HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2423052039v1 242/3/743    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Solazzo, S. A. Articles by Goldberg, S. N. Search for Related Content PubMed PubMed Citation Articles by Solazzo, S. A. Articles by Goldberg, S. N.

High-Power Generator for Radiofrequency Ablation: Larger Electrodes and Pulsing Algorithms in Bovine ex Vivo and Porcine in Vivo Settings¹

¹ From the Laboratory for Minimally Invasive Tumor Therapy Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215. Received December 14, 2005; revision requested February 9, 2006; revision received April 25; accepted May 31; final version accepted July 5. Supported by grants from the National Cancer Institute, National Institutes of Health, Bethesda, Md (RO1-CA87992-01A1), and Valleylab, Boulder, Colo. Address correspondence to S.N.G. (e-mail: sgoldber{at}caregroup.harvard.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Purpose: To prospectively maximize the extent of tissue coagulation by using a high-power (1000-W, 4000-mA) radiofrequency (RF) generator to optimize pulsing algorithms.

Materials and Methods: The institutional animal care and use committee approved the use of the animal model in the in vivo portion of this study. RF ablations (n = 258) were performed in ex vivo bovine livers by using a 500-kHz high-power generator. Through internally cooled 3.0-cm single and 2.5- and 4.0-cm cluster electrodes, RF energy was applied for 12 minutes. For each electrode, simplex optimization was used to determine the pulsing algorithms to be used (ie, 5–50-second "on" [energy application] and 10–50-second "off" [cooling without RF heating] periods). Three-dimensional contour maps expressing the relationship between pulsing parameters and resultant coagulation were constructed. Then, 31 RF ablations were performed with optimal settings in vivo in porcine livers, and the results were compared with those obtained in control ablations performed by using a 2000-mA commercial generator. Finally, in 108 experiments, RF energy was applied in ex vivo livers for 6, 12, and 20 minutes with maximum current settings (1000–4000 mA) by using the optimal on and off settings for all three electrodes, and the results were analyzed with multivariate analysis of variance (MANOVA).

Results: For all three electrodes, a relationship between the on and off times during the pulsing cycle and the resultant coagulation was established (P < .01). With 3.0-cm single electrodes, maximum coagulation (mean, 5.2 cm ± 0.1 [standard deviation] ex vivo and 3.6 cm ± 0.2 in vivo) was achieved with pulse settings of 10–18 seconds on and 11–20 seconds off. With cluster electrodes, greater coagulation was achieved (mean, 6.5 cm ± 0.6 ex vivo and 3.9 cm ± 0.3 in vivo with 2.5-cm tip; 8.3 cm ± 0.3 ex vivo and 5.2 cm ± 0.8 in vivo with 4.0-cm tip) with optimal pulse settings. Thus, use of the high-power generator yielded substantially increased tissue coagulation in vivo compared with the coagulation achieved with the standard generator. MANOVA revealed that increased maximum current and RF ablation durations of up to 20 minutes were associated with greater coagulation, the size of which also varied according to electrode type (P < .01).

Conclusion: Markedly larger coagulation zones can be achieved with optimized high-power RF ablation. This may require longer pulsing intervals compared with those previously used.

© RSNA, 2007

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Use of image-guided radiofrequency (RF) tumor ablation has expanded to the treatment of a wide spectrum of focal tumors in the liver (1–3), kidneys (4), bone (5,6), breasts (7–9), and lungs (10,11). Yet, despite rapid adoption of this technique and success in treating small tumors, clinicians have been unable to consistently achieve the desired goal of complete and/or predictable ablation for many larger tumors (1,3).

