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DOI: 10.1148/radiol.2361031249
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(Radiology 2005;236:132-139.)
© RSNA, 2005

Experimental Studies

Radiofrequency versus Microwave Ablation in a Hepatic Porcine Model1

Andrew S. Wright, MD, Lisa A. Sampson, CVT, Thomas F. Warner, MD, David M. Mahvi, MD and Fred T. Lee, Jr, MD

1 From the Departments of Surgery (A.S.W., D.M.M.), Radiology (L.A.S., F.T.L.), and Pathology (T.F.W.), University of Wisconsin, 600 Highland Ave, Madison, WI 53792-3252. Received August 11, 2003; revision requested October 28; final revision received August 4, 2004; accepted September 2. Address correspondence to F.T.L. (e-mail: ftlee{at}wisc.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To compare microwave (MW) and radiofrequency (RF) ablation in a hepatic porcine model.

MATERIALS AND METHODS: Institutional animal research committee approval was obtained. Nineteen pigs were divided into groups based on time of sacrifice (group A, immediate; group B, 2 days; group C, 28 days; group D, 28 days). Groups A, B, and C each underwent a combination of RF and MW ablation. Group D underwent either four MW or four RF ablations. Ablation was performed with a prototype MW device (915 Mhz, 40 W, 10 minutes) and a commercial RF system (150 W, 10 minutes, 3-cm deployment). Computed tomography (CT) was performed in groups B and C at 2 days and in group C at 28 days. Group D underwent serial laboratory testing. Specimens were serially sectioned, and short-axis diameter and length of each were measured. The percentage deflection caused by local blood vessels (heat-sink effect) was also measured in group A. Likelihood ratio tests and unpaired t tests were used for statistical analyses as appropriate.

RESULTS: MW ablation zones were longer at days 0, 2, and 28 (P < .05), but short-axis diameter was not different from that with RF ablation at any time point (P > .05). Local blood vessels caused 3.5% ± 5.3 (standard deviation) deflection at MW ablation compared with 26.2% ± 27.9 at RF ablation (P < .05). MW and RF ablation zones were indistinguishable at CT or pathologic evaluation. Laboratory test results were similar between RF ablation–only animals and MW ablation–only animals, with the exception of a slightly higher alkaline phosphatase levels at day 2 in RF ablation–only animals (P < .02).

CONCLUSION: MW and RF ablation zones are similar in pathologic appearance and imaging characteristics. Increased length with MW ablation is likely caused by the length of the radiating segment of the antenna. MW ablation may be less affected by the heat-sink effect that is thought to contribute to local recurrence after RF ablation.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Hepatic resection remains the reference standard in the treatment of malignant liver tumors; however, a large number of patients have disease that is not amenable to surgical therapy (1). This may be due to unfavorable anatomy, the presence of multiple tumors, or poor hepatic reserve (2). Therefore, several ablative treatment modalities have been developed for local control of liver tumors in patients with nonresectable hepatic tumors.

Radiofrequency (RF) ablation is the most frequently used of these methods because of its effectiveness, safety in both percutaneous and surgical settings, and relative ease of use. However, RF ablation is fundamentally restricted by the need to conduct electric energy into the body. As temperatures reach 100°C and boiling occurs, increased impedance limits further deposition of electricity into tissue (3). This becomes even more pronounced if charring occurs; the resultant eschar forms a highly effective insulator around the electrode. A number of different algorithms of energy deposition and several different types of electrodes are used to minimize this effect. Electrode types include multitined expandable electrodes, perfusion electrodes, and cooled-tip RF probes.

A further limitation of RF ablation is the relatively small zone of active heating created by ionic agitation (on the order of a few millimeters) (4). The majority of tissue heating is thus due to thermal conduction, which decreases exponentially away from the source. Finite-element computer modeling suggests that this results in an inefficient transformation of electrical energy into heat, especially at tissue-vessel interfaces where flowing blood thermally protects perivascular tissue and tumor (5). The high rate of local recurrence seen in some clinical series of RF ablation is almost certainly caused in part by the protective effect of blood flow in the liver, termed the heat-sink effect (6). Given the highly vascular nature of the liver, most large tumors will be in close proximity to at least one large blood vessel.

