Computer-aided dynamic simulation of microwave-induced thermal distribution in coagulation of liver cancer

IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 48, NO. 7, JULY 2001 821

Computer-Aided Dynamic Simulation ofMicrowave-Induced Thermal Distribution in

Coagulation of Liver CancerPing Liang*, Baowei Dong, Xiaoling Yu, Dejiang Yu, Zhigang Cheng, Li Su, Jiansu Peng, Qun Nan, and

Huaijun Wang

Abstract—To develop a method of dynamic three-dimensional(3-D) simulation of thermal distribution in ultrasound-guidedmicrowave coagulation therapy of liver cancer and to verify its ac-curacy. The specific absorption rate (SAR) values were establishedby measuring the temperature in equivalent phantom tests. Thosevalues were different under different power output condition.Dynamic 3-D temperature distributions were reconstructed witha finite-element model. Testing and rectification were performedthrough animal experiments and clinical trials, respectively. Thetemperature curves in the experiments corresponded well withsimulated onesin vitro—91.4% and 88.9% using single and doubleelectrodes, respectively. The measured coagulated boundary andsimulated temperature boundary had a good correspondencein 85.7% of the specimens. In both in vivo experiments andclinical trials, blood perfusion influenced the rise in temperaturesignificantly. Temperature curves between the simulations andactual measured results showed good correspondence—67.8%(19/28) in the patients with hepatocellular carcinoma. Distancebetween electrodes and combined thermal distributions wereboth optimized with computer-aided simulation during simulta-neous two-electrode coagulation. The results demonstrated thatcomputer-aided simulation of microwave thermal distributionis an accurate and reliable method which provides a theoreticaland technical basis for controlling coagulated tissue volume andplacement of the electrodes during microwave coagulation therapyof liver cancer.

Index Terms—Computer simulation, interstitial thermaltherapy, liver cancer, microwave coagulation, needle electrode,thermal field.

I. INTRODUCTION

H EPATOCELLULAR carcinoma (HCC) is responsible formore than one million deaths per year worldwide and,

thus, remains a challenging medical problem [1]. It is the secondmost common malignancy in China. As it is generally resis-tant to commercially available anti-neoplastic agents and ra-diation therapy, clinicians have widely used surgical resection,transcatheter arterial chemotherapy embolization (TACE), andultrasound (US)-guided percutaneous ethanol injection therapy

Manuscript received September 6, 2000; revised March 21, 2001.Asteriskindicates corresponding author.

*P. Liang is with the Department of Ultrasound, Chinese PLA General Hos-pital, Beijing 100853, China.

B. Dong, X. Yu, D. Yu, Z. Cheng, and L. Su are with the Department ofUltrasound, Chinese PLA General Hospital, Beijing 100853, China.

J. Peng, Q. Nan, and H. Wang are with the Beijing Polytechnic University,Beijing, China.

Publisher Item Identifier S 0018-9294(01)05141-2.

(PEIT) as the initial treatment for HCC. Unfortunately, surgicalresection is not an option for more than two-thirds of patientswith HCC [1] because of poor liver function, multiple lesionslocated in different hepatic segments, tumor being adjacent tolarge blood vessels of the liver, or other contra-indications. Fur-thermore, it has been confirmed that after TACE, viable tumorcells have been found mainly in the extracapsular zone in smallHCCs [2] and the prognosis in small tumors is significantlybetter for capsulated than noncapsulated tumor [3].

PEIT is widely performed as a local interstitial therapybecause of its simplicity and minimal invasiveness. However,PEIT has been found to be ineffective when there is intracap-sular or extracapsular invasion; the injected ethanol is blockedby the fibrous capsule and fails to reach the tumor cells. In somecases, the injected ethanol diffuses into the vessels surroundingthe tumor instead of causing tissue necrosis [4]. Additionaldisadvantages of PEIT are that it requires a large number oftreatment sessions and it does not always produce completenecrosis [5]–[7].

There are have papers on implanted microwave coagulationtherapy for HCC in recent years. Sekiet al. [8], [9], suggestedthat percutaneous microwave coagulation therapy was an effec-tive percutaneous local treatment for small HCCs, which can in-duce more complete tumor necrosis than PEIT. Murakamiet al.[10], reported that percutaneous microwave coagulation therapycould achieve complete tumor necrosis in five out of nine pa-tients with HCC. Donget al. [11], reported 41 cases with HCCand ten cases with hepatic metastasis treated with a modifiedUS-guided percutaneous microwave coagulation system whichproduces a necrosis volume of 3726 26 mm with 60 W300 s. As an encouraging result, the authors concluded that thistreatment appears to be safe and effective in the treatment ofliver cancer.