Results of previous studies have shown that RF ablation outcomes may be improved with various methods, including increased energy deposition and pulsed energy delivery (12). Although greater energy deposition enables increases in coagulation size (12), the technologic limitations of clinically available generators (with output no greater than 200 W) have thus far precluded the generation of RF currents sufficient to create volumes of ablation large enough to cover 3–5-cm-diameter tumors and the recommended 5–10-mm ablative margin during a single application of energy. This limitation is particularly apparent in vivo, where perfusion-mediated tissue cooling has been shown to dramatically limit the induction of coagulation (13). The use of progressive strategies, such as rapid RF application switching technology between multiple simultaneously applied electrodes, has increased the volumes of coagulation achieved in single ablation sessions (14–16). Nevertheless, these strategies require multiple electrode insertions. Furthermore, the electrode-switching technique is often underpowered to an even greater degree with existing generators (14–16). To overcome these limitations, a generator capable of depositing greater power (1000 W) and a stronger current (4000 mA) to achieve a larger area of ablation was recently developed. However, this generator had not been evaluated in formal optimization studies.

Given that energy deposition and heating in the area of an RF electrode decrease dramatically at relatively short distances from the electrode, various pulsing algorithms have been used to optimize RF energy applications and the resultant coagulation (12). Prior work with a single internally cooled electrode on a 2000-mA generator has revealed that such pulsing enables deeper tissue heating owing to the relationship between the period of high energy application (the "on" time during a pulsing cycle), during which tissues away from the electrode are heated, and the cooling period (the "off" time) that prevents tissue boiling near the electrode (12). However, to our knowledge, the optimization of cluster electrodes had never been reported on and the use of neither single nor cluster electrodes with the high-power generator had been systematically studied further to determine whether or not the pulsing algorithm designed for lower currents and smaller electrodes is appropriate, specifically for these technologic advances. Thus, the purpose of our study was to prospectively maximize the extent of created tissue coagulation by using a high-power (1000-W, 4000-mA) RF generator to optimize pulsing algorithms.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Support for this study was provided by Valleylab (Boulder, Colo), specifically with respect to high-power generator design, RF electrodes, and research support. The authors, all of whom are employees of Beth Israel Deaconess Medical Center, Harvard Medical School, had complete and independent control of study design, study data, and manuscript preparation (without any input from Valleylab). Since the completion of the study, the corresponding author (S.N.G.) has joined the medical advisory board of Valleylab.

Experimental Methods and Design
This study was divided into three phases. In phase one, the effects of high-current (2001–4000-mA) RF ablation were initially studied in ex vivo livers (258 ablations) by using 3.0-cm single electrodes, 2.5- and 4.0-cm cluster electrodes, and a generator (ART; Valleylab) capable of producing 1000 W (maximum, 4000 mA) of energy. A simplex optimization program (Multi-simplex 2.1; Grabitech, Sundsvall, Sweden) was used to select the two other pulsing parameters (ie, the minimum "on" and absolute "off" times) (Fig 1). Results for each electrode were mapped individually on separate three-dimensional surface responses (ie, contour maps), with the x-axis depicting the on time, the y-axis depicting the off time, and the z-axis depicting the average coagulation diameter. In phase two, involving 31 ablations, RF energy was applied at optimal settings to in vivo porcine livers by using the high-power generator (ART). As a control for the in vivo experiments, RF ablation was also performed by using a 2000-mA commercial generator (model CC-1; Valleylab). In phase three, RF ablation was applied in ex vivo livers for three lengths of time (6, 12, and 20 minutes) at three maximum current settings (2500, 3000, or 4000 mA, depending on electrode type) by using the optimal on and off settings from the first experiments involving all three tested electrodes (three experiments for each data point, for a total of 108 experiments).

View larger version (11K): [in this window] [in a new window] [Download PPT slide]   Figure 1: Schematic representation of RF pulsing algorithm. Current graphed over time demonstrates the application of RF energy with use of a pulsed algorithm. Region A denotes the period of energy application (on time), and region B denotes the cooling period (off time) that serves to prevent tissue boiling near the electrode. The successive on periods exhibit a programmed 100-mA current decrement when the on time is too short. For this particular example, a specified current of 2000 mA was programmed with a designated on time of 10 seconds. After the third pulse (A), the generator was unable to remain at maximum current for the specified on time owing to rapidly induced impedance rises. Thus, after the designated cooling time of 15 seconds (B), a current 100 mA below the maximum set current was applied to continue energy application and prevent tissue charring.

