Abstract

We developed and tested the feasibility of computational fluid modeling (CFM) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for quantitative estimation of interstitial fluid pressure (IFP) and velocity (IFV) in patients with head and neck (HN) cancer with locoregional lymph node metastases. Twenty-two patients with HN cancer, with 38 lymph nodes, underwent pretreatment standard MRI, including DCE-MRI, on a 3-Tesla scanner. CFM simulation was performed with the finite element method in COMSOL Multiphysics software. The model consisted of a partial differential equation (PDE) module to generate 3D parametric IFP and IFV maps, using the Darcy equation and values (min−1, estimated from the extended Tofts model) to reflect fluid influx into tissue from the capillary microvasculature. The Spearman correlation (ρ) was calculated between total tumor volumes and CFM estimates of mean tumor IFP and IFV. CFM-estimated tumor IFP and IFV mean ± standard deviation for the neck nodal metastases were 1.73 ± 0.39 (kPa) and 1.82 ± 0.9 × (10−7 m/s), respectively. High IFP estimates corresponds to very low IFV throughout the tumor core, but IFV rises rapidly near the tumor boundary where the drop in IFP is precipitous. A significant correlation was found between pretreatment total tumor volume and CFM estimates of mean tumor IFP (ρ = 0.50, P = 0.004). Future studies can validate these initial findings in larger patients with HN cancer cohorts using CFM of the tumor in concert with DCE characterization, which holds promise in radiation oncology and drug-therapy clinical trials.

Highlights

  • In solid tumors, interstitial fluid pressure (IFP) is elevated owing to increased permeability of abnormally formed tumor blood vessels and a lack of functional lymphatic removal pathways [1, 2]

  • The computational fluid modeling (CFM) estimation maps of IFP and interstitial fluid velocity (IFV) are shown in Figure 3 for representative patients #1, 2, 3 with and 4 with head and neck (HN) cancer

  • The Ktransvoxel values in the CFM were normalized by the mean Ktrans values in each tumor Regions of interest (ROIs)

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Summary

Introduction

Interstitial fluid pressure (IFP) is elevated owing to increased permeability of abnormally formed tumor blood vessels and a lack of functional lymphatic removal pathways [1, 2]. Elevated IFP serves to nullify the hydrostatic pressure differential between vasculature and the interstitium, hampering extravasation of drug into the tumor [3]. Previous studies have shown that elevated IFP is known to have serious implications for the effective delivery of anticancer drugs [4,5,6]. Elevated tumor IFP has been invasively assessed in previous clinical and preclinical studies and is not routinely measured in clinical practice [7,8,9,10]. A previous report [12] attests its TOMOGRAPHY.ORG I VOLUME 6 NUMBER 2 I JUNE 2020

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