To gain satisfactory clinical therapeutic effect, it is essential toensure complete coagulated necrosis volume covering the entiretumor. Many papers have discussed the evaluated coagulation ofcoagulated tissue necrosis during thermal therapies. Magneticresonance imaging (MRI) was one sensitive and useful tool.As Chen [12] has reported, MRI-derived temperatures were lin-early related to the fluoroptic tissue temperatures and can beused to guide thermo-ablation. However, using MRI as a meansof monitoring temperature is too expensive clinically.

Goldberg [13] reported radio-frequency (RF)-induced coag-ulated necrosis in rabbits enables immediate detection with USusing a synthetic microsphere contrast agent. Solbiati [14] used

0018–9294/01$10.00 © 2001 IEEE

822 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 48, NO. 7, JULY 2001

an US microbubble contrast agent to assess the therapeutic re-sults after RF ablation of hepatic metastases. The result assumedthat contrast-enhanced US may depict residual tumor after RFapplication and thereby enable additional directed therapy.

The above procedures proved to be time consuming andcostly methods for evaluating the results of thermal therapy.In the present study, we set out to establish a reliable methodto predict thermal distribution before microwave therapy. Toour knowledge, there are no existing reports on modeling 3-Dthermal distribution with computer for percutaneous microwavecoagulation treatment of liver cancer to date.

The purpose of this study is to model the temperature distri-bution in three dimensions during percutaneous microwave co-agulation therapy of liver cancer. Knowledge of the thermal dis-tribution will help determine: 1) the feasibility and accuracy ofcomputer-aided simulation; 2) the type of coagulated area thatcan be expected in three dimensions under different power leveland exposure times; and 3) the usefulness of computer-aidedsimulation in optimizing clinical therapeutic plans.

To model the thermal distribution, the specific absorptionrate (SAR) distribution must be determined for the needle elec-trode of percutaneous microwave therapeutic systems for livercancer. The SAR measurements were made in tissue-equivalentmicrowave phantom material and the SAR was determinedfrom the initial temperature transient at various locations in thephantom. The SAR distribution was then used in conjunctionwith a finite-element heat transfer model to determine thetemperature field. A parametric study of the effect of mi-crowave power and tissue perfusion on the rise in temperatureis also performed. The temperature curve of the finite-elementmodel (FEM) is compared to temperatures achieved during theexperimental and clinical studies.

II. M ATERIALS AND METHODS

A. Equipment

Microwave Coagulation:The UMC-I (US-guided Mi-crowave Coagulator) was designed by our department andInstitute 207 of Aerospace Industry Company (Beijing,People’s Republic of China). Its microwave generator operatedat 2450 MHz with a power output of 10–80 W. The system wasequipped with a low-loss cable and a needle electrode (1.4 mmin diameter) with a surface coating to prevent tissue adhesion.

Sonographic Systems:Acuson 128 XP10/ART andHDI-5000 with 3.5- to 7.0-MHz transducers were used.

B. SAR Study in Phantom

Phantom: As no liver-equivalent microwave phantom isavailable, the muscle-equivalent microwave phantom was usedinstead of liver tissue, as there are similar electric characteristicsbetween muscle and liver tissue [15].

FEM: The purpose of this FEM is to predict the temper-ature profile achieved during clinical thermal therapy of livercancer and to determine the effect of varying treatment parame-ters. These treatment parameters are 1) microwave power level(wattage and time) and 2) tissue blood perfusion. In this model,it assumed that the thermal properties are homogeneous and areconstant at all temperatures. Since the treatment lasts for 5–30

TABLE ISAR/�c VALUES IN DIFFERENTPOWER OUTPUTS(Z > 0; Z < 0)

min, the temperature distribution is assumed to be at a steadystate during most of the treatment. The tissue is assumed tobe uniformly perfused by blood. The effect of perfusion on thelocal tissue heat transfer is assumed to follow Pennes’ formula-tion [16], [17]. For the finite-element solution, a commerciallyavailable software package called ANSYS (V 5.3, Ansys Soft-ware Engineering Technology, Co., Ltd., Canonsburg, PA), isused.

