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Published online before print February 16, 2006, 10.1148/radiol.2383050262
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(Radiology 2006;239:94-102.)
© RSNA, 2006

Experimental Studies

Microwave Ablation: Results with a 2.45-GHz Applicator in ex Vivo Bovine and in Vivo Porcine Liver1

Andrew U. Hines-Peralta, MD, Nadeer Pirani, MD, Peter Clegg, PhD, Nigel Cronin, PhD, Thomas P. Ryan, PhD, Zhenjun Liu, MD and S. Nahum Goldberg, MD

1 From the Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308B, Boston, MA 02215 (A.U.H., N.P., Z.L., S.N.G.); Department of Physics, University of Bath, Bath, England (P.C., N.C.); and Microsulis Americas, Waltham, Mass (P.C., N.C., T.P.R.). From the 2004 RSNA Annual Meeting. Received February 15, 2005; revision requested April 12; revision received June 2; accepted June 21; final version accepted September 1. Supported by Microsulis. Address correspondence to S.N.G. (e-mail: sgolber{at}caregroup.harvard.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Purpose: To characterize the relationship between applied power and treatment duration in their effect on extent of coagulation produced with a 2.45-GHz microwave applicator in both an ex vivo and a perfused in vivo liver model.

Materials and Methods: All experimentation was approved by the Institute of Animal Care and Use Committee. Multiple tissue ablations were performed in ex vivo bovine liver (120 ablations) and in vivo porcine liver (45 ablations) with a 5.7-mm-diameter 2.45-GHz microwave applicator. The applied power was varied from 50 to 150 W (in 25-W increments ex vivo and 50-W increments in vivo), while treatment duration varied from 2 to 20 minutes (in eight time increments for ex vivo and five for in vivo liver). Three-dimensional contour maps of the resultant short- and long-axis coagulation diameters were constructed to identify the optimal parameters to achieve maximum coagulation in both ex vivo and in vivo models. Multivariate analysis was performed to characterize the relationship between applied power and treatment duration.

Results: Power and treatment duration were both associated with coagulation diameter in a sigmoidal fashion (ex vivo, R2 = 0.78; in vivo, R2 = 0.74). For ex vivo liver, the maximum short-axis coagulation diameter (7.6 cm ± 0.2 [standard deviation] by 12.3 cm ± 0.8) was achieved at greatest power (150 W) and duration (20 minutes). In vivo studies revealed a sigmoidal relationship between duration and coagulation size, with a relative plateau in coagulation size achieved within 8 minutes duration at all power levels. After 8 minutes of treatment at 150 W, the mean short-axis coagulation diameter for in vivo liver was 5.7 cm ± 0.2 by 6.5 cm ± 1.7, which was significantly larger than the corresponding result for ex vivo liver (P < .05).

Conclusion: Large zones of ablation can be achieved with the 2.45-GHz microwave applicator used by the authors. For higher-power ablations, larger zones of coagulation were achieved for in vivo liver than for ex vivo liver with short energy applications, a finding previously not seen with other ablation devices, to the authors' knowledge.

© RSNA, 2006


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Imaging-guided percutaneous tumor ablation continues to gain attention as a viable treatment option for the focal destruction of solid tumors, as it may provide some potential advantages over surgical resection, including reduced morbidity, outpatient therapy, and the ability to treat patients who are poor surgical candidates (1,2). Historically, the greatest attention has been given to the potential of radiofrequency (RF) ablation in the treatment of primary and metastatic hepatic malignancy, fueled in part by the substantial morbidity and mortality associated with hepatic resection (3–9). Given continued favorable outcomes, the clinical potential of RF ablation has been greatly expanded to include the treatment of neoplasms in other sites, including kidney (10–12), breast (13), bone (14,15), lung (16), retroperitoneum (17), thyroid (18), adrenal gland (19), spleen (20), and prostate (21), as well as pheochromocytomas (22).

A major obstacle to wide-scale adoption of this potentially advantageous treatment option, however, is the inability to reliably create adequate volumes of complete tumor destruction (1). Findings of long-term follow-up indicate that local tumor progression can occur in up to 35% of cases of colorectal liver metastases treated with percutaneous RF ablation (9). RF ablation can be effective for the destruction of small tumors (<3 cm) (23,24), but success for index tumors larger than 3.5 cm in diameter has been less robust (9,23).

