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.     

Radiofrequency ablation: modeling the enhanced temperature response to adjuvant NaCl pretreatment

PURPOSE: To characterize the effects of volume and concentration of adjuvant NaCl pretreatment on radiofrequency (RF) ablation and to model these results to determine their applicability to in vivo systems. MATERIALS AND METHODS: Standardized 1-L 5% agar phantoms were constructed with central wells of varying volume that were filled with a protein-based polymer gel of varying NaCl concentration (0%-35%). RF ablation to the maximum system current output (2000 mA) was applied to internally cooled 2-cm electrodes placed in the center of the gel wells. Remote thermometry was performed 20 mm from the electrode. Temperatures generated within the phantom were then used to model the response surface by using regression analysis. The generated model was then applied to previously published in vivo data to determine its applicability to a porcine liver tissue model. Statistical analyses included one-way analysis of variance to compare the temperatures reached with different NaCl concentrations and volumes with those reached without NaCl. In addition, modeled functions were evaluated for goodness of fit and the statistical significance of their coefficients. RESULTS: NaCl volume and concentration had significant effects on RF-generated heating of the agar phantoms. The mean maximum temperature, 91.4 degree C +/- 0.8 (SD), was reached with 3.5 mL of 10% NaCl gel. This was significantly higher than the mean temperature reached in phantoms containing 0% NaCl gel, 40.3 degree C +/- 4.9 (P <.001). Heat increases to the maximum temperature correlated strongly with the deposited RF energy, with maximum temperatures limited by the current output of the RF generator. The response surface was defined by a generator energy-dependent region and a generator current-limited region, which were best modeled by a modified gamma-variate function and an exponential function, respectively (r2 = 0.92). This model correlated well with previously published in vivo data (r2 = 0.86). CONCLUSION: Modulation of electrical conductivity has different effects on RF ablation response that are dependent on generator capabilities and the volume and concentration of NaCl pretreatment.     

Improved coagulation with saline solution pretreatment during radiofrequency tumor ablation in a canine model

PURPOSE: To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS: Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS: Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS: Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.     

Influence of NaCl Concentrations on Coagulation,Temperature, and Electrical Conductivity Using a Perfusion Radiofrequency Ablation System: An Ex Vivo Experimental Study

Purpose To determine, by means of an ex vivo study, the effect of different NaCl concentrations on the extent of coagulation obtained during radiofrequency (RF) ablation performed using a digitally controlled perfusion device. Method Twenty-eight RF ablations were performed with 40 W for 10 min using continuous NaCl infusion in fresh excised bovine liver. For perfusion, NaCl concentrations ranging from 0 (demineralized water) to 25% were used. Temperature, the amount of energy, and the dimensions of thermal-induced white coagulation were assessed for each ablation. These parameters were compared using the nonparametric Mann-Whitney test. Correlations were calculated according to the Spearman test. Results RF ablation performed with 0.9% to 25% concentrations of NaCl produced a mean volume of coagulation of 30.7 ± 3.8 cm³, with a mean short-axis diameter of 3.6 ± 0.2 cm. The mean amount of energy was 21,895 ± 1,674 W and the mean temperature was 85.4 ± 12.8°C. Volume of coagulation, short-axis diameter, and amount of energy did not differ significantly among NaCl concentrations (p > 0.5). A correlation was found between the NaCl concentration and the short-axis diameter of coagulation (r = 0.64) and between the NaCl concentration and the mean temperature (r = 0.67), but not between the NaCl concentration and volume of coagulation. Conclusion In an ex vivo model, continuous perfusion with high NaCl concentrations does not significantly improve the volume of thermal-induced coagulation. This may be because the use of a low-power generator cannot sufficiently exploit the potential advantage of better tissue conductivity provided by NaCl perfusion.     

Comparison of Wet Radiofrequency Ablation with Dry Radiofrequency Ablation and Radiofrequency Ablation Using Hypertonic Saline Preinjection: Ex Vivo Bovine Liver

Objective

We wished to compare the in-vitro efficiency of wet radiofrequency (RF) ablation with the efficiency of dry RF ablation and RF ablation with preinjection of NaCl solutions using excised bovine liver.