SAR Measurements:In order to minimize the number ofSAR measurements, the symmetry of the SAR distributionwas studied from preliminary experiments using the phantom.If the temperature distribution in the homogeneous phantomwas symmetric, then the heat sink was also symmetric alongthe same axis. Once the symmetry of the SAR had beenverified, SAR measurement was concentrated in the areas ofunique SAR distribution. In this area, thermocouples were usedto measure SAR during transient heating [18]. Preliminaryexperiments in the homogeneous phantom demonstrated thatthermal distribution was axially symmetric. However, in thedirection (along the electrode), the power deposition is asym-metrical. Therefore, temperature measurements were carriedout in two quadrants ( and ). The distal 27 mmof the electrode was naked and placed in the area of treatment.The highest temperature center was at distal 15 mm from theelectrode (Table I). Iron-constantan thermocouples (TCs) wereused to measure the temperature. TCs 0.075 mm in diameterfrom Omega Engineering, Inc., Stamford, CT, were usedbecause they have low microwave pickup, fast risetime, andgood sensitivity to temperature. Data acquisition (HP34970A,Hewlett Packard Company) with 16-bit analog output functionwas used. The reading rate of data acquisition was up to600 readings/s on a single channel and the scan rate was up to250 channels/s. The data acquisition module was connectedto a computer through an RS-232 interface to monitor thetemperature changes dynamically. Thermal distributions ofoutput power levels widely used by clinicians of 60 W 300 s,50 W 10 min, and 40 W 30 min were calculated and predictedwith computer-aided simulation. Sixteen thermocouples wereused to measure the transient temperature from which the SARvalues were determined. The data were acquired at a rate of10 Hz (Fig. 1).

The electrode is inserted and the TCs are placed in the planeof interest before phantom material sets [Fig. 1(b)]. Theaxisis along the electrode and theaxis is perpendicular to the elec-trode. The transient temperature rise of the TCs was measured atthe instant the microwave power was turned on. Power levels of

LIANG et al.: COMPUTER-AIDED DYNAMIC SIMULATION OF MICROWAVE-INDUCED THERMAL DISTRIBUTION 823

Fig. 1. (A) Thermal device in phantom microwave coagulator. (B) Position ofthermocouples and (C) electrode phantom, (D) container of ice-water mixture,(E) data acquisition, and (F) computer.

40 W, 50 W and 60 W were applied for 100 s, respectively, andtemperature measurements were recorded every 500 ms. After100 s, the power was turned off and the phantom was allowedto cool. If the temperature of the phantom did not change morethan 0.01 C, the same procedure was repeated. Such measure-ments were performed in 16 sites each time and at each site wererepeated 5–9 times at the same power output level. The final re-sults were the average of the above values.

C. In Vitro Study

In vitro experiments of pig liver were carried out to verifythe simulation of thermal distribution. Fresh pig livers of morethan 6 cm in thickness were used to observe the entire shapeof the coagulated area. Iron-constantan thermocouples were in-serted and fixed into 20G PTC needle sheathes with naked tipsof 5 mm to measure the temperature. The electrodes and ther-mocouples needles are fixed in a specially designed device se-curing them in place parallel to the electrode in a prefixed dis-tance [Fig. 2(A)]. The thermocouple needles were placed intothe liver at intervals of 5 mm from the electrode. In each exper-iment, 6–8 thermocouple needles were placed simultaneously.Measurement at each site was repeated 5–7 times. Such temper-atures measurements were made on 105 sites and 36 sites whilemicrowave radiation was emitted (60 W 300 s, 50 W 10 min,and 40 W 30 min) through single and double electrodes, respec-tively. To enlarge the coagulated tissue volume and optimizethe distance between electrodes, the thermal field distributionof double electrodes was studied. In order to simplify the cal-culation process, coagulated volumes were first simulated whentwo electrodes acted simultaneously with the same implantationdepth and energy output. The SAR value of two electrodes wascalculated by linear layering of each electrode SAR. The max-imal distance between two electrodes was set through computersimulation while maximizing the coagulated area and simulta-neously merging them into one bigger area which attains an in-tegrated shape, leaving no tumor tissue untreated. The distri-butions of three-dimensional thermal fields with computer sim-ulation were obtained under different power output levels andradiation times. Thermophysical properties of pig liverin vitroare shown in Table II.

