Phase Compensation Technique for Effective Heat Focusing in Microwave Hyperthermia Systems

applied sciences

Article Phase Compensation Technique for Effective Heat Focusing in Microwave Hyperthermia Systems

Seonho Lim and Young Joong Yoon *

The Electrical and Electronic Engineering Department, Yonsei University, Seoul 03772, Korea; [email protected] * Correspondence: [email protected]

Abstract: In this paper, effective electromagnetic (EM) focusing achieved with a phase compensation technique for microwave hyperthermia systems is proposed. To treat tumor cells positioned deep inside a human female breast, EM energy must be properly focused on the target area. A circular antenna array for microwave hyperthermia allows EM energy to concentrate on a specific target inside the breast tumor. Depending on the cancerous cell conditions in the breast, the input phases of each antenna are calculated for single and multiple tumor cell locations. In the case of multifocal breast cancer, sub-array beam focusing via the phase compensation technique is presented to enhance the ability of EM energy to concentrate on multiple targets while minimizing damage to normal cells. To demonstrate the thermal treatment effects on single and multiple tumor locations, the accumulation of the specific absorption rate (SAR) parameter and temperature changes were verified using both simulated and experimental results.

Keywords: microwave hyperthermia; circular array antenna; phase compensation technique; tumor treatment; electromagnetic beam focusing; female breast phantom

Citation: Lim, S.; Yoon, Y.J. Phase Compensation Technique for Effective Heat Focusing in 1. Introduction Microwave Hyperthermia Systems. Breast cancer treatments have been investigated throughout the past decade, and Appl. Sci. 2021, 11, 5972. https:// thermal treatments for breast cancer using microwaves are being rapidly developed to doi.org/10.3390/app11135972 reduce the dangerous side effects associated with conventional methods [1]. Primary breast cancer treatments include surgical operations, radiotherapy, chemotherapy, and Academic Editor: Akram Alomainy hyperthermia. Among these, microwave hyperthermia is an effective treatment that uses a beneﬁcial heating effect. Because cancerous tissues are highly vascularized, and it is harder Received: 6 May 2021 to remove excess heat from them than from healthy tissues, thermal damages are sensitive Accepted: 25 June 2021 Published: 27 June 2021 to the cancer [2]. A non-invasive microwave hyperthermia system for cancer treatment is reliable, cost effective, and painless compared with surgical operations. Furthermore,

Publisher’s Note: MDPI stays neutral hyperthermia has a synergistic effect when used in combination with radiation oncology with regard to jurisdictional claims in or chemotherapy [3–6]. In hyperthermic systems, tumor cells are damaged under the ◦ published maps and institutional affil- temperature range of 43–47 C, while normal cells are not damaged [7]. Non-invasive iations. microwave hyperthermia employing an antenna array is a reliable treatment method that can achieve effective breast tumor necrosis [8]. In this procedure, electromagnetic (EM) energy is radiated from array elements and concentrated on the tumor region, where heating is applied for treatment [9–11]. Microwave hyperthermia for deep-seated tumors inside the human breast should be Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. designed so that EM energy can be transferred well into the interior of the body. The human This article is an open access article body is composed of various dielectric tissues that make it difficult to provide a suitable distributed under the terms and EM energy concentration because of dielectric losses [12]. One of the challenges of this conditions of the Creative Commons treatment method is to design microwave hyperthermia systems that, while focusing the Attribution (CC BY) license (https:// EM energy into the human body, heat only malignant tissues, without overheating normal creativecommons.org/licenses/by/ tissues [13]. Mathematically, accurate EM energy focusing methods are essential for optimal 4.0/). accumulation. Many techniques, such as the time reversal method, specific absorption rate

Appl. Sci. 2021, 11, 5972. https://doi.org/10.3390/app11135972 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, 5972 2 of 15

