Zhengjun Liu

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.

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.

Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation

Purpose. To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Methods. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0–5 kg/m3-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2–5 cm, and RF application times (6–20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m-°C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor ±a 5 mm margin to >50°C were assessed. Results. Increasing background tissue thermal conductivity increases the time required to achieve a 50°C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m-°C) surrounded by fat (0.23 W/m-°C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m-°C) took longer to achieve the 50°C isotherm, and complete ablation could not be achieved at higher inner/outer perfusions (>4 kg/m3-s). For varied electrical conductivities in the setting of varied perfusion, greatest RF heating occurred for inner electrical conductivities simulating injection of saline around the electrode with an outer electrical conductivity of soft tissue, and the least amount of heating occurring while simulating renal cell carcinoma in normal kidney. Characterization of these scenarios demonstrated the role of electrical and thermal conductivity interactions, with the greatest differences in effect seen in the 3–4 cm tumor range, as almost all 2 cm tumors and almost no 5 cm tumors could be treated. Conclusion. Optimal combinations of thermal and electrical conductivity can partially negate the effect of perfusion. For clinically relevant tumor sizes, thermal and electrical conductivity impact which tumors can be successfully ablated even in the setting of almost non-existent perfusion.

Radiofrequency Ablation: Effect of Pharmacologic Modulation of Hepatic and Renal Blood Flow on Coagulation Diameter in a VX2 Tumor Model

PURPOSE To determine whether pharmacologic agents can be used to modulate blood flow in hepatic and renal tumors sufficiently to alter the extent of radiofrequency (RF)-induced coagulation. MATERIALS AND METHODS VX2 tumors (8-15 mm) were implanted in the liver (n = 25) or kidney (n = 8) of 33 New Zealand White rabbits. RF was applied to tumors for 6 minutes with use of conventional electrodes (125 mA +/- 35; 90 degrees C +/- 2 degrees C tip temperature). In the hepatic model, blood flow was modulated with use of halothane, epinephrine, or arsenic trioxide (2-6 mg/kg). Laser Doppler flowmetry was used to quantify changes in hepatic blood flow. Correlation of blood flow with induced coagulation diameter was performed. RF ablation was then performed in a renal model with and without arsenic trioxide. RESULTS For liver tumors, halothane and arsenic trioxide reduced blood flow to 40.3% +/- 17.8% and 29% +/- 15% of normal, respectively, whereas epinephrine increased blood flow to 207.8% +/- 97.9%. Correlation of blood flow to coagulation diameter was demonstrated (R(2) = 0.40). Coagulation measured 7 mm +/- 1 with epinephrine, 10 mm +/- 1 with normal blood flow, 12 mm +/- 3 with halothane, and 13 mm +/- 3 with arsenic trioxide (P <.04 compared with controls). In the renal model, arsenic trioxide decreased blood flow (44% +/- 16%) and increased coagulation diameter (10.9 mm +/- 1) compared with controls (84% +/- 11% and 7.6 mm +/- 1; P <.01, both comparisons). CONCLUSIONS RF-induced coagulation necrosis in rabbit hepatic and renal tumors is affected by tumor blood flow. Pharmacologic modulation of tumor blood flow may provide a noninvasive way to decrease blood flow during thermally mediated ablation therapy, potentially enabling the creation of larger zones of coagulation necrosis.

Hybrid Radiofrequency and Cryoablation Device: Preliminary Results in an Animal Model

PURPOSE To determine whether the simultaneous application of combined bipolar radiofrequency (RF) ablation and cryoablation in a hybrid system produces larger ablation zones than RF or cryoablation alone. MATERIALS AND METHODS Multiple 15-minute ablations were performed in ex vivo bovine liver (n = 167) with a hybrid applicator system with RF ablation alone (0.3-0.7 A), cryoablation alone (3,500 psi, two freeze/thaw cycles), and combined RF/cryoablation (0.4-0.7 A, 1,000-3,500 psi) with use of a novel applicator consisting of two 2.5-cm active bipolar RF poles located on the same 18-gauge needle separated by two embedded cryoablation nozzles. Resultant coagulation diameters were compared with use of analysis of variance for more than three groups or Student t tests for two groups. Confirmation of the optimal parameters of combination RF/cryoablation was performed by reassessing a range of argon pressure (1,000-3,500 psi) and RF current (0.4-0.7 A) in in vivo porcine liver (n = 36). Arrays of two to four RF/cryoablation applicators were also assessed in ex vivo (n = 54) and in vivo (n = 12) liver. RESULTS In ex vivo liver, simultaneous RF/cryoablation (0.6 A, 3,000 psi) produced 3.6 cm +/- 0.4 of short-axis coagulation. This was significantly larger than that achieved with optimal RF alone or cryoablation alone (1.5 cm +/- 0.3 and 1.6 cm +/- 0.3, respectively; F = 95; P < .01). The coagulation diameter with simultaneous combination RF/cryoablation was related in parabolic fashion to argon pressure and current with a multivariate r(2) of 0.68. For in vivo liver, optimal combination RF/cryoablation achieved 3.3 cm +/- 0.2 of coagulation, which was significantly larger than that achieved with RF alone (1.1 cm +/- 0.1; P < .01) or cryoablation alone (1.1 cm +/- 0.1 and 1.3 cm +/- 0.1; F = 203; P < .01). The greatest contiguous coagulation was achieved with multiple-applicator arrays. For ex vivo liver, short-axis coagulation measured 5.3 cm +/- 0.1, 6.4 cm +/- 0.1, and 7.6 cm +/- 0.1 for two-, three-, and four-applicator arrays, respectively. For in vivo liver, two-, three-, and four-applicator arrays produced 5.1 cm +/- 0.2, 5.8 cm +/- 0.5, and 7.0 cm +/- 0.5 of confluent coagulation, respectively. CONCLUSION Simultaneous combination RF and cryoablation with use of a novel applicator design yielded significantly larger zones of coagulation than either modality alone. The large ablation diameters achieved warrant further investigation of the device.

