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1.  Radiofrequency Ablation at Low Frequencies for Targeted Tumor Heating: In-vitro and computational modeling results 
Radiofrequency (RF) ablation uses RF current to heat and kill cancer applied via an electrode inserted under image-guidance. Tumor has about half the electrical resistivity of normal tissue below 20 kHz, but similar resistivity above 500 kHz. We placed normal porcine liver tissue in contact with Agar gel having similar resistivity as tumor within 20-450 kHz. A needle electrode was placed with half of the electrically active tip in each layer. We performed ablation with electric current applied for 12 min at 30W, either at 20 kHz or 450 kHz (n=7 each) while measuring temperature via thermocouples 4 and 8mm from the electrode. Mathematical heat-transfer models were created of an equivalent configuration and temperature profile determined at both frequencies. At 8 mm distance, at 450 kHz, tumor gel phantom and normal tissue obtained similar temperatures (57.5±1.4 vs 58.7±2.5°C); at 20 kHz, tumor phantom obtained significantly higher temperatures than normal tissue (65.6±2.0 vs 57.2±5.6°C, p<0.01). Computer models confirm these results, and show the ablation zone diameter to be larger within the tumor phantom at 20 kHz compared to 450 kHz. Heating at low radio frequencies may thus allow targeted heating of tumor tissue and reduced heating of normal tissue.
doi:10.1109/TBME.2010.2085081
PMCID: PMC3108076  PMID: 20934940
radiofrequency ablation; tumor ablation; bioheat transfer
2.  Contribution of Direct Heating, Thermal Conduction and Perfusion During Radiofrequency and Microwave Ablation 
Both radiofrequency (RF) and microwave (MW) ablation devices are clinically used for tumor ablation. Several studies report less dependence on vascular mediated cooling of MW compared to RF ablation. We created computer models of a cooled RF needle electrode, and a dipole MW antenna to determine differences in tissue heat transfer.
We created Finite Element computer models of a RF electrode (Cooled needle, 17 gauge), and a MW antenna (Dipole, 13 gauge). We simulated RF ablation for 12 min with power controlled to keep maximum tissue temperature at 100 ºC, and MW ablation for 6 min with 75 W of power applied. For both models we considered change in electric and thermal tissue properties as well as perfusion depending on tissue temperature. We determined tissue temperature profile at the end of the ablation procedure and calculated effect of perfusion on both RF and MW ablation.
Maximum tissue temperature was 100 ºC for RF ablation, and 177 ºC for MW ablation. Lesion shape was ellipsoid for RF, and tear-drop shaped for MW ablation. MW ablation is less affected by tissue perfusion mainly due to the shorter ablation time and higher tissue temperature, but not due to MW providing deeper heating than RF. Both MW and RF applicators only produce significant direct heating within mm of the applicator, with most of the ablation zone created by thermal conduction.
Both RF and MW applicators only directly heat tissue in close proximity of the applicators. MW ablation allows for higher tissue temperatures than RF since MW propagation is not limited by tissue desiccation and charring. Higher temperatures coupled with lower treatment times result in reduced effects of perfusion on MW ablation.
doi:10.2174/1874120700701010047
PMCID: PMC2701080  PMID: 19662127
3.  Overlapping Ablation Using a Coaxial Radiofrequency Electrode and Multiple Cannulae System: Experimental Study in ex-Vivo Bovine Liver 
Korean Journal of Radiology  2003;4(2):117-123.
Objective
To assess the sizes and configurations of thermal zones after overlapping ablations using a coaxial radiofrequency (RF) electrode and multiple cannulae in ex-vivo bovine liver.
Materials and Methods
For ablation procedures, a coaxial RF electrode and introducer set was used. Employing real-time ultrasound guidance and overlapping techniques in explanted, fresh bovine liver, we created five kinds of thermal zones with one (n=10), two (n=8), four (n=3), and six ablation spheres (n=3). Following ablation, MR images were obtained and the dimensions of all thermal zones were measured on the longitudinal or transverse section of specimens. The shape of the composite ablation zones was evaluated using three-dimensional MR image reconstruction.
Results
At gross pathologic examination of ten single-ablation zones (spheres), the long-axis (transverse) and short-axis lengths of zones ranged from 3.7 to 4.4 (mean, 4.1) cm and from 3.5 to 4.0 (mean, 3.7) cm, respectively. The long-axis (transverse) and short-axis lengths of double-ablation zones (cylinders) with 23% overlap ranged from 7.0 to 7.7 (mean, 7.3) cm and from 3.0 to 3.9 (mean, 3.5) cm, respectively; those with 58% overlap ranged from 6.0 to 6.4 (mean, 6.2) cm and from 3.8 to 4.6 (mean, 4.3) cm, respectively. The long-axis (diagonal) and short-axis lengths on a transverse section of four-ablation zones (cakes) ranged from 8.5 to 9.7 (mean, 9.1) cm and from 3.0 to 4.1 (mean, 3.7) cm, respectively. Gross pathologic examination of three composite six-ablation zones (spheres) showed that the long-axis (diagonal) and short-axis lengths of zones ranged from 9.0 to 9.9 (mean, 9.4) cm and from 6.8 to 7.5 (mean, 7.2) cm, respectively. T2-weighted MR images depicted low-signal thermal zones containing multiple curvilinear and spotty regions of hyperintensity.