(SAR) optimization, temperature optimization, and phased array, have been researched to prove the efficacy of hyperthermia treatments [14–19]. The SAR optimization technique can assume the correlation between SAR and temperature to anticipate deviations in thermal boundary conditions [14–16]. Temperature-based optimization seeks to optimize the temperature distribution; however, this method is dependent on the properties of the thermal tissue, which results in very large uncertainty and higher computational costs than the SAR-based optimization technique [14,19]. Therefore, the SAR optimization method for effective energy focusing using a phased array is a very attractive technique due to the practicality of its implementation and its simple procedure [14–17,19–21]. To deliver microwaves inside the breast, the input phase of each antenna should differ depending on the location of the tumor cells. Strong constructive interference in the target area can be achieved with accurate phase control. Narrowband phased-array antenna systems for treating single targets that operate on a single frequency best suited for healing superficial and single tumor locations are presented in [18,20,21]. However, these systems have some issues, such as the relatively large number of hot spots, poor resolutions, and their limitation to unicentric breast cancers. Multifocal/multicentric breast cancers, which occur when there is more than one distinct type of tumor cell in a single quadrant, are more aggressive and are associated with worse outcomes than unifocal cancers [22]. Hyperthermia therapy for multiple tumor locations has been studied by [23,24]. In [23], iron oxide nanoparticle-loaded nanocapsules were injected into different tumor positions to be used with magnetic hyperthermia therapy. In [24], a multi-frequency excitation approach for multiple tumor locations was proposed for enhanced EM energy penetration and the resolution of its localization. However, the nanocapsule must be injected into the treatment area [23], and the power source unit is too complex to provide the signals required for multiple-frequency excitation [24]. In this paper, effective EM focusing with a novel phase compensation technique for multifocal microwave hyperthermia is proposed. A narrowband signal at 2.45 GHz is applied to the array antenna elements to organize a simple power supply circuit. The antenna array configuration is optimized for application to a small female breast and for an effective electric field (E-field) concentration on the target area. To deliver a use- ful therapeutic result, each antenna excites an equal polarization signal, which requires elaborate control of the input phase. Depending on the tumor condition in the breast phantom, the input phases of each antenna are calculated for single and multiple targets with phase delay compensation. For multifocal breast cancer, the energy localization on each tumor cell is important for the minimization of damage to normal cells. To enhance the EM energy focused on multiple targets, the sub-arrays are designated near each tumor location for maximum energy transformation. Therefore, sub-array antennas with a phase compensation technique applying a modified phase are proposed for multicentric breast carcinoma. To demonstrate the thermal treatment effects under single and multiple tumor conditions, the SAR distributions and temperature changes are obtained via simulations and experiments with a breast phantom.

2. The Antenna Array System for Microwave Hyperthermia Treatment The antenna array configurations for breast cancer treatments are determined by the type, aperture size, and polarization characteristics of the designed single antenna. The prototype of the tapered slot antenna (TSA) and circular array configuration presented in this paper were proposed in our previous paper [25], which aimed to use the above elements in microwave imaging and hyperthermia systems. To verify the antenna performances, a 3D simulation of a cylindrical breast phantom was performed and the SAR and temperature results were presented in 2D planes. An antenna for delivering microwaves to a deep- seated tumor should be designed to induce strong constructive interference of the E-field. Therefore, an antenna array is used to deliver EM energy to tumor cells located deep inside the breast phantom. Each antenna is arranged vertically to be efficiently organized around the small female breast phantom and for effective E-field synthesis [16,21]. Appl. Sci. 2021, 11, 5972 3 of 15

deep inside the breast phantom. Each antenna is arranged vertically to be efficiently organized around the small female breast phantom and for effective E-field synthesis [16,21].