Although RF ablation is currently the most commonly used form of thermal ablation, multiple other energy sources, such as laser- (25), ultrasound- (26), and microwave-based forms of ablation (27–33), have recently been employed in an attempt to overcome inadequate tissue coagulation. Regardless of the primary energy source, all of these modalities induce cellular destruction by means of the direct effects of heat, with irreversible cellular damage occurring at temperatures above 50°C when applied for 4–6 minutes and almost instantaneously at temperatures above 60°C (24). Thus, the main difference between modalities lies in the ability to translate energy efficiently into heat throughout the entire tumor ablation target volume.

Results of studies of RF ablation suggest that the characteristics of the tissue, such as electrical conductivity, can substantially affect and occasionally retard energy deposition and heating throughout a tumor (34). Additionally, exponential rises in electrical impedances of tumor tissue may result from the application of high RF current, thus limiting the total amount of energy that can be delivered into tissue (24). This limits the amount of coagulation that can be achieved. On the other hand, microwave energy deposition is dominated by the absorption caused by the rapid rotation of the polar water molecule and is far less dependent on the electrical conductivities of tissue (35). However, few data are available on the extent of tumor destruction possible with microwave ablation, especially at frequencies near 2.45 GHz, which are now used in conventional microwave ovens given optimal heating profiles (35). Thus, the purpose of our study was to characterize the relationship between applied power and treatment duration in their effects on the extent of tissue coagulation achieved with a 2.54-GHz microwave applicator in both an ex vivo liver model and a perfused in vivo liver model.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Industry Support
Support for this study was provided by Microsulis (Denmeade Hampshire, England) in the form of ablation equipment and materials. All experimentation was performed in a blinded fashion by the authors not employed by the contributing company. (S.N.G., P.C., and N.C. are compensated for consulting time by the contributing company, A.U.H., N.P., and Z.L. are not associated with the contributing company in any manner, and T.P.R. is an employee of Microsulis.) Results from this study were made available to the contributing company only after all experimentation was complete. Results were prepared for publication independently of any influence of the company.

Overall Experimental Design
Experiments were performed in ex vivo bovine liver and in vivo porcine liver with a custom-designed microwave applicator. The applicator used for all experimentation was a 2.45 GHz, 150-W microwave device with an active 5.7-mm-diameter radiator, powered by a magnetron generator (Fig 1) (Microsulis). For ex vivo studies, the power setting was varied from 50 to 150 W in 25-W increments (50, 75, 100, 125, 150 W), and the duration of energy application was varied from 2 to 20 minutes (eight time points: 2, 4, 6, 8, 10, 12, 16, and 20 minutes). For the in vivo studies, the power setting was varied from 50 to 150 W in 50-W increments, while the treatment duration was again varied from 2 to 20 minutes (five time points: 2, 4, 8, 12, and 20 minutes). After treatment, ablated tissue was sectioned, and the resultant coagulation was assessed by means of gross examination with calipers in both the short-axis diameter (perpendicular to the applicator) and the long-axis diameter. Applied power levels and treatment durations for ex vivo and in vivo studies were both correlated with resultant ablation diameters. Finally, ex vivo findings were compared with in vivo findings for similar parameters.


Figure 1
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  		Figure 1: A 2.45-GHz microwave applicator. A ceramic microwave antenna is embedded within the 5.7-mm-diameter shaft (arrow). Energy is applied to the tissue via the applicator at 2.45 GHz.

 
Ex Vivo Bovine Liver Ablation
Microwave ablations (n = 120) were performed in ex vivo room-temperature (10°–15°C) bovine liver (adequate tissue for four ablations per liver; Bell Provision Slaughterhouse, Milton, Mass) for a range of treatment durations and power settings, as described in the previous section. Eight time increments (2, 4, 6, 8, 10, 12, 16, 20 minutes) and five power increments (50, 75, 100, 125, 150 W) were used, constituting 40 time-power combinations. For each combination of parameters, trials were performed in triplicate, for a total of 120 ablations. With direct visualization, the applicator was submerged 15 cm into the liver with 10 cm of tissue available in the perpendicular axis, in order to provide a satisfactory margin for even the largest ablations. Vessels larger than 5 mm were identified with ultrasonography (US) and were avoided. All ablations were performed by the first author (A.U.H.), who had experience performing more than 1000 ablations with various devices.

