title: The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.
abstract: This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.
authors.affiliation: Department of Radiology, Box 218, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Medical Physics, Box 152, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Electronic address: andrew.gill@addenbrookes.nhs.uk.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Gill
authors.affiliation: Department of Oncology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK. Electronic address: Gayathri.ShankargallAnandapp@icr.ac.uk.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Anandappa
authors.affiliation: Department of Radiology, Box 219, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Electronic address: andrew.patterson@addenbrookes.nhs.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Patterson
authors.affiliation: Department of Radiology, Box 219, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Electronic address: andrew.priest@addenbrookes.nhs.uk.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Priest
authors.affiliation: Department of Radiology, Box 218, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Medical Physics, Box 152, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK; Department of Radiology, Box 219, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Electronic address: mjg40@cam.ac.uk.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Graves
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. Electronic address: tj212@cam.ac.uk.
authors.forename: Tobias
authors.initials: T
authors.lastname: Janowitz
authors.affiliation: Department of Oncology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. Electronic address: dij21@cam.ac.uk.
authors.forename: Duncan I
authors.initials: DI
authors.lastname: Jodrell
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. Electronic address: tgqe2@medschl.cam.ac.uk.
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Department of Radiology, Box 218, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Radiology, Box 219, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Electronic address: djl15@radiol.cam.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lomas
mesh_terms: D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D019540:Area Under Curve; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008962:Models, Theoretical; D009362:Neoplasm Metastasis; D015203:Reproducibility of Results; D012984:Software
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab
keywords: DCE-MRI; error analysis; metastatic renal cell carcinoma; pharamacokinetic modeling; repeatability