D. In Vivo Study

Experiments were performed according to a protocol ap-proved by our institution’s animal care and use committee andaccording to the guidelines issued by the National Institutes ofHealth for the care of laboratory animals. Six pigs, weighing100–150 kg, were anesthetized with a 2.5% solution of sodiumthiopental administered intravenously. Using an aseptic tech-nique, the sonographically guided microwave coagulationwas performed at laparotomy ten times. The temperaturesof 32 spots in pig liver were recorded under three differentpower outputs (60 W 300 s, 50 W 10 min, and 40 W 30 min).Specimens were obtained from the above sites through biopsiesand examined with light and electrical microscopy. The proce-dures and placementsin vivo were the same as thosein vitro[Fig. 2(A)]. The precise positions of electrodes and thermalneedles were monitored with US [Fig. 2(B)]. Thermophysicalproperties of pig liverin vivo are shown in Table III.

E. Clinical Study

Clinically, all treatments were performed at the Chinese PLAGeneral Hospital with approval from the institutional ethicscommittee. Written informed consent was obtained from allpatients at enrollment. During the clinical procedure, the poweroutputs were set at 60 W 300 s, 50 W 10 min, and 40 W 30 min.

Based on the above resultsin vivo, the level of bloodperfusion influenced temperature significantly. In the HCC,this condition was more complex. Combining color Dopplerfindings with known blood perfusion properties of tissue, theblood flow within the tumor can be divided into 4 grades.I: no blood flow within the tumor; II: 1 2 spots showingDoppler signals of blood flow within the tumor; III: 34 spotsof Doppler blood flow signals showing or 12 small bloodvessels within the tumor; and IV: 4 spots of Doppler bloodflow signals within the tumor or 2 small blood vessels. Theblood perfusion in the tumor was then set correspondingly as1.5 3.0 Kg/m /s, 3.0 4.5 Kg/m /s, 4.5 6.0 Kg/m /s, and6.0 8.0 Kg/m /s. Other thermophysical properties are shownin Table III.

In order to test and rectify simulating thermal fields of livertumor, measurements of temperatures using thermocouple nee-dles were performed in ten patients with HCC during proce-dures of percutaneous microwave coagulation therapy. Beforetreatment, a detailed plan was worked out on an individual basis.According to the above criteria of blood flow and correspondinggrades of tissue blood perfusion, there were two cases of GradeI, 4 cases of Grade II, three cases of Grade III and one case ofGrade IV among these ten patients. With the help of sonographyand the needle-guided device, the electrode could be insertedinto the designated site within the tumor. One to three thermalneedles were placed at different sites within the tumor. The tem-peratures of 24 spots within the tumor of the ten patients with tennodules were compared to the temperatures of the FEM values.Rebiopies were performed in the ten patients at the above 16temperature measurement spots after seven days of microwavecoagulation therapy. Specimens were examined with light mi-croscopy.


Fig. 2. (A) Animal experiments in pig liver. (B) The position of electrode and thermal needles was observed with intraoperative US (electrode, T1 4 thermalneedles).

TABLE IITHERMOPHYSICAL PROPERTIES OFPIG LIVER in vitro [19]

III. RESULTS

A. Determination of SAR in Phantom Studies

At the instant, power is switched on, the conduction heattransfer in the phantom is negligible, and the partial derivativeof temperature is in respect to the SAR. Therefore, the bioheattransfer equation can be simplified as follows:

SAR

where is the density of the phantom andis the specific heat.Fig. 3 shows the representative plot of transient temperature

increase for two TCs at different power output levels. The tran-sient temperature rise was proportional to the slope of the line(Fig. 3). The SAR data are used with an FEM to predict the risein temperature during microwave radiation. It was convenientto represent the SAR data as an analytical expression. Thus, anequation fits the SAR data in three dimensions. As thermal dis-tribution was axially symmetric, variation in thedirection wasnegligible. In the direction, SAR shows an exponential decay.In the direction, it corresponds to a third-order polynomial.SAR values are different in the and in the direc-tions. The SAR data are determined from the transient tempera-

TABLE IIITHERMOPHYSICAL PROPERTIES INLIVER AND LIVER TUMOR [20]

Fig. 3. Transient temperature in the phantom material atz =0 cm forθ= 0 Candr = 5 mm. The transient temperature rise is proportional to the slope of theline.Y = 0.4038x+ 25.087,Y = 0.3632x+ 21.088.

ture early in the heating cycle. A linear least-squares residual fitis performed to the temperature in time. These slopes are pro-portional to the SAR at the location of the corresponding TC.SAR/ data under different power output levels in theand directions are shown in Table I.

