Abstract Purpose Virtual (in silico) imaging trials (VITs), involving computerized phantoms and models of the imaging process, provide a modern alternative to clinical imaging trials. VITs are faster, safer, and enable otherwise‐impossible investigations. Current phantoms used in VITs are limited in their ability to model functional behavior such as contrast perfusion which is an important determinant of dose and image quality in CT imaging. In our prior work with the XCAT computational phantoms, we determined and modeled inter‐organ (organ to organ) intravenous contrast concentration as a function of time from injection. However, intra‐organ concentration, heterogeneous distribution within a given organ, was not pursued. We extend our methods in this work to model intra‐organ concentration within the XCAT phantom with a specific focus on the liver. Methods Intra‐organ contrast perfusion depends on the organ's vessel network. We modeled the intricate vascular structures of the liver, informed by empirical and theoretical observations of anatomy and physiology. The developed vessel generation algorithm modeled a dual‐input‐single‐output vascular network as a series of bifurcating surfaces to optimally deliver flow within the bounding surface of a given XCAT liver. Using this network, contrast perfusion was simulated within voxelized versions of the phantom by using knowledge of the blood velocities in each vascular structure, vessel diameters and length, and the time since the contrast entered the hepatic artery. The utility of the enhanced phantom was demonstrated through a simulation study with the phantom voxelized prior to CT simulation with the relevant liver vasculature prepared to represent blood and iodinated contrast media. The spatial extent of the blood–contrast mixture was compared to clinical data. Results The vascular structures of the liver were generated with size and orientation which resulted in minimal energy expenditure required to maintain blood flow. Intravenous contrast was simulated as having known concentration and known total volume in the liver as calibrated from time–concentration curves. Measurements of simulated CT ROIs were found to agree with clinically observed values of early arterial phase contrast enhancement of the parenchyma (～5$ sim 5$ HU). Similarly, early enhancement in the hepatic artery was found to agree with average clinical enhancement (180$(180$ HU). Conclusions The computational methods presented here furthered the development of the XCAT phantoms allowing for multi‐timepoint contrast perfusion simulations, enabling more anthropomorphic virtual clinical trials intended for optimization of current clinical imaging technologies and applications.
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