Microwave (MW) ablation offers many of the advantages of RF ablation while possibly overcoming some of the limitations. Since MW ablation does not rely on conduction of electricity into tissue, it is not limited by charring. Therefore, temperatures greater than 100°C are readily achieved, which potentially results in a larger zone of ablation, faster treatment time, and more complete tumor kill. In addition, MW ablation has a much broader power field than does RF ablation—up to 2 cm in diameter (7). This may allow for larger zones of thermal ablation and a more uniform tumor kill. Because the cooling effect of blood flow is most pronounced within the zone of conductive rather than active heating, a larger power field may also enhance treatment of perivascular tissue.

With several theoretic and practical advantages, MW ablation is a promising new option in the treatment of surgically unresectable liver tumors. Currently, several investigators in Asia have reported successful treatment with MW ablation of both hepatocellular carcinoma (8–10) and metastatic colorectal cancer (11). These MW systems have been relatively limited by high-power feedback, necessitating a short duration of power application. Ablation zones, therefore, are somewhat small, and multiple overlapping ablations are required for most tumors. Recent advances in MW engineering have allowed the design of a new MW system with reduced feedback and the potential for larger, more controlled ablation zones. Thus, the purpose of our study was to compare a prototype MW ablation system with a commercially available RF device in a hepatic porcine model.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Description of Ablation Devices
The MW ablation device used in this study is a prototype developed by Vivant Medical (Mountain View, Calif). The antenna is a 15-cm 13-gauge coaxial dipole design with a 3.6-cm radiating segment (Fig 1 ). An MW generator is used to drive the system at 915 MHz, with power output controlled by means of a laptop computer with custom software. MW ablation was performed at a power of 40 W and a duration of 10 minutes.



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  		Figure 1a. (a) Prototype 15-cm 13-gauge MW antenna and (b) commercially available 10-cm 14-gauge RF electrode deployed to 3 cm.

 


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  		Figure 1b. (a) Prototype 15-cm 13-gauge MW antenna and (b) commercially available 10-cm 14-gauge RF electrode deployed to 3 cm.

 
RF ablation was performed with a commercially available system (Starburst XL; RITA Medical, Mountain View, Calif). This device features an expandable needle electrode coupled to a generator capable of delivering up to 150 W of power (model 1500; RITA Medical). All RF ablation was performed by using temperature control, with a goal average temperature of 100°C for 10 minutes at a 3-cm deployment.

Treatment Protocol and Imaging
Our institutional animal research committee gave protocol approval for this study. All policies on humane care and use of laboratory animals were followed.

Nineteen crossbred female swine from a commercial vendor (Arlington Farms, Arlington, Wis; mean weight, 45 kg; range, 41–50 kg) were divided into four groups. Group A animals (n = 4) were sacrificed immediately after the surgical procedure. Group B animals (n = 3) were allowed to recover and were then sacrificed after 2 days. There were a total of nine MW and nine RF ablation zones created in group A and six MW and six RF ablation zones created in group B.

Groups C and D were followed for 28 days prior to sacrifice. Each animal in group C (n = 4) underwent three MW and one RF ablations. In group D (n = 8), four animals underwent four MW ablations each and four animals underwent four RF ablations each. Blood was drawn in each animal in group D at days 2, 7, 14, and 21 to evaluate complete blood count and levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and lactate dehydrogenase.

The purpose of group A was to reveal the effects of MW and RF ablation in the same animal at immediate sacrifice. Group B was intended to study computed tomographic (CT) and pathologic characteristics of MW and RF ablation zones in the same animal at 2 days. The purpose of group C was similar to that of group B, but animals were sacrificed at 28 days to study pathologic and imaging changes over time. Each animal in group D underwent only one type of ablation so that we could study the effects of RF-only and MW-only ablation on laboratory values over time.