Animal Model
Institutional animal care and use committee approval was obtained for use of the animal model used in the in vivo portion of this study. RF ablation was performed in vivo by using a porcine liver model. Seven Yorkshire pigs (Parsons, Hadley, Mass) weighing 80–100 kg were used to ensure that the livers used were large and similar to human livers. RF ablation was performed with the high-power generator and/or the commercial generator in the same animal in a randomized fashion. Three to five ablations (total of 31) were performed in each animal, depending on the animal's size. The animals were anesthetized with 2% isoflurane, and their skin was shaved and cleaned for grounding pad placement. The liver was exposed by means of laparotomy, and ultrasonography was used to place the electrode so as to avoid puncturing large vessels. The circuit was completed by placing four 18.5 x 10.5-cm grounding pads (Valleylab) firmly on the animal's inner and outer thighs.

RF Energy Application
Ex vivo experiments.—RF energy was applied to the ex vivo bovine livers (S.A.S., 3 years RF experience). A 500-kHz monopolar RF generator (ART) capable of delivering 4000 mA and 1000 W was used. The RF energy was applied through internally cooled 17-gauge single (3.0-cm active tip length) and cluster (2.5- and 4.0-cm active tips) electrodes (Valleylab). The 3.0-cm single and 2.5-cm cluster electrodes were chosen because they are commercially available and are used in clinical settings (17,18). The 4.0-cm cluster electrode was chosen to determine whether longer electrodes, as compared with clinically available electrodes, could produce larger ablative zones at high power. RF energy was applied for 12 minutes, and electrode tip temperatures were maintained at 10°–15°C during RF application by perfusing the electrode with 0°C water.

In vivo experiments.—A total of 31 in vivo experiments were performed. First, RF energy was applied (A.U.H., 3 years RF experience) for 12 minutes by using the high-power generator (ART) (18 ablations) and the same three electrodes (4.0- and 2.5-cm cluster electrodes, 3.0-cm single electrode). RF energy was applied by using the pulse settings (ie, on and off times) that were in the respective optimal ranges for each electrode, as determined in the ex vivo experiments. RF ablation trials were performed at the maximum current that could be applied without causing uncontrollable rises in impedance.

RF ablations (n = 10) were also performed by using the 500-kHz monopolar RF generator (CC-1), which is capable of delivering 2000 mA into a 50- load. This second generator was chosen for comparison because it is the only generator currently available in the clinical setting for use with internally cooled electrodes (ie, it is the predicate device). The extent of coagulation achieved with these ablations was compared with the extent of coagulation achieved by using the high-power generator at the determined optimal settings.

Further experiments were performed by using the 4.0-cm cluster electrode and the high-power generator at a lower current of 3000 mA, both while the animal was alive and postmortem (three ablations, additional pair-matched trials in the same animals). These latter parameters were chosen to determine the effects of reduced current and directly assess the effects of perfusion-mediated tissue cooling on ablation outcome.

RF Pulsing Parameters
Ex vivo experiments.—To prevent rapid tissue boiling or charring, the initial RF current was ramped at 67 mA/sec to the 2500-, 3000-, and 4000-mA current limits for the 3.0-cm single, 2.5-cm cluster, and 4.0-cm cluster electrodes, respectively. These current increases required 37 seconds (2500 mA, 3.0-cm single electrode), 45 seconds (3000 mA, 2.5-cm cluster electrode), and 60 seconds (4000 mA, 4.0-cm cluster electrode) of total initial ramp time. The on period of energy application ranged from 5 to 50 seconds, and the off period of cooling without RF heating ranged from 10 to 50 seconds. The pulsing algorithm used was based on the triggering of the on and off periods of energy application to impedance rises and was similar to previously published algorithms (12). Thus, RF energy was applied at the specified maximum current until the impedance rose owing to tissue boiling. Once the impedance rises by 10 from the baseline measurement, the computer software on the generator senses the rise in impedance and shuts off the generator for the specified off period. If a specified on time could not be met without a rise in impedance, then by a programmed response, the generator reduced the current by 100 mA to enable a longer and more effective period of RF energy deposition (Fig 1). RF properties, including power, impedance, current, and voltage, were recorded every millisecond by the generator's inherent data-monitoring system.