FEM is used in two ways. First, the model is used to simulatethe clinical protocol for liver therapy and to predict thermal dis-tributions. Second, FEM is used to determine the influence ofenergy output and tissue perfusion on the temperature.


(a)

(b)

Fig. 4. Comparison of measured coagulated temperatures in normal pig liverwith simulated temperaturesin vitro along z direction (θ = 0 C). (a) Orangeperipheral rim (54 C) in thermographic map is corresponding to coagulatedarea in experiment The coagulated area is 3� 4.5 cm (single electrode).(b) Peripheral blue rim (54 C) in thermographic map is corresponding tocoagulated area in experiment The coagulated area is 6.0� 6.0 cm (doubleelectrodes).

B. Tissue Experiment

A lot of temperature data under different power outputs wereobtained through measuring 105 or 36 spots with single anddouble electrode, respectively. The result of experimental tem-perature curves compared well with FEM simulation in 91.4%(96/105) and 88.9(32/36) using single and double electrode,respectively. A comparison between the measured coagulationboundary (52 54 C) in normal pig liver and the simulated tem-perature boundary of 54C had a good correspondence in 18 of21 specimens with single or double electrodes in three dimen-sions. (Figs. 4 and 5). The coagulated volume (the temperatureprofile defined as the boundary of tissue at 54C) with com-puter simulation in three dimensions is shown in Fig. 6.

C. Animal Experiments

The FEM can be used with the SAR measurements to simu-late the temperature rise during animal experiments. During theprocedure, the power outputs are set at 60 W 300 s, 50 W 10min and 40 W 30 min. The effect of blood perfusion has beentaken into consideration and it has been assumed that the perfu-sion in normal liver is 9.19 Kg/m/s [20]. The thermal proper-ties have been shown in Table III. The temperature curves of 32sites within pig liver were compared to temperatures of FEM.Comparing the temperature curves of measured values with thecomputer simulation curves, good correspondence (defined asthe difference 3 C) was achieved in 20 of 32 spots (62.5%);

small deviations (defined as the difference3 C 6 C)were found in five of 32 spots (15.6%); significant deviations(defined as the difference6 C) were seen in seven of 32 spots(21.9%). The blood perfusion influenced the rise in tempera-ture significantly. The temperature difference between differentlevels of blood perfusion between 3.0 Kg/m/s and 8.0 Kg/m/swas close to 30C in the same spots (Fig. 7). The comparisonof coagulated volumes betweenin vitro and in vivo studies isshown in Table IV. The local temperature was lower in the ex-periments than that in the simulation when the electrode wasclose to large blood vessels (defined as -mm portal veinor hepatic vein, -mm hepatic artery). In four spots, thetemperature increase reached a plateau quickly; further increaseof the temperature could be attained only through output powerincreases, but not through an increase in the duration. Patho-logic findings from biopsy showed hepatocellular vacuolar de-generation in cytoplasm, organelles reduction in cytoplasm andKaryolysis in nucleus under light and electrical microscopy, re-spectively, as soon as the temperature reached 54C or more inthe liver tissue.

D. Comparison of Temperature in Liver Tumorwith FEM Values

The temperatures were dynamically acquired during the mi-crowave radiation in 28 sites in ten patients. Comparing the tem-perature curves of measured values with the computer simula-tion curves, good correspondence occurred in 19 of 28 spots(67.8%) (Fig. 8); small deviations were found in five of 28 spots(17.9%); significant deviations were seen in four of 28 spots(14.3%). Posttreatment biopsies were performed in the aboveten patients who consented to receive a second biopsy sevendays after the microwave therapy. The specimens were takenfrom different temperature measurement spots within or aroundthe tumor. Biopsies showed complete necrosis of tumor tissueand no viable tumor cells within the tumor as the temperaturessurpassed 50C within the tumor or around the tumor. On theother hand, it was showed that incomplete necrosis of the tumorwhen the measured temperature was less than 50C, whichneeded a second coagulation therapy.

It was also demonstrated that measured temperatures cor-responded well with computer simulation when there are nolarge tumor blood vessels (defined as -mm portal vein,

-mm hepatic artery) within or around the mass. Whenlarge feeder blood vessels existed within the tumor in two spots,the measured temperatures were lower than simulated ones.Thermal efficiency of microwave coagulation will be improvedif preinduction high power output (80 W) or mechanical meansare used to block large tumor feeder vessels.