Anesthetic and Surgical Technique
For all procedures, including the initial ablation surgery and subsequent CT scanning, animals were anesthetized with an intramuscular injection of 7 mg per kilogram of body weight of tiletamine hydrochloride and zolazepam hydrochloride (Telazol; Fort Dodge Animal Health, Fort Dodge, Iowa) and 0.45 mg/kg xylazine (Rompun; Phoenix Pharmaceutical, St. Joseph, Mo). For ablation surgery, animals were intubated, and anesthesia was maintained with inhaled isoflurane (Isoflo; Abbott Laboratories, North Chicago, Ill). One author (A.S.W.) performed all ablation procedures by means of open laparotomy through a midline incision, with up to five ablations performed in each animal. There was a minimum distance of 5 cm between ablation zones. Probes were placed to ensure that entire ablation zones would be within the liver parenchyma. No attempt was made to place probes at specific distances from the hepatic or portal veins; however, the hilum of the liver and the confluence of hepatic veins and vena cava were generally avoided.

Imaging
Selected ablation zones (RF, n = 5; MW, n = 17) were observed by means of intraoperative ultrasonography (US) (HDI 5000; ATL, Bothell, Wash). Short-axis diameter and length were estimated by using US at the end of these ablation procedures. CT scanning (CTi; GE Medical Systems, Milwaukee, Wis) with contrast material enhancement (2.0 mL/kg Omnipaque; Nycomed, New York, NY) was performed in all animals in groups B and C at 2 days (5.0-mm section thickness, 1:1 pitch). The diameter of each zone of ablation at CT was measured and recorded. Group C also underwent CT scanning at 28 days. Ablation zone diameters were again recorded. Two authors (F.T.L. and A.S.W.) performed all imaging and image analysis.

Pathologic Evaluation
At the time of sacrifice, anticoagulation was achieved with 5000 units of heparin (Ekins-Sinn, Cherry Hill, NJ), and animals were then euthanized with 10 mL of Beuthanasia-D (390 mg/mL pentobarbital sodium and 50 mg/mL phenytoin sodium; Schering-Plough, Union, NJ). After removal of the liver, 10% buffered formalin was infused through the portal vein until the liver was completely blanched. Individual specimens were then removed and stored in formalin. After complete fixation, specimens were sectioned transverse to the long axis of the ablation zone at 3-mm intervals. Each section was then digitized at 300 dots per inch by using an Astra 4000U scanner (UMAX Technologies, Fremont, Calif). Two authors (A.S.W. and L.A.S.) performed all specimen collection and preparation.

Image analysis software (ImageJ; National Institute of Mental Health, Bethesda, Md) was used to determine the minimum and maximum diameters of the largest section of each specimen. The minimum diameter is reported as the short-axis diameter. Length was calculated by multiplying the number of sections by the section thickness. Volume was calculated by integrating the areas of each cross section over the length. All size measurements were based on the "white zone" of coagulated tissue and not the "red zone" of hemorrhagic tissue (12).

The heat-sink effect is defined as tissue cooling by adjacent visible vessels (>1 mm in diameter) that causes deflection of the ablation zone away from the vessel (12). There is no standard way to measure the impact of the heat-sink effect. We elected to quantify the heat-sink effect by measuring the diameter of the zone of ablation at a blood vessel and the diameter of the same zone of ablation next to the same blood vessel. We expressed the deflection of the ablation zone caused by the heat-sink effect as the percentage difference between these two diameters.

The percentage deflection was measured at one large (>3 mm) vessel for each ablation zone in group A. Because the heat-sink effect is likely a result of the proximity and size of the blood vessel, the vessel diameter and the distance from the probe tract were also measured. Two ablation zones from group A (both RF ablation zones) had no visible blood vessels within 2 cm, and, therefore, deflection was not measured for these two zones. One author (A.S.W.) performed all image analysis. Representative specimens were stained with hematoxylin-eosin and examined microscopically for postablative changes by one author (T.F.W.). Image and pathologic analyses were performed in a blinded fashion.