In vivo experiments.—Settings were chosen according to the surface responses generated from the ex vivo experiments and in the zone of optimal ablation parameters. The conditions used to operate the high-power generator were modified slightly to enable a successful transition to the in vivo experiments. Namely, the current ramp used in vivo was doubled to 134 mA/sec to ensure that the maximum current was achieved in 30 seconds. The ex vivo ramp setting of 67 mA/sec was too slow for the in vivo environment, as impedance rises prevented the generator from reaching the maximum current. In addition, within the optimal setting zone for the on and off times, parameters with shorter off times were selected in an attempt to minimize overcooling of the tissue due to a prolonged off time.

Simplex Approach
For each electrode, the simplex optimization program (Multi-simplex 2.1) was used to determine the optimal pulsing algorithms (ie, on period of energy application and off period of cooling without RF heating). Lobo et al (19) previously used this simplex approach to determine the surface response contour for RF coagulation and electrical conductivity by using altered NaCl volumes and concentrations. A small-step variable-size sequential simplex design was used. The first three points (k + 1) chosen to construct the initial surface response were selected on the basis of the programmed algorithm (10 seconds on, 15 seconds off) of the commercial generator. The simplex program used this original value as a base point to calculate three points on opposing regions of the three-dimensional scale. The program then compared coagulation diameters obtained at the calculated points with those achieved at the original setting to calculate successive iterations and thus determine future points that would gradually reveal the optimal algorithmic value. Each simplex-formulated parameter was run in triplicate. Iterations were repeated until no significant difference was seen for three consecutive iterations.

Statistical Analyses
For the ex vivo experiments, RF ablations were sectioned perpendicularly to the electrode and calipers were used to measure coagulation diameter. A metal stylus was placed in the electrode track to note the angle at which the ablative zone was positioned after removal of the electrode from the liver. Multiple tissue sections were obtained to identify electrode tracks and ensure optimal measurement. The average diameter of a section was calculated by averaging the diameters measured at two observations. Resultant coagulation diameters, expressed as means ± standard deviations, were measured and used with Dataplot graphing software (DPlot, Vicksburg, Miss) to construct three-dimensional contour maps (ie, surface responses) that expressed the relationship between pulsing parameters and resultant coagulation. Three separate surface responses were created (by S.A.S.).

For the in vivo experiments, RF ablative zones were harvested and sectioned parallel to the electrode, and the short and long axes of each ablative zone were measured in consensus by two observers (S.A.S., A.U.H.). Electrode orientation was documented prior to the procedure; thus, the axis orientation was taken into account during gross analysis. In addition, multiple sections were taken (S.A.S., A.U.H.). By using multivariate analysis of variance, we compared the short-axis diameters of each ablative zone among the ablation parameter groups. Multivariate analysis of variance performed with SAS software (SAS Institute, Cary, NC) was used for analysis of RF energy applied with different maximum currents and for different durations to determine the effects of these variables on ablation outcome (S.A.S., S.N.G.). Groups were compared (Table 1) and significance (P < .05) was established by using a two-tailed t test.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

View larger version (42K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Effects of varying on times (x-axis values, in centimeters) and off times of RF application on coagulation size achieved with 2.5-cm cluster electrode. (a) Two-dimensional and (b) three-dimensional surface responses for the 2.5-cm cluster electrode demonstrate that coagulation diameters of 4.0–6.0 cm can be achieved, depending on the combination of on and off times selected. The 2.5-cm cluster electrode exhibits an optimal "ridge" at an on time range of 23–35 seconds and an off time range of 28–38 seconds. Use of this electrode yielded a mean maximum coagulation diameter of 6.5 cm ± 0.6 at pulse settings of 33 seconds on and 38 seconds off at 3000 mA.