2.1. The Antenna for the Array Configuration Since this paper is a part of ongoing research related to our existing work, the antenna for microwave hyperthermia used in this study was a TSA, based on our previous study [25]. The designed TSA has a small aperture size for easier application, and has been optimized to effectively deliver EM energy into the breast. The design configuration of a Appl. Sci. 2021, 11, 5972 single antenna is presented in Figure 1a. To verify the EM effects on the 2D plane, a cylin-3 of 15 drical shaped artificial breast phantom that takes into account the breast’s fatty component (휀r = 5.14, σ = 0.137 S/m) was modelled as homogeneous medium [26]. The designed TSA was printed on an 0.8-mm-thick FR-4 substrate (휀 = 4.3, tanδ = 0.025) over an 80 mm 2.1. The Antenna for the Array Configuration r × 40 mm area, as shown in Figure 1b [25]. The meander line was designed beneath the taperedSince slot this ofpaper the TSA is ato part operate of ongoing at 2.45 researchGHz for the related microwave to our existing hyperthermia work, thetreatment. antenna forIn microwaveFigure 2, the hyperthermia simulated and used measured in this study reflection was a coefficients TSA, based are on ourcompared. previous The study reflec- [25]. Thetion designed coefficient TSA (푆 has11) awas small measured aperture under size for the easier condition application, presented and hasin Fig beenure optimized 1a, where to effectivelythe designed deliver antenna EM i energys in direct into contact the breast. with Thethe phantom. design configuration For the antenna of a singlemeasurement antenna isand presented thermal inexperiment, Figure1a. a To gelatin verify-based the EM phantom effects was on the fabricated 2D plane,, and a cylindricalthe dielectric shaped prop- artificialerty of performed breast phantom phantom that is takes휀r = 5.1 into at account 2.45 GHz the [27]. breast’s fatty component (εr = 5.14, σ = 0.137For effective S/m) was electric modelled field concentration as homogeneous in the mediumfemale breast [26]. phantom, The designed each antenna TSA was is printedarranged on verticall an 0.8-mm-thicky. For these FR-4 antennas substrate’ arrangement, (εr = 4.3, tan theδ same= 0.025) linear over polarization an 80 mm profile× 40 mm in area,each asarray shown antenna in Figure element1b is [ 25related]. The to meander the effective line hyperthermia was designed treat beneathment. In the Figure tapered 3, slotthe ofE-field the TSAdistribution to operate at 2.45 at 2.45GHz GHz in the for breast the microwavephantom, including hyperthermia in the tumor treatment., is pre- In Figuresented.2, A the spherical simulated breast and tumor measured of radius reflection r = 5 mm coefficients is positioned are compared. in the center The of reflectionthe cylin- coefficientdrical phantom.(S11) Aswas shown measured in this underfigure, thethe conditionpolarization presented of the single in FigureTSA antenna1a, where is well the- designedformed along antenna the z is-axis. in direct A full contact simulation with thewas phantom. performed For with the FIT antenna-based measurementCST Studio Suite and thermal2019 [28]. experiment, a gelatin-based phantom was fabricated, and the dielectric property of performed phantom is εr = 5.1 at 2.45 GHz [27].

(a) (b)

Appl. FigureSci.Figure 2021 1., 1.11 (,(a a5972)) Simulation configuration conﬁguration of of the the single single tapered tapered slot slot antenna antenna (TSA) (TSA) and ( andb) geometry (b) geometry of this ofantenna this antenna for micro- for4 of 15

microwavewave hyperthermia hyperthermia [25]. [25].

FigureFigure 2.2. TheThe simulatedsimulated andand measuredmeasured reﬂectionreflection coefﬁcientscoefficients forforthe theused used TSA TSA antenna. antenna.

For effective electric field concentration in the female breast phantom, each antenna is arranged vertically. For these antennas’ arrangement, the same linear polarization profile in each array antenna element is related to the effective hyperthermia treatment. In Figure3 , the E-field distribution at 2.45 GHz in the breast phantom, including in the tumor, is presented. A spherical breast tumor of radius r = 5 mm is positioned in the center of the

Figure 3. Simulated E-field distribution at 2.45 GHz in the breast phantom derived from a single TSA antenna.

2.2. Antenna Array Configuration for Effective Electric Field Concentration As mentioned in the previous section, the designed TSA antenna is linearly polarized along the radiation direction, and each antenna should be aligned along the surface of the cylindrical phantom for effective E-field synthesis. The number of radiators, which should be determined for the successful E-field concentration on the target area, was set at 12 due to the SAR accumulation in the breast phantom, in accordance with our previous study [25]. The array configurations for inducing microwave hyperthermia along the xz- and xy-planes are presented in Figure 4a,b, respectively. To feed the array antenna, simultaneous excitation is induced with an EM simulation tool. To apply the input power to each antenna, a discrete port is assigned to each TSA and the open boundary condition in CST is set to analyze the antennas’ performances. The narrowband antennas are arranged at regular intervals for vertical linear polarization along the z-axis.

