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  1. Ooi EH, Ooi ET
    Comput Biol Med, 2021 10;137:104832.
    PMID: 34508975 DOI: 10.1016/j.compbiomed.2021.104832
    Switching bipolar radiofrequency ablation (bRFA) is a thermal treatment modality used for liver cancer treatment that is capable of producing larger, more confluent and more regular thermal coagulation. When implemented in the no-touch mode, switching bRFA can prevent tumour track seeding; a medical phenomenon defined by the deposition of cancer cells along the insertion track. Nevertheless, the no-touch mode was found to yield significant unwanted thermal damage as a result of the electrodes' position outside the tumour. It is postulated that the unwanted thermal damage can be minimized if ablation can be directed such that it focuses only within the tumour domain. As it turns out, this can be achieved by partially insulating the active tip of the RF electrodes such that electric current flows in and out of the tissue only through the non-insulated section of the electrode. This concept is known as unidirectional ablation and has been shown to produce the desired effect in monopolar RFA. In this paper, computational models based on a well-established mathematical framework for modelling RFA was developed to investigate if unidirectional ablation can minimize unwanted thermal damage during time-based switching bRFA. From the numerical results, unidirectional ablation was shown to produce treatment efficacy of nearly 100%, while at the same time, minimizing the amount of unwanted thermal damage. Nevertheless, this effect was observed only when the switch interval of the time-based protocol was set to 50 s. An extended switch interval negated the benefits of unidirectional ablation.
  2. Cheong JKK, Ooi EH, Ooi ET
    Int J Numer Method Biomed Eng, 2020 09;36(9):e3374.
    PMID: 32519516 DOI: 10.1002/cnm.3374
    Recent studies have demonstrated the effectiveness of switching bipolar radiofrequency ablation (bRFA) in treating liver cancer. Nevertheless, the clinical use of the treatment remains less common than conventional monopolar RFA - likely due to the lack of understanding of how the tissues respond thermally to the switching effect. The problem is exacerbated by the numerous possible switching combinations when bRFA is performed using bipolar needles, thus making theoretical deduction and experimental studies difficult. This article addresses this issue via computational modelling by examining if significant variation in the treatment outcome exists amongst six different electrode configurations defined by the X-, C-, U-, N-, Z- and O-models. Results indicated that the tissue thermal and thermal damage responses varied depending on the electrode configuration and the operating conditions (input voltage and ablation duration). For a spherical tumour, 30 mm in diameter, complete ablation could not be attained in all configurations with 70 V input voltage and 5 minutes ablation duration. Increasing the input voltage to 90 V enlarged the coagulation zone in the X-model only. With the other configurations, extending the ablation duration to 10 minutes was found to be the better at enlarging the coagulation zone.
  3. Ooi ET, Ganesananthan S, Anil R, Kwok FY, Sinniah M
    Med J Malaysia, 2008 Dec;63(5):401-5.
    PMID: 19803300
    This is a retrospective study of the gastrointestinal symptoms, signs and laboratory parameters in adult dengue patients admitted to Kuala Lumpur Hospital from 1st December 2004 to 31st December 2004. Clinical and laboratory parameters that may predict the need for intensive care were investigated. Six hundred sixty-six patients with clinical and biochemical features consistent with dengue infection were identified. Patients were stratified into those who required intensive care and those who were managed in non high dependency wards. Serum alanine aminotransaminase (ALT) levels were normal in 22.8% of patients and 5.9% of patients had acute fulminant hepatitis. More patients with dengue haemorrhagic fever (DHF) had elevated ALT levels as compared to patients with classic dengue fever (DF) (p = 0.012). Patients with DF had a statistically significant lower mean ALT level as compared to patients with DHF. Abdominal pain (p = 0.01) and tenderness (p<0.001), gastrointestinal bleed (p<0.001), jaundice (p<0.001), hepatomegaly (p<0.001) and ascites (p<0.001) were predictors of need for intensive care. We conclude that gastrointestinal manifestations are very common in dengue patients. Presence of abdominal pain and tenderness, gastrointestinal bleed, jaundice, hepatomegaly and ascites can be used to triage patients requiring intensive care.
  4. Kho AS, Ooi EH, Foo JJ, Ooi ET
    Comput Biol Med, 2021 01;128:104112.
    PMID: 33212331 DOI: 10.1016/j.compbiomed.2020.104112