Statistical Analysis
Ablation zone size, volume, length, maximum diameter, and short-axis diameter were analyzed by using a likelihood ratio test because of the paired and unpaired nature of the data. That is, since both types of ablation procedure were used in some animals, and only one type was used in other animals, we compared likelihoods of a model including an "ablation type" effect and a model without that effect. Both models included a random pig effect to account for the within-animal variability of the data. At individual time points, pairwise comparisons were made by using a t test based on covariate-adjusted means, which were the estimated means had the design been balanced. Prior to analysis, data were log transformed to better meet the assumptions of the test. P values less than .05 were considered to indicate a significant difference. All analyses were performed by using SAS statistical software (release 6.12; SAS Institute, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
One RF ablation–only animal in Group D died on postoperative day 5 because of a complete small-bowel obstruction. Because zones of ablation change size with time and there were no comparable MW ablation zones analyzed at day 5, data from this animal were excluded from analysis of ablation zone dimensions. Laboratory data from this animal were included at day 2.

Heat-Sink Effect
MW ablation was less affected by blood vessel–mediated cooling (the heat-sink effect), with a mean deflection of only 3.5% ± 5.3 (standard deviation). This was compared with 26.2% ± 27.9 deflection at RF ablation (Figs 2, 3; P < .02). There was one outlier in the RF ablation group, with a deflection of 81% in the presence of two vessels (0.2 and 0.6 cm in diameter). Even with this outlier excluded, the difference between MW and RF ablation was still significant (3.5% ± 5.3 vs 17.0% ± 15.0, P < .02). Vessel size (0.5 cm ± 0.1 at MW ablation vs 0.4 cm ± 0.2 at RF ablation, P = .10) and distance from ablation zone center (0.6 cm ± 0.1 at MW ablation vs 0.6 cm ± 0.2 at RF ablation, P = .35) were comparable between the ablation types (Table).



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  		Figure 2a. Gross image comparison of heat-sink effect of local blood vessels at (a) RF ablation and (b) MW ablation. Note deflection of the coagulation zone at RF ablation (arrow) and the absence of deflection after MW ablation (arrow).

 


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  		Figure 2b. Gross image comparison of heat-sink effect of local blood vessels at (a) RF ablation and (b) MW ablation. Note deflection of the coagulation zone at RF ablation (arrow) and the absence of deflection after MW ablation (arrow).

 


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  		Figure 3. Graph of vascular-mediated deflection of ablation zone, measured as percentage difference between diameter across the lesion at a blood vessel and diameter just next to this vessel. Note markedly decreased deflection seen at MW ablation.

 

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  		Percentage of Deflection Measured at One Large (>3 mm) Blood Vessel for Each Ablation Zone in Group A

 
Ablation Zone Size
At day 0 (group A), MW ablation resulted in significantly larger zones of coagulation than did RF ablation (13.9 cm3± 8.2 vs 6.0 cm3± 3.2, P = .03; Fig 4). This was due to longer lengths of the coagulated zone (6.8 cm ± 1.0 vs 3.8 cm ± 0.9, P < .01; Fig 5), as there was no significant difference between MW and RF ablation for short-axis diameter (1.7 cm ± 0.4 vs 1.7 cm ± 0.5, P = .91) or maximum diameter (2.4 cm ± 0.5 vs 2.1 cm ± 0.9, P = .56).



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  		Figure 4. Graph compares RF and MW ablation zone volume at days 0, 2, and 28. Note greater volume with MW ablation at day 0.

 


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  		Figure 5. Graph compares RF and MW ablation zone length at days 0, 2, and 28. Note greater length with MW ablation at all three time points.

 
MW coagulation zone length continued to be significantly greater than RF coagulation zone length at day 2 (group B) (5.4 cm ± 1.0 vs 3.85 cm ± 0.58, P = .02). Although volume was still greater, this difference was no longer significant (15.3 cm3± 7.5 vs 8.0 cm3± 3.5, P = .12). Short-axis diameters (2.0 cm ± 0.5 vs 1.9 cm ± 0.5, P = .36) and maximum diameters (3.2 cm ± 0.8 vs 2.5 cm ± 0.5, P = .24) were not different between MW and RF ablation.