(a) (b) Figure 4. The 3D model of the cylindrical TSA antenna array with vertical polarization: (a) xz-plane and (b) xy-plane. Appl. Sci. 2021, 11, 5972 4 of 15

Appl. Sci. 2021, 11, 5972 4 of 15

Appl. Sci. 2021, 11, 5972 4 of 15 Figure 2. The simulated and measured reflection coefficients for the used TSA antenna.

cylindrical phantom. As shown in this ﬁgure, the polarization of the single TSA antenna is well-formed along the z-axis. A full simulation was performed with FIT-based CST Studio SuiteFigure 2019 2. The [28 simulated]. and measured reflection coefficients for the used TSA antenna.

Figure 3. Simulated E-field distribution at 2.45 GHz in the breast phantom derived from a single TSA antenna.

2.2. FigureAntennaFigure 3.3. Simulated SimulatedArray Configuration E-fieldE-field distributiondistribution for Effective atat 2.452.45 GHzElectricGHz inin thethe Field breastbreast Concentration phantomphantom derivedderived fromfrom aasingle single TSATSA antenna.antenna. As mentioned in the previous section, the designed TSA antenna is linearly polarized along2.2.2.2. the AntennaAntenna radiation ArrayArray direction, ConfigurationConfiguration and for foreach EffectiveEffective antenna ElectricElectric should FieldField ConcentrationbeConcentration aligned along the surface of the cylindricalAsAs mentionedphantmentionedom for inin theeffectivethe previousprevious E-field section,section, synthesis. thethe designeddesigned The TSAnumberTSA antennaantenna of radiators, isis linearlylinearly which polarizedpolarized should be determinedalongalong thethe radiation for the successfuldirection, and and E- fieldeach each antennaconcentration antenna should should onbe be alignedthe aligned target along along area, the thewas surface surface set atof the12 of due to thethecylindrical SAR cylindrical accumulation phant phantomom for ineffective for the effective breast E-field E-field phantom synthesis. synthesis., inThe accordance number The number of radiators,with of radiators,our which previous whichshould study [25]should.be The determined array be determined configurations for the forsuccessful the successfulfor Einducing-field E-fieldconcentration microwave concentration on thehyperthermia ontarget the area, target was area,along set was atthe 12 set xz due at- and xy-planes12to duethe SAR toare the presented accumulation SAR accumulation in Figurein the inbreast 4a the,b, breastrespectively.phantom phantom,, in accordance To in feed accordance the with array our with previousantenna, our previous studysimulta- study [25]. The array configurations for inducing microwave hyperthermia along the neous[25] excitation. The array is configurationsinduced with foran EMinducing simulation microwave tool. hyperthermiaTo apply the alonginput thepower xz- andto eac h xz- and xy-planes are presented in Figure4a,b, respectively. To feed the array antenna, antenna,xy-planes a discrete are presented port is assignedin Figure to4a ,eachb, respectively. TSA and theTo feedopen the boundary array antenna, condition simulta- in CST simultaneousneous excitation excitation is induced is induced with an with EM ansimulation EM simulation tool. To tool. apply To the apply input the power input powerto each is set to analyze the antennas’ performances. The narrowband antennas are arranged at toantenna, each antenna, a discrete a discrete port is port assigned is assigned to each to TSA each and TSA the and open the open boundary boundary condition condition in CST in regular intervals for vertical linear polarization along the z-axis. CSTis set is to set analyze to analyze the theantenna antennas’s’ performances. performances. The The narrowband narrowband antennas antennas are are arranged arranged at atregular regular intervals intervals for for vertical vertical linear linear polarization polarization along along the the z- z-axis.axis.

(a) (a) (b()b ) FigureFigure Figure4. The 4. 4.3DThe The model 3D3D modelmodel of the ofof cylindrical thethe cylindricalcylindrical TSA TSA TSA antenna antenna antenna array array array with with with vertical vertical vertical polarization: polarization:polarization: ( a( a()a) xz-plane )xz xz-plane-plane and and and ( b(b) ) xy-plane.( bxy) -xyplane.-plane.