    Infusion of saline prior to radiofrequency ablation (RFA) is known to enlarge the thermal coagulation zone. The abundance of ions in saline elevate the electrical conductivity of the saline-saturated region. This promotes greater electric current flow inside the tissue, which increases the amount of RF energy deposition and subsequently enlarges the coagulation zone. In theory, infusion of higher concentration of saline should lead to larger coagulation zone due to the greater number of ions. Nevertheless, existing studies on the effects of concentration on saline-infused RFA have been conflicting, with the exact role of saline concentration yet to be fully elucidated. In this paper, computational models of saline-infused RFA were developed to investigate the role of saline concentration on the outcome of saline-infused RFA. The elevation in tissue electrical conductivity was modelled using the microscopic mixture model, while RFA was modelled using the coupled dual porosity-Joule heating model. Results obtained indicated that the presence of a concentration threshold to which no further elevation in tissue electrical conductivity and enlargement in thermal coagulation can occur. This threshold was determined to be at 15% NaCl. Analysis of the Joule heating distribution revealed the presence of a secondary Joule heating site located along the interface between wet and dry tissue. This secondary Joule heating was responsible for the enlargement in coagulation volume and its rapid growth phase during ablation.
  5. Yap S, Ooi EH, Foo JJ, Ooi ET
    Comput Biol Med, 2021 04;131:104273.
    PMID: 33631495 DOI: 10.1016/j.compbiomed.2021.104273
    Radiofrequency ablation (RFA) is a thermal ablative treatment method that is commonly used to treat liver cancer. However, the thermal coagulation zone generated using the conventional RFA system can only successfully treat tumours up to 3 cm in diameter. Switching bipolar RFA has been proposed as a way to increase the thermal coagulation zone. Presently, the understanding of the underlying thermal processes that takes place during switching bipolar RFA remains limited. Hence, the objective of this study is to provide a comprehensive understanding on the thermal ablative effects of time-based switching bipolar RFA on liver tissue. Five switch intervals, namely 50, 100, 150, 200 and 300 s were investigated using a two-compartment 3D finite element model. The study was performed using two pairs of RF electrodes in a four-probe configuration, where the electrodes were alternated based on their respective switch interval. The physics employed in the present study were verified against experimental data from the literature. Results obtained show that using a shorter switch interval can improve the homogeneity of temperature distribution within the tissue and increase the rate of temperature rise by delaying the occurrence of roll-off. The coagulation volume obtained was the largest using switch interval of 50 s, followed by 100, 150, 200 and 300 s. The present study demonstrated that the transient thermal response of switching bipolar RFA can be improved by using shorter switch intervals.
  6. Yap S, Ooi EH, Foo JJ, Ooi ET
    Comput Biol Med, 2021 Jul;134:104488.
    PMID: 34020132 DOI: 10.1016/j.compbiomed.2021.104488
    Switching bipolar radiofrequency ablation (bRFA) is a cancer treatment technique that activates multiple pairs of electrodes alternately based on a predefined criterion. Various criteria can be used to trigger the switch, such as time (ablation duration) and tissue impedance. In a recent study on time-based switching bRFA, it was determined that a shorter switch interval could produce better treatment outcome than when a longer switch interval was used, which reduces tissue charring and roll-off induced cooling. In this study, it was hypothesized that a more efficacious bRFA treatment can be attained by employing impedance-based switching. This is because ablation per pair can be maximized since there will be no interruption to RF energy delivery until roll-off occurs. This was investigated using a two-compartment 3D computational model. Results showed that impedance-based switching bRFA outperformed time-based switching when the switch interval of the latter is 100 s or higher. When compared to the time-based switching with switch interval of 50 s, the impedance-based model is inferior. It remains to be investigated whether the impedance-based protocol is better than the time-based protocol for a switch interval of 50 s due to the inverse relationship between ablation and treatment efficacies. It was suggested that the choice of impedance-based or time-based switching could ultimately be patient-dependent.
  7. Kho ASK, Foo JJ, Ooi ET, Ooi EH
    Comput Methods Programs Biomed, 2020 Feb;184:105289.
    PMID: 31891903 DOI: 10.1016/j.cmpb.2019.105289
    BACKGROUND AND OBJECTIVE: The majority of the studies on radiofrequency ablation (RFA) have focused on enlarging the size of the coagulation zone. An aspect that is crucial but often overlooked is the shape of the coagulation zone. The shape is crucial because the majority of tumours are irregularly-shaped. In this paper, the ability to manipulate the shape of the coagulation zone following saline-infused RFA by altering the location of saline infusion is explored.