Conclusion
Using a coaxial RF electrode and multiple cannulae, together with ultrasound guidance and precise overlapping ablation techniques, we successfully created predictable thermal zones in ex-vivo bovine liver.
doi:10.3348/kjr.2003.4.2.117
PMCID: PMC2698069  PMID: 12845307
Radiofrequency (RF) ablation; Liver, interventional procedure; Animals
4.  CT-guided radiofrequency liver tumour ablation: use of a two-step coaxial system with a fine guide needle wire unit for high-risk cases 
The British Journal of Radiology  2010;83(996):1077-1079.
Accurate radiofrequency (RF) needle targeting to liver lesions under CT guidance is technically difficult and generally requires multiple needle manipulations, which carries potential risk. This approach is hardly applicable for precariously located lesions or for patients who have difficulty holding their breath. The aim of this study was to develop a novel two-step coaxial system to facilitate CT-guided RF ablation in difficult cases. The study group comprised 11 patients with 12 hepatic lesions. The coaxial system consisted of two parts: a 21-gauge pencil-tip guide needle wire (GNW) unit comprising a 150-mm-long needle segment and a 250-mm-long wire segment; and a 140-mm-long outer cannula with its stylet, which accepts a 17-gauge RF electrode needle. The GNW was inserted until the route of the GNW was confirmed to be positioned correctly. The cannula with the stylet was then advanced along the GNW. Lesions were successfully accessed using the GNW, even in patients who could not hold their breath, and manipulation was feasible within the limited space of the CT gantry. The light GNW also facilitated step-by-step CT-guided angular manipulations, unlike heavy RF electrodes, which are unstable during hands-free use unless deeply inserted. Therefore, this system enabled sequential ablations of large tumours by ensuring three different routes in advance by using the GNW. Insertion of the cannula along the GNW was simple. In conclusion, the two-step coaxial system enabled CT-guided RF tumour ablation to be performed in cases conventionally contraindicated owing to high risk of serious complications.
doi:10.1259/bjr/21804442
PMCID: PMC3473614  PMID: 21088092
5.  Hepatic radiofrequency ablation at low frequencies preferentially heats tumour tissue 
Purpose
Radiofrequency ablation is a clinically accepted treatment modality for liver cancer. There are significant differences in dielectric properties between normal and cancer tissue in the liver, which are particularly pronounced at frequencies below 100 kHz. This study performed computer simulations to determine whether radiofrequency (RF) ablation at lower frequencies than currently employed (450-500 kHz) can take advantage of this differenceto preferentially deposit energy within the tumour.
Materials and methods
Finite Element Method computer models were created for a cooled needle electrode and a multi-tine RF electrode inserted into a 2 cm diameter tumour. RF ablation was simulated and current density as well as tissue temperature distribution determined. In vivo data were used on electrical conductivity of normal and cancer tissue in the models to simulate RF ablation in liver at the currently used frequency of 500 kHz and at 10 kHz.
Results
At 500 kHz there was little difference in RF current density and final tissue temperature between normal and cancer tissue. Due to the more pronounced differences in electrical conductivity at 10 kHz, cancer tissue was heated preferentially at this frequency. Depending on power control algorithm, this resulted in either higher intra-tumour temperatures or lower temperatures outside the tumour at 10 kHz compared to 500 kHz.
Conclusion
Radiofrequency ablation at lower frequencies than currently used may preferentially heat the tumour and preserve normal tissue. A targeted device for selective tumour destruction may be designed to make use of this principle.
doi:10.1080/02656730601024727
PMCID: PMC2408946  PMID: 17079214
Radiofrequency ablation; RF ablation; thermal therapy; cancer; tumour ablation
6.  Microwave coagulation using a perfusion microwave electrode: Preliminary experimental study using ex vivo and in vivo liver 
To assess the coagulation capability of a perfusion microwave electrode (PME) as a key component of microwave coagulation therapy, a preliminary experimental study was performed using ex vivo and in vivo livers. For a microwave electrode, a PME was employed. Using a PME, saline was passed through the electrode and injected continuously into the target tissue. Using an ex vivo bovine liver, the range of tissue coagulation was measured for various volumes of infused saline and microwave outputs. Using an in vivo porcine liver, the efficiency of coagulation by a PME was compared with that of radiofrequency ablation (RFA) using a cool-tip needle. In an ex vivo bovine liver, the range of tissue coagulation increased as the flow rate of saline increased. In the in vivo porcine liver, the range of coagulation was similar to that found in the ex vivo bovine liver. With a PME under conditions of a microwave output of 80 W, a flow rate of 3 ml/min and irradiation time of 5 min, the range of coagulation was 44.8±2.8 mm [maximum vertical diameter: (a)] x 31.2±2.4 mm [maximum transverse diameter: (b)]. The range of RFA (cool-tip needle) at 12 min was 46.0±2.0 mm (a) x 30.2±2.0 mm (b). With only 5 min of microwave irradiation, the use of a PME enabled induction of the same range of coagulation that was obtainable by RFA for 12 min. In comparison with microwave coagulation without saline infusion, the use of a PME made it possible to extend the range of tissue coagulation to a range equal to that of RFA in a short time. Microwave coagulation using a PME may be one of the suitable tissue coagulation systems for local ablation treatment.
doi:10.3892/etm.2011.380
PMCID: PMC3438625  PMID: 22969871
perfusion microwave electrode; microwave coagulation; radiofrequency ablation
7.  Combined Radiofrequency Ablation and Acetic Acid Hypertonic Saline Solution Instillation: An In Vivo Study of Rabbit Liver 
Korean Journal of Radiology  2004;5(1):31-38.
Objective
We wanted to determine whether combined radiofrequency ablation (RFA) and acetic acid-hypertonic saline solution (AHS) instillation can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. We also wished to determine the optimal concentration of the solution in order to maximize its effect on extent of the RFA-induced coagulation.
