An analysis of the pharmacokinetic parameter ratios in DCE-MRI using the reference region model

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed by obtaining sequential MRI images, before, during and after the injection of a contrast agent. It is usually used to observe the exchange of contrast agent between the vascular space and extravascular extracellular space (EES), and provide information about blood volume and microvascular permeability. To estimate the kinetic parameters derived from the pharmacokinetic model, accurate knowledge of the arterial input function (AIF) is very important. However, the AIF is usually unknown, and it remains very difficult to obtain such information noninvasively. In this article, without knowledge of the AIF, we applied a reference region (RR) model to analyze the kinetic parameters. The RR model usually depends on kinetic parameters found in previous studies of a reference region. However, both the assignment of reference region parameters (intersubject variation) and the selection of the reference region itself (intrasubject variation) may confound the results obtained by RR methods. Instead of using literature values for those pharmacokinetic parameters of the reference region, we proposed to use two pharmacokinetic parameter ratios between the tissue of interest (TOI) and the reference region. Specifically, one parameter K(R) is calculated as the ratio between the volume transfer constant K(trans) of the TOI and RR. Similarly, another parameter V(R) is calculated as the ratio between the extravascular extracellular volume fraction v(e) of the TOI and RR. To investigate the consistency of the two ratios, the K(trans) of the RR was varied ranging from 0.1 to 1.0 min(-1), covering the cited literature values. A simulated dataset with different levels of Gaussian noises and an in vivo dataset acquired from five canine brains with spontaneous occurring brain tumors were used to study the proposed ratios. It is shown from both datasets that these ratios are independent of K(trans) of the RR, implying that there is potentially no need to obtain information about literature values from the reference region for future pharmacokinetic modeling and analysis.