An in silico derived dosage and administration guide for effective thermochemical ablation of biological tissues with simultaneous injection of acid and base.

BACKGROUND AND OBJECTIVES: Thermochemical ablation (TCA) is a thermal ablation technique involving the injection of acid and base, either sequentially or simultaneously, into the target tissue. TCA remains at the conceptual stage with existing studies unable to provide recommendations on the optimum injection rate, and reagent concentration and volume. Limitations in current experimental methodology have prevented proper elucidation of the thermochemical processes inside the tissue during TCA. Nevertheless, the computational TCA framework developed recently by Mak et al. [Mak et al., Computers in Biology and Medicine, 2022, 145:105494] has opened new avenues in the development of TCA. Specifically, a recommended safe dosage is imperative in driving TCA research beyond the conceptual stage. METHODS: The aforesaid computational TCA framework for sequential injection was applied and adapted to simulate TCA with simultaneous injection of acid and base at equimolar and equivolume. The developed framework, which describes the flow of acid and base, their neutralisation, the rise in tissue temperature and the formation of thermal damage, was solved numerically using the finite element method. The framework will be used to investigate the effects of injection rate, reagent concentration, volume and type (weak/strong acid-base combination) on temperature rise and thermal coagulation formation. RESULTS: A higher injection rate resulted in higher temperature rise and larger thermal coagulation. Reagent concentration of 7500 mol/m3 was found to be optimum in producing considerable thermal coagulation without the risk of tissue overheating. Thermal coagulation volume was found to be consistently larger than the total volume of acid and base injected into the tissue, which is beneficial as it reduces the risk of chemical burn injury. Three multivariate second-order polynomials that express the targeted coagulation volume as functions of injection rate and reagent volume, for the weak-weak, weak-strong and strong-strong acid-base combinations were also derived based on the simulated data. CONCLUSIONS: A guideline for a safe and effective implementation of TCA with simultaneous injection of acid and base was recommended based on the numerical results of the computational model developed. The guideline correlates the coagulation volume with the reagent volume and injection rate, and may be used by clinicians in determining the safe dosage of reagents and optimum injection rate to achieve a desired thermal coagulation volume during TCA.

A computational framework to simulate the thermochemical process during thermochemical ablation of biological tissues.

Thermochemical ablation (TCA) is a thermal ablation therapy that utilises heat released from acid-base neutralisation reaction to destroy tumours. This procedure is a promising low-cost solution to existing thermal ablation treatments such as radiofrequency ablation (RFA) and microwave ablation (MWA). Studies have demonstrated that TCA can produce thermal damage that is on par with RFA and MWA when employed properly. Nevertheless, TCA remains a concept that is tested only in a few animal trials due to the risks involved as the result of uncontrolled infusion and incomplete acid-base reaction. In this study, a computational framework that simulates the thermochemical process of TCA is developed. The proposed framework consists of three physics, namely chemical flow, neutralisation reaction and heat transfer. An important parameter in the TCA framework is the neutralisation reaction rate constant, which has values in the order of 108 m3/(mol⋅s). The present study will demonstrate that since the rate constant impacts only the rate and direction of the reaction but has little influence on the extent of reaction, it is possible to replicate the thermochemical process of TCA by employing significantly smaller values of rate constant that are numerically tractable. Comparisons of the numerical results against experimental studies from the literature supports this. The aim of this framework is for researchers to advance and develop TCA to gain an in-depth understanding of the fundamental mechanisms of TCA and to develop a safe treatment protocol of TCA in the hope of advancing TCA into clinical trials.

The effects of electrical and thermal boundary condition on the simulation of radiofrequency ablation of liver cancer for tumours located near to the liver boundary.

Effects of different boundary conditions prescribed across the boundaries of radiofrequency ablation (RFA) models of liver cancer are investigated for the case where the tumour is at the liver boundary. Ground and Robin-type conditions (electrical field) and body temperature and thermal insulation (thermal field) conditions are examined. 3D models of the human liver based on publicly-available CT images of the liver are developed. An artificial tumour is placed inside the liver at the boundary. Simulations are carried out using the finite element method. The numerical results indicated that different electrical and thermal boundary conditions led to different predictions of the electrical potential, temperature and thermal coagulation distributions. Ground and body temperature conditions presented an unnatural physical conditions around the ablation site, which results in more intense Joule heating and excessive heat loss from the tissue. This led to thermal damage volumes that are smaller than the cases when the Robin type or the thermal insulation conditions are prescribed. The present study suggests that RFA simulations in the future must take into consideration the choice of the type of electrical and thermal boundary conditions to be prescribed in the case where the tumour is located near to the liver boundary.

A numerical study on the no-touch bipolar radiofrequency ablation.

The commonly used radiofrequency ablation (RFA) technique for treating liver cancer is in the monopolar mode. This requires the insertion of the RF electrode directly into the tumor tissue, which increases the risks of tumor track seeding (TTS). One way to overcome TTS is by employing the bipolar RFA, implemented in the no-touch mode. In the no-touch mode, two RF electrodes are inserted into the healthy tissue that surrounds the tumor. The distance between the electrodes and the tumor is defined as the no-touch gap. The ability of the no-touch bipolar RFA to overcome TTS has been demonstrated in laboratory studies; however, little is known about the thermo-physiological responses of the tissue during the ablation process of the no-touch procedure. This will be investigated numerically in the present study. A 3D model of the liver tissue is developed and the no-touch bipolar RFA implemented using a pair of RF electrodes is simulated using the finite element method. In particular, the effects of the no-touch gap on the treatment outcome of the RFA procedure are investigated. Results show that a larger no-touch gap may result incomplete tumor destruction due to the central region of the tumor not being directly affected by the Joule heating phenomenon that is more prominent around the electrodes. This suggests that an improperly selected no-touch gap may result in a reduced efficiency of the no-touch bipolar RFA.

Comparison between single- and dual-porosity models for fluid transport in predicting lesion volume following saline-infused radiofrequency ablation.

A recent study by Ooi and Ooi (EH Ooi, ET Ooi, Mass transport in biological tissues: Comparisons between single- and dual-porosity models in the context of saline-infused radiofrequency ablation, Applied Mathematical Modelling, 2017, 41, 271-284) has shown that single-porosity (SP) models for describing fluid transport in biological tissues significantly underestimate the fluid penetration depth when compared to dual-porosity (DP) models. This has raised some concerns on whether the SP model, when coupled with models of radiofrequency ablation (RFA) to simulate saline-infused RFA, could lead to an underestimation of the coagulation size. This paper compares the coagulation volumes obtained following saline-infused RFA predicted based on the SP and DP models for fluid transport. Results showed that the SP model predicted coagulation zones that are consistently 0.5 to 0.9 times smaller than that of DP model. This may be explained by the low permeability value of the tissue interstitial space, which causes the majority of the saline to flow through the vasculature. The absence of fluid flow tracking in the vasculature in the SP model meant that any flow of saline into the vasculature is treated as losses and do not contribute to the saline penetration depth of the tissue. Comparisons with experimental results from the literature revealed that the DP models predicted coagulation zone sizes that are closer to the experimental values than the SP models. This supports the hypothesis that the SP model is a poor choice for simulating the outcome of saline-infused RFA.