Evaluation of a Voxelized Model Based on DCE-MRI for Tracer Transport in Tumor

Abstract

Recent advances in the treatment of cancer involving therapeutic agents have shown promising results. However, treatment efficacy can be limited due to inadequate and uneven uptake in solid tumors, thereby making the prediction of drug transport important for developing effective therapeutic strategies. In this study, a patient-specific computational porous media model (voxelized model) was developed for predicting the interstitial flow field and distribution of a systemically delivered magnetic resonance (MR) visible tracer in a tumor. The benefits of a voxel approach include less labor and less computational time (approximately an order of magnitude reduction compared to the traditional computational fluid dynamics (CFD) approach developed earlier by our group). The model results were compared with that obtained from a previous approach based on unstructured meshes along with MR-measured tracer concentration data within tumors, using statistical analysis and qualitative representations. The statistical analysis indicated the similarity between the structured and unstructured models' results with a low root mean square error (RMS) and a high correlation coefficient. The voxelized model captured features of the flow field and tracer distribution such as high interstitial fluid pressure inside the tumor and the heterogeneous distribution of the tracer. Predictions of tracer distribution by the voxelized approach also resulted in low RMS error when compared with MR-measured data over a 1 h time course. The similarity in the voxelized model results with experiment and the nonvoxelized model predictions were maintained across three different tumors. Overall, the voxelized model serves as a reliable and swift alternative to approaches using unstructured meshes in predicting extracellular transport within tumors.

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

“…CED created additional pressure gradients (≈0.65 kPa/mm along the infusion plane) around the infusion site which were absent with systemic delivery. There was also significant pressure gradients at the anterior edge of the tumor-host tissue interface (≈0.67 kPa/mm) which was also observed without CED [32]. It should be noted that the pressure gradient outside the skin does not contribute to the extracellular fluid flow due to the very low hydraulic conductivity assigned in those voxels.…”

“…The predicted velocity field was heterogeneous with maximum velocity near the infusion site (35 µm/s). There were also significant outwardly-directed flows at the tumor-host tissue interface especially near the anterior end of the tumor (≈0.45–3.2 µm/s) which was also observed with systemic delivery [32]. Thus CED has resulted in alterations of endogenous flows closer to the infusion site to a far larger magnitude.…”

Numerical Study of Transport of Anticancer Drugs in Heterogeneous Vasculature of Human Brain Tumors Using Dynamic Contrast Enhanced-Magnetic Resonance Imaging

“…Zhan et al modeled human liver tumor vasculature and concluded that not only drug accumulates faster in well vascularized regions but also clears out from these regions quickly, facilitating less tumor cell killing [11]. Attempts have also been made to model the heterogeneous vasculature of tumor tissues [12]. However, most of the studies had certain assumptions such as use of homogeneous model of tumors, use of global intravascular concentration or arterial input function (AIF), and heterogeneous models developed for animals with use of simple tofts kinetic model [13].…”

Spatiotemporal Quantification of Local Drug Delivery Using MRI

“…Sarntinoranont and coworkers have studied delivery of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) delivery to brain tumors [30], and they calculate concentration of the Gd-DTPA using a method validated in an agarose phantom [31]. Sarntinoranont et al's studies seem to accurately calculate concentration with good spatial resolution; however, in our attempts to utilize a similar method for a different area of the body, additional studies into the potential sources of error and methods to minimize and quantify that error are warranted.…”