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Sensitivity of thermophysiological models of cryoablation to the thermal and biophysical properties of tissues

Chan JY, Ooi EH

Cryobiology, 2016 12;73(3):304-315.
PMID: 27789380 DOI: 10.1016/j.cryobiol.2016.10.006

Advancement in biomedical simulation and imaging modality have catalysed the development of in silico predictive models for cryoablation. However, one of the main challenges in ensuring the accuracy of the model prediction is the use of proper thermal and biophysical properties of the patient. These properties are difficult to measure clinically and thus, represent significant uncertainty that can affect the model prediction. Motivated by this, a sensitivity analysis is carried out to identify the model parameters that have the most significant impact on the lesion size during cryoablation. The study is initially carried out using the Morris method to screen for the most dominant parameters. Once determined, analysis of variance (ANOVA) is performed to quantitatively rank the order of importance of each parameter and their interactions. Results from the sensitivity analysis revealed that blood perfusion, water transport and ice nucleation parameters are critical in predicting the lesion size, suggesting that the acquisition of these parameters should be prioritised to ensure the accuracy of the model prediction.
Unidirectional ablation minimizes unwanted thermal damage and promotes better thermal ablation efficacy in time-based switching bipolar radiofrequency ablation

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.
Effects of aqueous humor hydrodynamics on human eye heat transfer under external heat sources

Tiang KL, Ooi EH

Med Eng Phys, 2016 Aug;38(8):776-84.
PMID: 27340100 DOI: 10.1016/j.medengphy.2016.05.011

The majority of the eye models developed in the late 90s and early 00s considers only heat conduction inside the eye. This assumption is not entirely correct, since the anterior and posterior chambers are filled aqueous humor (AH) that is constantly in motion due to thermally-induced buoyancy. In this paper, a three-dimensional model of the human eye is developed to investigate the effects AH hydrodynamics have on the human eye temperature under exposure to external heat sources. If the effects of AH flow are negligible, then future models can be developed without taking them into account, thus simplifying the modeling process. Two types of external thermal loads are considered; volumetric and surface irradiation. Results showed that heat convection due to AH flow contributes to nearly 95% of the total heat flow inside the anterior chamber. Moreover, the circulation inside the anterior chamber can cause an upward shift of the location of hotspot. This can have significant consequences to our understanding of heat-induced cataractogenesis.
A mathematical framework for minimally invasive tumor ablation therapies

Hall SK, Ooi EH, Payne SJ

Crit Rev Biomed Eng, 2014;42(5):383-417.
PMID: 25745803

Minimally invasive tumor ablations (MITAs) are an increasingly important tool in the treatment of solid tumors across multiple organs. The problems experienced in modeling different types of MITAs are very similar, but the development of mathematical models is mostly performed in isolation according to modality. Fundamental research into the modeling of specific types of MITAs is indeed required, but to choose the optimal treatment for an individual the primary clinical requirement is to have reliable predictions for a range of MITAs. In this review of the mathematical modeling of MITAs 4 modalities are considered: radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. The similarities in the mathematical modeling of these treatments are highlighted, and the analysis of the models within a general framework is discussed. This will aid in developing a deeper understanding of the sensitivity of MITA models to physiological parameters and the impact of uncertainty on predictions of the ablation zone. Through robust validation and analysis of the models it will be possible to choose the best model for a given application. This is important because many different models exist with no objective comparison of their performance. The collection of relevant in vivo experimental data is also critical to parameterize such models accurately. This approach will be necessary to translate the field into clinical practice.
Thermal and thermal damage responses during switching bipolar radiofrequency ablation employing bipolar needles: A computational study on the effects of different electrode configuration, input voltage and ablation duration

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.
Neural network modeling of the kinetics of SO2 removal by fly ash-based sorbent

Raymond-Ooi EH, Lee KT, Mohamed AR, Chu KH

J Environ Sci Health A Tox Hazard Subst Environ Eng, 2006;41(2):195-210.
PMID: 16423725