IV. DISCUSSION ANDCONCLUSION

Percutaneous induction of coagulated necrosis with thermalenergy sources such as microwave [8]–[10], RF [21]–[23], andlaser [24], [25] energy has recently been promoted as a mini-mally invasive technique for tumor coagulation. Potential ben-efits of this technique include treatment of nonsurgical candi-dates, reduced morbidity compared to surgery, and ability for


(a)

(b)

Fig. 5. Comparison of measured coagulated temperatures in normal pig liver with simulated temperaturesin vitro z = 0 direction. (a) Peripheral yellow rim(54 C) in thermographic map is corresponding to coagulated area in the experiment. The coagulated area is 3.4� 3.4 cm. (Single electrode (50 W 10 min.) (b)Peripheral yellow rim (54C) in thermographic map is corresponding to coagulated area in the experiment. The coagulated area is 4.7� 3.4 cm. (Double electrode(50 W 10 min.)

real-time imaging guidance. For this procedure, a needle elec-trode is placed directly into the tumor with imaging guidance.Most often, this procedure is performed using ultrasonography,as this modality is widely available and allows for real-timevisualization with precise, accurate placement of the electrode[13].

It is essential to coagulate the whole tumor and its margin.However, many studies have demonstrated that findings fromgray-scale, color, and power Doppler US after coagulation donot correlate well with the extent of the induced coagulation[13], [21]–[23]. Either underestimation or overestimation of thecoagulated area may occur using US. Furthermore, the US ap-pearance of treated area changes rapidly after ablation such thatthe actual size of the necrosis is difficult to estimate with US.Many investigators have used contrast US, contrast computed

tomography (CT) [9], [11] and gadolinnium-enhanced magneticresonance imaging (MRI) to determine the extent of inducedcoagulation. The absence of perfusion has been shown to corre-spond to regions of coagulated necrosis [21]–[23]. Contrast US,contrast CT and gadolinnium-enhanced MRI can not predict thethermal distribution before thermal therapy.

To our knowledge, the thermal distribution is regular duringthe thermal coagulation, which can be expressed by temperaturechanges. Furthermore, temperature correlates well with the ex-tent of the coagulated necrosis. Most authors believe that com-plete necrosis of normal hepatocytes can be achieved at a tem-perature of 54 C for 1 min or instantly when the temperaturereaches 60C. Liver tumor cells are more sensitive to heat thannormal hepatocytes [11]. The present study shows that completenecrosis can be obtained when the temperature reaches 54C


Fig. 6. The coagulated volume on 3-D with a power of 50 W 10 minin vitro.The blue surface temperature is 54C.

TABLE IVCOMPARISON OFCOAGULATED VOLUME in vitro AND in vivo (r� θ � zcm)

Fig. 7. Effect of perfusion on temperature atr = 5 mm,z = 0 andθ= 0 Cagainst time with a power output of 60 W 300 s.

in normal liver tissue or 50C in liver tumor tissue instantly.Therefore, temperature is an objective criterion to evaluate co-agulated necrosis. With previous means of temperature mea-surement, the temperatures in some spots were recorded onlywhile the power was turned off. It was obvious that the en-tire temperature field distribution in three dimensions could notbe reconstructed by means of measuring temperature in somespots. The thermal fields of microwave radiation induced by im-planted microwave electrodes were studied in order to observethermal distribution of microwave radiation and to improve theobjectivity and predictability of microwave therapy.

As axial symmetry of the thermal distribution (and di-rections), the temperature measurements are carried out in two

Fig. 8. Comparison of temperature curves between simulation andmeasurement in clinical patients with HCC. Temperature changes against timeat 60 W 320 s (10-s interval in each 100 s) atr = 10 mm, (θ= 0 C, andZ =�15 mm.

quadrants (along the electrode in and direc-tions). The speed of the temperature increase in the di-rection was faster than that in the one. The coagulatedvolume was asymmetric along the electrode in thedirection.It was larger in the direction than in the direction(Fig. 4). The coagulated volume was an asymmetrical ellipse,which was a better shape for clinical applications.

It was essential to point out that the SAR measurement corre-sponded to the specific tissue type and specific power outputlevel. At different power outputs, SAR distribution was dif-ferent. In the present experiment, the SAR values at 40 W, 50 W,and 60 W were determined. Furthermore, there was no linear re-lationship between the SAR distribution and power outputs.

