring multicompartment tumor models for adequate description. For consistent comparisons among tumors or among successive studies of the same tumor, we propose to estimate the total contrast agent-accessible volume fraction of tumor, including blood plasma, v(pe), and an average transfer rate constant across all tumor compartments, K(trans.av), by fitting a three-compartment tumor model and then calculating the area under the tumor impulse-response function (= v(pe)) and the ratio area under the tumor impulse response function over mean residence time in tumor (= K(trans.av)). If the duration of dynamic contrast enhanced MRI was too short to extrapolate the tumor impulse-response function to infinity with any confidence, then conditional parameters v(pe)(*) and K(trans.av*) should be calculated from the available incomplete impulse response function. Median decreases of 33% were found for both v(pe)(*) and K(trans.av*) in glioblastoma patients (n = 16) 24 hours after the administration of bevacizumab (P < 0.001). Median total contrast-enhancing tumor volume was reduced by 18% (P < 0.0001). The combined changes of tumor volume, v(pe)(*), and K(trans.av*) suggest a reduction of true v(pe), possibly accompanied by a reduction of true K(trans.av). The proposed method provides estimates of a scale and a shape parameter to describe contrast agent kinetics of varying complexity in a uniform way.
authors.affiliation: Early Development PKPD, Genentech Inc, South San Francisco, California, USA. rport@gene.com
authors.forename: Ruediger E
authors.initials: RE
authors.lastname: Port
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Bernstein
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barboriak
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Timothy P L
authors.initials: TP
authors.lastname: Roberts
authors.forename: Nicholas
authors.initials: N
authors.lastname: van Bruggen
mesh_terms: D000328:Adult; D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008959:Models, Neurological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab; D019786:Gadolinium DTPA