title: A Bayesian hierarchical model for the analysis of a longitudinal dynamic contrast-enhanced MRI oncology study.
abstract: Imaging in clinical oncology trials provides a wealth of information that contributes to the drug development process, especially in early phase studies. This article focuses on kinetic modeling in DCE-MRI, inspired by mixed-effects models that are frequently used in the analysis of clinical trials. Instead of summarizing each scanning session as a single kinetic parameter--such as median k(trans) across all voxels in the tumor ROI-we propose to analyze all voxel time courses from all scans and across all subjects simultaneously in a single model. The kinetic parameters from the usual nonlinear regression model are decomposed into unique components associated with factors from the longitudinal study; e.g., treatment, patient, and voxel effects. A Bayesian hierarchical model provides the framework to construct a data model, a parameter model, as well as prior distributions. The posterior distribution of the kinetic parameters is estimated using Markov chain Monte Carlo (MCMC) methods. Hypothesis testing at the study level for an overall treatment effect is straightforward and the patient- and voxel-level parameters capture random effects that provide additional information at various levels of resolution to allow a thorough evaluation of the clinical trial. The proposed method is validated with a breast cancer study, where the subjects were imaged before and after two cycles of chemotherapy, demonstrating the clinical potential of this method to longitudinal oncology studies.
authors.affiliation: Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Volker J
authors.initials: VJ
authors.lastname: Schmid
authors.forename: Brandon
authors.initials: B
authors.lastname: Whitcher
authors.forename: Anwar R
authors.initials: AR
authors.lastname: Padhani
authors.forename: N Jane
authors.initials: NJ
authors.lastname: Taylor
authors.forename: Guang-Zhong
authors.initials: GZ
authors.lastname: Yang
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001185:Artificial Intelligence; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D016000:Cluster Analysis; D003198:Computer Simulation; D003287:Contrast Media; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008495:Medical Oncology / Q000379:methods; D008954:Models, Biological; D015233:Models, Statistical; D010363:Pattern Recognition, Automated / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media