Characterization of the RF ablation-induced ‘oven effect’: The importance of background tissue thermal conductivity on tissue heating

Purpose: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling.

Method: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2?cm diameter, 4?cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48?W?m^?1°C (normal liver) to 0.23?W?m^?1°C (fat) by adding a fat-saturated oil-based solute (10–90%) to the agar. RF ablation was applied at 2000?mA current for 2?min. Temperatures were recorded up to 4?cm from the electrode tip at 1?cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2–24?min duration for tumours measuring 2–4?cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0–5?kg?m^?3?s^?1) (n?=?44). A comparison of results was performed.

Results: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r²?=?0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1?cm from the electrode tip) as the fat content of the outer compartment increased (p?<?0.01). Thus, temperatures at 2?min measured 31.5?±?2.2°C vs 45.1?±?3.1°C for thermal conductivities of 0.46?W?m^?1°C (10% fat) and 0.23?W?m^?1°C (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2?±?0.3°C for 90% fat vs. 1.1?±?0.05°C for 10% fat, p?<?0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r²?=?0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5°C difference between background thermal conductivities of fat and soft tissue for a 3?cm tumour with perfusion of 2?kg?m^?3?s^?1, treated for 12?min.

Conclusion: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the ‘oven effect’ (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.     

Characterization of the RF ablation-induced 'oven effect': the importance of background tissue thermal conductivity on tissue heating.

PURPOSE: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling. METHOD: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2 cm diameter, 4 cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48 W m-1 degrees Celsius (normal liver) to 0.23 W m-1 degrees Celsius (fat) by adding a fat-saturated oil-based solute (10-90%) to the agar. RF ablation was applied at 2000 mA current for 2 min. Temperatures were recorded up to 4 cm from the electrode tip at 1 cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2-24 min duration for tumours measuring 2-4 cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0-5 kg m-3 s-1) (n = 44). A comparison of results was performed. RESULTS: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r2 = 0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1 cm from the electrode tip) as the fat content of the outer compartment increased (p < 0.01). Thus, temperatures at 2 min measured 31.5 +/- 2.2 degrees Celsius vs 45.1 +/- 3.1 degrees Celsius for thermal conductivities of 0.46 W m-1 degrees Celsius (10% fat) and 0.23 W m-1 degrees Celsius (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2 +/- 0.3 degrees Celsius for 90% fat vs. 1.1 +/- 0.05 degrees Celsius for 10% fat, p < 0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r2 = 0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5 degrees Celsius difference between background thermal conductivities of fat and soft tissue for a 3 cm tumour with perfusion of 2 kg m-3 s-1, treated for 12 min. CONCLUSION: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the 'oven effect' (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.     

Radiofrequency ablation lesion detection using MR-based electrical conductivity imaging: A feasibility study of ex vivo liver experiments

Abstract

Purpose: The aim of this study was to show the potential of magnetic resonance electrical impedance tomography (MREIT) conductivity imaging in terms of its capability to detect ablated lesions and differentiate tissue conditions in liver radiofrequency (RF) ablation. Materials and methods: RF ablation procedures were performed in bovine livers using a LeVeen RF needle electrode. Ablation lesions were created using a power-controlled mode at 30, 50, and 70?W for 1, 3, and 5?min of exposure time, respectively. After the ablation, the liver was cut into several blocks including the ablated lesion, and positioned inside a phantom filled with agarose gel. Electrodes were attached on the side of the phantom and it was placed inside the MRI bore. For MREIT imaging, multi-spin-echo pulse sequence was used to obtain the magnetic flux density data according to the injection currents. Results: The conductivity of ablation lesions was significantly changed with the increase of exposure time (pKW?<?0.01, Kruskal-Wallis test). With RF powers of 30 and 50?W, significant differences between the coagulation necrosis and hyperaemic rim were observed for more than 5?min and 3?min, respectively (pMW?<?0.01, Mann-Whitney test). At 70?W, all cases showed significant differences except 3?min (pMW?<?0.01). The positive correlation between the exposure time and tissue conductivity was observed in both two ablation areas (pSC?<?0.01, Spearman correlation). Conclusions: This ex vivo feasibility study demonstrates that current MREIT conductivity imaging can detect liver RF ablation lesions without using any contrast media or additional MR scan.     