The mechanistic modeling of the sulfation reaction between fly ash-based sorbent and SO2 is a challenging task due to a variety reasons including the complexity of the reaction itself and the inability to measure some of the key parameters of the reaction. In this work, the possibility of modeling the sulfation reaction kinetics using a purely data-driven neural network was investigated. Experiments on SO2 removal by a sorbent prepared from coal fly ash/CaO/CaSO4 were conducted using a fixed bed reactor to generate a database to train and validate the neural network model. Extensive SO2 removal data points were obtained by varying three process variables, namely, SO2 inlet concentration (500-2000 mg/L), reaction temperature (60-80 degreesC), and relative humidity (50-70%), as a function of reaction time (0-60 min). Modeling results show that the neural network can provide excellent fits to the SO2 removal data after considerable training and can be successfully used to predict the extent of SO2 removal as a function of time even when the process variables are outside the training domain. From a modeling standpoint, the suitably trained and validated neural network with excellent interpolation and extrapolation properties could have immediate practical benefits in the absence of a theoretical model.
Fulltext Pneumocephalus and air travel: an experimental investigation on the effects of aircraft cabin pressure on intracranial pressure

Lim E, Lan BL, Ooi EH, Low HL

Sci Rep, 2020 08 12;10(1):13626.
PMID: 32788610 DOI: 10.1038/s41598-020-70614-w

This study investigates the effects of aircraft cabin pressure on intracranial pressure (ICP) elevation of a pneumocephalus patient. We propose an experimental setup that simulates the intracranial hydrodynamics of a pneumocephalus patient during flight. It consists of an acrylic box (skull), air-filled balloon [intracranial air (ICA)], water-filled balloon (cerebrospinal fluid and blood) and agarose gel (brain). The cabin was replicated using a custom-made pressure chamber. The setup can measure the rise in ICP during depressurization to levels similar to that inside the cabin at cruising altitude. ΔICP, i.e. the difference between mean cruising ICP and initial ICP, was found to increase with ICA volume and ROC. However, ΔICP was independent of the initial ICP. The largest ΔICP was 5 mmHg; obtained when ICA volume and ROC were 20 ml and 1,600 ft/min, respectively. The postulated ICA expansion and the subsequent increase in ICP in pneumocephalus patients during flight were successfully quantified in a laboratory setting. Based on the quantitative and qualitative analyses of the results, an ICA volume of 20 ml and initial ICP of 15 mmHg were recommended as conservative thresholds that are required for safe air travel among pneumocephalus patients. This study provides laboratory data that may be used by doctors to advise post-neurosurgical patients if they can safely fly.
Role of saline concentration during saline-infused radiofrequency ablation: Observation of secondary Joule heating along the saline-tissue interface

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.
Influence of natural convection on gold nanorods-assisted photothermal treatment of bladder cancer in mice

Ooi EH, Popov V, Alfano M, Cheong JKK

Int J Hyperthermia, 2020;37(1):634-650.
PMID: 32538190 DOI: 10.1080/02656736.2020.1771437

Background: The thermally-induced urine flow can generate cooling that may alter the treatment outcome during hyperthermic treatments of bladder cancer. This paper investigates the effects of natural convection inside the bladder and at skin surface during gold nanorods (GNR) - assisted photothermal therapy (PTT) of bladder cancer in mice. Methods: 3D models of mouse bladder at orientations corresponding to the mouse positioned on its back, its side and its abdomen were examined. Numerical simulations were carried out for GNR volume fractions of 0.001, 0.005 and 0.01% and laser power of 0.2 and 0.3 W. Results: The obtained results showed that cooling due to natural convection inside the bladder and above the skin depends on the mouse orientation. For a mouse positioned on its back, on its side or on its abdomen, the maximum temperature achieved inside the tumour at 0.001% GNR volume fraction and 0.2 W laser power was 55.2°C, 50.0°C and 52.2°C, respectively compared to 56.8°C when natural convection was not considered. The average thermal gradients when natural convection was considered were also lower, suggesting a more homogenous temperature distribution. Conclusions: Natural convection inside the bladder can be beneficial but also detrimental to GNR-assisted PTT depending on the level of heating. At low levels of heating due to low GNR volume fraction and/or laser power, flow inside the bladder may dissipate heat from the targeted tissue; making the treatment ineffective. At high levels of heating due to high GNR volume fraction and/or laser power, cooling may prevent excessive thermal damage to surrounding tissues.
Bipolar radiofrequency ablation treatment of liver cancer employing monopolar needles: A comprehensive investigation on the efficacy of time-based switching

