In silico analysis reveals the prospects of renal anisotropy in improving chronic kidney disease detection using ultrasound shear wave elastography.

Renal anisotropy is a complex property of the kidney and often poses a challenge in obtaining consistent measurements when using shear wave elastography to detect chronic kidney disease. To circumvent the challenge posed by renal anisotropy in clinical settings, a dimensionless biomarker termed the 'anisotropic ratio' was introduced to establish a correlation between changes in degree of renal anisotropy and progression of chronic kidney disease through an in silico perspective. To achieve this, an efficient model reduction approach was developed to model the anisotropic property of kidneys. Good agreement between the numerical and experimental data were obtained, as percentage errors of less than 5.5% were reported when compared against experimental phantom measurement from the literature. To demonstrate the applicability of the model to clinical measurements, the anisotropic ratio of sheep kidneys was quantified, with both numerical and derived experimental results reporting a value of .667. Analysis of the anisotropic ratio with progression of chronic kidney disease demonstrated that patients with normal kidneys would have a lower anisotropic ratio of .872 as opposed to patients suffering from renal impairment, in which the anisotropic ratio may increase to .904, as determined from this study. The findings demonstrate the potential of the anisotropic ratio in improving the detection of chronic kidney disease using shear wave elastography.

The role of shear viscosity as a biomarker for improving chronic kidney disease detection using shear wave elastography: A computational study using a validated finite element model.

The application of ultrasound shear wave elastography for detecting chronic kidney disease, namely renal fibrosis, has been widely studied. A good correlation between tissue Young's modulus and the degree of renal impairment has been established. However, the current limitation of this imaging modality pertains to the linear elastic assumption used in quantifying the stiffness of renal tissue in commercial shear wave elastography systems. As such, when underlying medical conditions such as acquired cystic kidney disease, which may potentially influence the viscous component of renal tissue, is present concurrently with renal fibrosis, the accuracy of the imaging modality in detecting chronic kidney disease may be affected. The findings in this study demonstrate that quantifying the stiffness of linear viscoelastic tissue using an approach similar to those implemented in commercial shear wave elastography systems led to percentage errors as high as 87%. The findings presented indicate that use of shear viscosity to detect changes in renal impairment led to a reduction in percentage error to values as low as 0.3%. For cases in which renal tissue was affected by multiple medical conditions, shear viscosity was found to be a good indicator in gauging the reliability of the Young's modulus (quantified through a shear wave dispersion analysis) in detecting chronic kidney disease. The findings show that percentage error in stiffness quantification can be reduced to as low as 0.6%. The present study demonstrates the potential use of renal shear viscosity as a biomarker to improve the detection of chronic kidney disease.

A computational framework for the multiphysics simulation of microbubble-mediated sonothrombolysis using a forward-viewing intravascular transducer.

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.

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.

How does saline backflow affect the treatment of saline-infused radiofrequency ablation?

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.

Shear Wave Elastography: A Review on the Confounding Factors and Their Potential Mitigation in Detecting Chronic Kidney Disease.

Early detection of chronic kidney disease is important to prevent progression of irreversible kidney damage, reducing the need for renal transplantation. Shear wave elastography is ideal as a quantitative imaging modality to detect chronic kidney disease because of its non-invasive nature, low cost and portability, making it highly accessible. However, the complexity of the kidney architecture and its tissue properties give rise to various confounding factors that affect the reliability of shear wave elastography in detecting chronic kidney disease, thus limiting its application to clinical trials. The objective of this review is to highlight the confounding factors presented by the complex properties of the kidney, in addition to outlining potential mitigation strategies, along with the prospect of increasing the versatility and reliability of shear wave elastography in detecting chronic kidney disease.

Comparisons between impedance-based and time-based switching bipolar radiofrequency ablation for the treatment of liver cancer.

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.

Bipolar radiofrequency ablation treatment of liver cancer employing monopolar needles: A comprehensive investigation on the efficacy of time-based switching.

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.

Role of saline concentration during saline-infused radiofrequency ablation: Observation of secondary Joule heating along the saline-tissue interface.

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.

Shape-shifting thermal coagulation zone during saline-infused radiofrequency ablation: A computational study on the effects of different infusion location.

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.

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.