Materials and Methods

Radiofrequency was applied to excised bovine livers in a monopolar mode for 10 minutes using a 200 W generator and a perfused-cooled electrode with or without injection or slow infusion of NaCl solutions. After placing the perfused-cooled electrode in the explanted liver, 50 ablation zones were created with five different regimens: group A; standard dry RF ablation, group B; RF ablation with 11 mL of 5% NaCl solution preinjection, group C; RF ablation with infusion of 11 mL of 5% NaCl solution at a rate of 1 mL/min, group D; RFA with 6 mL of 36% NaCl solution preinjection, group E; RF ablation with infusion of 6 mL of 36% NaCl solution at a rate of 0.5 mL/min. In groups C and E, infusion of the NaCl solutions was started 1 min before RF ablation and then maintained during RF ablation (wet RF ablation). During RF ablation, we measured the tissue temperature at 15 mm from the electrode. The dimensions of the ablation zones and changes in impedance, current and liver temperature during RF ablation were then compared between the groups.

Results

With injection or infusion of NaCl solutions, the mean initial tissue impedance prior to RF ablation was significantly less in groups B, C, D, and E (43-75 Ω) than for group A (80 Ω) (p < 0.05). During RF ablation, the tissue impedance was well controlled in groups C and E, but it was often rapidly increased to more than 200 Ω in groups A and B. In group D, the impedance was well controlled in six of ten trials but it was increased in four trials (40%) 7 min after starting RF ablation. As consequences, the mean current was higher for groups C, D, and E than for the other groups: 401 ± 145 mA in group A, 287 ± 32 mA in group B, 1907 ± 96 mA in group C, 1649 ± 514 mA in group D, and 1968 ± 108 mA in group E (p < 0.05). In addition, the volumes of RF-induced coagulation necrosis were greater in groups C and E than in group D, which was greater than in groups A and B than in group E (p < 0.05); 14.3 ± 3.0 cm³ in group A; 12.4 ± 3.8 cm³ in group B; 80.9 ± 9.9 cm³ in group C; 45.3 ± 11.3 cm³ in group D and 81.6 ± 8.6 cm³ in group E. The tissue temperature measured at 15 mm from the electrode was higher in groups C, D and E than other groups (p < 0.05): 53 ± 12℃ in group A, 42 ± 2℃ in group B, 93 ± 8℃ in group C; 79 ± 12℃ in group D and 83 ± 8℃ in group E.

Conclusion

Wet RF ablation with 5% or 36% NaCl solutions shows better efficiency in creating a large ablation zone than does dry RF ablation or RF ablation with preinjection of NaCl solutions.     

Radiofrequency ablation of the porcine liver in vivo: increased coagulation with an internally cooled perfusion electrode

RATIONALE AND OBJECTIVES: A major limitation of radiofrequency (RF) ablation is its inability to produce a large enough diameter of coagulation necrosis to encompass hepatic tumors with an appropriate ablative margin at a single RF application. We evaluated the in vivo efficiency of RF ablation (RFA) using an internally cooled perfusion (ICP) electrode with hypertonic saline infusion to induce coagulation necrosis compared with that of RFA using single needle electrode types. MATERIALS AND METHODS: RF was applied to a porcine liver in monopolar mode using a 200 W generator and an internally cooled electrode (group A) or an ICP electrode (group B) at 200 W for 12 minutes or using a 60 W generator with a perfusion electrode at 40 W for 20 minutes (group C). In total, 36 (3 x 12) ablation zones were created using the three different regimens. In group B, 14.6% NaCl solution was infused at 1 mL/minute and in group C, 0.9% NaCl solution was infused at 1.5 mL/minute. The three groups were compared in terms of amount of delivered RF energy and dimensions and the coefficients of variation of the ablation zones. RESULTS: The mean energies applied in the three groups were 52.3 +/- 10.3 kJ for group A, 115.4 +/- 10.5 kJ for group B, and 38.5 +/- 11.5 kJ for group C, respectively (P < .05). The mean ablation volumes in groups A, B and C were 13.1 +/- 4.7 cm3 in group A, 43.7 +/- 17.5 cm3 in group B, and 26.3 +/- 20.2 cm3 in group C, respectively (P < .05). In addition, the coefficients of variation of the volumes of the ablation zones in groups A, B, and C were 0.36, 0.4, and 0.78, respectively. CONCLUSIONS: RFA using the ICP electrode showed better performance in terms of creating a larger ablation zone than RFA using an internally cooled or a perfusion electrode.     