2.3. The Specific Absorption Rate and Temperature Increase The EM field produced by the TSA antenna array elements propagates toward the inside of the breast phantom and concentrates in the target area. The localized EM energy is used to calculated the SAR parameter, which is defined as a measure of energy absorbed per unit mass of the human body in the unit time t. The SAR is defined as the time derivative of the incremental energy (dW) absorbed by the incremental mass (dm) [29].

d dW d dW SAR = = (1) dt dm dt ρ(dV) Appl. Sci. 2021, 11, 5972 5 of 15

The incremental mass dm can be replaced with a volume element dV for a given density of the tissue ρ. The SAR factor can also be deﬁned for time-harmonic E-ﬁelds using the Poynting vector theorem [30]: σ 2 SAR = E (2) 2ρ i

where σ is the electrical conductivity of the tissue material and Ei is the intensity of the internal E-field in volts per meter. The average SAR parameter is defined as the ratio of the total power absorption per unit mass of the exposed human body. The induced E-field interacts with the body and changes the temperature depending on the square of the magnitude of the E-field strength. The analysis of temperature distribution as a function of the applied external E-field was conducted to broaden our study to incoporate multiphysics methods. To show the rate of temperature increase in human tissue exposed to external microwave energy, the Pennes bioheat equation is given below [31]:

∂T 1 2 ρC = σ E + ∇·(k∇T) + W C (T − T)v (3) p ∂t 2 b b b

where ρ, Cp, k, and σ are the density, heat capacity, thermal conductivity, and electric conductivity of tissue, respectively, and Wb and Cb are the perfusion rate and heat capacity of blood, respectively. The external E-ﬁeld is an essential factor for determining the temperature increase in the exposed tissue over a certain period of time following the EM exposure of the TSA antennas’ array.

3. Electromagnetic Focusing for Microwave Hyperthermia 3.1. Electromagnetic Focusing for Unifocal Breast Cancers Each TSA antenna radiates with precise input phase characteristics to provide effective treatment to randomly positioned cancer cells in the breast phantom. The radius of the breast tumor for microwave hyperthermia treatment was set at 5 mm. The breast tissue properties of the fat and the tumor applied to all simulations are presented in Table1 to verify the SAR and temperature distributions.

Table 1. Dielectric and thermal properties of breast tissues at 2.45 GHz [32].

Properties Fat Tumor

Dielectric permittivity εr 5.14 55 Loss tangent tan δ 0.137 0.29 Density ρ (kg/m3) 920 920 Thermal conductivity σ (W/K/m) 0.42 0.42 Heat capacity Cp (J/K/kg) 3000 3000

The phase delay of each antenna (ϕn) should be compensated to focus the E-field on the target position, thereby localizing the heat operation to a treatment area. The input phase characteristics of the TSA antenna array can be defined by compensating the phase delay caused by the different path lengths of the antennas to the target tumor. Hence, the in-phase condition of the radiated E-fields can be satisfied with an unifocal breast cancer, leading to strong constructive interference. Figure5 presents a schematic view of the EM waves focusing on the breast phantom while the array configuration encircles the breast phantom. The phase delay of each antenna is calculated to meet the requirements for the in-phase condition of the E-field deep inside the phantom. The locations of the antennas are defined as (xn, yn) and the cancer location in the phantom is defined as (xt1, yt1). The path length from each antenna to the cancer location defined by 2D Cartesian coordinates can be defined as: q 2 2 PLn = (xt1 − xn) + (yt1 − yn) (4) Appl. Sci. 2021, 11, 5972 6 of 15

Appl. Sci. 2021, 11, 5972 6 of 15

where n is the current antenna number. The radius of the breast phantom is 50 mm, with the middle deﬁned as (0,0), so with Cartesian coordinates, each path length between wherethe radiating n is the antenna current andantenna cancer number. location The can radius be calculated of the breast and phantom converted is 50 to themm phase, with theas follows: middle defined as (0,0), so with Cartesian coordinates, each path length between the 180 2π 180 radiating antenna and ϕcancer= locationk × PL can× be calculated= × andPL converted× to the phase as fol-(5) PLn n π λ n π lows: eff where k is the wave number, and λeff is the effective wavelength in the phantom (εr = 5.14) Tableat 2.45 1. GHz.Dielectric To determineand thermal the properties input phasesof breast of tissues each antenna,at 2.45 GHz the [32]. phase delay should be calculated accordingly: Properties Fat Tumor ϕn = ϕPLn − ϕmin (6) Dielectric permittivity 휀r 5.14 55 where ϕmin isLoss the tangent minimum tan 훿 phase value among0.137 the 12 path lengths.0.29 Therefore, the 3 calculated ﬁnalDensity input phase휌 (kg/ϕmn is) the total compensating920 input phase to satisfy920 the in-phase conditionThermal on the conductivity focusing area. σ (W/K/m) Thus, ϕ n of each antenna0.42 is calculated depending0.42 on the tumor position.Heat capacity 퐶p (J/K/kg) 3000 3000

