A Computational Modeling Approach to Investigate the Influence of Hyperthermia on the Tumor Microenvironment

Summary

The article describes a protocol to simulate the transient temperature profiles and the coupled spatiotemporal variation of the interstitial fluid pressure following the heating delivered by a dipolar radiofrequency hyperthermia system. The protocol can be used to assess the response of biophysical parameters characterizing the tumor microenvironment to interventional hyperthermia techniques.

Abstract

The biophysical properties of the tumor microenvironment differ substantially from normal tissues. A constellation of features, including decreased vascularity, lack of lymphatic drainage, and elevated interstitial pressure, diminishes the penetration of therapeutics into tumors. Local hyperthermia within the tumor can alter microenvironmental properties, such as interstitial fluid pressure, potentially leading to improvements in drug penetration. In this context, multi-physics computational models can provide insight into the interplay between the biophysical parameters within the tumor microenvironment and can guide the design and interpretation of experiments that test the bioeffects of local hyperthermia.

This paper describes a step-by-step workflow for a computational model coupling partial differential equations describing electrical current distribution, bioheat transfer, and fluid dynamics. The main objective is to study the effects of hyperthermia delivered by a bipolar radiofrequency device on the interstitial fluid pressure within the tumor. The system of mathematical expressions linking electrical current distribution, bioheat transfer, and interstitial fluid pressure is presented, emphasizing the changes in the distribution of the interstitial fluid pressure that could be induced by the thermal intervention.

Introduction

Elevated interstitial fluid pressure (IFP) is a hallmark of solid tumors¹. The leakage of fluid into the interstitium from hyperpermeable blood vessels is imbalanced by the egress of fluid due to compressed intratumoral veins and absent lymphatics^1,2,3. In concert with other biophysical parameters that are abnormal within the tumor microenvironment (TME), including solid stress and stiffness, elevated IFP undermines the efficacy of both systemic and local drug delivery^4,5,

Protocol

1. Build the model of a bipolar radiofrequency system

1. Preliminary steps to set the interface
   1. Launch COMSOL Multiphysics and click on Model Wizard.
   2. Select 3D as Space Dimension.
   3. Select AC/DC Physics module | Electric Fields and Currents | Electric Currents.
   4. Select Heat Transfer module | Heat Transfer in Solids.
   5. Select Mathematics .......

Discussion

We present a computational modeling protocol to couple transient electric-thermal simulations with fluid-dynamic simulations to study the impact of RF-hyperthermia on thermal and interstitial fluid pressure profiles in tumors. The key aspect is in the building of a numerical workflow capable of capturing the relationship existing between temperature and vascular pressure, which in turn drives the changes in interstitial fluid pressure.

We used the relationship between vascular pressure and blo.......

Materials

Name	Company	Catalog Number	Comments
COMSOL Multiphysics (v. 6.0)	COMSOL AB, Stockholm, Sweden		Software used to implement the computational workflow described in the protocol
Dell 1.8.0, 11th Gen Intel(R) Core(TM) i7-11850H @ 2.50GHz, 2496 Mhz, 8 Core(s), 16 Logical Processor(s), 32 GB RAM	Dell Inc.		Laptop used to run computational simulations