Materials and Methods
Forty thermal ablation zones were produced in 40 rabbits by using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound guidance. The rabbits were assigned to one of four groups: group A: RFA alone (n=10); group B: RFA with 50% AHS instillation (n=10); group C: RFA with 25% AHS instillation (n=10); group D: RFA with 15% AHS instillation (n=10). A range of acetic acid concentrations diluted in 36% NaCl to a total volume of 1 mL were instilled into the liver before RFA. The RF energy (30 W) was applied for three minutes. After RFA, in each group, the maximum diameters of the thermal ablation zones in the gross specimens were compared. Technical success and the complications that arose were evaluated by CT and on the basis of autopsy findings.
Results
All procedures are technically successful. There were six procedure-related complications (6/40; 15%): two localized perihepatic hematomas and four chemical peritonitis. The incidence of chemical peritonitis was highest for group B with the 50% AHS solution instillation (30%). With instillation of 15% AHS solution, a marked decrease of tissue impedance (24.5 ± 15.6 Ω) and an increase of current (250 mA) occurred as compared to RFA alone. With instillation of the solutions before RFA (group B, C and D), this produced a greater mean diameter of coagulation necrosis than the diameters for rabbits not instilled with the solution (group A) (p < 0.05). However, there was no significant difference between group B, C, and D.
Conclusion
Combined AHS instillation and RFA can increase the dimension of coagulation necrosis in the liver with a single application. A low concentration of AHS (15%) showed similar effects in increasing the extent of RF-induced coagulation, but there were less side effects as compared to the high concentration of AHS.
doi:10.3348/kjr.2004.5.1.31
PMCID: PMC2698111  PMID: 15064557
Liver interventional procedures; Experimental study; Radiofrequency (RF) ablation
8.  High-Powered Gas-Cooled Microwave Ablation: Shaft Cooling Creates an Effective Stick Function Without Altering the Ablation Zone 
Ajr. American Journal of Roentgenology  2012;198(3):W260-W265.
OBJECTIVE
The purpose of our study was to validate the ability of a new gas-cooled microwave device to secure antennas into tissue before ablation via shaft cooling and to verify that such cooling does not compromise the intended ablation.
MATERIALS AND METHODS
The force required to extract several types of applicators from ex vivo bovine liver before and after ablation was measured. Six groups were compared: cooled needle and multitined radiofrequency electrodes, secured and unsecured cryoprobes, and gas-cooled microwave antennas (n = 6 each). Ablations were next created in in vivo porcine livers for 2 and 10 minutes (n = 6 each) using the gas-cooled microwave system at 140 W. Extraction force was again measured before and after ablation and compared between groups using analysis of variance with post hoc Student t tests. Histologic analysis of the ablation zone was performed to evaluate cellular necrosis along the antenna shaft.
RESULTS
Ex vivo, the secured cryoprobe and microwave antenna required significantly more force to remove than unsecured radiofrequency, cryoprobe, and microwave applicators (p < 0.05, all comparisons). The multitined radiofrequency electrode and cooled radiofrequency electrode required significantly more force to remove after ablation than before ablation (p = 0.006 and 0.02, respectively). In vivo, the secured antenna required significantly more force to remove before ablation than after ablation at both 2 (p < 0.0001) and 10 minutes (p < 0.0001). There was no histologic evidence of cell preservation along the antenna shaft.
CONCLUSION
The gas cooling used in this microwave device can effectively secure antennas into tissue without altering ablation shape or reducing the intended thermal damage.
doi:10.2214/AJR.11.6503
PMCID: PMC3298039  PMID: 22358023
cryogenic cooling; microwave ablation; thermal ablation
9.  Radiofrequency Ablation of Rabbit Liver In Vivo: Effect of the Pringle Maneuver on Pathologic Changes in Liver Surrounding the Ablation Zone 
Korean Journal of Radiology  2004;5(4):240-249.
Objective
We wished to evaluate the effect of the Pringle maneuver (occlusion of both the hepatic artery and portal vein) on the pathologic changes in the hepatic vessels, bile ducts and liver parenchyma surrounding the ablation zone in rabbit livers.
Materials and Methods
Radiofrequency (RF) ablation zones were created in the livers of 24 rabbits in vivo by using a 50-W, 480-kHz monopolar RF generator and a 15-gauge expandable electrode with four sharp prongs for 7 mins. The tips of the electrodes were placed in the liver parenchyma near the porta hepatis with the distal 1 cm of their prongs deployed. Radiofrequency ablation was performed in the groups with (n=12 rabbits) and without (n=12 rabbits) the Pringle maneuver. Three animals of each group were sacrificed immediately, three days (the acute phase), seven days (the early subacute phase) and two weeks (the late subacute phase) after RF ablation. The ablation zones were excised and serial pathologic changes in the hepatic vessels, bile ducts and liver parenchyma surrounding the ablation zone were evaluated.