Computer modeling of the effect of perfusion on heating patterns in radiofrequency tumor ablation

Purpose: To use an established computer simulation model of radiofrequency (RF) ablation to further characterize the effect of varied perfusion on RF heating for commonly used RF durations and electrode types, and different tumor sizes.

Methods: Computer simulation of RF heating using 2-D and 3-D finite element analysis (Etherm) was performed. Simulated RF application was systematically modeled on clinically relevant application parameters for a range of inner tumor perfusion (0–5?kg/m³-s) and outer normal surrounding tissue perfusion (0–5?kg/m³-s) for internally cooled 3-cm single and 2.5-cm cluster electrodes over a range of tumor diameters (2–5?cm), and RF application times (5–60?min; n?=?4618 simulations). Tissue heating patterns and the time required to heat the entire tumor?±?a 5-mm margin to >50°C were assessed. Three-dimensional surface response contours were generated, and linear and higher order curve-fitting was performed.

Results: For both electrodes, increasing overall tissue perfusion exponentially decreased the overall distance of the 50°C isotherm (R²?=?0.94). Simultaneously, increasing overall perfusion exponentially decreased the time required to achieve thermal equilibrium (R²?=?0.94). Furthermore, the relative effect of inner and outer perfusion varied with increasing tumor size. For smaller tumors (2?cm diameter, 3-cm single; 2–3?cm diameter, cluster), the ability and time to achieve tumor ablation was largely determined by the outer tissue perfusion value. However, for larger tumors (4–5?cm diameter single; 5?cm diameter cluster), inner tumor perfusion had the predominant effect.

Conclusion: Computer modeling demonstrates that perfusion reduces both RF coagulation and the time to achieve thermal equilibrium. These results further show the importance of considering not only tumor perfusion, but also size (in addition to background tissue perfusion) when attempting to predict the effect of perfusion on RF heating and ablation times.     

Radiofrequency ablation: The effect of distance and baseline temperature on thermal dose required for coagulation

Purpose: To determine the effects of applied current, distance from an RF electrode and baseline tissue temperature upon thermal dosimetry requirements to induce coagulation in ex vivo bovine liver and in vivo porcine muscle models.

Materials and methods: RF ablation was performed in ex vivo liver at varying baseline temperatures–19–21°C (n = 114), 8–10°C (n = 27), and 27–28°C (n = 27)–using a 3-cm tip electrode and systematically varied current 400–1,300 mA, to achieve defined diameters of coagulation (20, 30 and 40 ± 2 mm), and in in vivo muscle (n = 18) to achieve 35 mm ± 2 mm of coagulation. Thermal dose required for coagulation was calculated as the area under the curve and cumulative equivalent minutes at 43°C.

Results: Thermal dose correlated with current in a negative exponential fashion for all three diameters of coagulation in ex vivo experiments (p < 0.001). The temperatures at the end of RF heating at the ablation margin were not reproducible, but varied 38°C–74.7°C, for 30 mm coagulation in ex vivo liver, and 59.8°C–68.4°C in the in vivo experiment. CEM₄₃ correlated with current as a family of positive exponential functions (r² = 0.76). However, a very wide range of CEM₄₃ values (on the order of 10¹⁵) was noted. Although baseline temperatures in the ex vivo experiment did not change required thermal dose, the relationships between end temperature at the ablation margin and RF current were statistically different (p < 0.001) as analysed at the 400 mA intercept.

Conclusions: In both models, thermal dosimetry required to achieve coagulation was not constant, but current and distance dependent. Hence, other formulas for thermal dose equivalence may be needed to predict conditions for thermal ablation.     

Fast conductivity imaging in magnetic resonance electrical impedance tomography (MREIT) for RF ablation monitoring

Purpose: This study shows the potential of magnetic resonance electrical impedance tomography (MREIT) as a non-invasive RF ablation monitoring technique.

Materials and methods: We prepared bovine muscle tissue with a pair of needle electrodes for RF ablation, a temperature sensor, and two pairs of surface electrodes for conductivity image reconstructions. We used the injected current non-linear encoding with multi-echo gradient recalled echo (ICNE-MGRE) pulse sequence in a series of MREIT scans for conductivity imaging. We acquired magnetic flux density data induced by externally injected currents, while suppressing other phase artefacts. We used an 8-channel RF head coil and 8 echoes to improve the signal-to-noise ratio (SNR) in measured magnetic flux density data. Using the measured data, we reconstructed a time series of 180 conductivity images at every 10.24?s during and after RF ablation.