View larger version (44K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Effects of varying on times (x-axis values, in centimeters) and off times of RF application on coagulation size achieved with 2.5-cm cluster electrode. (a) Two-dimensional and (b) three-dimensional surface responses for the 2.5-cm cluster electrode demonstrate that coagulation diameters of 4.0–6.0 cm can be achieved, depending on the combination of on and off times selected. The 2.5-cm cluster electrode exhibits an optimal "ridge" at an on time range of 23–35 seconds and an off time range of 28–38 seconds. Use of this electrode yielded a mean maximum coagulation diameter of 6.5 cm ± 0.6 at pulse settings of 33 seconds on and 38 seconds off at 3000 mA.

View larger version (18K): [in this window] [in a new window] [Download PPT slide]   Figure 3: Effects of varying on and off times of RF application on the coagulation (radius denoted by color scale at right, in centimeters) achieved by using 4.0-cm cluster electrode. The surface response for this electrode demonstrates a zone of maximum coagulation comparable to that achieved with the 2.5-cm cluster electrode. The zone of maximum coagulation achieved with the 4.0-cm cluster electrode corresponds to an on time range of 21–27 seconds and an off time range of 22–31 seconds. Notably, this electrode produced drastically larger coagulation diameters, generating a mean maximum coagulation diameter of 8.3 cm ± 0.3 with pulse settings of 24 seconds on and 25 seconds off at 4000 mA.

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 4: Effects of varying on and off times of RF application on the coagulation (radius denoted by color scale at right, in centimeters) achieved by using 3.0-cm single electrode. The surface response for this electrode exhibits a ridge structure similar to that seen for the 2.5- and 4.0-cm cluster electrodes. Smaller zones of coagulation were achieved. The zone of maximum coagulation corresponds to an on time range of 10–18 seconds and an off time range of 11–20 seconds. The 3.0-cm single electrode yielded a mean maximum coagulation diameter of 5.2 cm ± 0.1 with pulse settings of 15 seconds on and 16 seconds off at 2500 mA.

With the 4.0-cm cluster electrode, the high-power generator produced considerably larger zones of ablation than did the commercial generator. High-power generator applications of RF energy with the 4.0-cm cluster electrode at 4000 mA produced a mean coagulation diameter of 5.2 cm ± 0.8 compared with the mean coagulation diameter of 3.3 cm ± 1.0 created at 2000 mA with the commercial generator (P < .05). RF ablations performed with the high-power generator at the lower current of 3000 mA produced a mean coagulation diameter of 5.0 cm ± 0.7. This was not statistically different from the diameter produced with RF energy application at 4000 mA (P > .05). Postmortem RF ablation with the high-power generator at 3000 mA yielded larger coagulation diameters (mean, 6.2 cm ± 0.4) than did premortem in vivo RF ablation but smaller diameters than did ex vivo ablation at 4000 mA (P < .03 for both comparisons).

No significant difference between the high-power and commercial generators was seen when the 2.5-cm cluster electrode was used. In vivo trials yielded mean coagulation diameters of 3.8 cm ± 0.1 with use of the high-power generator and 3.7 cm ± 0.3 with use of the commercial generator (P = .82).

Use of the high-power generator with the 3.0-cm single electrode at 2000 mA also yielded larger ablative zones than did use of the commercial generator. Use of the 3.0-cm single electrode with the high-power generator, which was able to generate 2000 mA of power, resulted in a mean RF ablative zone size of 3.6 cm ± 0.2. Compared with use of the high-power generator, use of the commercial generator in conjunction with the 3.0-cm single electrode yielded a mean ablative zone size of 2.6 cm ± 0.4 (P < .05), as 1606 mA ± 104 was actually delivered.