The temperatures were decreased progressively from theelectrode center to the surrounding tissue. The temperaturecurves of computer simulation were close to the experimentalonesin vitro in 91.4% (96/105) and 88.9(32/36) in single anddouble electrodes, respectively. There was good correspon-dence in 85.7% (18/21) of the specimens in three dimensions incomparison between the measured coagulated tissue boundaryand simulated temperature boundary of 54C with FEMin vitro, which demonstrated that the method using FEM tosimulate the thermal distribution is feasible. However, ininvivoanimal experiments and clinical studies the results showedthe blood perfusion influenced the temperature curves signifi-cantly. Due to changes in tissue perfusion, temperature increasein vivo was more complex than thosein vitro. It was clearlyindicated that the coagulation volumes (54 C) were smallerin vivo than thosein vitro under the same energy output levels(Table IV). Our studies demonstrated there was little differencebetween coagulated volumes at higher power outputs (60 W)betweenin vitro and in vivo experiments. At decreasing levelsof power output, the differences of coagulated tissue volumesbetweenin vitro andin vivo studies became obvious gradually.

When the electrode was close to large liver blood vessels orlarge feeder blood vessels of the tumor, the temperature curveincreased slowly. Larger central portal veins had increasedblood flow and a larger heat sink compared to smaller periph-eral portal veins. Sometimes the temperatures reached a plateauwithout further increase with over time. The likely reasons isthat computer-predicted temperature models assumed that theperfusion was constant and independent of space, time and tem-


perature, while in actuality it was known that perfusion variedin space and that perfusion increased during hyperthermia.When there were large intrahepatic vessels present, the heat wastaken away more rapidly by local blood flow. Therefore, thelocal temperature increase slowed dramatically. Sometimes themeasured temperatures were lower by about 5C–15 C thanthose of simulated temperatures. This phenomenon could bealtered by blockage of large tumor feeder blood vessels withinliver tumors before coagulation therapy. In our experience, ahigh power output (80 W 300 s) could block portal vein orhepatic vein flow if less than 5 mm in diameter. For the hepaticartery, this power output only blocked arteries less than 0.7 mmin diameter. Blockage of blood vessels larger than the aboverequired trans-vessel embolization or mechanical means. Inour clinical trial, good correspondence was most likely in thetumors with blood perfusion, Grade I or II. Large deviationswere most likely in tumors with blood perfusion of Grade IVor with large tumor feeder vessels.

Another promising aspect of thermal therapies is that anumber of investigators have shown novel methods of creatinglarge volumes of coagulated tissue necrosis. In radiofrequencytherapy, Goldberg [26] demonstrated that increased tissuedestruction could be performed using multiple probes. Mc-Gahan [27], [28] showed that bipolar radiofrequency could bean effective method of causing increased tissue coagulationcompared to the monopolar technique. The authors reveal thatcreating large areas of tissue destruction may be helpful intreatment of liver metastasis or HCC. In the present study,maximum width ( direction) of coagulated tissue volume usinga single electrode at different power outputs (60 W 300 s, 50 W10 min, and 40 W 30 min) varied from 2.6 to 3.4 cmin vivo.To eliminate the tumor cells at the periphery, an area of 5 mmbeyond the tumor should be included in the coagulation andat the same time the tumors should be possibly covered in oneemission or multiple emissions as close together as possible.Therefore, for the nodules smaller than or equal to 2.4 cm indiameter, only one puncture and one emission was required.For nodules over 2.4 cm in diameter, double electrodes ormultiple electrodes were required. A large coagulated volumecould be obtained when double electrodes were used inand

directions.There was a good correspondence between computer simula-

tion and clinical studies in 67.8% of the measured temperaturespots. Double electrode computer simulation provided a theo-retical and technical basis for computer simulating thermal dis-tribution using multi-electrodes. It also provided the possibilityfor adjusting and controlling the thermal field using computersimulation in large and irregular tumors. In previous studies[8]–[10], the decision to use multiple-puncture and -emission,and determining the needle position depended mainly on the ex-perience of doctors and had no basis in objective criteria. There-fore, overlapping coagulation may have occurred and the coag-ulated volume was not enlarged adequately if the two electrodeswere placed too close together or incomplete tumor necrosismay occur between the two centers if the two electrodes wereplaced too far apart. In this study, optimized distance betweenelectrodes was determined with computer simulation. This en-sured a large coagulated necrosis volume without the potentialpresence of residual small central foci of malignancy.