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

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

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.
A computational model to investigate the influence of electrode lengths on the single probe bipolar radiofrequency ablation of the liver

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

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.
Fulltext Fractal grid-induced turbulence strength characterization via piezoelectric thin-film flapping velocimetry

Lee TS, Ooi EH, Chang WS, Foo JJ

Sci Rep, 2021 Dec 02;11(1):23322.
PMID: 34857825 DOI: 10.1038/s41598-021-02680-7

The centerline streamwise and cross-sectional (x/Dh = 0.425) turbulence characteristics of a 2D planar space-filling square-fractal-grid (SFG) composed of self-similar patterns superimposed at multiple length-scales is experimentally unveiled via piezoelectric thin-film flapping velocimetry (PTFV). The fluid-structure-interaction between a flexible piezoelectric thin-film and SFG-generated turbulent flow at ReDh = 4.1 × 104 is investigated by analysis of the thin-film's mechanical response. Measurements of the thin-film-tip deflection δ and induced voltage V demonstrate increasing flow fluctuation strength in the turbulence generation region, followed by rapid decay further downstream of the SFG. Interestingly, SFG-induced turbulence enables the generation of maximum centerline thin-film's response (Vrms, δrms) and millinewton turbulence-forcing (turbulence-induced excitation force acting on the thin-film) Frms which are respectively, 7× and 2× larger than the classical square-regular-grid of similar blockage ratio. The low frequency, large-scale energy-containing eddies at SFG's central opening plays a critical role in driving the thin-film vibration. Most importantly, the SFG-generated turbulence at (y/T = 0.106, z/T = 0.125) away from the centerline allows equivalent mechanical characteristics of turbulence generation and decay, with peak of 1.9× nearer from grid. In short, PTFV provides a unique expression of the SFG-generated turbulence, of which, the equivalent turbulence length-scale and induced-forcing deduced could aid in deciphering the flow dynamics for effective turbulence management.
Fulltext SPTV sheds light on flow dynamics of fractal-induced turbulence over a plate-fin array forced convection

Hoi SM, Ooi EH, Chew IML, Foo JJ

Sci Rep, 2022 Jan 07;12(1):76.
PMID: 34996902 DOI: 10.1038/s41598-021-02872-1

A 3D stationary particle tracking velocimetry (SPTV) with a unique recursive corrective algorithm has been successfully established to detect the instantaneous regional fluid flow characteristics. The veracity of SPTV is corroborated by conducting actual displacement measurement validation, which gives a maximum percentage deviation of about 0.8%. This supports the accuracy of the current SPTV system in 3D position detection. More importantly, the SPTV detected velocity fluctuations are highly repeatable. In this study, SPTV is proven to be able to express the nature of chaotic fractal grid-induced regional turbulence, namely: the high turbulence intensity attributed to multilength-scale wake interactions, the Kolmogorov's -5/3 law decay, vortex shedding, and the Gaussian flow undulations immediately leeward of the grid followed by non-Gaussian behaviour further downstream. Moreover, by comparing the flow fields between control no-grid and fractal grid-generated turbulence of a plate-fin array, SPTV reveals vigorous turbulence intensity, smaller regional integral-length-scale, and energetic vortex shedding at higher frequency for the latter, particularly between fins. Thereupon, it allows the unravelling of detailed thermofluid interplays of plate-fin heat sink heat transfer augmentation. The novelty of SPTV lies in its simplicity, use of low-cost off-the-shelf components, and most remarkably, low computational complexity in detecting fundamental characteristics of turbulent fluid flow.
An in silico assessment on the potential of using saline infusion to overcome non-confluent coagulation zone during two-probe, no-touch bipolar radiofrequency ablation of liver cancer

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

Lim WTH, Ooi EH, Foo JJ, Ng KH, Wong JHD, Leong SS

Ultrasound Med Biol, 2021 08;47(8):2033-2047.
PMID: 33958257 DOI: 10.1016/j.ultrasmedbio.2021.03.030

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.
Fulltext Rapid sperm capture: high-throughput flagellar waveform analysis