Radiofrequency tumor ablation: insight into improved efficacy using computer modeling

OBJECTIVE: To use computer modeling of the Bio-Heat equation to demonstrate factors influencing RF ablation tissue heating. CONCLUSION: Computer modeling demonstrates the importance of energy deposition, tumor and background tissue electrical and thermal conductivity, and perfusion on RF ablation outcomes.     

Radiofrequency ablation in pig lungs: in vivo comparison of internally cooled, perfusion and multitined expandable electrodes

The purpose of this study was to compare the amounts of in vivo coagulation obtained by radiofrequency (RF) ablation in porcine lung, using three types of electrodes. 15 in vivo ablation procedures were performed in the lungs of five pigs using three kinds of currently available RF devices under CT guidance. After placing an electrode in the lung, three ablation zones were created at each of three different regimens: Group A: RF ablation with an internally cooled electrode; Group B: RF ablation with a perfusion electrode, with instillation of 0.9% NaCl solution at a rate of 1.5 ml min(-1); Group C: RF ablation with a multitined expandable electrode. According to the manufacturer's recommendations, RF application times were 12 min in group A and 20 min in group B. In group C, RF energy was delivered for 7 min after a mean temperature of 110 degrees C was reached at 5 cm deployment. 36 min after the procedures, contrast-enhanced CT scans were obtained to evaluate the volume of zone of coagulation, and lungs were harvested for gross measurements. After macroscopic and histopathological analyses of 5 mm-thick lung sections, diameters, volumes and variation coefficients of regions of central coagulation were assessed. During RF ablation, the perfusion electrode allowed a larger energy delivery than the internally cooled or the multitined expandable electrodes, i.e. 33.6+/-4.7 kJ in group A, 40.0+/-8.2 kJ in group B and 23.5+/-6.1 kJ in group C (p<0.05). On gross observation, the cut surface of the gross specimen containing RF-induced coagulation showed that the ablated tissue appeared to be a central, firm, dark-brown area surrounded by an irregular outer margin (approximately 3-10 mm thick) of bright red tissue. In vivo studies showed that RF ablation using the perfusion electrode achieved larger coagulation volume than RF ablation using the other electrodes (p<0.05): 7.2+/-4.1 cm3 in group A; 16.9+/-5.5 cm3 in group B; 7.5+/-3.3 cm3 in group C. The corresponding variation coefficients were 0.55, 0.31, and 0.45, respectively. Our study shows that RF ablation using a perfusion electrode achieves a larger coagulation volume with an irregular margin than RF ablation using internally cooled or multitined expandable electrodes in the porcine lung.     

Effects of vascular perfusion on coagulation size in radiofrequency ablation of ex vivo perfused bovine livers

OBJECTIVES: A standardized perfused ex vivo bovine liver model was used to evaluate the effect of organ perfusion on coagulation size and energy deposition during radiofrequency ablation (RFA) procedures. MATERIALS AND METHODS: Bovine livers were perfused in a tank after rinsing the prepared liver vessels with anticoagulants. Tyrode's solution, oxygenated and heated to 36.5 degrees C, was used as perfusion medium. A flow and pressure controlled pump regulated Portal vein circulation; a dialysis machine provided pulsatile arterial circulation. Impedance-guided radiofrequency ablations were performed with 4-cm LeVeen electrodes with and without underlying liver perfusion. Two-dimensional diameters (Dv, Dh) of each ablation area were measured after dissecting the livers. RESULTS: In 4 bovine livers weighing 8.85 +/- 0.83 kg per organ (min, 7.7 kg; max, 9.7 kg) altogether 40 RF ablations were performed. A total of 20 ablations were generated with underlying liver perfusion (group 1) and 20 ablations with no liver perfusion (group 2). In group 1, Dv was 28.4 +/- 5.3 mm, Dh 38.6 +/- 7.8 mm, and energy deposition 36.9 +/- 18.0 kJ. The 20 ablation areas generated without liver perfusion displayed statistically significant differences, with Dv being 35.7 +/- 6.5 mm (P = 0.001), Dh 49.5 +/- 9.4 mm (P = 0.001), and energy deposition 25.5 +/- 13.0 kJ (P = 0.018). CONCLUSION: The model reproduced the cooling effect of perfused tissue during RFA. The ablation areas produced under perfusion conditions had smaller diameters despite longer exposure times and higher energy deposition.     