Results
With the Pringle maneuver, portal vein thrombosis was found in three cases (in the immediate [n=2] and acute phase [n=1]), bile duct dilatation adjacent to the ablation zone was found in one case (in the late subacute phase [n=1]), infarction adjacent to the ablation zone was found in three cases (in the early subacute [n=2] and late subacute [n=1] phases). None of the above changes was found in the livers ablated without the Pringle maneuver. On the microscopic findings, centrilobular congestion, sinusoidal congestion, sinusoidal platelet and neutrophilic adhesion, and hepatocyte vacuolar and ballooning changes in liver ablated with Pringle maneuver showed more significant changes than in those livers ablated without the Pringle maneuver (p < 0.05)
Conclusion
Radiofrequency ablation with the Pringle maneuver created more severe pathologic changes in the portal vein, bile ducts and liver parenchyma surrounding the ablation zone compared with RF ablation without the Pringle maneuver. Therefore, we suggest that RF ablation with the Pringle maneuver should be performed with great caution in order to avoid unwanted thermal injury.
doi:10.3348/kjr.2004.5.4.240
PMCID: PMC2698168  PMID: 15637474
Animals; Liver, interventional procedure; Radiofrequency (RF) ablation
10.  Temperature Isotherms during Pulmonary Cryoablation and their Correlation with the Zone of Ablation 
PURPOSE
To determine the expected ablation zone size and associated isotherms when using clinically available percutaneous cryoprobes for pulmonary cryoablation in a porcine lung model.
MATERIALS AND METHODS
Seven ablations were performed in the lungs of three adult pigs using clinically available 2.4-mm cryoprobes (Endocare, Inc, Irvine, California) and a 10-minute double-freeze protocol. Five 18-gauge thermocouples were positioned at 5-mm increments (ie, 5, 10, 15, 20, and 25 mm) from the cryoprobe. Real-time tissue temperatures were recorded during the cryoablation. The isotherms obtained during the ablation and the pathological ablation zones were measured.
RESULTS
The pathologic zone of complete necrosis had a mean diameter of 2.4 ± 0.2 cm, with a mean area of 4.6 ± 0.6 cm2 and a circularity of 0.95 ± 0.04. In comparison, the mean diameter (± standard deviation) of the 0°C, −20°C, and −40°C isotherms were 3.1 ± 0.2 cm, 2.3 ± 0.3 cm, and 1.8 ± 0.4 cm, respectively. The −20°C isotherm was most closely related to the pathologic zone of ablation.
CONCLUSIONS
This study establishes the temperature isotherms and associated ablation zone size that can be expected with modern percutaneous cryoprobes in an in vivo porcine lung model.
doi:10.1016/j.jvir.2010.04.029
PMCID: PMC3158241  PMID: 20688532
11.  Usefulness of Real-Time 4D Ultrasonography during Radiofrequency Ablation in a Case of Hepatocellular Carcinoma 
We report a case of hepatocellular carcinoma (HCC) with chronic hepatitis C virus infection successfully treated with percutaneous radiofrequency ablation (RFA) under live four-dimensional (4D) echo guidance. A 65-year-old Japanese man had a HCC nodule in the liver S5 region 2.0 cm in diameter. We performed real-time 4D ultrasonography during RFA therapy with a LeVeen needle electrode. The echo guidance facilitated an accurate approach for the needle puncture. The guidance was also useful for confirming whether an adequate safety margin for the nodule had been obtained. Thus real-time 4D ultrasonography echo technique appears to provide safe guidance of RFA needles via accurate targeting of HCC nodules, thereby allowing real-time visualization when combined with echo contrast. Furthermore the position of the needle in a still image was confirmed in every area using a multiview procedure.
doi:10.1159/000321721
PMCID: PMC3082483  PMID: 21526141
Real-time 4D ultrasonography; Radiofrequency ablation; Hepatocellular carcinoma
12.  A Comparative Experimental Study of the In-vitro Efficiency of Hypertonic Saline-Enhanced Hepatic Bipolar and Monopolar Radiofrequency Ablation 
Korean Journal of Radiology  2003;4(3):163-169.
Objective
To compare the in-vitro efficiency of a hypertonic saline (HS)-enhanced bipolar radiofrequency (RF) system with monopolar RF applications by assessing the temperature profile and dimensions of RF-created coagulation necrosis in bovine liver.
Materials and Methods
A total of 27 ablations were performed in explanted bovine livers. After placement of two 16-gauge open-perfused electrodes at an interelectrode distance of 3 cm, 5% HS was instilled into tissue at a rate of 1 mL/min through the electrode. Seventeen thermal ablation zones were created in the monopolar mode (groups A, B), and ten more were created using the two open-perfused electrodes in the bipolar mode (group C). RF was applied to each electrode for 5 mins (for a total of 10 mins, group A) or 10 mins (for a total of 20 mins, group B) at 50W in the sequential monopolar mode, or to both electrodes for 10 min in the bipolar mode (group C). During RF instillation, we measured tissue temperature at the midpoint between the two electrodes. The dimensions of the thermal ablation zones and changes in impedance and wattage during RFA were compared between the groups.
Results
With open-perfusion electrodes, the mean accumulated energy output value was lower in the bipolar mode (group C: 26675 ± 3047 Watt·s) than in the monopolar mode (group A: 28778 ± 1300 Watt·s) but the difference was not statistically significant (p > 0.05). In the bipolar mode, there were impedance rises of more than 700 Ω during RF energy application, but in the monopolar modes, impedance did not changed markedly. In the bipolar mode, however, the temperature at the mid-point between the two probes was higher (85℃) than in the monopolar modes (65℃, 80℃ for group A, B, respectively) (p < 0.05). In addition, in HS-enhanced bipolar RFA (group C), the shortest diameter at the midpoint between the two electrodes was greater than in either of the monopolar modes: 5.4 ± 5.6 mm (group A); 28.8 ± 8.2 mm (group B); 31.2 ± 7.6 mm (group C) (p < 0.05)
Conclusion
Using an open perfusion system, HS-enhanced bipolar RFA more efficiently created larger areas of thermal ablation and higher tissue temperatures than monopolar RFA.
doi:10.3348/kjr.2003.4.3.163
PMCID: PMC2698083  PMID: 14530645
Liver, interventional procedures; Radiofrequency ablation; Experimental study
13.  The use of radiofrequency in cancer 
British Journal of Cancer  2005;92(10):1825-1829.