Results: Tissue conductivity values in the lesion increased with temperature during RF ablation. After reaching 60?°C, a steep increase in tissue conductivity values occurred with relatively little temperature increase. After RF ablation, tissue conductivity values in the lesion decreased with temperature, but to values different from those before ablation due to permanent structural changes of tissue by RF ablation.

Conclusion: We could monitor temperature and also structural changes in tissue during RF ablation by producing spatio-temporal maps of tissue conductivity values using a fast MREIT conductivity imaging method. We expect that the new monitoring method could be used to estimate lesions during RF ablation and improve the efficacy of the treatment.     

Hepatic radiofrequency ablation at low frequencies preferentially heats tumour tissue

Purpose: Radiofrequency ablation is a clinically accepted treatment modality for liver cancer. There are significant differences in dielectric properties between normal and cancer tissue in the liver, which are particularly pronounced at frequencies below 100?kHz. This study performed computer simulations to determine whether radiofrequency (RF) ablation at lower frequencies than currently employed (450–500?kHz) can take advantage of this difference to preferentially deposit energy within the tumour.

Materials and methods: Finite Element Method computer models were created for a cooled needle electrode and a multi-tine RF electrode inserted into a 2?cm diameter tumour. RF ablation was simulated and current density as well as tissue temperature distribution determined. In vivo data were used on electrical conductivity of normal and cancer tissue in the models to simulate RF ablation in liver at the currently used frequency of 500?kHz and at 10?kHz.

Results: At 500?kHz there was little difference in RF current density and final tissue temperature between normal and cancer tissue. Due to the more pronounced differences in electrical conductivity at 10?kHz, cancer tissue was heated preferentially at this frequency. Depending on power control algorithm, this resulted in either higher intra-tumour temperatures or lower temperatures outside the tumour at 10?kHz compared to 500?kHz.

Conclusion: Radiofrequency ablation at lower frequencies than currently used may preferentially heat the tumour and preserve normal tissue. A targeted device for selective tumour destruction may be designed to make use of this principle.     

Microwave ablation of ex vivo bovine tissues using a dual slot antenna with a floating metallic sleeve

Purpose: To study the efficiency of a dual slot antenna with a floating metallic sleeve on the ablation of different ex vivo bovine tissues.

Materials and methods: COMSOL Multiphysics® version 4.4 (Stockholm, Sweden), which is based on finite element methods (FEM), was used to design and simulate monopole and dual slot with sleeve antennas. Power, specific absorption rate (SAR), temperature and necrosis distributions in the selected tissues were determined using these antennas. Monopole and dual slot with sleeve antennas were designed, simulated, constructed and applied in this study based on a semi-rigid coaxial cable. Ex vivo experiments were performed on liver, lung, muscle and heart of bovine obtained from a public animal slaughter house. The microwave energy was delivered using a 2.45?GHz solid-state microwave generator at 40 W for 3, 5 and 10?min. Aspect ratio, ablation length and ablation diameter were also determined on ablated tissues and compared with simulated results. Student’s t-test was used to compare the statistically significant difference between the performance of the two antennas.

Results: The dual slot antenna with sleeve produces localised microwave energy better than the monopole antenna in all ablated tissues using simulation and experimental validation methods. There were significant differences in ablation diameter and aspect ratio between the sleeve antenna and monopole antenna. Additionally, there were no significant differences between the simulation and experimental results.

Conclusions: This study demonstrated that the dual slot antenna with sleeve produced larger ablation zones and higher sphericity index in ex vivo bovine tissues with minimal backward heating when compared with the monopole antenna.     

Analysis of minimally invasive directional antennas for microwave tissue ablation

Abstract

Purpose: Microwave ablation (MWA) applicators capable of creating directional heating patterns offer the potential of simplifying treatment of targets in proximity to critical structures and avoiding the need for piercing the tumour volume. This work reports on improved directional MWA antennas with the objectives of minimising device diameter for percutaneous use (≤ ～13 gauge) and yielding larger ablation zones.