At day 28 (groups C and D), MW coagulation zone length was again greater than that at RF ablation (3.6 cm ± 1.2 vs 2.2 cm ± 0.68, P < .01). MW and RF ablation zones were not significantly different in volume (6.4 cm3± 4.5 vs 4.4 cm3± 4.0, P = .22), short-axis diameter (1.5 cm ± 0.5 vs 1.5 cm ± 0.6, P = .36), or maximum diameter (2.2 cm ± 0.9 vs 2.3 cm ± 0.9, P = .15).

Volume declined significantly over time for both MW and RF ablation zones (P < .01). There was no interaction between the type of ablation and the amount of volume decrease over time (P = .48).

Laboratory Data
Among animals in group D (28-day survival, either four MW or four RF ablation zones each), all animals were relatively thrombocytopenic at day 2 (platelet count of 234 000 x 10–6/L ± 34 000 vs 310 000 x 10–6/L ± 133 000 at baseline, P < .001; normal range, 120 000–720 000 x 10–6/L) with no significant difference between animals with only MW or only RF ablation zones (235 000 x 10–6/L ± 95 000 vs 233 000 x 10–6/L ± 34 000, P = .48). Alkaline phosphatase level was elevated at day 2 (200 IU/L ± 50, P < .03). This was due to a significantly greater increase in alkaline phosphatase level among animals that underwent RF ablation only in comparison with those that underwent MW ablation only (245 IU/L ± 39 vs 167 IU/L ± 32, P < .02). This held true even after excluding the laboratory data from the RF ablation–only animal that died at day 5 (without this animal, the mean RF ablation–only alkaline phosphatase level was 230 IU/L ± 19; P < .04). By day 7, both platelet count and alkaline phosphatase level had normalized among all animals. There were no significant alterations in white cell count or in hematocrit, aspartate aminotransferase, alanine aminotransferase, total bilirubin, or lactate dehydrogenase levels at any time point.

Imaging
Both MW and RF ablation zones were hyperechoic at intraoperative US, with no significant difference in estimated ablation zone diameters (1.7 cm ± 0.3 vs 1.8 cm ± 0.3, P = .41). At CT, both MW and RF ablation zones were hypoattenuating (Fig 6): At 2 days, MW and RF ablation zones measured 43 HU ± 5 in comparison with a mean normal liver value of 85 HU ± 14 (P < .001); at 28 days, MW and RF ablation zones measured 48 HU ± 7 in comparison with a mean normal liver value of 95 HU ± 2 at 28 days (P < .001). There was no significant difference in attenuation between MW and RF ablation zones at 2 days (43 HU ± 3 vs 43 HU ± 5, P = .39). At 28 days, RF ablation zones were slightly more hypoattenuating than were MW ablation zones (42 HU ± 10 vs 50 HU ± 5, P < .02).



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  		Figure 6. CT appearance of RF (black arrow) and MW (white arrow) ablation zones at 2 (left) and 28 (right) days. Both modalities created hypoattenuating zones of ablation with involution over time.

 
There were no significant differences in size of ablation zones between MW and RF ablation at CT. Short-axis diameters on CT scans at 2 days were 2.4 cm ± 0.3 for MW ablation and 2.3 cm ± 0.3 for RF ablation (P = .20), and lengths were 5.5 cm ± 1.1 and 3.5 cm ± 0.7, respectively (P = .12). At 28 days, minimum diameter at CT was 1.5 cm ± 0.3 for MW ablation zones and 1.8 cm ± 0.2 for RF ablation zones (P = .20), and lengths were 4.7 cm ± 2.4 and 3.2 cm ± 1.0, respectively (P = .15).