Radiofrequency ablation (RFA) provides an effective technique for minimally invasive tissue destruction. An alternating current delivered via a needle electrode causes localised ionic agitation and frictional heating of the tissue around the needle. Image-guided, percutaneous ablation techniques have been developed in most parts of the body, but the most widely accepted applications are for the treatment of hepatocellular carcinoma (HCC) in early cirrhosis, limited but inoperable colorectal liver metastases, inoperable renal cell carcinoma and inoperable primary or secondary lung tumours. The procedures are well tolerated and the complication rates low. Patients with coexistent morbidity who are not suitable for surgery are often able to undergo RFA. Most treatments in the lung, kidney and for HCC are performed under conscious sedation with an overnight hospital stay or as a day-case. Larger more complicated ablations, for example, in hepatic metastases may require general anaesthesia. Limitations of RFA include the volume of tissue that can be ablated in a timely fashion, that is, most centres will treat 3–5 tumours up to 4–5 cms in diameter. Early series reporting technical success and complications are available for lung and renal ablation. Liver ablation is better established and 5-year survival figures are available from several centres. In patients with limited but inoperable colorectal metastases, the 5-year survival ranges from 26 to 30% and for HCC it is just under 50%. In summary, RFA provides the opportunity for localised tissue destruction of limited volumes of tumour; it can be offered to nonsurgical candidates and used in conjunction with systemic therapy.
doi:10.1038/sj.bjc.6602582
PMCID: PMC2361772  PMID: 15870717
thermal ablation; radiofrequency; hepatocellular carcinoma; liver metastases; inoperable pulmonary malignancy; renal cell carcinoma
14.  Percutaneous Radiofrequency Thermal Ablation with Hypertonic Saline Injection: In Vivo Study in a Rabbit Liver Model 
Korean Journal of Radiology  2003;4(1):27-34.
Objective
To determine whether hypertonic saline (HS, 36% NaCl) injection prior to or during radiofrequency ablation (RFA) can increase the extent of thermally mediated coagulation in in-vivo rabbit liver tissue, and also to establish the ideal injection time in relation to RFA in order to maximize its effect on the extent of radiofrequency (RF)-induced coagulation.
Materials and Methods
In 26 rabbits, 43 RFA lesions were produced using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound (US) guidance. Rabbits were assigned to one of three groups: Group A: RFA alone (n=8); Group B: RFA after the instillation of 1 mL HS (n=8); Group C: RFA after and during the instillation of 0.5 mL HS (n=10). RF energy (30 W) was applied for 3 minutes, and changes occurring in tissue impedance, current, power output, and the temperature of the electrode tip were automatically measured. After RFA, contrast-enhanced spiral CT was performed, and in each group the maximum diameters of the thermal lesions in gross specimens were compared. Technical success and the complications arising were evaluated by CT and on the basis of autopsy findings.
Results
All procedures were technically successful. There were six procedure-related complications (6/26; 23%), including five localized perihepatic hematomas and one thermal injury to the stomach. With instillation of HS in group B rabbits, markedly decreased tissue impedance (73Ω ± 5) and increased current (704 mA ± 41) were noted, compared to RF ablation without saline infusion (116.3Ω ± 13, 308 mA ± 80). With instillation of the solution before RFA (group B), coagulation necrosis was greater (14.9 mm ± 3.8) than in rabbits not injected (group A: 11.5 mm ± 2.4; Group A vs. B: p < .05) and in those injected before and during RFA (group C: 12.5 mm ± 3.1; Group B vs. C: p > .05).
Conclusion
RFA using HS instillation can increase the volume of RFA-induced necrosis of the liver with a single application, thereby simplifying and accelerating the treatment of larger lesions. In addition, HS instillation before RFA more effectively achieves coagulation necrosis than HS instillation before and during RFA.
doi:10.3348/kjr.2003.4.1.27
PMCID: PMC2698055  PMID: 12679631
Experimental study; Liver, interventional procedures; Radiofrequency ablation
15.  Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods 
Background
Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases.
Results
A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode resulted in the lowest pressure as compared with the single-step or cool-tip methods. There was no significant difference in the ablation time between the multi-step and cool-tip ablation methods, although the single-step methods had longer ablation times than the other ablation procedures. In HCC cases, the multi-step method had a significantly shorter ablation time than the single-step or cool-tip methods.
Conclusion
We demonstrated that the multi-step method was useful to reduce the ablation time and to suppress the increase in pressure. The multi-step method using a LeVeen needle may be a clinically applicable procedure for RFA.
doi:10.1186/1476-5926-5-10
PMCID: PMC1764754  PMID: 17181870
16.  High Fidelity Computer Models for Prospective Treatment Planning of RF Ablation with in vitro Experimental Correlation 
Purpose
To evaluate the accuracy of computer simulation in predicting the thermal damage region produced by a radiofrequency (RF) ablation procedure in an in vitro perfused bovine liver model. The thermal dose end point in the liver model is used to quantitatively assess computer prediction for use in prospective treatment planning of RF ablation procedures.