Figure 5. The EMEM waveswaves focusing focusing on on the the breast breast phantom phantom with with different different path path lengths lengths from TSAfrom antennas. TSA antennas. To verify that the EM was focusing on the unifocal cancer, the input phases of each antenna when the tumor was positioned at (20,0) mm and (15,15) mm were calculated 180 2π 180 for the xy-plane in Table2휑. These= 푘 calculated× PL × input= phases× PL (×ϕn) were aimed to enhance(5) PL푛 푛 π 휆 푛 π the constructive interference of the E-ﬁeld at the focaleff point, which leads to a high SAR wheredistribution k is the on the wave treatment number, area. and The 휆eff maximum is the effective SAR distribution wavelength values in the at (20,0) phantom mm (and휀r = (15,15)5.14) mmat 2.45 according GHz. To todetermine the xy-planes the input presented phases in of Figure each antenna,6a,b are 23.1the phase W/kg delay and should27.7 W/kg, be calculated respectively, accordingly: at the focal points. 휑 = 휑 − 휑 Table 2. Calculated input phases for unifocal푛 breastPL푛 cancer.min (6)

where 휑min is the minimum phase value among the 12 path lengths. Therefore, the cal- Position of culated final input phase 휑푛 isAntenna the total Number compensating input phase to satisfy the in-phase Single Tumor condition on the focusing area. Thus, 휑 of each antenna is calculated depending on the (x ,y ) 푛 t1 t1 1 2tumor 3 position. 4 5 6 7 8 9 10 11 12 (20, 0) mm 159◦ 90.6◦ 27.8To ◦verify0◦ that the27.8 EM◦ was90.6 ◦focusing159◦ on the216.3 unifocal◦ 253.7 cancer,◦ 266.7 the ◦input253.7 phases◦ 216.3of each◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ (15,15) mm 53.8 0 antenna0 when53.8 the tumor126.6 was194.2 positioned244.6 at (20,0)271.3 mm and271.3 (15,15)244.6 mm were194.2 calculated126.6 for the xy-plane in Table 2. These calculated input phases (휑푛) were aimed to enhance the constructive interference of the E-field at the focal point, which leads to a high SAR distribution on the treatment area. The maximum SAR distribution values at (20,0) mm and (15,15) mm according to the xy-planes presented in Figure 6a,b are 23.1 W/kg and 27.7 W/kg, respectively, at the focal points.

Appl. Sci. 2021, 11, 5972 7 of 15 Appl. Sci. 2021, 11, 5972 7 of 15

(a) (b)

FigureFigure 6. 6.The The 2D 2D section section of of SAR SAR distributions distributions focusedfocused at different tumor tumor positions: positions: (a ()a (20,0)) (20,0) mm mm and and (b) ( b(15,15)) (15,15) mm. mm.