During the present microwave coagulation procedure, weused the double electrode radiation simultaneously for twocoagulation sites instead of coagulating two spots separatelywith a single electrode each. The advantage of double electrodesimultaneous radiation was to get a larger coagulated volumeunder the same power output conditions. This method increasedthe efficiency of thermal compensation between coagulationpoints and shortened the temperature rising time, so the coagu-lation effect was improved. Using double electrodes (Table IV),diameter of coagulation was significantly enlarged in thedirection. Slight enlargement of the diameter occurred in thedirection and there was no change in thedirection. In order toenlarge the coagulation volume in three dimensions, we shoulduse three or four electrodes.

Due to differences in blood perfusion, homogeneity and den-sity of tumor tissue, there are varying thermophysical proper-ties in different tumor tissue. Therefore, temperature deviationwould occur between computer simulation and actual measuredtemperature. Generally speaking, this deviation was less than5 C. Studies of thermophysical properties in different liver tu-mors are on-going.

In conclusion, localized microwave coagulation therapy forliver cancer is one of the available nonsurgical modalities. Theuse of the microwave electrode was investigated, and this studymodeled the temperatures achieved during animal experimentsand clinical procedures on those results. A comparison of com-puter simulation with animal experimentsin vitro and in vivo,and with clinical studies was also presented. The results indi-cated that the experimentsin vitro compared well with computersimulation. In thein vivoexperiments and clinical trials, the risein temperature had a strong dependence on the level of bloodperfusion. The measured temperatures were lower than the sim-ulated temperature in the tumor with rich blood flow. Underthese conditions, thermal needles placed in regions of rich bloodflow must have with feedback control of the energy output levelto compensate for the heat carried away by the increase in bloodflow. The level of temperature increase corresponded well withpathological changes of tissue damage and necrosis.

The results of the experiments and clinical trials demon-strated that predicting microwave thermal distribution withcomputer simulation is an accurate and reliable method, whichcan dynamically monitor the temperature curve in 3-D. Itprovides a theoretical and technical basis for controlling thesize of the thermal field and temperatures during the microwavehyperthermia treatment of liver cancer and reaches the aim ofeliminating the tumor in situ after one treatment in most cases.

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Ping Liang received the M.D. degree in medical sci-ence in 1986 from the Second Military Medical Uni-versity, Shanghai, China.

She completed her residency in surgery from1986 to 1988 and has been with the DiagnosticUltrasound Department at the Chinese PLA GeneralHospital, Beijing, China, from 1987 to present. Shewas promoted to Professor in 2000. She has studiedpercutaneous microwave ablation of liver cancerwith sonographic guidance for nearly ten years.She has done the research in microwave thermaldistribution for five years. Her research interests

include the application of bioheat and mass transfer analysis to medical science,microwave-tissue thermal interactions, and hyperthermia treatment of tumorsand computer-aided thermal distribution.

Baowei Dongreceived the M.D. degree in medicalscience from the Peking Union Medical College in1965.

He worked as General Surgeon from 1965 to 1979.He began in clinical diagnostic ultrasound in 1979.He was an Associate Professor and Chief of the Di-agnostic Ultrasound Department from 1985 to 1991.He was promoted to Professor in 1989. Since 1992,he has been Professor and Supervisor of Ph.D degreecandidates and Head of the Ultrasound Departmentat the Chinese PLA General Hospital and Chinese

PLA Military Medical Graduate College, Beijing, China. He has studied per-cutaneous microwave ablation of liver cancer with ultrasound guidance for thelast ten years, including microwave thermal research, which were supported fi-nancially four times by the National Natural Science Foundation of China. Hewas Vice Chairman of Ultrasonography at the Chinese Medical Society andChairman of Ultrasonography Society of Beijing from 1995 to 2000.

Xiaoling Yu , photograph and biography not available at time of publication.

Dejiang Yu, photograph and biography not available at time of publication..

Zhigang Cheng, photograph and biography not available at time of publication..

Li Su, photograph and biography not available at time of publication..

Jiansu Peng, photograph and biography not available at time of publication..

Qun Nan, photograph and biography not available at time of publication..

Huaijun Wang , photograph and biography not available at time of publication.

Documents

Computer-aided dynamic simulation of microwave-induced thermal distribution in coagulation of liver cancer