    METHODS: A 3D model of the liver tissue was developed. Saline infusion was described using the dual porosity model, while RFA was described using the electrostatic and bioheat transfer equations. Three infusion locations were investigated, namely at the proximal end, the middle and the distal end of the electrode. Investigations were carried out numerically using the finite element method.

    RESULTS: Results indicated that greater thermal coagulation was found in the region of tissue occupied by the saline bolus. Infusion at the middle of the electrode led to the largest coagulation volume followed by infusion at the proximal and distal ends. It was also found that the ability to delay roll-off, as commonly associated with saline-infused RFA, was true only for the case when infusion is carried out at the middle. When infused at the proximal and distal ends, the occurrence of roll-off was advanced. This may be due to the rapid and more intense heating experienced by the tissue when infusion is carried out at the electrode ends where Joule heating is dominant.

    CONCLUSION: Altering the location of saline infusion can influence the shape of the coagulation zone following saline-infused RFA. The ability to 'shift' the coagulation zone to a desired location opens up great opportunities for the development of more precise saline-infused RFA treatment that targets specific regions within the tissue.

  8. Cheong JKK, Yap S, Ooi ET, Ooi EH
    Comput Methods Programs Biomed, 2019 Jul;176:17-32.
    PMID: 31200904 DOI: 10.1016/j.cmpb.2019.04.028
    BACKGROUND AND OBJECTIVES: Recently, there have been calls for RFA to be implemented in the bipolar mode for cancer treatment due to the benefits it offers over the monopolar mode. These include the ability to prevent skin burns at the grounding pad and to avoid tumour track seeding. The usage of bipolar RFA in clinical practice remains uncommon however, as not many research studies have been carried out on bipolar RFA. As such, there is still uncertainty in understanding the effects of the different RF probe configurations on the treatment outcome of RFA. This paper demonstrates that the electrode lengths have a strong influence on the mechanics of bipolar RFA. The information obtained here may lead to further optimization of the system for subsequent uses in the hospitals.

    METHODS: A 2D model in the axisymmetric coordinates was developed to simulate the electro-thermophysiological responses of the tissue during a single probe bipolar RFA. Two different probe configurations were considered, namely the configuration where the active electrode is longer than the ground and the configuration where the ground electrode is longer than the active. The mathematical model was first verified with an existing experimental study found in the literature.

    RESULTS: Results from the simulations showed that heating is confined only to the region around the shorter electrode, regardless of whether the shorter electrode is the active or the ground. Consequently, thermal coagulation also occurs in the region surrounding the shorter electrode. This opened up the possibility for a better customized treatment through the development of RF probes with adjustable electrode lengths.

    CONCLUSIONS: The electrode length was found to play a significant role on the outcome of single probe bipolar RFA. In particular, the length of the shorter electrode becomes the limiting factor that influences the mechanics of single probe bipolar RFA. Results from this study can be used to further develop and optimize bipolar RFA as an effective and reliable cancer treatment technique.

  9. Kho ASK, Ooi EH, Foo JJ, Ooi ET
    Comput Methods Programs Biomed, 2021 Nov;211:106436.
    PMID: 34601185 DOI: 10.1016/j.cmpb.2021.106436
    BACKGROUND AND OBJECTIVE: Saline infusion is applied together with radiofrequency ablation (RFA) to enlarge the ablation zone. However, one of the issues with saline-infused RFA is backflow, which spreads saline along the insertion track. This raises the concern of not only thermally ablating the tissue within the backflow region, but also the loss of saline from the targeted tissue, which may affect the treatment efficacy.

    METHODS: In the present study, 2D axisymmetric models were developed to investigate how saline backflow influence saline-infused RFA and whether the aforementioned concerns are warranted. Saline-infused RFA was described using the dual porosity-Joule heating model. The hydrodynamics of backflow was described using Poiseuille law by assuming the flow to be similar to that in a thin annulus. Backflow lengths of 3, 4.5, 6 and 9 cm were considered.

    RESULTS: Results showed that there is no concern of thermally ablating the tissue in the backflow region. This is due to the Joule heating being inversely proportional to distance from the electrode to the fourth power. Results also indicated that larger backflow lengths led to larger growth of thermal damage along the backflow region and greater decrease in coagulation volume. Hence, backflow needs to be controlled to ensure an effective treatment of saline-infused RFA.