3.2.Table Electromagnetic 2. Calculated Focusing input phases for Multifocal for unifocal Breast breast Cancer cancer. Position of In the case of multifocalAntenna breast Number cancer, time and costs can be reduced by treating Single Tumor 1 2 multiple3 tumors4 simultaneously5 6 rather7 than sequentially.8 9 Unlike10 for a single11 tumor,12 the (풙 , 풚 ) 퐭ퟏ 퐭ퟏ calculation method for the input phases (ϕn) for multiple targets should be modified to (20, 0) mm 159° 90.6deliver° 27.8 precise° 0 EM° energy27.8° deposition.90.6° 159 In° deep-seated 216.3° 253.7 tumors,° 266.7 the°TSA 253.7 antennas° 216.3 should° ° ° ° ° ° ° ° ° ° ° ° ° (15,15) mm 53.8 0 transfer 0 adequate53.8 energy126.6 to necrotize194.2 244.6 the tumor 271.3 cells without271.3 harming244.6 194.2 the normal 126.6 tissue. To enhance the thermal focusing, an exquisite phase control technique should be applied 3.2. Electromagnetic Focusing for Multifocal Breast Cancer to each microwave antenna, and unwanted electric field focusing should be avoided. Thus, the multipleIn the case E-field of multifocal focusing breast technique cancer, with time a sub-arrayand costs can antenna be reduced configuration by treating and mul- phase compensationtiple tumors simultaneously technique will rather be discussed. than sequentially. Unlike for a single tumor, the cal- culationThe configurationmethod for the ofinput the phases E-field focused(휑푛) for onmultiple two breast targets tumors should withbe modified an antenna to de- sub- arrayliver is precise presented EM energy in Figure deposition.7. The radii In deep of the-seated two tumors,breast tumors the TSA for antennas multifocal should breast cancertransfer were adequate set at energy 5 mm asto well.necrotize The the magnitude tumor cells of without the radiated harming E-field the isnormal decreased tissue. due To enhance the thermal focusing, an exquisite phase control technique should be applied to the dielectric loss component of the breast phantom. Therefore, in terms of the tumor to each microwave antenna, and unwanted electric field focusing should be avoided. positions, designating the antennas that are closest to the tumor cell as a sub-array ensures Thus, the multiple E-field focusing technique with a sub-array antenna configuration and E-field concentration on each breast tumor. Therefore, as shown in Figure7, sub-arrays #1 phase compensation technique will be discussed. and #2 consist of antennas #1–6 and #7–#12, respectively. Tumor cells #1 and #2 are located The configuration of the E-field focused on two breast tumors with an antenna sub- at positions (x , y ) and (x , y ) in the phantom, respectively. To focus the E-field on array is presentedt1 t1in Figure t27. Thet2 radii of the two breast tumors for multifocal breast two breast tumors at the same time, each antenna sub-array radiates the E-field onto tumor cancer were set at 5 mm as well. The magnitude of the radiated E-field is decreased due cellsto the #1 dielectric and #2. The loss input component phase ofof eachthe breast antenna phantom. sub-array Therefore, should in be terms calculated of the separately tumor topositions, provide designating optimal focusing the antennas depending that are on closest the multiple to the tumor targets. cell Theas a sub phase-array delay ensures of each antennaE-field concentration is calculated toon meeteach breast the requirement tumor. Therefore, of the in-phase as shown condition in Figure of7, sub the- E-fieldarrays #1 deep insideand #2 the consist phantom. of antenna Hence,s #1 the–6 and path #7 length–#12, respectively. from each antenna Tumor cells sub-array #1 and to #2 the are tumor located cells using 2D Cartesian coordinates can be defined as follows: at positions (푥t1, 푦t1) and (푥t2, 푦t2) in the phantom, respectively. To focus the E-field on two breast tumorsq at the same time, each antenna sub-qarray radiates the E-field onto tu- 2 2 2 2 mor cellsPL n#11 and= #2.(x Thet1 − inputxn1) phase+ (yt1 of− eachyn1) antennaPLn2 = sub-(arrayxt2 − shouldxn2) + be( ycalculatedt2 − yn2) sep- (7) arately to provide optimal focusing depending on the multiple targets. The phase delay whereof eachn 1antennaand n 2isare calculated the antenna to meet numbers the requirement of sub-arrays of the in #1-phase and #2,condition respectively. of the E The- calculatedfield deep pathinside lengths the phantom. can be Hence, converted the topath the length phases from of eacheach sub-arraysantenna sub accordingly:-array to the tumor cells using 2D Cartesian coordinates can be defined as follows: 180 2π 180 180 2π 180 ϕ = k × PL × = × PL × ϕ = k × PL 2× = 2 × PL × (8) PLn1 n1 π λ n1 πPL푛PL1 =n2 √(푥t1 − 푥푛1n)2 + (푦πt1 − 푦푛λ1) n2 π eff eff (7) √( )2 ( )2 where k is the wave number andPL푛2λ=eff is the푥t2 effective− 푥푛2 + wavelength푦t2 − 푦푛2 in the phantom (εr = 5.14)

at 2.45 GHz, and ϕPLn1 and ϕPLn2 are the calculated phases of antenna sub-arrays #1 and Appl. Sci. 2021, 11, 5972 8 of 15

