title: An automated method for nonparametric kinetic analysis of clinical DCE-MRI data: application to glioblastoma treated with bevacizumab.
abstract: Here, we describe an automated nonparametric method for evaluating gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) kinetics, based on dynamic contrast-enhanced-MRI scans of glioblastoma patients taken before and after treatment with bevacizumab; no specific model or equation structure is assumed or used. Tumor and venous blood concentration-time profiles are smoothed, using a robust algorithm that removes artifacts due to patient motion, and then deconvolved, yielding an impulse response function. In addition to smoothing, robustness of the deconvolution operation is assured by excluding data that occur prior to the plasma peak; an exhaustive analysis was performed to demonstrate that exclusion of the prepeak plasma data does not significantly affect results. All analysis steps are executed by a single R script that requires blood and tumor curves as the sole input. Statistical moment analysis of the Impulse response function yields the area under the curve (AUC) and mean residence time (MRT). Comparison of deconvolution results to fitted Tofts model parameters suggests that AUCMRT and AUC of the Impulse response function closely approximate fractional clearance from plasma to tissue (K(trans)) and fractional interstitial volume (v(e)). Intervisit variability is shown to be comparable when using the deconvolution method (11% [AUCMRT] and 13%[AUC]) compared to the Tofts model (14%[K(trans)] and 24%[v(e)]). AUC and AUCMRT both exhibit a statistically significant decrease (P < 0.005) 1 day after administration of bevacizumab.
authors.affiliation: Early Development PKPD, Genentech, Inc, South San Francisco, California 94080, USA. gregoryf@gene.com
authors.forename: Gregory Z
authors.initials: GZ
authors.lastname: Ferl
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Michel
authors.initials: M
authors.lastname: Friesenhahn
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Bernstein
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barboriak
authors.forename: Ruediger E
authors.initials: RE
authors.lastname: Port
mesh_terms: D000328:Adult; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; 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; D021621:Imaging, Three-Dimensional / Q000379:methods; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003287:Contrast Media; D000068258:Bevacizumab; D019786:Gadolinium DTPA