    CONCLUSIONS: There is no risk of ablating tissues around the needle insertion track due to backflow. Instead, the risk of underablation as a result of the loss of saline due to backflow was found to be of greater concern.

  10. Yip WP, Kho ASK, Ooi EH, Ooi ET
    Med Eng Phys, 2023 Feb;112:103950.
    PMID: 36842773 DOI: 10.1016/j.medengphy.2023.103950
    No-touch bipolar radiofrequency ablation (bRFA) is known to produce incomplete tumour ablation with a 'butterfly-shaped' coagulation zone when the interelectrode distance exceeds a certain threshold. Although non-confluent coagulation zone can be avoided by not implementing the no-touch mode, doing so exposes the patient to the risk of tumour track seeding. The present study investigates if prior infusion of saline into the tissue can overcome the issues of non-confluent or butterfly-shaped coagulation. A computational modelling approach based on the finite element method was carried out. A two-compartment model comprising the tumour that is surrounded by healthy liver tissue was developed. Three cases were considered; i) saline infusion into the tumour centre; ii) one-sided saline infusion outside the tumour; and iii) two-sided saline infusion outside the tumour. For each case, three different saline volumes were considered, i.e. 6, 14 and 22 ml. Saline concentration was set to 15% w/v. Numerical results showed that saline infusion into the tumour centre can overcome the butterfly-shaped coagulation only if the infusion volume is sufficient. On the other hand, one-sided infusion outside the tumour did not overcome this. Two-sided infusion outside the tumour produced confluent coagulation zone with the largest volume. Results obtained from the present study suggest that saline infusion, when carried out correctly, can be used to effectively eradicate liver cancer. This presents a practical solution to address non-confluent coagulation zone typical of that during two-probe bRFA treatment.
  11. 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.

  12. Tan ZQ, Ooi EH, Chiew YS, Foo JJ, Ng EYK, Ooi ET
    Ultrasonics, 2023 May;131:106961.
    PMID: 36812819 DOI: 10.1016/j.ultras.2023.106961
    Sonothrombolysis is a technique that utilises ultrasound waves to excite microbubbles surrounding a clot. Clot lysis is achieved through mechanical damage induced by acoustic cavitation and through local clot displacement induced by acoustic radiation force (ARF). Despite the potential of microbubble-mediated sonothrombolysis, the selection of the optimal ultrasound and microbubble parameters remains a challenge. Existing experimental studies are not able to provide a complete picture of how ultrasound and microbubble characteristics influence the outcome of sonothrombolysis. Likewise, computational studies have not been applied in detail in the context of sonothrombolysis. Hence, the effect of interaction between the bubble dynamics and acoustic propagation on the acoustic streaming and clot deformation remains unclear. In the present study, we report for the first time the computational framework that couples the bubble dynamic phenomena with the acoustic propagation in a bubbly medium to simulate microbubble-mediated sonothrombolysis using a forward-viewing transducer. The computational framework was used to investigate the effects of ultrasound properties (pressure and frequency) and microbubble characteristics (radius and concentration) on the outcome of sonothrombolysis. Four major findings were obtained from the simulation results: (i) ultrasound pressure plays the most dominant role over all the other parameters in affecting the bubble dynamics, acoustic attenuation, ARF, acoustic streaming, and clot displacement, (ii) smaller microbubbles could contribute to a more violent oscillation and improve the ARF simultaneously when they are stimulated at higher ultrasound pressure, (iii) higher microbubbles concentration increases the ARF, and (iv) the effect of ultrasound frequency on acoustic attenuation is dependent on the ultrasound pressure. These results may provide fundamental insight that is crucial in bringing sonothrombolysis closer to clinical implementation.
  13. Ooi EH, Lee KW, Yap S, Khattab MA, Liao IY, Ooi ET, et al.
    Comput Biol Med, 2019 03;106:12-23.
    PMID: 30665137 DOI: 10.1016/j.compbiomed.2019.01.003
    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.
  14. Ooi EH, J Y Chia N, Ooi ET, Foo JJ, Liao IY, R Nair S, et al.
    Int J Hyperthermia, 2018 12;34(8):1142-1156.
    PMID: 29490513 DOI: 10.1080/02656736.2018.1437282
    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.
  15. 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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