Radio-frequency thermal ablation with hypertonic saline solution injection of the lung: ex vivo and in vivo feasibility studies

The aim of this study was to assess the effects of simultaneous instillation of NaCl solutions during radio-frequency ablation (RFA) on the dimension of the ablated lesion in ex vivo bovine lung tissue and in vivo rabbit lung tissue. The RFA was induced in ex vivo bovine lung tissue which was inflated with room air and in vivo rabbit lung tissue by a 500-kHz RF generator and a 17-G cooled-tip electrode. In in vivo experiments, RFA was performed using CT guidance. The RF energy was applied for 5 min with or without instillation of 0.9 or 36% NaCl solutions. The changes in tissue impedance, current, power output, and temperature of the electrode tip were automatically measured. The maximum diameter of all thermal lesions was measured perpendicular to the electrode axis by two observers. In an ex vivo study, the mean lesion diameters using 36 and 0.9% NaCl solutions were larger than those of the control group: 51±8, 34±6, and 5±2 mm (p<0. 05). In in vivo rabbit lung tissue, the mean lesion diameter with NaCl solution (15.3±3.1 mm) was larger than that of the lesion without NaCl solution (8.5±1.4 mm; p<0.05). With instillation of NaCl solutions, a marked decrease of tissue impedance (>100 Ω) and corresponding increase of current flow occurred in both ex vivo and in vivo studies. This experimental study demonstrates that RF ablation with simultaneous NaCl solution infusion of the lung is more effective in achieving coagulation necrosis than conventional RFA procedure.     

Combined Radiofrequency Ablation and Acetic Acid Hypertonic Saline Solution Instillation: An In Vivo Study of Rabbit Liver

Objective

We wanted to determine whether combined radiofrequency ablation (RFA) and acetic acid-hypertonic saline solution (AHS) instillation can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. We also wished to determine the optimal concentration of the solution in order to maximize its effect on extent of the RFA-induced coagulation.

Materials and Methods

Forty thermal ablation zones were produced in 40 rabbits by using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound guidance. The rabbits were assigned to one of four groups: group A: RFA alone (n=10); group B: RFA with 50% AHS instillation (n=10); group C: RFA with 25% AHS instillation (n=10); group D: RFA with 15% AHS instillation (n=10). A range of acetic acid concentrations diluted in 36% NaCl to a total volume of 1 mL were instilled into the liver before RFA. The RF energy (30 W) was applied for three minutes. After RFA, in each group, the maximum diameters of the thermal ablation zones in the gross specimens were compared. Technical success and the complications that arose were evaluated by CT and on the basis of autopsy findings.

Results

All procedures are technically successful. There were six procedure-related complications (6/40; 15%): two localized perihepatic hematomas and four chemical peritonitis. The incidence of chemical peritonitis was highest for group B with the 50% AHS solution instillation (30%). With instillation of 15% AHS solution, a marked decrease of tissue impedance (24.5 ± 15.6 Ω) and an increase of current (250 mA) occurred as compared to RFA alone. With instillation of the solutions before RFA (group B, C and D), this produced a greater mean diameter of coagulation necrosis than the diameters for rabbits not instilled with the solution (group A) (p < 0.05). However, there was no significant difference between group B, C, and D.

Conclusion

Combined AHS instillation and RFA can increase the dimension of coagulation necrosis in the liver with a single application. A low concentration of AHS (15%) showed similar effects in increasing the extent of RF-induced coagulation, but there were less side effects as compared to the high concentration of AHS.     

Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model

PURPOSE: To determine the effect of surrounding tissue type on coagulation necrosis from radiofrequency (RF) ablation in a homogeneous animal tumor model. MATERIALS AND METHODS: Thirty canine venereal sarcomas were implanted in three tissue sites (subcutaneous, kidney, and lung) in 13 mildly immunosuppressed dogs. Five of 25 tumors, which were 19 mm +/- 3 (mean +/- SD) in diameter, were allocated to each of five groups: (a) subcutaneous tumors, (b) kidney tumors, (c) lung tumors with blood flow, and (d) subcutaneous and (e) renal tumors without blood flow, which was achieved by sacrificing the animal to eliminate tumor perfusion. A sixth group comprised larger subcutaneous tumors (mean diameter, 46 mm +/- 4) that were also treated. RF ablation was performed with a 1-cm tip and 5 minutes of ablation at 90 degrees C +/- 1. Impedance, temperature, and resultant coagulation diameter were recorded and compared. Data were analyzed statistically, including one-way analysis of variance to determine the effect of tissue conductivity (ie, systemic impedance) on necrosis size and tissue temperatures. Linear regression analysis was used to compare changes in impedance between the control and experimental groups. RESULTS: Increasing linear correlation was observed between tumor coagulation diameter and overall baseline system impedance (R(2) = 0.65). RF ablation of lung tumors resulted in the greatest coagulation diameter (13.0 mm +/- 3.5) compared with that in the other groups (P <.01). The smallest coagulation diameter was observed in kidney tumors in the presence of blood flow (7.3 mm +/- 0.6) compared with that in the other groups (P <.01). Elimination of blood flow in kidney tumors increased coagulation diameter to 10.3 mm +/- 0.6 (P <.01). After RF ablation, coagulation diameter in the subcutaneous tumor groups was the same (mean, 9.8 mm +/- 1.0) (difference not significant), regardless of tumor size or presence of blood flow. CONCLUSION: The characteristics of tissue that surrounds tumor, including vascularity and electric conductivity, affect ablation outcome. Predominance of tissue-specific characteristics will likely result in site-specific differences in RF-induced coagulation necrosis.     

Dynamic intrahepatic flow and cellular alterations during radiofrequency ablation of liver tissue in mice

PURPOSE: The purpose of this study was to identify microvascular and other associated changes that occur in the liver during focal heating with monopolar radiofrequency (RF). MATERIALS AND METHODS: Intravital video microscopy was performed on exteriorized transilluminated livers of 15 live mice during RF-induced heating of liver parenchyma. Microvascular flow parameters, flow reversibility, microbubble formation, phagocytic activity, and endothelial permeability were recorded throughout a range of tip temperatures (40 degrees C-95 degrees C). RESULTS: During RF application, five discrete zones extended outward from the electrode surface: (i) tissue coagulation, (ii) cellular edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v) normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm) vessels occurred at tip temperatures below 50 degrees C. This zone of stasis corresponded to the hyperemic zone on histologic analysis. Although alterations in permeability and phagocytic activity were first identified at 43 degrees C, tip temperatures higher than 55 degrees C always produced local endothelial leakiness to carbon microparticles at the periphery and always inhibited phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble formation occurred with bubbles ultimately tracking through necrotic tissue into patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of coagulation. CONCLUSION: Although coagulation occurs at tip temperatures higher than 50 degrees C, RF heating induced reversible microvascular stasis at temperatures lower than 50 degrees C. Increased sinusoidal endothelial permeability occurs at near-coagulative temperatures. Therefore, targeted endovascular microparticle delivery through this leaky endothelium may provide an additional and complimentary adjunct for RF ablation therapy.     

Ex Vivo Experiment of Saline-Enhanced Hepatic Bipolar Radiofrequency Ablation with a Perfused Needle Electrode: Comparison with Conventional Monopolar and Simultaneous Monopolar Modes