Materials and Methods
Geometric details of the tri-cooled-tip electrode were modeled. The resistive heating of a pulsed voltage delivery was simulated in 4D using finite element methods (FEM) implemented on high performance parallel computing architectures. A range of physically realistic blood perfusion parameters, 3.6–53.6kg/s/m3 were considered in the computer model. An Arrhenius damage model was used to predict the thermal dose. Dice similarity coefficients (DSC) were the metric used to compare computational predictions to T1-weighted contrast enhanced images of the damage obtained from a RF procedure performed on an in vitro perfused bovine liver model.
Results
For a perfusion parameter greater than 16.3kg/s/m3, simulations predict the temporal evolution of the damaged volume is perfusion limited and will reach a maximum value. Over a range of physically meaningful perfusion values, 16.3–33.1kg/s/m3, the predicted thermal dose reaches the maximum damage volume within two minutes of the delivery and is in good agreement, DSC > 0.7, with experimental measurements obtained from the perfused liver model.
Conclusions
As measured by the computed volumetric DSC, computer prediction accuracy of the thermal dose shows good correlation with ablation lesions measured in vitro perfused bovine liver models over a range of physically realistic perfusion values.
doi:10.1016/j.jvir.2010.07.022
PMCID: PMC2966506  PMID: 20920840
17.  First In Vivo Use of a Capacitive Micromachined Ultrasound Transducer Array–Based Imaging and Ablation Catheter 
Objectives
The primary objective was to test in vivo for the first time the general operation of a new multifunctional intracardiac echocardiography (ICE) catheter constructed with a microlinear capacitive micromachined ultrasound transducer (ML-CMUT) imaging array. Secondarily, we examined the compatibility of this catheter with electroanatomic mapping (EAM) guidance and also as a radiofrequency ablation (RFA) catheter. Preliminary thermal strain imaging (TSI)-derived temperature data were obtained from within the endocardium simultaneously during RFA to show the feasibility of direct ablation guidance procedures.
Methods
The new 9F forward-looking ICE catheter was constructed with 3 complementary technologies: a CMUT imaging array with a custom electronic array buffer, catheter surface electrodes for EAM guidance, and a special ablation tip, that permits simultaneous TSI and RFA. In vivo imaging studies of 5 anesthetized porcine models with 5 CMUT catheters were performed.
Results
The ML-CMUT ICE catheter provided high-resolution real-time wideband 2-dimensional (2D) images at greater than 8 MHz and is capable of both RFA and EAM guidance. Although the 24-element array aperture dimension is only 1.5 mm, the imaging depth of penetration is greater than 30 mm. The specially designed ultrasound-compatible metalized plastic tip allowed simultaneous imaging during ablation and direct acquisition of TSI data for tissue ablation temperatures. Postprocessing analysis showed a first-order correlation between TSI and temperature, permitting early development temperature-time relationships at specific myocardial ablation sites.
Conclusions
Multifunctional forward-looking ML-CMUT ICE catheters, with simultaneous intracardiac guidance, ultrasound imaging, and RFA, may offer a new means to improve interventional ablation procedures.
PMCID: PMC3420825  PMID: 22298868
ablation; capacitive micromachined ultrasound transducer; electroanatomic mapping; electrophysiology; intracardiac echocardiography; intracardiac imaging; microelectromechanical system; thermal strain
18.  3D Electrode Displacement Elastography using the Siemens C7F2 fourSight 4D Ultrasound Transducer 
Ultrasound in medicine & biology  2008;34(8):1307-1316.
Because ablation therapy alters the elastic modulus of tissues, emerging strain imaging methods may enable clinicians for the first time to have readily available, cost effective, real-time guidance to identify the location and boundaries of thermal lesions. Electrode displacement elastography is a method of strain imaging tailored specifically to ultrasound-guided electrode-based ablative therapies (eg. radiofrequency ablation). Here tissue deformation is achieved by applying minute perturbations to the unconstrained end of the treatment electrode, resulting in localized motion around the end of the electrode embedded in tissue. In this paper, we present a method for 3D elastographic reconstruction from volumetric data acquired using the C7F2 fourSight 4D ultrasound transducer, provided by Siemens Medical Solutions. Lesion reconstruction is demonstrated for a spherical inclusion centered in a tissue-mimicking phantom, which simulates a thermal lesion embedded in a normal tissue background. Elastographic reconstruction is also performed for a thermal lesion created in vitro in canine liver using radiofrequency ablation. Post-processing is done on the acquired raw radiofrequency data to form surface-rendered 3D elastograms of the inclusion. Elastographic volume estimates of the inclusion compare reasonably well with the actual known inclusion volume, with 3D electrode displacement elastography slightly underestimating the true inclusion volume.
doi:10.1016/j.ultrasmedbio.2008.01.007
PMCID: PMC2597045  PMID: 18374467
3D; 4D; Ablation; Compression; Displacement; Elastography; Elastogram; Elasticity; Elasticity Imaging; Electrode Displacement; Radiofrequency Ablation; Strain; Strain Imaging; Ultrasound
19.  Ultrasound Simulation of Real-Time Temperature Estimation during Radiofrequency Ablation using Finite Element Models 
Ultrasonics  2007;48(1):40-55.
Radiofrequency ablation is the most common minimally invasive therapy used in the United States to treat hepatocellular carcinoma and liver metastases. The ability to perform real-time temperature imaging while a patient is undergoing ablation therapy may help reduce the high recurrence rates following ablation therapy. Ultrasound echo signals undergo time shifts with increasing temperature due to sound speed and thermal expansion, which are tracked using both 1D cross correlation and 2D block matching based speckle tracking methods. In this paper, we present a quantitative evaluation of the accuracy and precision of temperature estimation using the above algorithms on both simulated and experimental data.