Effect of Duration on ex Vivo RF Application
RF ablation was performed in ex vivo livers by using standardized optimal on and off times, as determined in phase one with three different electrodes (3.0-cm single, 2.5- and 4.0-cm cluster) at different current-limited settings. Substantial increases in coagulation diameter were observed with increasing RF duration (6, 12, and 20 minutes) with all electrode sizes at all current levels (P < .05 for all comparisons) (Table 2).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

Previous studies have revealed the utility of pulsed energy algorithms in increasing the tissue heating at RF ablation and other thermal ablative strategies (12). Goldberg et al (12) achieved substantial increases in tissue coagulation and decreases in system impedance in ex vivo and in vivo experiments by using a pulsed algorithm with 15-second on and off times. These changes are the basis for the pulsed algorithm currently used in some 2000-mA-maximum clinically available generators. The results of our study demonstrate that pulsing algorithms and the duration of pulsing, particularly with an electrode of large surface area, substantially influence ablative zone diameter and tissue heating. The results also show that a fairly narrow ridge of pulsing cycle parameters is required to achieve optimal coagulation. We attribute this coupling of on and off times to the need for a balance between heat application (on time) and cooling (off time). Our surface responses also clearly demonstrate that large applications of heat followed by insufficient cooling times or applications of heat followed by cooling times that are too short result in smaller ablative zone sizes.

Our results show that pulsing parameters, most notably the optimal on and off times during the pulsing cycle for higher currents, probably should be of longer duration than those currently used. We found optimal "on" and "off" times of 15 and 16 seconds for the 3.0-cm single electrode and of 33 and 38 seconds for the 2.5-cm cluster electrodes compared with currently used times of 10 and 15 seconds. Greater degrees of heating near the electrode from the higher RF current output probably require greater degrees of tissue cooling during an extended off period. Yet, too short of an on time (especially with a long off time) will lead to excessive tissue cooling and thus a reduced extent of coagulation.

In our study, optimal on and off periods of heating were found to be specific to each electrode. Specifically, longer on and off times were noted with larger and cluster electrodes, whereas the on and off times—and resultant tissue coagulation—for the more conventional 3.0-cm internally cooled electrode were similar (15 seconds) to the optimized settings reported by Goldberg et al for the same electrode with use of a lower power RF generator (12). These findings suggest that the maximum RF generator output, which is reflected in the optimal on and off times, and overall tissue coagulation are in part functions of the current density of the electrode and that increasing RF generator output probably requires the development of electrodes that have correspondingly increased current density. Regardless of these factors, these results underscore the importance of confirming optimal pulse settings for different devices and possibly different tissue types.

Our results with single electrodes in vivo confirm that tissues cannot tolerate a current density above a certain maximum. In addition, the maximum current tolerated is likely to be tissue specific: We observed differences in tolerance, particularly with the smallest electrode tested (3.0-cm single), even between tissues as similar as in vivo porcine (2000-mA maximum) and ex vivo bovine (2500-mA maximum) livers. Elucidation of the factors that account for these differences requires further study, but these factors probably include differences in temperature, blood flow, and thermal and possibly electrical conductivity.

Our results of substantial ex vivo increases in coagulation in contrast to more limited gains in coagulation in vivo confirm that at higher RF energy applications, perfusion-mediated tissue cooling continues to restrict tissue coagulation in in vivo settings. This cooling effect is well documented in experimental animal studies and in multiple clinical settings (1,20–24). Our findings suggest that tissue blood flow will likely be of continued importance, even at higher RF energy input levels. Interestingly, the ablation diameters achieved by using the 2.5-cm cluster electrode in vivo with the high-power generator were similar or only slightly larger than those achieved by using the commercial generator. This result is attributed to currently available commercial electrodes having already been optimized for lower power and/or the extent of the negative effect of blood flow. Overall, the results suggest that a larger electrode is probably needed to gain the advantages of using a high-output generator.