The purpose of this study was to validate the saline-enhanced bipolar radiofrequency ablation (RFA) technique using a perfused electrode to increase RF-created coagulation necrosis, to compare that technique with monopolar RFAs and to find appropriate concentrations and volumes of perfused NaCl solution for the bipolar RFA. A total of 90 ablations were performed in explanted bovine livers. In the initial experiments to determine appropriate conditions for bipolar RFA, we created five thermal ablation zones in each condition, with instillations of varied concentrations (0.9–36%) or injection rates (30 mL/hr–120 mL/hr) of NaCl solution. After placement of one or two 16-gauge open-perfused electrodes into bovine livers, the NaCl solution was instilled into the tissue through the electrode. In the second part of the study, 10 ablation zones were created using one or two perfused electrodes for each of five groups under different conditions: a conventional monopolar mode with 0.9% NaCl solution (group A) or with 6% NaCl solution (group B), a simultaneous monopolar mode with 6% NaCl solution (group C) and a bipolar mode with 6% NaCl solution (groups D and E). RF was applied to each electrode for 20 min in groups A, B, C, and E, or for 10 min in group D. During RFA, we measured the tissue temperature 15 mm from the electrode. The temperature changes during the RFA and the dimensions of the ablation zones were compared among the groups. Bipolar RFA created larger short-axis diameters of coagulation necrosis with 6% NaCl solution (35.8 ± 15 mm) than with 0.9% NaCl solution (17 ± 9.7 mm) (P < 0.05). However, concentrations of NaCl solution above 6% did not further increase the extent of coagulation necrosis. In addition, bipolar RFA with 6% NaCl solution instillation at a rate of 1.0 mL/min (37.9 ± 5.4 mm) or 2.0 mL/min (35.6 ± 9.3 mm) produced larger diameters at the mid-point between the electrodes of the ablated lesion than did 0.5 mL/min (25.8 ± 9.3 mm) (P < 0.05). The bipolar mode showed a more rapid increase in temperature at the mid-point between the two probes, up to 60°C, than did the monopolar modes (P < 0.05). In addition, the bipolar RFA (group E) treated for 20 min showed a larger value of the short-axis diameter than did the conventional or simultaneous monopolar modes (P < 0.05), and bipolar RFA (group D) treated for 10 min, showed similar results with conventional monopolar modes treated for 20 min (P > 0.05): 31.0 ± 5.4 mm (group A); 28.8 ± 3.8 mm (group B); 25.5 ± 6.4 mm (group C); 32.6 ± 4.2 mm (group D); 49.4 ± 5.0 mm (group E). Bipolar RFA with instillation of 6% NaCl solution through an open perfusion system demonstrates better efficacy in creating a larger ablation zone than does conventional or simultaneous monopolar modes at the various times examined. Therefore, hypertonic saline-enhanced bipolar RFA seems to be a promising approach for treating larger liver tumors.     

Combination radiofrequency ablation with intratumoral liposomal doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types in animals

PURPOSE: To determine whether use of radiofrequency (RF) ablation combined with intravenously (IV) administered liposomal doxorubicin, as compared with use of RF ablation or doxorubicin alone, facilitates increased tissue coagulation and interstitial drug accumulation in animal models. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. In experiment 1, multiple canine sarcomas were implanted in seven mildly immunosuppressed dogs and grown to a mean diameter of 4.8 cm. Tumors were assigned to three treatment groups: internally cooled RF ablation (12 minutes, 2000-mA pulsed technique) followed by IV liposomal doxorubicin (10 mg per animal) (n = 6), RF ablation alone (n = 6), and liposomal doxorubicin alone (n = 4). In experiment 2, the livers and kidneys of 10 rabbits and the thigh muscles of 10 rats were randomly assigned to one of two treatment groups: conventional RF ablation (90 degrees C +/- 2, 5 minutes) followed by IV liposomal doxorubicin (5 mg per rabbit, 1 mg per rat) or RF ablation alone (n = 5, each). Coagulation diameter and interstitial doxorubicin concentration (tissues were homogenized in acid alcohol, with doxorubicin extracted for 24 hours at 5 degrees C and quantified with fluorimetry) were measured 48 hours after treatment and compared. Multivariate analysis of variance and subsequent pairwise t tests (alpha = .05, two-tailed test) were performed. RESULTS: Data are means +/- standard errors of the mean. A larger diameter of tumor destruction was observed in canine sarcomas treated with RF ablation-liposomal doxorubicin (3.7 cm +/- 0.6) compared with that in tumors treated with RF ablation (2.3 cm +/- 0.1) or liposomal doxorubicin (0.0 cm +/- 0.0) alone (P < .01). A new finding was a completely necrotic red zone (1.6 cm +/- 0.7) surrounding the central RF ablation-induced white coagulation zone. Greater but nonuniform drug uptake was observed particularly in this red zone (77.0 ng/g +/- 18.2) compared with uptake in the central zone (15.1 ng/g +/- 3.2), peripheral area of untreated tumor (38.9 ng/g +/- 8.0), and tumors treated with liposomal doxorubicin alone (43.9 ng/g +/- 6.7 for all regions) (P < .01 for all individual comparisons). In experiment 2, use of combined therapy led to increased coagulation in all tissues (liver: 17.6 mm +/- 3.1, P = .03; kidney: 11.0 mm +/- 3.1, P = .03; muscle: 13.1 mm +/- 1.3, P < .01) compared with use of RF ablation alone (liver, 13.4 mm +/- 1.5; kidney, 7.9 mm +/- 0.7; muscle, 8.6 mm +/- 0.5). Combined therapy, as compared with liposomal doxorubicin therapy alone, was also associated with increased doxorubicin accumulation in liver, kidney, and muscle (1.56 microg/g +/- 0.34, 4.36 microg/g +/- 1.78, and 3.63 microg/g +/- 1.43, respectively, vs 1.00 microg/g +/- 0.18, 1.23 microg/g +/- 0.32, and 0.87 microg/g +/- 0.53, respectively) (P < or = .01 for all individual comparisons). CONCLUSION: Use of RF ablation combined with liposomal doxorubicin facilitates increased tissue coagulation and interstitial doxorubicin accumulation in multiple tissues and tumor types and may be useful for treatment of large tumors and achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors.     