A finite element analysis simulation of radiofrequency ablation of hepatic tissue was developed. Finite element analysis provides a method to obtain the exact temperature distribution along with a mapping of the tissue displacement due to thermal expansion. These local displacement maps were combined with the displacement due to speed of sound changes and utilized to generate ultrasound radiofrequency frames at specified time increments over the entire ablation procedure. These echo signals provide an ideal test-bed to evaluate the performance of both speckle tracking methods, since the estimated temperature results can be compared directly to the exact finite element solution. Our results indicate that the 1D cross-correlation (CC) method underestimates the cumulative displacement by 0.20 mm, while the underestimation with 2D block matching (BM) is about 0.14 mm after 360 seconds of ablation. The 1D method also overestimates the size of the ablated region by 5.4% when compared to 2.4% with the 2D method after 720 seconds of ablation. Hence 2D block matching provides better tracking of temperature variations when compared to the 1D cross-correlation method over the entire duration of the ablation procedure. In addition, results obtained using 1D cross-correlation diverge from the ideal finite element results after 7 minutes of ablation and for temperatures greater than 65°C.
In a similar manner, experimental results presented using a tissue-mimicking phantom also demonstrate that the maximum percent difference with 2D block matching was 5%, when compared to 31% with the 1D method over the 700 second heating duration on the phantom.
doi:10.1016/j.ultras.2007.10.005
PMCID: PMC2777513  PMID: 18082236
Ablation; elastography; elasticity; imaging; radiofrequency ablation; strain; speed of sound; thermal strain; thermal expansion; temperature imaging; thermal imaging; ultrasound; finite element analysis
20.  Doppler signals observed during high temperature thermal ablation are the result of boiling 
Purpose
To elucidate the causation mechanism of Spectral Doppler ultrasound signals (DUS) observed during high temperature thermal ablation and evaluate their potential for image-guidance.
Methods
Sixteen ex vivo ablations were performed in fresh turkey breast muscle, eight with radiofrequency ablation (RFA) devices, and eight with a conductive interstitial thermal therapy (CITT) device. Temperature changes in the ablation zone were measured with thermocouples located at 1 to 10mm away from the ablation probes. Concomitantly, DUS were recorded using a standard diagnostic ultrasound scanner. Retrospectively, sustained observations of DUS were correlated with measured temperatures. Sustained DUS was arbitrarily defined as the Doppler signals lasting more than 10 s as observed in the diagnostic ultrasound videos captured from the scanner.
Results
For RFA experiments, minimum average temperature (T1±SD) at which sustained DUS were observed was 97.2±7.3°C, while the maximum average temperature (T2±SD) at which DUS were not seen was 74.3±9.1°C. For CITT ablation, T1 and T2 were 95.7±5.9°C and 91.6±7.2°C, respectively. It was also observed, especially during CITT ablation, that temperatures remained relatively constant during Doppler activity.
Conclusions
The value of T1 was near the standard boiling point of water (99.61°C) while T2 was below it. Together, T1 and T2 support the conclusion that DUS during high temperature thermal ablation are the result of boiling (phase change). This conclusion is also supported by the nearly constant temperature histories maintained at locations from which DUS emanated.
doi:10.3109/02656731003801469
PMCID: PMC2922477  PMID: 20569109
boiling; conductive interstitial thermal therapy; doppler ultrasound; radio frequency ablation; tissue water; vaporization
21.  Evaluation of the In Vivo Efficiency and Safety of Hepatic Radiofrequency Ablation Using a 15-G Octopus® in Pig Liver 
Korean Journal of Radiology  2013;14(2):194-201.
Objective
To determine in vivo efficacy of radiofrequency ablation (RFA) in porcine liver by using 15-gauge Octopus® (15-G Octopus®) electrodes to create a large coagulation.
Materials and Methods
A total of 18 coagulations were created by using a 180-W generator and 15-G Octopus® electrodes during laparotomy, performed in 14 pigs. Coagulation necrosis was created in the pig livers by the use of one of three RFA protocols: 1) group A, monopolar RFA using a 15-G Octopus® electrode with a 5-mm inter-electrode distance (n = 4); 2) group B, monopolar RFA using a 15-G Octopus® electrode with a 10-mm inter-electrode distance (n = 6); and 3) group C, switching monopolar RFA using two 15-G Octopus® electrodes (n = 8). The energy efficiency, shape, maximum and minimum diameters (Dmx and Dmi), and the volume of the coagulation volume were measured in each group. The Summary statistics were obtained and Mann-Whitney test was were performed.
Results
The mean ablated volume of each group was 49.23 cm3 in A, 64.11 cm3 in B, and 72.35 cm3 in C. The mean Dmx and Dmi values were 5.68 cm and 4.58 cm in A and 5.97 cm and 4.97 cm in B, respectively. In group C, the mean diameters of Dmx and Dmi were 6.80 cm and 5.11 cm, respectively. The mean ratios of Dmi/Dmx were 1.25, 1.20, and 1.35 in groups A, B, and C, respectively. There was one animal death during the RFA procedure, the cause of which could not be subsequently determined. However, there were no other significant, procedure-related complications during the seven-hour-delayed CT scans.
Conclusion
RFA procedures using 15-G Octopus® electrodes are useful and safe for creating a large ablation in a single electrode model as well as in the multiple electrodes model.
doi:10.3348/kjr.2013.14.2.194
PMCID: PMC3590330  PMID: 23482995
Pulsed radiofrequency treatment; Liver; Ablation techniques
22.  Does Artificial Ascites Induce the Heat-Sink Phenomenon during Percutaneous Radiofrequency Ablation of the Hepatic Subcapsular Area?: an in vivo Experimental Study Using a Rabbit Model 
Korean Journal of Radiology  2009;10(1):43-50.