In Vivo Porcine Liver Ablation
All animals were cared for according to the approved guidelines of the Institute of Animal Care and Use Committee. All experimentation was directly approved by this committee before initiation of the study. Yorkshire pigs were obtained (n = 14; Parkman Farms, Farmington, Mass) at a size of 80–90 kg and were allowed to acclimate to the animal research facility for 48 hours before experimentation. Prior to ablation (45 ablations), the pigs were sedated by means of intramuscular administration of ketamine (15 mg per kilogram of body weight) (Fort Dodge Laboratories, Fort Dodge, Iowa) and then intubated and maintained in deep anesthesia with isoflorane (1%–4%) (Baxter Healthcare, Deerfield, Ill). The abdomen was opened through a midline incision, and an applicator was inserted into liver parenchyma with direct visualization. Once the applicator was inserted into the liver, US (7.5-MHz linear transducer; SSD-500, Aloka, Tokyo, Japan) was used to guide and further position the applicator away from (>5 mm) as many vessels as possible. Given the extensive zones of coagulation anticipated, applicators were positioned away from adjacent organs (eg, stomach, small intestine) to minimize thermal injury to these vital structures. Multiple applications were performed in each animal (three ablations per liver). All ablations were performed by the first author (A.U.H., with assistance from N.P. and Z.L.). Five time increments (2, 4, 8, 11, 20 minutes) and three power increments (50, 100, 150 W) were used, constituting 15 time-power combinations. For each combination, trials were performed in triplicate, for a total of 45 ablations. After all ablations were performed, the animal was euthanized with intravenous pentobarbital (Fatal Plus; Vortech Pharmaceuticals, Dearborn, Mich).

Pathologic Studies
For ex vivo liver, RF-ablated tissue was excised and sectioned along the applicator needle axis by the first author. The short-axis (perpendicular to needle) and long-axis (along needle axis) diameters were assessed by means of gross examination with calipers, as previously described (36). In addition, both diameters were used to calculate the sphericity of the ablation (see Statistical Analysis). All sections were independently examined in blinded fashion by two of the authors (A.U.H. and S.N.G., with 2 years and >10 years of experience, respectively, in evaluating coagulation diameters). For in vivo studies, the liver was removed en bloc immediately after the animal was euthanized. After removal, ablated liver tissue was sectioned along the device axis.

Cell viability, as indicated by mitochondrial enzyme activity, was assessed by incubating tissue sections for 30 minutes in 2% 2,3,5-triphenyl tetrazolium chloride (Fisher Scientific, Fairlawn, NJ) at 20°–25°C. The absence of mitochondrial enzyme activity has been shown to accurately reveal irreversible cellular injury induced by percutaneous tumor ablation (37). With this method, viable tissue with intact mitochondrial enzyme activity is stained red, while ablated tissue appears white. With in vivo ablation, a "red zone" is often seen surrounding the white zone and develops as a reaction to hyperthermia. Following accepted ablation protocols, the red zone was not measured, as it often contains viable tissue (38). Calipers were used to measure the extent of gross coagulation in the short and long axes of the ablation. Coagulation or thermal injury to adjacent structures was not evaluated in this study, as special attempts to minimize unwanted thermal injury were undertaken to optimize the health of the animal during the ablation session.

Statistical Analysis
For all ex vivo and in vivo experiments, ablations were performed in triplicate for each power-time combination, and results were reported as means ± standard deviations (SDs). The coagulation diameter perpendicular to the device axis (short axis) was used as the primary outcome measure for all statistical analyses (38). Analysis of variance was used to identify significant differences for comparisons of three or more groups (Origin 6.1; OriginLab, Northampton, Mass), while Student t tests were used to identify significant differences ({alpha} = .05; two-tailed test) between two groups. Given the multiplicity of groups in this study, two-group comparisons were performed only if the comparison reflected the change in an underlying trend among multiple groups. Diameters in the long axis are also reported here for both ex vivo and in vivo studies in order to suggest the size of tumors that are potentially treatable. The ablations were ellipsoidal and completely contiguous, unless otherwise stated.