Methods: Two directional MWA antenna designs, with a modified monopole radiating element and spherical and parabolic reflectors are proposed. A 3D-coupled electromagnetic heat transfer with temperature-dependent material properties was implemented to characterise MWA at 40 and 77 W, for 5 and 10?min. Simulations were also used to assess antenna impedance matching within liver, kidney, lung, bone and brain tissue. The two antenna designs were fabricated and experimentally evaluated with ablations in ex vivo tissue at the two power levels and treatment durations (n?=?5 repetitions for each group).

Results: The computed specific absorption rate (SAR) patterns for both antennas were similar, although simulations indicated slightly greater forward penetration for the parabolic antenna. Based on simulations for antennas inserted within different tissues, the proposed antenna design appears to offer good impedance matching for a variety of tissue types. Experiments in ex vivo tissue showed radial ablation depths of 19?±?0.9?mm in the forward direction for the applicator with spherical reflector and 18.7?±?0.7?mm for the applicator with parabolic reflector.

Conclusion: These results suggest the applicator may be suitable for creating localised directional ablation zones for treating small and medium-sized targets with a percutaneous approach.     

The impact of frequency on the performance of microwave ablation

Abstract

Purpose: The use of higher frequencies in percutaneous microwave ablation (MWA) may offer compelling interstitial antenna design advantages over the 915?MHz and 2.45?GHz frequencies typically employed in current systems. To evaluate the impact of higher frequencies on ablation performance, we conducted a comprehensive computational and experimental study of microwave absorption and tissue heating as a function of frequency.

Methods: We performed electromagnetic and thermal simulations of MWA in ex vivo and in vivo porcine muscle at discrete frequencies in the 1.9–26?GHz range. Ex vivo ablation experiments were performed in the 1.9–18?GHz range. We tracked the size of the ablation zone across frequency for constant input power and ablation duration. Further, we conducted simulations to investigate antenna feed line heating as a function of frequency, input power, and cable diameter.

Results: As the frequency was increased from 1.9 to 26?GHz the resulting ablation zone dimensions decreased in the longitudinal direction while remaining relatively constant in the radial direction; thus at higher frequencies the overall ablation zone was more spherical. However, cable heating at higher frequencies became more problematic for smaller diameter cables at constant input power.

Conclusion: Comparably sized ablation zones are achievable well above 1.9?GHz, despite increasingly localised power absorption. Specific absorption rate alone does not accurately predict ablation performance, particularly at higher frequencies where thermal diffusion plays an important role. Cable heating due to ohmic losses at higher frequencies may be controlled through judicious choices of input power and cable diameter.     

Bipolar radiofrequency ablation with 2 × 2 electrodes as a building block for matrix radiofrequency ablation: Ex vivo liver experiments and finite element method modelling

Abstract

Purpose: Size and geometry of the ablation zone obtained by currently available radiofrequency (RF) electrodes is highly variable. Reliability might be improved by matrix radiofrequency ablation (MRFA), in which the whole tumour volume is contained within a cage of x?×?y parallel electrodes. The aim of this study was to optimise the smallest building block for matrix radiofrequency ablation: a recently developed bipolar 2?×?2 electrode system. Materials and methods: In ex vivo bovine liver, the parameters of the experimental set-up were changed one by one. In a second step, a finite element method (FEM) modelling of the experiment was performed to better understand the experimental findings. Results:The optimal power to obtain complete ablation in the shortest time was 50–60?W. Performing an ablation until impedance rise was superior to ablation for a fixed duration. Increasing electrode diameter improved completeness of ablation due to lower temperature along the electrodes. A chessboard pattern of electrode polarity was inferior to a row pattern due to an electric field void in between the electrodes. Variability of ablation size was limited. The FEM correctly simulated and explained the findings in ex vivo liver. Conclusions: These experiments and FEM modelling allowed a better insight in the factors influencing the ablation zone in a bipolar 2?×?2 electrode RF system. With optimal parameters, complete ablation was obtained quickly and with limited variability. This knowledge will be useful to build a larger system with x?×?y electrodes for MRFA.     

Temperature–density hysteresis in X-ray CT during HIFU thermal ablation: Heating and cooling phantom study

Purpose: This paper investigated the effects of thermal ablation treatment on imaged X-ray computed tomography (CT) Hounsfield units (HU), for the purpose of monitoring tissue denaturation and coagulation.