Objective
To evaluate the effect of the heat-sink phenomenon induced by artificial ascites on the size of the ablation zone during percutaneous radiofrequency (RF) ablation of the hepatic subcapsular area in an in vivo rabbit model.
Materials and Methods
A total of 21 percutaneous rabbit liver RF ablations were performed with and without artificial ascites (5% dextrose aqueous solution). The rabbits were divided into three groups: a) control group (C, n = 7); b) room temperature ascites group (R, n = 7); and c) warmed ascites group (W, n = 7). The tip of a 1 cm, internally cooled electrode was placed on the subcapsular region of the hepatic dome via ultrasound guidance, and ablation was continued for 6 min. Changes in temperature of the ascites were monitored during the ablation. The size of the ablation zones of the excised livers and immediate complications rates were compared statistically between the groups (Mann-Whitney U test, Kruskal-Wallis test, linear-by-linear association, p = 0.05).
Results
One rabbit from the "W" group expired during the procedure. In all groups, the ascites temperatures approached their respective body temperatures as the ablations continued; however, a significant difference in ascites temperature was found between groups "W" and "R" throughout the procedures (39.2±0.4℃ in group W and 33.4±4.3℃ in group R at 6 min, p = 0.003). No significant difference was found between the size of the ablation zones (782.4±237.3 mL in group C, 1,172.0±468.9 mL in group R, and 1,030.6±665.1 mL in group W, p = 0.170) for the excised liver specimens. Diaphragmatic injury was identified in three of seven cases (42.9%) upon visual inspection of group "C" rabbits (p = 0.030).
Conclusion
Artificial ascites are not likely to cause a significant heat-sink phenomenon in the percutaneous RF ablation of the hepatic subcapsular region.
doi:10.3348/kjr.2009.10.1.43
PMCID: PMC2647166  PMID: 19182502
Radiofrequency (RF) ablation; Liver, interventional procedure; Ascites; Carcinoma, Hepatocellular; Neoplasm, Metastasis
23.  Radiofrequency ablation of hepatocellular carcinoma extended into the portal vein: Preliminary results 
Journal of Ultrasound  2009;12(1):32-37.
Introduction
We report our preliminary results of radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and neoplastic portal thrombus (NPT) in cirrhotic patients.
Methods
Ten patients (7 males and 3 females; mean age 68 yrs) with 10 HCC nodules (37–49 mm) extended into the main portal vein (MPV) underwent RF ablation. Diagnosis of NPT was achieved by fine-needle biopsy. RF ablation was performed firstly on the NPT and then on the HCC. RF ablation was considered successful when complete necrosis of the HCC and complete recanalization of the MPV were achieved. HCC necrosis was evaluated using contrast-enhanced CT. Recanalization of the portal vessels (PV) was analyzed using Color Doppler (CD). RF ablation was performed under ultrasonographic (US) guidance using a perfused electrode needle.
Results
Complete necrosis of the HCC with complete recanalization of the PV was observed in 7 patients (success rate: 70%). In the remaining 3, necrosis of the HCC ranged from 70% to 95%, and recanalization of the PV was not complete. No major complications occurred. In 2 cases, mild ascites and increased aspartate aminotransferase/alanine aminotransferase (AST/ALT) values were observed. The follow-up ranged from 4 to 24 months; 1 and 2-year survival rates were 77% and 77%, respectively. At the last follow-up, the 7 successful patients were alive and the portal system was still patent. The 3 unsuccessful patients died within 5 months due to progressive disease.
Conclusion
RF ablation can destroy HCC and NPT achieving a high rate of efficacy and low rate of complications. However, to confirm these results a control group and a longer follow-up are required.
doi:10.1016/j.jus.2008.12.004
PMCID: PMC3553089  PMID: 23396977
Hepatocellular carcinoma; Cirrhosis; Portal vein; Tumor thrombus
24.  Radiofrequency Thermal Ablation of Hepatocellular Carcinomas 
Korean Journal of Radiology  2000;1(4):175-184.
Although surgical resection remains the best option as potentially curative therapy for hepatocellular carcinoma, radiofrequency thermal ablation has begun to receive much attention as an effective minimally invasive technique for the local control of unresectable malignant hepatic tumors. Most recent radiofrequency devices equipped with a powerful generator and larger needle electrode permit larger thermal lesions, up to 5 cm in diameter, with a single ablation. In this article, the author reviews the technical developments and early clinical results obtained with radiofrequency ablation techniques.
doi:10.3348/kjr.2000.1.4.175
PMCID: PMC2718198  PMID: 11752952
Liver neoplasms, CT; Liver neoplasms, US; Radiofrequency (RF) ablation
25.  Use of a novel coaxial guide needle-wire (GNW) combination system for computed tomography guided radiofrequency tumor ablation 
We developed a novel coaxial system using a fine guide needle wire (GNW) to safely and easily place the radiofrequency needle under CT-guidance. The GNW consists of a fine needle (diameter, 21-gauge; length, 150 mm) and a wire (0.018 inch, 250 mm). An exclusive radiofrequency cannula (14-gauge; 160 mm) was also used. This system was used for the treatment of six hepatocellular carcinomas in six patients. All lesions were located deeper than 10 cm from the needle entry site. This system was useful in performing CT-guided RF ablation for deeply or precariously located liver lesions particularly in patients who are unable to hold their breath.
doi:10.1186/1477-7819-9-127
PMCID: PMC3204259  PMID: 21995771

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