Placement of a Sodium Hyaluronate Solution onto the Liver Surface as a Supportive Procedure for Radiofrequency Ablation of Hepatocellular Carcinomas Located on the Liver Surface: A Preliminary Report

PurposeTo evaluate safety and efficacy of the placement of sodium hyaluronate solution onto the liver surface as a supportive procedure for radiofrequency (RF) ablation of hepatocellular carcinomas (HCCs) located on the liver surface as a possible alternative to RF ablation via laparoscopic approach or with the creation of artificial ascites.Materials and MethodsChanges in temperature of a sodium hyaluronate layer placed onto an egg white were measured during coagulation of the egg white by an RF ablation needle. A phase I study was performed to evaluate the safety of intraperitoneal injection of a maximum of 20 mL of sodium hyaluronate solution into humans by observing for the occurrence of intraperitoneal inflammation and adhesion. After these studies, RF ablation with ultrasound-guided injection of sodium hyaluronate onto the liver surface was performed, targeting 28 HCC nodules located on the liver surface. Treatment outcomes and complications of this procedure were investigated.ResultsIn the in vitro experiment, the maximum temperature of sodium hyaluronate solution was 41°C during RF ablation. No intraperitoneal inflammation or adhesions were observed after intraperitoneal injection of sodium hyaluronate in the phase I study. HCC was completely ablated with sufficient margins after one session of RF ablation, without any burn injuries to the abdominal wall or adjacent organs. Local recurrence was observed in one of 28 patients (3.6%) during 30.1 months of follow-up.ConclusionsRF ablation can be safely and effectively performed on HCCs located close to the liver surface with placement of sodium hyaluronate onto the liver surface, thereby preventing burn injuries to abdominal wall or adjacent organs.     

Percutaneous radiofrequency tissue ablation: optimization of pulsed-radiofrequency technique to increase coagulation necrosis.

PURPOSE: To develop a computerized algorithm for pulsed, high-current percutaneous radiofrequency (RF) ablation, which maximally increases the extent of induced coagulation necrosis. MATERIALS AND METHODS: An automated, programmable algorithm for pulsed-RF deposition was designed to permit high-current deposition by periodically reducing current for 5-30 seconds during RF application. Two strategies for pulsed-RF deposition were evaluated: (i) constant peak current (900-1,800 mA) of variable duration and (ii) variable peak current (1,200-2,000 mA) for a specified minimum duration. The extent of induced coagulation was compared to results obtained with continuous (lower current) RF application. Trials were performed in ex vivo calf liver (n = 115) and in vivo porcine liver (n = 30) and muscle (n = 18) with use of 2-4-cm tip, internally cooled electrodes. RESULTS: For 3-cm electrodes in ex vivo liver, applying pulsed-RF with constant peak current for 12 minutes produced 3.5 cm +/- 0.2 of necrosis. Greater necrosis was produced with use of the variable current strategy, in which 4.5 cm +/- 0.2 of coagulation was achieved with use of an initial current > or =1,500 mA (minimum peak-RF duration of 10 sec, with 15 sec of reduced current to 100 mA between peaks; P < .01). This variable peak current algorithm also produced 3.7 cm +/- 0.6 of necrosis in in vivo liver, and 6.5 cm +/- 0.9 in in vivo muscle. Without pulsing, a maximum of 750 mA, 1,100 mA, and 1,500 mA could be applied in ex vivo liver, in vivo liver, and in vivo muscle, respectively, which resulted in 2.9 cm +/- 0.2, 2.4 cm +/- 0.2, and 5.1 cm +/- 0.4 of coagulation (P < .05, all comparisons). CONCLUSIONS: A variable peak current algorithm for pulsed-RF deposition can increase coagulation necrosis diameter over other ablation strategies. This innovation may ultimately enable the percutaneous treatment of larger tumors.     