Pathologic Evaluation
At gross inspection, all ablation zones at day 0 consisted of a central zone of charring surrounded by an area of coagulation and a rim of hyperemia (Fig 7). There was no visible difference between MW and RF ablation zones at gross or microscopic analysis. On hematoxylin-eosin stained specimens (Fig 8), hepatocytes in the area of coagulation necrosis retained their nuclei but had amorphous cytoplasm and absent cell walls. The sinusoidal lining cells were separated from the cell plates, and red cells were lysed. Compression of parenchyma was present around gas bubbles that were present in the center of the zone of ablation. Both RF and MW ablation zones were bordered by a hemorrhagic zone with partial necrosis of hepatocytes, which corresponded to the hyperemic rim seen at CT.



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  		Figure 7. Gross appearance of MW and RF ablation zones at days 0, 2, and 28. Note white zone of coagulation and surrounding red zone of hyperemia.

 


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  		Figure 8. Microscopic appearance at day 0 of MW ablation zone with area of coagulation (A), hyperemic rim (B), and normal liver (C). (Hematoxylin-eosin stain; original magnification, x100.)

 
At 2 days, the central area was unchanged compared with that at day 0. This area was surrounded by three layers of tissue response, as follows: infiltration of lymphocytes and macrophages; layers of necrotic hepatocytes, many of which had accumulated calcium; and a necrotic zone with hemorrhage and disintegrating polymorphonuclear neutrophils. The three layers measured 1–2 mm each in thickness.

By day 28, zones of ablation were well outlined by a 1–2-mm layer of collagenous fibrous tissue, fibroblastic tissue, and lymphocytic infiltrates. This fibrous layer surrounded an inner zone of degenerating polymorphonuclear neutrophils with necrosis. At this stage, there were large areas of the ablated zone without a trace of nuclei and with a homogeneous appearance or with a mere trace of lobular outlines and hepatic cell plates. Giant cells often surrounded the outer aspects of these advanced areas of necrosis.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
There are few published data regarding the expected size, quality, and pathologic changes of MW ablation zones. In this article we describe for the first time the characteristics of a prototype MW ablation system and compare this system with a commercially available RF ablation device. In our in vivo animal model, hepatic MW ablation generated zones of ablation that were significantly larger in volume and length but not in short-axis diameter. The increase in length and corresponding greater volume seen with MW ablation is likely because of the radiating length of the prototype MW antenna. As will be discussed in a subsequent paragraph, the efficiency of MW ablation is subject to power feedback due to impedance mismatches between the antenna and the surrounding tissue (13). The radiating length was thus chosen to minimize power feedback. The greater length and volume seen in this study are specific to this antenna and cannot be generalized to other MW or RF ablation devices.

Of note, this study was designed as a comparison of the pathologic characteristics of RF and MW ablation zones at different time points. Certainly, RF can generate larger zones of ablation with cluster electrodes (14), larger multitined expandable electrodes, or perfusion electrodes (3). Similarly, MWs can create larger zones of ablation with larger (15) or multiple probes (16). More important is the finding that MW ablation is less affected by the presence of blood vessels than is RF ablation. On average, RF ablation was deflected by 26% in the presence of local blood vessels, while MW ablation was deflected by only 4%.

Results of a number of studies have demonstrated the effect of blood flow on RF and MW ablation, with ablated zones becoming both larger and more uniform during vascular occlusion of hepatic inflow (17–20). Local tumor recurrence rates following RF ablation vary depending on the equipment, tumor types, and technique, but range from 2.4% to 39.0% (21–24). A large portion of tumor recurrence is thought to be due to thermal protection of tumor cells by perfusion-mediated cooling (6). The majority of tissue heating at RF ablation is caused by thermal conduction, which computer modeling suggests is affected greatly by the heat-sink effect of local blood flow (5). MW ablation, on the other hand, has a much larger zone of active heating (25,26), with the area of active heating being a function of the wavelength of the applied energy. The prototype system used in this study should have an area of active heating approximately 2 cm in diameter. Because of the larger zone of active heating, MW ablation is thought to be less dependent on thermal conduction. This may explain why, in this study, MW ablation is less affected by the heat-sink effect of local blood vessels.