Although the use of high currents for RF ablation has advantages, caution is in order, as the use of increased currents is not without increased risk. The use of 4000 mA in vivo was associated with deleterious effects: We observed burns to the bowel in two cases. It is likely that this high current was sufficient to alter the electrical field at the tissue interface with air and cause a local rise in temperature (ie, the "edge effect") sufficient to induce burning (25). Death was observed in another case, and the possibility of electrically induced arrhythmia cannot be excluded. Nevertheless, it is important to stress that no complications were observed in the five trials performed by using a 3000-mA or lower current. Use of 3000 mA with the 4.0-cm cluster electrode yielded a mean ablative zone size of 5.0 cm ± 0.7, similar to the size of the ablative zone produced at 4000 mA. Thus, at this time, we consider 3000 mA to be a safe upper limit for in vivo ablation while advocating additional studies to better characterize the potential hazards of using high-power generators.

The limitations of this study must be addressed. First, on the basis of our inability to measure coagulation in all three dimensions, we believe it is difficult to assess the true volume and ultimate shape of ablative zones that will be created in thicker tissues. Furthermore, the findings of this study reflect certain model-specific characteristics, and the outcomes in other more clinically relevant tumor models may differ. Therefore, extrapolation to other types of tissues and tumors should be performed with caution.

Practical application: Our results show that by using optimized pulsing algorithms for RF ablation with increased power and current in conjunction with increased electrode surface area, large ablation volumes may be attained, and that optimal pulsing algorithms are electrode specific. These findings highlight the potential use of high-power generators in the clinical setting for more effective and complete ablation of large-volume tumors.

	ADVANCES IN KNOWLEDGE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

• Pulsing algorithms and the duration of pulsing, particularly with an electrode of large surface area, substantially influence ablation diameter and tissue heating.
  
• Optimal on and off periods of heating were found to be specific to each electrode rather than to one general setting.
  
• A fairly narrow ridge of pulsing cycle parameters is required to achieve optimal coagulation.
  

	FOOTNOTES

 

Abbreviations: RF = radiofrequency

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantor of integrity of entire study, S.N.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, S.A.S., M.A., S.N.G.; experimental studies, S.A.S., M.A., Z.L., S.N.G.; statistical analysis, S.A.S., M.A., A.U.H., S.N.G.; and manuscript editing, all authors