The short- and long-axis coagulation diameters were used to calculate a sphericity index, defined as the volume of ablation divided by the volume of a sphere using only the longest diameter. The volume of ablation in this study was defined as the calculated volume of an ellipsoid obtained by using the short-axis (r1) and long-axis (r2) radii (4{pi}r12r2/3). The volume of a sphere obtained by using the long axis was calculated as 4{pi}r23/3. Thus, the sphericity index can be simplified to r12/r22. A perfect sphere has an index of 1.0, and ellipsoids have indexes of less than 1.0. As a reference, an ellipsoid with a long-axis diameter twice the length of the short-axis diameter will have a sphericity index of 0.25.

Three-dimensional contour plots of power, time, and coagulation diameter were constructed by using DPlot 1.7.5 (HydeSoft Computing, Vicksburg, Miss). Multivariate regressions that employed linear and nonlinear (exponential, logarithmic Boltzman sigmoidal, and quadratic) regression models were performed with Origin 6.1 (OriginLab). These nonlinear regressions were performed to enable regression to pharmacologic dose-response and biologic growth-decay regression models, with the strength of the best-fit regression curves reported as R2 computations.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Ex Vivo Results
Excellent uniformity of the ablation zones was achieved; the SDs of short-axis coagulation diameter ranged from 0.2 to 0.6 cm for all applied power settings and treatment durations studied. For long-axis coagulation diameters, SDs ranged from 0.2 to 1.2 cm, and greater variability was observed with increased duration. For example, for durations of at least 12 minutes at an applied power of 150 W, SDs ranged from 0.8 to 1.2 cm, compared with SDs of 0.6 cm or less for applications no longer than 10 minutes (P < .05).

Both the applied power and treatment duration correlated with short-axis coagulation diameter in a Boltzman sigmoidal curve fashion (multivariate R2 = 0.78). For power settings of 75 W or higher, 90% of the maximum short coagulation diameter was achieved within 8 minutes or less (Fig 2). For higher power settings, the sigmoidal relationship was more linear, with continued increases in coagulation achieved after 8 minutes duration. For example, at 150 W, the short-axis coagulation diameter was 4.9 cm ± 0.2 after 8 minutes and 7.6 cm ± 0.2 after 20 minutes. Thus, the largest coagulation diameter was achieved at maximum settings (150 W and 20 minutes), producing ablations 7.6 cm ± 0.2 by 12.3 cm ± 0.8 in diameter (Table).


Figure 2
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  		Figure 2a: Graphs show short-axis coagulation diameters for microwave ablation of (a) ex vivo and (b) in vivo liver. For ex vivo coagulation, longer treatment durations result in continuing gains in short-axis diameter. In contrast, in vivo coagulation reaches a relative plateau by 8 minutes, with no substantial further increase in coagulation observed after longer treatment applications.

 

Figure 2
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  		Figure 2b: Graphs show short-axis coagulation diameters for microwave ablation of (a) ex vivo and (b) in vivo liver. For ex vivo coagulation, longer treatment durations result in continuing gains in short-axis diameter. In contrast, in vivo coagulation reaches a relative plateau by 8 minutes, with no substantial further increase in coagulation observed after longer treatment applications.

 

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  		Coagulation Diameters and Sphericity Index for Selected Treatment Durations and Power Settings

 
Long-axis coagulation diameter also correlated with both applied power setting and duration (R2 = 0.73) in sigmoidal fashion, though the amplitude of the curve (ie, coagulation diameter) was higher, giving rise to ellipsoidal ablations. The sphericity index of coagulation at 50 W was 0.75 ± 0.19 at 4 minutes but trended lower, to 0.38 ± 0.03, by 20 minutes (P < .01). At settings of 100 and 150 W, ex vivo ablations continued to be ellipsoidal, with a mean sphericity index for all ablations of 0.39 ± 0.05.