The zones of thermal injury created by RF and MW ablation appear similar at gross and microscopic pathologic evaluation. Acutely, RF and MW ablation both demonstrate a central coagulated zone with loss of cell membranes and amorphous cytoplasm, but with retained nuclei. Over time, the ablated zones begin to involute and become characterized by the presence of macrophages and giant cells at the outer aspect. This is similar to previous reports of the pathologic appearance of both RF (27,28) and MW (29,30) ablation zones and likely reflects the common thermal mechanism of both procedures. Ohno et al (31) described increasing amounts of apoptosis over 12 hours following MW ablation, with a corresponding expansion in the size of the ablated zone. We did not see any increase in ablation zone size from 0 days to 2 days; however, we did not specifically examine apoptotic rates for either RF or MW ablation.

At intraoperative US, estimated size closely approximated actual size (1.7 vs 1.7 cm for MW ablation zones and 1.8 vs 1.7 cm for RF ablation zones). Ablated zones appeared hyperechoic. Both MW and RF ablation zones were hypoattenuating on CT scans at 2 and 28 days, with close approximation to actual ablation zone sizes. Again, these findings are similar to those previously reported for both MW (32) and RF (33,34) ablation.

There have been several reports of MW ablation used in the treatment of hepatocellular carcinoma. Lu et al (35) found a 6% local recurrence rate with a median 9-month follow-up. Most recurrences were found after treatment of tumors greater than 2 cm in diameter that were close to the portal vein. Abe et al (36) showed a similar local recurrence rate of 6.7% at a mean follow-up of 16 months and with a complication rate of 14% (two intraabdominal hemorrhages, three pneumothoraces, and one hepatic infarction). MW ablation has been used as a bridge to transplantation in patients with hepatocellular carcinoma and cirrhosis (37). MW ablation may also be useful in the treatment of hepatic metastases from colorectal cancers. Shibata et al (11) randomized 30 patients with hepatic colorectal metastases to undergo either resection or MW ablation. Mean survival was 27 months in the MW ablation group and 25 months in the resection group, with a 3-year survival that was not significantly different (14% and 23%, respectively). Local tumor recurrence was not reported.

Most investigators of MW ablation have used the Microtaze tissue coagulator (Nippon Shoji, Osaka, Japan) described by Tabuse et al (13,38). This system emits MWs at 2450 MHz with up to 150 W of power through a monopolar needle applicator. Lu et al (35) used a similar device, the UMC-1 MW delivery system (Institute 207 of the Aerospace Industry Company and PLA General Hospital, Beijing, China), which also operates at 2450 MHz and delivers up to 80 W of power through a monopolar antenna. MW ablation has been limited by power reflection as high as 50% that is caused by mismatches in impedance between the MW system and the tissue to be ablated (13). This necessitates short application duration, usually on the order of 30–90 seconds at a power of 60 W. The MW system used in this study is a prototype dipole antenna driven at 915 MHz by a generator capable of producing up to 60 W of power. The antenna is specifically designed to limit impedance mismatches and subsequent power feedback. Typically, reflected power is less than 10% (M. Prakash, oral communication, 2002), which allows more efficient power deposition and longer durations of application.

Although RF ablation was performed in this study according to the manufacturer's suggested procedure for a 3-cm ablation zone, the mean minimum diameter was only 1.7 cm. This may be due in part to fixation of specimens in formalin, which can cause up to 30% tissue shrinkage (39). However, this finding also suggests caution in accepting claims of size derived from marketing materials, which may more accurately describe maximum diameter. Adequate treatment of a particular tumor is probably better reflected by the short-axis diameter of the zone of coagulation. Careful procedural monitoring with US or other imaging modalities is essential.

In this study, the short-axis diameter was less than 2 cm for both MW and RF ablation zones. This would limit both techniques to the treatment of tumors under 1 cm in diameter, to allow an adequate margin. There are several strategies taken by manufacturers of RF ablation devices to enhance ablation zone size, including multitined expandable arrays (40), bipolar arrays (41), internally cooled electrodes (14,42), and perfusion of surrounding tissue with saline to increase electric and thermal conductivity (43,44). MW ablation zone diameter may be increased in the future with application of a higher level of power or with further developments in antenna design (25,26,45–47).