Gallagher MT, Cupples G, Ooi EH, Kirkman-Brown JC, Smith DJ

Hum Reprod, 2019 07 08;34(7):1173-1185.
PMID: 31170729 DOI: 10.1093/humrep/dez056

STUDY QUESTION: Can flagellar analyses be scaled up to provide automated tracking of motile sperm, and does knowledge of the flagellar waveform provide new insight not provided by routine head tracking?
SUMMARY ANSWER: High-throughput flagellar waveform tracking and analysis enable measurement of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses, which are not possible by tracking the sperm head alone.
WHAT IS KNOWN ALREADY: The clinical gold standard for sperm motility analysis comprises a manual analysis by a trained professional, with existing automated sperm diagnostics [computer-aided sperm analysis (CASA)] relying on tracking the sperm head and extrapolating measures. It is not currently possible with either of these approaches to track the sperm flagellar waveform for large numbers of cells in order to unlock the potential wealth of information enclosed within.
STUDY DESIGN, SIZE, DURATION: The software tool in this manuscript has been developed to enable high-throughput, repeatable, accurate and verifiable analysis of the sperm flagellar beat.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the software tool [Flagellar Analysis and Sperm Tracking (FAST)] described in this manuscript, we have analysed 176 experimental microscopy videos and have tracked the head and flagellum of 205 progressive cells in diluted semen (DSM), 119 progressive cells in a high-viscosity medium (HVM) and 42 stuck cells in a low-viscosity medium. Unscreened donors were recruited at Birmingham Women's and Children's NHS Foundation Trust after giving informed consent.
MAIN RESULTS AND THE ROLE OF CHANCE: We describe fully automated tracking and analysis of flagellar movement for large cell numbers. The analysis is demonstrated on freely motile cells in low- and high-viscosity fluids and validated on published data of tethered cells undergoing pharmacological hyperactivation. Direct analysis of the flagellar beat reveals that the CASA measure 'beat cross frequency' does not measure beat frequency; attempting to fit a straight line between the two measures gives ${\mathrm{R}}^2$ values of 0.042 and 0.00054 for cells in DSM and HVM, respectively. A new measurement, track centroid speed, is validated as an accurate differentiator of progressive motility. Coupled with fluid mechanics codes, waveform data enable extraction of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses. We provide a powerful and accessible research tool, enabling connection of the mechanical activity of the sperm to its motility and effect on its environment.
LARGE SCALE DATA: The FAST software package and all documentation can be downloaded from www.flagellarCapture.com.
LIMITATIONS, REASONS FOR CAUTION: The FAST software package has only been tested for use with negative phase contrast microscopy. Other imaging modalities, with bright cells on a dark background, have not been tested but may work. FAST is not designed to analyse raw semen; it is specifically for precise analysis of flagellar kinematics, as that is the promising area for computer use. Flagellar capture will always require that cells are at a dilution where their paths do not frequently cross.
WIDER IMPLICATIONS OF THE FINDINGS: Combining tracked flagella with mathematical modelling has the potential to reveal new mechanistic insight. By providing the capability as a free-to-use software package, we hope that this ability to accurately quantify the flagellar waveform in large populations of motile cells will enable an abundant array of diagnostic, toxicological and therapeutic possibilities, as well as creating new opportunities for assessing and treating male subfertility.
STUDY FUNDING/COMPETING INTEREST(S): M.T.G., G.C., J.C.K-B. and D.J.S. gratefully acknowledge funding from the Engineering and Physical Sciences Research Council, Healthcare Technologies Challenge Award (Rapid Sperm Capture EP/N021096/1). J.C.K-B. is funded by a National Institute of Health Research (NIHR) and Health Education England, Senior Clinical Lectureship Grant: The role of the human sperm in healthy live birth (NIHRDH-HCS SCL-2014-05-001). This article presents independent research funded in part by the NIHR and Health Education England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The data for experimental set (2) were funded through a Wellcome Trust-University of Birmingham Value in People Fellowship Bridging Award (E.H.O.).The authors declare no competing interests.
An in silico derived dosage and administration guide for effective thermochemical ablation of biological tissues with simultaneous injection of acid and base

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.

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