In Vivo Results
For in vivo perfused liver, power setting and treatment duration were also associated with short-axis coagulation diameter, again following a Boltzman curve (multivariate R2 = 0.74) (Fig 3). The maximum short-axis coagulation diameter was achieved at an applied power of 150 W within 8 minutes of treatment, yielding an ablation 5.7 cm ± 0.2 by 6.5 cm ± 1.7. After 20 minutes, the ablation still measured 5.8 cm ± 0.2 by 5.5 cm ± 0.4, roughly unchanged (Fig 2).


Figure 3
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  		Figure 3: Three-dimensional contour plots. Left: Three-dimensional map for ex vivo findings shows relationship between treatment duration (x-axis), applied power (y-axis), and short-axis coagulation diameter (z-axis). Note that coagulation diameter continues to increase even after 8 minutes. Right: For the in vivo short-axis coagulation diameter, the greatest increase in coagulation occurs within 8 minutes, with a relative plateau for longer treatment durations.

 
Long-axis coagulation diameters also correlated with both power setting and duration (R2 = 0.73), with a curve and amplitude similar to those of short-axis coagulation diameters. This similar curve and amplitude result in more spherical ablations in vivo for all power settings and duration, compared with ex vivo results. The mean sphericity index for all in vivo ablations was 0.59 ± 0.21, significantly more spherical than the mean for ex vivo ablations (0.45 ± 0.13, P < .01). Unlike the index for ex vivo tissues, the in vivo sphericity index increased with increases in the power setting (P < .05). For example, the sphericity index at 20 minutes was 0.90 ± 0.03 at a setting of 150 W, compared with 0.48 ± 0.02 at 50 W.

The SDs for short-axis in vivo coagulation diameters ranged from 0.2 to 1.1 cm (mean, 0.4 cm). The SDs for long-axis coagulation diameter ranged from 0.2 to 2.2 cm (mean, 0.8 cm). This variability was associated with biologic parameters and not with applied power or treatment duration (short-axis R2 = 0.1; long-axis R2 = 0.1).

Comparison of in Vivo and ex Vivo Coagulation
Depending on the parameters, for a combination of ablation parameters, either larger or smaller coagulations were achieved with in vivo ablation than with in ex vivo ablation. The greatest variation was seen at the highest power setting, 150 W. For treatment durations of at least 8 minutes and a power setting of 150 W, the short-axis coagulation diameter for in vivo studies was significantly greater than that for ex vivo studies. For example, at 8 minutes duration, the in vivo coagulation diameter was 5.7 cm ± 0.2, significantly larger than the ex vivo coagulation diameter (4.9 cm ± 0.2, P < .01) (Fig 4). For treatments longer than 8 minutes, the ex vivo coagulation diameter continued to increase, while the in vivo coagulation diameter remained constant. The result is larger in vivo coagulation diameters for shorter treatment durations (≤8 minutes) and larger ex vivo coagulation diameters for longer durations (Fig 5). Similarly, at 100 W, in vivo coagulation diameters were still slightly larger than ex vivo coagulation diameters (P = .10) for treatment durations of 8 minutes or less, although ex vivo coagulation diameters were larger for longer durations (≥12 minutes, P < .05). At 50 W, in vivo coagulation diameters were similar to ex vivo coagulation diameters for treatment durations of 8 minutes or less, but ex vivo coagulation diameters continued to increase after 8 minutes, while in vivo coagulation diameters leveled to a plateau (Fig 2).


Figure 4
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  		Figure 4: Graph compares ex vivo and in vivo coagulation diameters at selected applied power settings. At 150 W and 100 W (not shown), in vivo diameters were larger than ex vivo diameters for treatment durations of 8 minutes or less. However, for durations longer than 8 minutes, ex vivo diameters were larger than in vivo diameters. At 50 W, ex vivo diameters are greater than in vivo diameters, a finding typical of ablation devices.