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 + bRc expdR σ f expgσ) for RF generator-energy dependent situations and (T = h + k expmR + n exppσ) 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.

Image-guided Percutaneous Chemical and Radiofrequency Tumor Ablation in an Animal Model

PURPOSE To determine whether combining acetic acid instillation before radiofrequency (RF) ablation can improve local tissue electrical conductivity, RF energy deposition, intratumoral heating, and tumor necrosis in a large animal model. MATERIALS AND METHODS Multiple hypovascular canine venereal sarcomas were implanted in 11 mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to 4.2 cm +/- 0.6 in diameter. Treatment strategies included 10% and 15% acetic acid diluted in distilled water, 10% and 15% acetic acid diluted in saturated NaCl solution, 50% acetic acid, and 100% ethanol, with 6 mL of each injected alone or in combination with RF ablation (internally cooled, 1-cm tip; 12 minutes). Two additional control groups were studied in which tumors received either RF alone or distilled water injected alone. Comparisons were also made with groups treated with 36% NaCl with and without RF ablation. Resultant coagulation for these ablative strategies, along with local temperatures and RF parameters such as impedance, current, and power, were compared. RESULTS Increasing coagulation was observed with increasing acetic acid concentrations (1.7 cm +/- 0.4, 2.8 cm +/- 0.6, and 3.5 cm +/- 0.3 for 10%, 15%, and 50% acetic acid alone, respectively; P <.01). The combination of RF ablation with acetic acid resulted in greater coagulation than with either therapy alone (P <.05). However, maximum heating and coagulation were observed with 10% acetic acid diluted in NaCl, with which the entire tumor (diameter, 4.5 cm +/- 0.4) was completely ablated in every case. This was equivalent to results for tumors treated with 36% NaCl combined with RF. RF with a 50% acetic acid concentration resulted in coagulation measuring only 3.7 cm +/- 0.3 (P <.01). Significantly greater RF heating (89.7 degrees C +/- 12.3 at 10 mm) was observed when the tumors were pretreated with 10% or 15% acetic acid in saturated NaCl, compared with 67.9 degrees C +/- 13.7 observed when acetic acid was diluted in water (P <.02). RF combined with ethanol produced less coagulation (2.8 cm +/- 0.3) than combinations with acetic acid because rapid and irreversible impedance increases were observed. CONCLUSION Addition of acetic acid injections to RF ablation substantially increases tumor destruction compared with RF or injection therapy alone. However, lower acetic acid concentrations in saturated NaCl produced greater tumor coagulation, suggesting that, in this hypovascular tumor model, alterations in electrical conductivity play a more important role in increasing tumor ablation efficiency than do the additional ablative effects of acetic acid.

Chemical tumor ablation with use of a novel multiple-tine infusion system in a canine sarcoma model.