Materials and methods: Eight phantoms of water, oil, and chicken serum albumin as well as 15 ex vivo tissue samples were heated by applying high intensity focused ultrasound (HIFU) for 10 to 29?min to obtain denaturation temperatures, (i.e. >50?°C). X-ray CT scanning was performed simultaneously during heating and post-ablation cooling stages, and the HU at the focal zone were registered. The temperature profile versus time was also monitored under similar conditions using a thermocouple probe. The results were plotted and correlated as curves of HU versus temperature.

Results: In all specimens studied, HU values depicted an exponential curve as a function of temperature during the heating stage. However, linear behaviour was observed during the cool-down stage for both chicken serum albumin and ex vivo bovine liver. Thus, a hysteresis phenomenon occurred only when the thermal conditions induced irreversible changes in the sample with quantification demonstrating high correlation with the maximal temperature reached during treatment (R^2?>?0.9) for the chicken serum albumin.

Conclusions: Our results demonstrate a HU–temperature hysteresis phenomenon for HIFU ablation, which is detectible by X-ray CT. This hysteresis is related to the amount of heat induced into the tissue and could potentially indicate irreversible tissue damage. Accordingly, this measurable phenomenon can be utilised as a quantitative method for non-invasive monitoring of thermal ablation.     

Computer modeling of the effect of perfusion on heating patterns in radiofrequency tumor ablation.

PURPOSE: To use an established computer simulation model of radiofrequency (RF) ablation to further characterize the effect of varied perfusion on RF heating for commonly used RF durations and electrode types, and different tumor sizes. METHODS: Computer simulation of RF heating using 2-D and 3-D finite element analysis (Etherm) was performed. Simulated RF application was systematically modeled on clinically relevant application parameters for a range of inner tumor perfusion (0-5 kg/m3-s) and outer normal surrounding tissue perfusion (0-5 kg/m3-s) for internally cooled 3-cm single and 2.5-cm cluster electrodes over a range of tumor diameters (2-5 cm), and RF application times (5-60 min; n = 4618 simulations). Tissue heating patterns and the time required to heat the entire tumor +/- a 5-mm margin to > 50 degrees C were assessed. Three-dimensional surface response contours were generated, and linear and higher order curve-fitting was performed. RESULTS: For both electrodes, increasing overall tissue perfusion exponentially decreased the overall distance of the 50 degrees C isotherm (R2 = 0.94). Simultaneously, increasing overall perfusion exponentially decreased the time required to achieve thermal equilibrium (R2 = 0.94). Furthermore, the relative effect of inner and outer perfusion varied with increasing tumor size. For smaller tumors (2 cm diameter, 3-cm single; 2-3 cm diameter, cluster), the ability and time to achieve tumor ablation was largely determined by the outer tissue perfusion value. However, for larger tumors (4-5 cm diameter single; 5 cm diameter cluster), inner tumor perfusion had the predominant effect. CONCLUSION: Computer modeling demonstrates that perfusion reduces both RF coagulation and the time to achieve thermal equilibrium. These results further show the importance of considering not only tumor perfusion, but also size (in addition to background tissue perfusion) when attempting to predict the effect of perfusion on RF heating and ablation times.     

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers

Purpose: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models.

Materials and methods: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103?°C and 30?W for 3?min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days’ post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103?°C, at both 30?W and 60?W, for 30?min. Ablation diameters and volumes were measured by two examiners.

Results: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days’ post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30?W and 60?W (p?3 and 6.84 (SD?=?0.36) cm, respectively.

Conclusions: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.     

Mathematical spatio-temporal model of drug delivery from low temperature sensitive liposomes during radiofrequency tumour ablation

Purpose: Studies have demonstrated a synergistic effect between hyperthermia and chemotherapy, and clinical trials in image-guided drug delivery combine high-temperature thermal therapy (ablation) with chemotherapy agents released in the heating zone via low temperature sensitive liposomes (LTSL). The complex interplay between heat-based cancer treatments such as thermal ablation and chemotherapy may require computational models to identify the relationship between heat exposure and pharmacokinetics in order to optimise drug delivery.

Materials and methods: Spatio-temporal data on tissue temperature and perfusion from heat-transfer models of radiofrequency ablation were used as input data. A spatio-temporal multi-compartmental pharmacokinetic model was built to describe the release of doxorubicin (DOX) from LTSL into the tumour plasma space, and subsequent transport into the extracellular space, and the cells. Systemic plasma and tissue compartments were also included. We compared standard chemotherapy (free-DOX) to LTSL-DOX administered as bolus at a dose of 0.7 mg/kg body weight.