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.     

Bipolar saline-enhanced electrode for radiofrequency ablation: results of experimental study of in vivo porcine liver

PURPOSE: To evaluate whether a bipolar saline-enhanced radiofrequency (RF) ablation system embedded in one needle is able to consistently produce homogeneous and predictable areas of coagulation necrosis with or without the Pringle maneuver of vascular inflow occlusion. MATERIALS AND METHODS: RF ablation (480 kHz) of the liver was performed in 24 healthy pigs by means of laparotomy: group A (n = 5), 4-cm distance between electrodes 1 and 2; group B (n = 7), 4-cm distance and the Pringle maneuver; group C (n = 5), 2-cm distance; and group D (n = 7), 2-cm distance with the Pringle maneuver. Twenty percent NaCl solution was infused continuously at a rate of 100 mL/h via each electrode during the procedure. The pigs were followed up, and they were euthanized on the 7th day. Livers were removed for histologic assessment. Time, impedance, current, power output, specific voltage of the contacts, energy output, temperatures in the liver, volume of the lesion, and energy delivered per lesion volume were determined and compared among groups. Predictability of lesion volume was evaluated with the coefficient of variability. Mean values of the variables were compared among the groups by means of one-way analysis of variance or Kruskall-Wallis test. RESULTS: Impedance at the end of the RF ablation procedure was almost twofold lower than the corresponding initial value in all groups. In Pringle groups B and D, regular ellipsoids of coagulation necrosis were created (mean lesion volume, 149.50 cm3 +/- 34.26 and 69.43 cm3 +/- 15.48, respectively). In non-Pringle groups A and C, the shape of coagulation necrosis was influenced by the vessels encountered, and mean lesion size was lower than that in the Pringle groups (P <.01). The coefficient of variability of lesion size was lower in the Pringle groups (23% and 22%, respectively) than that in the non-Pringle groups (75% and 30%, respectively). CONCLUSION: The bipolar saline-enhanced RF ablation method produces homogeneous and predictable areas of coagulation necrosis between two electrodes, regardless of the distance between them, preferably with vascular inflow occlusion.     

MR-guided radiofrequency ablation in a 0.2-T open MR system: technical success and technique effectiveness in 100 liver tumors

PURPOSE: To evaluate the feasibility and technique effectiveness of magnetic resonance (MR)-guided radiofrequency (RF) ablation of hepatic malignancies. MATERIALS AND METHODS: In 64 patients, 100 primary (N = 19) or secondary (N = 81) liver tumors (mean diameter = 24.7 mm; range = 4-60 mm) were treated with 87 sessions of MR-guided RF ablation. The entire ablation procedure was carried out at an 0.2-T open MR system by using MR-compatible internally cooled electrodes. T2-weighted turbo spin echo sequences (TR/TE = 3500 msec/110 msec) were used to monitor thermally induced coagulation. Technique effectiveness was assessed four months after the last RF ablation by dynamic MR imaging at 1.5-T. RESULTS: MR-guided RF ablation procedures were technical successful in 85 of 87 (97.7%) assessed at the end of each session. Complete coagulation was intended in 99 of 100 tumors. Technique effectiveness was observed in 92 of 99 (92.9%) of these tumors. To achieve complete coagulation 82 of 92 (89.1%) tumors required a single session. T2-weighted sequences were accurate to monitor the extent of coagulation and were supportive to guide overlapping ablation. There were two of 87 (2.3%) major and seven of 87 (8.0%) minor complications. CONCLUSION: MR-guided RF ablation is a safe and effective therapy in the treatment of hepatic malignancies. MR imaging offers an accurate monitoring of thermally-induced coagulation, thus enabling complete tumor coagulation in a single session.