 

Figure 5
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  		Figure 5: Gross pathologic appearance of microwave ablation. Ablated tissue is shown sectioned perpendicular to the applicator axis. At 150 W after 8 minutes of treatment, the in vivo (left) "white zone" coagulation diameter is 5.7 cm ± 0.2 (arrows), significantly larger than the corresponding ex vivo (right) diameter of 4.9 cm ± 0.2 (arrows).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 References
 
Large Zones of Coagulation with Short Treatment Duration
The data indicate that 2.45-GHz microwave ablation devices can be used to achieve large zones of coagulation with relatively short durations of energy application in both an ex vivo liver and a perfused in vivo liver model. Specifically, after only 8 minutes, coagulation diameters of 5.7 cm ± 0.2 and 4.9 cm ± 0.2 were observed for in vivo perfused liver and ex vivo liver, respectively. Given the clinical demand to treat ever larger zones of coagulation coupled with the need to secure an adequate "ablative margin," microwave ablation devices such as the one used in this study represent a potential advance in imaging-guided tissue coagulation. Indeed, to our knowledge, coagulation diameters larger than 5.5 cm have not been achieved to date in less than 8 minutes with other methods of thermal ablation in an in vivo porcine liver model. For example, for most RF systems the manufacturer recommends at least 12 minutes of treatment—50% longer than the upper boundary of necessary treatment duration in this study—to achieve similar volumes of coagulation (39–41).

Furthermore, these data represent the results from a single applicator, not from a conglomerate of electrodes or multiple tines (32,39). In clinical terms, this may likely translate to greater ease and faster and more efficient positioning, which, coupled with shorter treatment duration, may decrease total treatment time. Given findings from prior microwave research, it is likely that even greater volumes can be ablated with this system, if necessary, by simultaneously applying energy to an array of applicators (42). However, this possibility will require further study.

In Vivo Coagulation Greater than ex Vivo Coagulation
Perhaps the most important finding in this study is the significantly greater in vivo coagulation observed at short durations compared with ex vivo coagulation. This finding is in contradistinction to virtually all prior reports concerning RF and microwave ablation, where in vivo results have been substantially smaller than those achieved ex vivo, a well-studied disparity that is largely attributed to the negative effects of blood perfusion. Perfusion induces a powerful "heat-sink" effect that swiftly removes heat from the site of ablation (43). With constant cooling, tissue that is not in very close proximity to a substantial heat source is usually not able to achieve the requisite 50°C necessary for irreversible cellular damage.

The findings observed here, however, suggest not only that microwave ablation, when applied correctly, can partly overcome the negative effects of perfusion, at least over short durations of energy application, but also that additional aspects of in vivo tissue composition substantially improve the outcome of microwave ablation. The difference between how RF and microwave waveforms translate into heat energy may provide insight into this novel observation. RF current is known to induce heat via friction from ionic tissue resistance, analogous to the production of heat in an electrical resistor (44). For this reason, the effectiveness of RF is substantially affected by various tissue factors, including the electrical conductivities of both the tumor tissue and surrounding organ parenchyma (34).

Microwave radiation, on the other hand, heats tissue by forcing the dipole of a water molecule to reorient continuously in the oscillating electric field of the electromagnetic radiation (35). According to research with conventional microwave ovens, a frequency of 2.45 GHz is slightly below the optimal frequency for maximum dipole oscillation but yields superior tissue penetration, as radiation is not completely absorbed by the first layer of water, enabling deeper and more even heating (35). Additionally, since microwave ablation creates heat by means of the interaction of water dipoles, we hypothesize that the greater water content of in vivo tissue rich in blood (that likely replenishes during ablation) may provide superior microwave-tissue matching, resulting in greater heat production than in ex vivo liver, which has a lower baseline water content (and no source of replenishment or rehydration for the desiccation that occurs during ablation). If this hypothesis proves true, the higher water content of tumors may yield superior microwave tumor ablation than that achieved in these experiments with normal liver. Additionally, it may also permit more targeted ablation of the tumor rather than relatively less-hydrated background tissues, such as cirrhosis, fat, and bone.

This does not mean that the negative effects of perfusion are no longer in effect during ablation in vivo. Perfusion will still draw heat away from the ablation site regardless of whether the heat was created with microwaves, RF, or another energy source. Thus, while the water content of blood may itself be beneficial as a water-rich substrate for increased heating, rapidly flowing blood (ie, perfusion) continues to impede coagulation by the better understood heat-sink effect. At some point, a balance must occur between the negative effects of the heat sink and the benefit of microwave interacting with the greater water content of in vivo tissues. This balance was observed in our study when coagulation achieved a flat plateau (after 8 minutes at 150 W and after 4 minutes at 100 W). In nonperfused tissue, however, we continued to observe more linear increases in coagulation, even after 8 minutes, which is expected given the absence of the antagonizing effect of perfusion.

