In vitro pharmacokinetic phantom for two-compartment modeling in DCE-MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established minimally-invasive method for assessment of extravascular leakage, hemodynamics, and tissue viability. However, differences in acquisition protocols, variety of pharmacokinetic models, and uncertainty on physical sources of MR signal hamper the reliability and widespread use of DCE-MRI in clinical practice. Measurements performed in a controlled in vitro setup could be used as a basis for standardization of the acquisition procedure, as well as objective evaluation and comparison of pharmacokinetic models. In this paper, we present a novel flow phantom that mimics a two-compartmental (blood plasma and extravascular extracellular space/EES) vascular bed, enabling systemic validation of acquisition protocols. The phantom consisted of a hemodialysis filter with two compartments, separated by hollow fiber membranes. The aim of this phantom was to vary the extravasation rate by adjusting the flow in the two compartments. Contrast agent transport kinetics within the phantom was interpreted using two-compartmental pharmacokinetic models. Boluses of gadolinium-based contrast-agent were injected in a tube network connected to the hollow fiber phantom; time-intensity curves (TICs) were obtained from image series, acquired using a T1-weighted DCE-MRI sequence. Under the assumption of a linear dilution system, the TICs obtained from the input and output of the system were then analyzed by a system identification approach to estimate the trans-membrane extravasation rates in different flow conditions. To this end, model-based deconvolution was employed to determine (identify) the impulse response of the investigated dilution system. The flow rates in the EES compartment significantly and consistently influenced the estimated extravasation rates, in line with the expected trends based on simulation results. The proposed phantom can therefore be used to model a two-compartmental vascular bed and can be employed to test and optimize DCE-MRI acquisition sequences in order to determine a standardized acquisition procedure leading to consistent quantification results.