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

1. Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000;214(3):761–768.[Abstract/Free Full Text]
2. Lencioni R, Cioni D, Bartolozzi C. Percutaneous radiofrequency thermal ablation of liver malignancies: techniques, indications, imaging findings, and clinical results. Abdom Imaging 2001;26(4):345–360.[CrossRef][Medline]
3. Solbiati L, Livraghi T, Goldberg SN, et al. Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 2001;221(1):159–166.[Abstract/Free Full Text]
4. Hines-Peralta A, Goldberg SN. Review of radiofrequency ablation for renal cell carcinoma. Clin Cancer Res 2004;10(18 pt 2):6328S–6334S.[Abstract/Free Full Text]
5. Callstrom MR, Charboneau JW, Goetz MP, Rubin J, Beres R, Regge D. Percutaneous CT/US-guided radiofrequency ablation of painful metastases involving bone: a multicenter international study [abstr]. Radiology 2002;225(P):163.
6. Rosenthal DI, Hornicek FJ, Wolfe MW, Jennings LC, Gebhardt MC, Mankin HJ. Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment. J Bone Joint Surg Am 1998;80(6):815–821.[Abstract/Free Full Text]
7. Lamuraglia M, Lassau N, Garbay JR, et al. Doppler US with perfusion software and contrast medium injection in the early evaluation of radiofrequency in breast cancer recurrences: a prospective phase II study. Eur J Radiol 2005;56(3):376–381.[CrossRef][Medline]
8. Agnese DM, Burak WE Jr. Ablative approaches to the minimally invasive treatment of breast cancer. Cancer J 2005;11(1):77–82.[Medline]
9. Huston TL, Simmons RM. Ablative therapies for the treatment of malignant diseases of the breast. Am J Surg 2005;189(6):694–701.[CrossRef][Medline]
10. Simon CJ, Dupuy DE. Current role of image-guided ablative therapies in lung cancer. Expert Rev Anticancer Ther 2005;5(4):657–666.[CrossRef][Medline]
11. Bojarski JD, Dupuy DE, Mayo-Smith WW. CT imaging findings of pulmonary neoplasms after treatment with radiofrequency ablation: results in 32 tumors. AJR Am J Roentgenol 2005;185(2):466–471.[Abstract/Free Full Text]
12. Goldberg SN, Stein MC, Gazelle GS, Sheiman RG, Kruskal JB, Clouse ME. Percutaneous radiofrequency tissue ablation: optimization of pulsed-RF technique to increase coagulation necrosis. J Vasc Interv Radiol 1999;10(7):907–916.[Medline]
13. Nahum Goldberg S, Dupuy DE. Image-guided radiofrequency tumor ablation: challenges and opportunities—part I. J Vasc Interv Radiol 2001;12(9):1021–1032.[Medline]
14. Lee FT Jr, Haemmerich D, Wright AS, Mahvi DM, Sampson LA, Webster JG. Multiple probe radiofrequency ablation: pilot study in an animal model. J Vasc Interv Radiol 2003;14(11):1437–1442.[Medline]
15. Haemmerich D, Lee FT Jr, Schutt DJ, et al. Large-volume radiofrequency ablation of ex vivo bovine liver with multiple cooled cluster electrodes. Radiology 2005;234(2):563–568.[Abstract/Free Full Text]
16. Haemmerich D, Lee FT Jr. Multiple applicator approaches for radiofrequency and microwave ablation. Int J Hyperthermia 2005;21(2):93–106.[CrossRef][Medline]
17. Ahmed M, Goldberg SN. Thermal ablation therapy for hepatocellular carcinoma. J Vasc Interv Radiol 2002;13(9 pt 2):S231–S244.
18. Goldberg SN, Ahmed M. Minimally invasive image-guided therapies for hepatocellular carcinoma. J Clin Gastroenterol 2002;35(5 suppl 2):S115–S129.[CrossRef][Medline]
19. Lobo SM, Afzal KS, Ahmed M, Kruskal JB, Lenkinski RE, Goldberg SN. Radiofrequency ablation: modeling the enhanced temperature response to adjuvant NaCl pretreatment. Radiology 2004;230(1):175–182.[Abstract/Free Full Text]
20. Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K, Okita K. Percutaneous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow: comparison with standard percutaneous radiofrequency ablation therapy. Cancer 2002;95(11):2353–2360.[CrossRef][Medline]
21. Horkan C, Ahmed M, Liu Z, et al. Radiofrequency ablation: effect of pharmacologic modulation of hepatic and renal blood flow on coagulation diameter in a VX2 tumor model. J Vasc Interv Radiol 2004;15(3):269–274.[Medline]
22. Chang CK, Hendy MP, Smith JM, Recht MH, Welling RE. Radiofrequency ablation of the porcine liver with complete hepatic vascular occlusion. Ann Surg Oncol 2002;9(6):594–598.[Abstract/Free Full Text]
23. Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg 1998;227(4):559–565.[CrossRef][Medline]
24. Goldberg SN, Hahn PF, Tanabe KK, et al. Percutaneous radiofrequency tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol 1998;9(1 pt 1):101–111.[Medline]
25. Solazzo SA, Liu Z, Lobo SM, et al. Radiofrequency ablation: importance of background tissue electrical conductivity—an agar phantom and computer modeling study. Radiology 2005;236(2):495–502.[Abstract/Free Full Text]

This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2423052039v1 242/3/743    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Solazzo, S. A. Articles by Goldberg, S. N. Search for Related Content PubMed PubMed Citation Articles by Solazzo, S. A. Articles by Goldberg, S. N.