Results: Modelling LTSL-DOX treatment resulted in tumour tissue drug concentration of ～9.3 µg/g with highest values within 1 cm outside the ablation zone boundary. Free-DOX treatment produced comparably uniform tissue drug concentrations of ～3.0 µg/g. Administration of free-DOX resulted in a considerably higher peak level of drug concentration in the systemic plasma compartment (16.1 µg/g) compared to LTSL-DOX (4.4 µg/g). These results correlate well with a prior in vivo study.

Conclusions: Combination of LTSL-DOX with thermal ablation allows localised drug delivery with higher tumour tissue concentrations than conventional chemotherapy. Our model may facilitate drug delivery optimisation via investigation of the interplays among liposome properties, tumour perfusion, and heating regimen.     

Dual mode single agent thermochemical ablation by simultaneous release of heat energy and acid: Hydrolysis of electrophiles

Purpose: This study aimed to investigate two readily available electrophilic reagents, acetyl chloride (AcCl), and acetic anhydride (Ac₂O), for their potential in tissue ablation.

Materials and methods: Reagents were diluted in diglyme as solutions up to 8?mol/L and tested in a gel phantom with NaOH solutions and ex vivo in porcine liver. Temperature, pH, and volume measurements were obtained. Infrared and gross pathological images were obtained in bisected specimens immediately after injection.

Results: AcCl was much more reactive than Ac₂O and AcCl was therefore used in the tissue studies. Temperature increases of up to 37°C were noted in vitro and 30°C in ex vivo tissues using 4?mol/L AcCl solutions. Experiments at 8?mol/L were abandoned due to the extreme reactivity at this higher concentration. A change in pH of up to 4 log units was noted with 4?mol/L solutions of AcCl with slight recovery over time. Ablated volumes were consistently higher than injected volumes.

Conclusions: Reaction of electrophiles in tissues shows promise as a new thermochemical ablation technique by means of only a single reagent. Further studies in this area are warranted.     

RF tumour ablation: Computer simulation and mathematical modelling of the effects of electrical and thermal conductivity

This study determined the effects of thermal conductivity on RF ablation tissue heating using mathematical modelling and computer simulations of RF heating coupled to thermal transport. Computer simulation of the Bio-Heat equation coupled with temperature-dependent solutions for RF electric fields (ETherm) was used to generate temperature profiles 2?cm away from a 3?cm internally-cooled electrode. Multiple conditions of clinically relevant electrical conductivities (0.07–12?S?m^?1) and ‘tumour’ radius (5–30?mm) at a given background electrical conductivity (0.12?S?m^?1) were studied. Temperature response surfaces were plotted for six thermal conductivities, ranging from 0.3–2?W?m^?1?°C (the range of anticipated clinical and experimental systems). A temperature response surface was obtained for each thermal conductivity at 25 electrical conductivities and 17 radii (n?=?425 temperature data points). The simulated temperature response was fit to a mathematical model derived from prior phantom data. This mathematical model is of the form (T?=?a?+?bR^c exp^dR σ^?f exp^gσ) for RF generator-energy dependent situations and (T?=?h?+?k exp^mR?+?n?exp^pσ) for RF generator-current limited situations, where T is the temperature (°C) 2?cm from the electrode and a, b, c, d, f, g, h, k, m, n and p are fitting parameters. For each of the thermal conductivity temperature profiles generated, the mathematical model fit the response surface to an r² of 0.97–0.99. Parameters a, b, c, d, f, k and m were highly correlated to thermal conductivity (r²?=?0.96–0.99). The monotonic progression of fitting parameters permitted their mathematical expression using simple functions. Additionally, the effect of thermal conductivity simplified the above equation to the extent that g, h, n and p were found to be invariant. Thus, representation of the temperature response surface could be accurately expressed as a function of electrical conductivity, radius and thermal conductivity. As a result, the non-linear temperature response of RF induced heating can be adequately expressed mathematically as a function of electrical conductivity, radius and thermal conductivity. Hence, thermal conductivity accounts for some of the previously unexplained variance. Furthermore, the addition of this variable into the mathematical model substantially simplifies the equations and, as such, it is expected that this will permit improved prediction of RF ablation induced temperatures in clinical practice.     