PURPOSE To determine whether larger confluent zones of ablation can be achieved in chemical ablation with use of a multiple-tine infusion device compared with standard needle infusion in a solid tumor model. MATERIALS AND METHODS Multiple canine venereal sarcomas (N=42) were implanted in nine mildly immunosuppressed dogs (treated with 10 mg/kg cyclosporin A twice daily). Tumors incubated for 8-12 weeks grew to a diameter of 5.4 cm+/-1.0. With ultrasound guidance, 8-56 mL of 100% ethanol or 15% acetic acid (diluted in saturated saline solution) were injected in aliquots (2-8 mL) at multiple distances (radius of 0-2 cm) from the needle axis with use of a multiple-tine infusion device. Presence of fluid reflux at the needle puncture site and resultant coagulation diameters were measured within 1 hour and compared with the results of infusion with a standard 18-gauge needle. RESULTS Multiple-tine infusion enabled greater fluid infusion (15 mL+/-3 to 53 mL+/-3 depending on protocol) than standard needle injection (8 mL+/-1) before reflux was observed at the puncture site (P<.01). Additionally, progressive gains in contiguous tumor coagulation were achieved because acetic acid was infused as far as 2 cm from the needle axis with the multiple-tine device (P<.01; R(2)=0.59; y=0.5x+2.9). Optimal coagulation was achieved with the infusion of 4-mL aliquots at 0.5 cm and 1.0 cm from the needle, followed by three 4-mL or 8-mL aliquots (40 degrees rotation between infusions) at 1.5 cm and 2.0 cm from the needle (32 mL+/-0 and 53 mL+/-3 total, respectively). This yielded confluent short-axis coagulation diameters of 4.9 cm+/-1.0 and 5.4 cm+/-1.0, respectively, which were significantly greater than the measurement of 3.1 cm+/-0.4 achieved with standard needle infusion (P<.01). Smaller and noncontiguous foci of coagulation foci (1.7 cm+- 0.5) were seen with the use of ethanol for standard needle and multiple-tine infusions. CONCLUSIONS Chemical ablation with 15% acetic acid with use of a multiple-tine infusion device resulted in larger diameters of contiguous tumor coagulation and enabled greater volumes of infusion than standard needle infusion or ethanol ablation. This suggests that chemical ablation with acetic acid infused with use of a multiple-tine device may overcome some of the difficulties seen with the use of conventional needle chemical ablation injection alone, such as irregular ablation and fluid reflux up the needle tract.

Micromachined Electrical Conductivity Probe for RF Ablation of Tumors

RF ablation is an important technique in cancer treatment. It has been proposed that the effective area treated via RF ablation can be increased by increasing the local electrical conductivity. This is achieved by injection of NaCl solution into the tissue. For an accurate and effective RF ablation treatment using this new method, it is necessary to measure the local electrical conductivity, which varies spatially due to diffusion of sodium chloride. In this paper, we propose a micro probe to measure the local tissue electrical conductivity. The probe consists of two in-plane miniature electrodes separated by a small gap. When the electrodes are in contact with the tissue, the electrical resistance across them can be used to calculate the electrical conductivity. The probe is fabricated by standard photolithography techniques. The substrate material is polyimide and the electrodes are made of gold. A four-electrode probe is used to calibrate the new electrical conductivity micro probe using different concentrations of saline water. The resistance measurements are carried out using an impedance analyzer on different frequencies. The frequency of choice for RF ablation of tumors is 500k Hz and is the one selected for calibration and testing. The micro-probe calibration is then verified by measuring electrical conductivity of a phantom and comparing it with the result measured by the four-electrode probe. Finally, some in vivo tests are performed and the results are compared with literate data.Copyright

Computer Modeling of Factors that Affect the Minimum Safety Distance Required for Radiofrequency Ablation Near Adjacent Nontarget Structures

PURPOSE To use computer modeling of radiofrequency (RF) ablation to evaluate the effects of (i) composition and varying perfusion of intervening tissue and (ii) electrode orientation and type on the required distance to avoid heating damage of adjacent nontarget structures. MATERIALS AND METHODS Systematic three-dimensional finite-element computer simulation of RF heating (6-20 minutes) was performed (3,128 simulations). The distance (5-25 mm) between the electrode and the potentially injured structure and tissue composition as layers of tumor/soft tissue, fat, and/or fluid was varied (thermal conductivity, 0.46, 0.23, and 0.7 W/m- degrees C; electrical conductivity, 0.5, 0.1, and 1 S/m, respectively). Varying perfusion (0-5 kg/m(3)-s), electrode orientation (parallel or perpendicular), and electrode type (ie, noncooled and internally cooled 3-cm single or 2.5-cm cluster) were also studied. The time required to reach various temperatures (eg, the time to reach 50 degrees C designated as t50) and the distances at which the temperatures occurred and the distances required to avoid threshold temperatures at the margin of adjacent structures were compared. RESULTS In all cases, increasing the amount of intervening fat increased t50 compared with tumor/soft tissue and/or fluid. With no perfusion, 9 mm of fat or 14 mm of tumor/soft tissue or fluid was required for perpendicular insertion (internally cooled single electrode) to prevent a temperature of 50 degrees C with 12 minutes of heating, compared with 12 mm of fat or 23 mm of tumor/soft tissue or fluid for parallel insertion. Less intervening fat was needed for noncooled electrodes (<8 mm parallel, <5 mm perpendicular), with more intervening tissue required for cluster electrodes (>13 mm) for an RF application of 20 minutes. Finally, the amount of intervening tissue required to prevent damage also decreased linearly with increasing perfusion for each tissue and electrode (r(2) = 0.74 for parallel; r(2) = 0.98 for perpendicular). CONCLUSIONS In the computer model described in the present study, thermal and perfusion characteristics between the electrode and adjacent nontarget structures (specifically the presence of fat) and the electrode characteristics themselves (including parallel versus perpendicular insertion) have been shown to affect the minimum safe distance required for the prevention of thermal injury.