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  1. Mak NL, Ooi EH, Lau EV, Ooi ET, Pamidi N, Foo JJ, et al.
    Comput Methods Programs Biomed, 2022 Dec;227:107195.
    PMID: 36323179 DOI: 10.1016/j.cmpb.2022.107195
    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.

  2. Mak NL, Ng WH, Ooi EH, Lau EV, Pamidi N, Foo JJ, et al.
    Comput Methods Programs Biomed, 2024 Jan;243:107866.
    PMID: 37865059 DOI: 10.1016/j.cmpb.2023.107866
    BACKGROUND AND OBJECTIVES: Thermochemical ablation (TCA) is a cancer treatment that utilises the heat released from the neutralisation of acid and base to raise tissue temperature to levels sufficient to induce thermal coagulation. Computational studies have demonstrated that the coagulation volume produced by sequential injection is smaller than that with simultaneous injection. By injecting the reagents in an ensuing manner, the region of contact between acid and base is limited to a thin contact layer sandwiched between the distribution of acid and base. It is hypothesised that increasing the frequency of acid-base injections into the tissue by shortening the injection interval for each reagent can increase the effective area of contact between acid and base, thereby intensifying neutralisation and the exothermic heat released into the tissue.

    METHODS: To verify this hypothesis, a computational model was developed to simulate the thermochemical processes involved during TCA with sequential injection. Four major processes that take place during TCA were considered, i.e., the flow of acid and base, their neutralisation, the release of exothermic heat and the formation of thermal damage inside the tissue. Equimolar acid and base at 7.5 M was injected into the tissue intermittently. Six injection intervals, namely 3, 6, 15, 20, 30 and 60 s were investigated.

    RESULTS: Shortening of the injection interval led to the enlargement of coagulation volume. If one considers only the coagulation volume as the determining factor, then a 15 s injection interval was found to be optimum. Conversely, if one places priority on safety, then a 3 s injection interval would result in the lowest amount of reagent residue inside the tissue after treatment. With a 3 s injection interval, the coagulation volume was found to be larger than that of simultaneous injection with the same treatment parameters. Not only that, the volume also surpassed that of radiofrequency ablation (RFA); a conventional thermal ablation technique commonly used for liver cancer treatment.

    CONCLUSION: The numerical results verified the hypothesis that shortening the injection interval will lead to the formation of larger thermal coagulation zone during TCA with sequential injection. More importantly, a 3 s injection interval was found to be optimum for both efficacy (large coagulation volume) and safety (least amount of reagent residue).

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