A proof-of-concept pipeline to guide evaluation of tumor tissue perfusion by dynamic contrast-agent imaging: Direct simulation and inverse tracer-kinetic procedures

Dynamic contrast-enhanced (DCE) perfusion imaging has shown great potential to non-invasively assess cancer development and its treatment by their characteristic tissue signatures. Different tracer kinetics models are being applied to estimate tissue and tumor perfusion parameters from DCE perfusion imaging. The goal of this work is to provide an in silico model-based pipeline to evaluate how these DCE imaging parameters may relate to the true tissue parameters. As histology data provides detailed microstructural but not functional parameters, this work can also help to better interpret such data. To this aim in silico vasculatures are constructed and the spread of contrast agent in the tissue is simulated. As a proof of principle we show the evaluation procedure of two tracer kinetic models from in silico contrast-agent perfusion data after a bolus injection. Representative microvascular arterial and venous trees are constructed in silico. Blood flow is computed in the different vessels. Contrast-agent input in the feeding artery, intra-vascular transport, intra-extravascular exchange and diffusion within the interstitial space are modeled. From this spatiotemporal model, intensity maps are computed leading to in silico dynamic perfusion images. Various tumor vascularizations (architecture and function) are studied and show spatiotemporal contrast imaging dynamics characteristic of in vivo tumor morphotypes. The Brix II also called 2CXM, and extended Tofts tracer-kinetics models common in DCE imaging are then applied to recover perfusion parameters that are compared with the ground truth parameters of the in silico spatiotemporal models. The results show that tumor features can be well identified for a certain permeability range. The simulation results in this work indicate that taking into account space explicitly to estimate perfusion parameters may lead to significant improvements in the perfusion interpretation of the current tracer-kinetics models.