Tissue shrinkage in microwave ablation of liver: an ex vivo predictive model

Abstract

Purpose: The aim of this study was to develop a predictive model of the shrinkage of liver tissues in microwave ablation.

Methods: Thirty-seven cuboid specimens of ex vivo bovine liver of size ranging from 2?cm to 8?cm were heated exploiting different techniques: 1) using a microwave oven (2.45?GHz) operated at 420 W, 500 W and 700 W for 8 to 20?min, achieving complete carbonisation of the specimens, 2) using a radiofrequency ablation apparatus (450?kHz) operated at 70 W for a time ranging from 6 to 7.5?min obtaining white coagulation of the specimens, and 3) using a microwave (2.45?GHz) ablation apparatus operated at 60 W for 10?min. Measurements of specimen dimensions, carbonised and coagulated regions were performed using a ruler with an accuracy of 1?mm. Based on the results of the first two experiments a predictive model for the contraction of liver tissue from microwave ablation was constructed and compared to the result of the third experiment.

Results: For carbonised tissue, a linear contraction of 31?±?6% was obtained independently of the heating source, power and operation time. Radiofrequency experiments determined that the average percentage linear contraction of white coagulated tissue was 12?±?5%. The average accuracy of our model was determined to be 3?mm (5%).

Conclusions: The proposed model allows the prediction of the shrinkage of liver tissues upon microwave ablation given the extension of the carbonised and coagulated zones. This may be useful in helping to predict whether sufficient tissue volume is ablated in clinical practice.     

The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo

Purpose: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA.

Materials and methods: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20?mm, energy input 40?kJ). A saline-perfused glass tube (‘vessel’) was placed parallel to the applicators in order to simulate a natural liver vessel. Five applicator-to-vessel geometries were tested. A liquid-filled glass tube without perfusion was used as a dry run. Ablations were orthogonally cut to the applicators at a defined height. Cooling effects were analysed qualitatively and quantitatively along these cross sectional areas.

Results: Thirty-six ablations were performed. A cooling effect could be seen in all ablations with perfused vessels compared to the dry run. While this cooling effect did not have any influence on the ablation areas (859–1072?mm² versus 958?mm² in the dry run, p?>?0.05), it had a distinctive impact on ablation shape. A vascular cooling effect could be observed in all ablations with perfusion directly around the vessel independent of the applicator position compared to the dry run (p?Conclusions: A vascular cooling effect occurred in all multipolar RFA with simulated liver vessels ex vivo independent of the applicator-to-vessel geometry. While the cooling effect did not influence the total ablation area, it had a distinctive impact on the ablation shape.     

Perivascular extension of microwave ablation zone: demonstrated using an ex vivo porcine perfusion liver model*

Microwave ablation (MWA) has been proposed to suffer less from the heat sink effect compared to radiofrequency ablation but has been reported to cause extension of the ablation zone along intrahepatic vessels in clinical practice. To study this effect in detail, eight fresh porcine livers were perfused in an ex vivo organ perfusion system. Livers were perfused with oxygenated, O-positive human blood at 37?°C. Perfusion was discontinued immediately before ablation in the non-perfused group (n?=?4) whilst in the perfused group (n?=?4) perfusion was maintained during MWA (140?W X 2?min). Large intrahepatic vessels (>?6?mm) were avoided using ultrasound. MWA zones were bisected within 30?min of perfusion termination and sections were fixed in formalin and stained with H&;E and NADH to assess cell viability. Magnetic resonance imaging (MRI) was performed on two livers (one perfused, one non-perfused) to provide imaging correlation before sectioning. Twenty-one out of a total of 30?MW ablation zones (70%) showed extension of the ablation zone along a vessel. There was no statistically significant difference (p?=?1) in the incidence of ablation zone extension between perfused (9/13, 69%) and non-perfused organs (12/17, 71%). MRI also demonstrated ablation zone extension along blood vessels correlating with macroscopy in two livers. NADH staining also confirmed extension of the ablation zone. Liver MWA appears to be commonly associated with propagated thermal injury along adjacent vessels and occurs independent of active blood flow. In order to avoid possible complications through non-target tissue injury, this effect requires further investigation.