Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) is an important tool for detecting subtle kinetic changes in cancerous tissue. Quantitative analysis of DCE-MRI typically involves the convolution of an arterial input function (AIF) with
a nonlinear pharmacokinetic model of the contrast agent concentration. Parameters of the kinetic model are biologically meaningful, but the optimization of the non-linear model has significant computational issues. In practice, convergence of the optimization algorithm is not guaranteed and the accuracy of the model fitting may be compromised. To overcome this problems, this paper proposes a semi-parametric penalized spline smoothing approach, with which the AIF is convolved with a set of B-splines to produce a design matrix using locally adaptive smoothing parameters based on Bayesian penalized spline models (P-splines). It has been shown that kinetic parameter estimation can be obtained from the resulting deconvolved response function, which also includes the onset of contrast enhancement. Detailed validation of the method, both with simulated and in vivo data, is provided.
Imaging in clinical oncology trials provides a wealth of information that contributes to the drug development process, especially in early phase studies. This paper focuses on kinetic modeling in DCE-MRI, inspired by mixed-effects models that are fre
quently used in the analysis of clinical trials. Instead of summarizing each scanning session as a single kinetic parameter -- such as median $ktrans$ 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 non-linear 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 in order 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.