Another strategy for treating large tumors is the placement of multiple overlapping zones of ablation. Results of computer modeling performed by Dodd et al (48) suggest that six overlapping 3-cm ablation zones are required to adequately treat a 1.75-cm tumor with a 1-cm margin. Increasing the number of overlapping ablation zones to 14 allows treatment of a 3-cm tumor. If the size of the ablated zone is increased to 5 cm, a 4.25-cm tumor can be adequately treated with six overlapping ablations. RF ablation is limited by electric interference to only one active electrode at a time (4,49). Overlapping ablation zones must therefore be created by using a single electrode placed and activated sequentially in multiple positions. This can become a quite lengthy, expensive, and technically difficult process.

MW ablation offers the ability to simultaneously place multiple antennae without interference. By using the same prototype system as described in this study, simultaneous placement of three overlapping MW ablations generates a round confluent zone of coagulation with a short-axis diameter of 3.5 cm (16). Simultaneous placement had a synergistic effect when compared with sequential placement of three antennae, for which short-axis diameter of the zone was only 1.8 cm. Simultaneous multiple probe ablation also appeared to preferentially ablate perivascular tissue, with zones of ablation actually extending outward as far as 7 mm along blood vessels that were up to 5 mm in diameter. MW ablation is not limited to three probes, so even larger zones of coagulation are likely possible.

This study was limited by the lack of an appropriate large animal tumor model. Human tumors may be less vascular than normal liver, with areas of necrotic tissue. Although live porcine liver has been used in a number of studies as a proxy for human liver tumors, it is likely that there are differences between normal liver and tumor in perfusion-mediated cooling. Tissue properties may also differ between normal porcine livers and human liver tumors that could affect the performance of both MW and RF ablation. For example, RF ablation is dependent on tissue resistivity, while MW ablation is dependant on tissue permittivity.

This study compared the impact of the heat-sink effect on both RF and MW ablation. This comparison is limited by lack of a standard measurement of the heat-sink effect. We elected to compare the diameter of the zone of ablation both at and away from a blood vessel. This measurement is hampered by variability in the size of the vessel and in the distance between the vessel and the probe.

Finally, this study was limited by the use of technology still in development. RF devices are evolving rapidly, while the MW device used in this study is undergoing continued development. Results may not apply to other ablation devices, such as the internally cooled RF electrode.

Practical applications: The current study shows that MW ablation is similar to RF ablation in the pathologic appearance and imaging characteristics of ablation zones. MW ablation, however, appears to be less affected by the heat-sink effect of local blood vessels. Improved performance near blood vessels may be caused by the large zone of active heating at MW ablation in comparison to the relative dependence of RF ablation on passive thermal conduction. Alternatively, high temperatures generated at MW ablation may overcome the cooling effect of blood flow.

The improved performance of MW ablation near blood vessels, combined with the ability to use multiple simultaneous probes, makes MW ablation a promising alternative to conventional ablative therapies. If local tumor recurrence is often due to survival of tumor cells near local blood vessels, MW ablation may help reduce recurrence following ablative therapy. Future animal and clinical studies will need to be designed to evaluate the relative performance of MW and RF ablation with respect to local recurrence of hepatic tumors.


   FOOTNOTES
 

Abbreviations: MW = microwave • RF = radiofrequency

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, A.S.W., F.T.L.; study concepts, A.S.W., D.M.M., F.T.L.; study design, A.S.W., F.T.L.; literature research, A.S.W., F.T.L.; experimental studies, A.S.W., L.A.S., T.F.W., F.T.L.; data acquisition, A.S.W., L.A.S., T.F.W., F.T.L.; data analysis/interpretation, A.S.W.; statistical analysis, A.S.W.; manuscript preparation, definition of intellectual content, and editing, A.S.W., F.T.L.; manuscript revision/review and final version approval, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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