Sphericity Index
Given that most tumors treatable with thermal ablation are spherical, the shape of ablation should also approximate a sphere, in order to create a sufficient ablative margin while minimizing the destruction of normal surrounding tissue. In this study, we noted ellipsoidal ex vivo ablations at higher powers (100 and 150 W), with sphericity indexes of 0.39 ± 0.03. This indicates a short-axis diameter that is roughly two-thirds of the long-axis diameter. Though the exact mechanism is unclear, the disparity likely results from applicator shaft heating that occurs with longer duration and higher-power ablation. Reflected energy up the shaft enables the shaft to heat, which likely contributes to long-axis coagulation by way of thermal conduction. At 50 W, after 4 minutes of treatment the sphericity index is 0.75 ± 0.19, but as the power setting and treatment duration increase, applicator shaft heating leads to proportionately larger long-axis coagulation diameters. Consequently, the sphericity index is poor (0.38 ± 0.03 at 150 W and 20 minutes).

In the in vivo setting, however, the sphericity index is superior. This is likely due to perfusion-mediated cooling that limits heating of the applicator shaft from reflected microwave energy. Thus, the applicator does not absorb as much heat to induce coagulation along the applicator shaft. In fact, increasing the power yields superior tissue penetration in the perpendicular axis without extension along the applicator shaft. As a result, the sphericity index for in vivo ablation improves with higher power settings, with an average index of 0.79 ± 0.18 at 150 W with treatment durations of at least 8 minutes, a sphericity index comparable to commercially available RF equipment (41). If this hypothesis is true, a form of shaft cooling could likely further improve the sphericity index and the reproducibility of ablation in the long axis.

Study Limitations and Technical Considerations
This study establishes the initial feasibility of using 2.45-GHz microwave ablation in imaging-guided tissue ablation, but it does not suggest an immediate application for percutaneous interventional use. Though the findings of these initial feasibility studies are very encouraging, the applicator in its current form has a 5.7-mm diameter. While the diameter may be acceptable for use as a laparoscopic instrument in its current configuration, we suspect that the risks of imaging-guided percutaneous insertion are too great. In this study we used an open laparotomy approach to enable easier applicator positioning and thus were unable to assess the risks of a percutaneous approach using the device in its current configuration. Nevertheless, these data suggest that smaller microwave radiation applicators could represent a clear advantage compared with other energy sources currently used for thermally mediated tumor ablation and that the development of a thinner applicator for percutaneous interventional use could result in considerable benefit.

Given the large zones of coagulation capable with high-power microwave ablation at 2.45 GHz, it is likely that power and duration need to be carefully titrated to treat smaller tumors appropriately without overtreating the ablation margins. Large-scale ablation may also be associated with a greater risk of thermal injury to adjacent structures without proper technical precautions. In this study, we did not observe unwanted thermal injury, but we specifically positioned applicators away from adjacent structures, given the risk of this potential complication. Large-scale ablation may also be associated with larger variability in coagulation diameters, and more investigation will be necessary to evaluate the predictability of coagulation size in different tissue environments. Given the multiple parameters to be evaluated, another limitation of our study is the small sample sizes used in many of the comparisons. Many of the results, while promising, need to be interpreted carefully, pending further corroboration from larger studies.

Microwave tumor ablation at 2.45 GHz can achieve large zones of coagulation in a relatively short time, which may ultimately be proved advantageous for imaging-guided tumor ablation in the clinical setting. More important, our results suggest that microwave ablation achieves similar and occasionally even larger zones of coagulation in an in vivo setting, a clinically important finding given the negative effects of perfusion. Thus, given the potential benefit and the paucity of data for microwave radiation as a source for percutaneous tumor ablation, further study is warranted in additional models.


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


   FOOTNOTES
 

Abbreviations: RF = radiofrequency • SD = standard deviation

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, P.C., N.C., T.P.R., S.N.G.; experimental studies, A.U.H., N.P., T.P.R., Z.L., S.N.G.; statistical analysis, A.U.H., T.P.R., S.N.G.; and manuscript editing, A.U.H., P.C., N.C., T.P.R., S.N.G.


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

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