where 푛1 and 푛2 are the antenna numbers of sub-arrays #1 and #2, respectively. The calculated path lengths can be converted to the phases of each sub-arrays accordingly: 180 2π 180 휑PL푛1 = 푘 × PL푛1 × = × PL푛1 × π 휆eff π (8) 180 2휋 180 휑PL푛2 = 푘 × PL푛2 × = × PL푛2 × π 휆eff π Appl. Sci. 2021, 11, 5972 8 of 15 where k is the wave number and 휆eff is the effective wavelength in the phantom ( ) 휀r = 5.14 at 2.45 GHz, and 휑PL푛1 and 휑PL푛2 are the calculated phases of antenna sub- arrays #1 and #2, respectively. To decide the input phases of each antenna, the phase delay #2,should respectively. be calculated To decide as follows: the input phases of each antenna, the phase delay should be calculated as follows: 휑푛1 = 휑PL푛1 − 휑min1 (9) ϕ = ϕ − ϕ ϕn = ϕ − ϕ (9) n1 PLn1 휑푛2min1= 휑PL푛22 − 휑minPLn22 min2

wherewhereϕ 휑min1min1and andϕ min2휑minare2 are the the minimum minimum phase phase values values of of the the phases phases in in sub-array sub-array #1 #1 and and #2,#2, respectively.respectively. Therefore, the calculated final ﬁnal input input phases phases 휑ϕ푛n1 andand ϕ휑n푛22 areare the the total total compensatingcompensating inputinput phasesphases toto satisfysatisfy thethe in-phasein-phase conditioncondition ofof eacheach tumor.tumor. Thus,Thus, ϕ휑n푛11 andand ϕ휑n2푛2of of each each antenna antenna are are calculated calculated and and applied applied depending depending onon thethe positionposition ofof thethe tumortumor cells. cells.

FigureFigure 7. 7.Conﬁguration Configuration ofof thethe six-elementsix-element antenna antenna sub-array sub-array focusing focusing system system for for two two breast breast tumors. tumors.

TheThe positionspositions ofof twotwo tumor cells at (15,10) (15,10) mm mm and and ( (−−15,15,−10)−10) mm mm on onthe the xy-xy-planeplane are arepresented presented in Figure in Figure 8a.8 a.Antennas Antennas #1– #1–#6#6 transmit transmit microwaves microwaves to totumor tumor #1, #1, while while #7 #7––#12 #12transmit transmit EMEM energy energy to tumor to tumor #2 in #2 the in thesimultaneous simultaneous cancer cancer treatment treatment regimen. regimen. The The cal- calculatedculated input input phases phases aimed aimed to toconcentrate concentrate the the E-field E-field on onthe the two two tumors tumors in different in different po- positions.sitions. However, However, the the SAR SAR patterns patterns were were formed formed at positions at positions away away from from the desired the desired loca- locations,tions, and andan unwanted an unwanted E-field E-field was applied was applied to the breast to the phantom breast phantom,, as shown as in shownFigure in8b. Figure8b. Although each antenna sub-array focused the electric field on different targets Although each antenna sub-array focused the electric field on different targets (tumors #1 (tumors #1 and #2), incorrect field synthesis occurred outside of the target area due to and #2), incorrect field synthesis occurred outside of the target area due to the interactions the interactions of the E-fields passing through the tumor cells. In addition, unwanted of the E-fields passing through the tumor cells. In addition, unwanted E-field synthesis E-field synthesis was observed due to interferences from the TSA antennas, which were was observed due to interferences from the TSA antennas, which were facing each other. facing each other. To minimize unwanted interference and provide a correct beamforming To minimize unwanted interference and provide a correct beamforming condition to the condition to the target positions, the phase compensation technique will be discussed in target positions, the phase compensation technique will be discussed in the next section. the next section.

3.3. Phase Compensation Technique for Multiple Focusing As mentioned in the previous section, unwanted E-ﬁeld focusing occurred due to the interactions between the sub-arrays. In circular antenna arrays, the interferences between the antennas on opposite sides are most severe. An inaccurate synthesis of the E-ﬁeld inside the breast phantom can degrade the success of the hyperthermia treatment. Therefore, in this section, the phase compensation technique is applied to enhance the SAR focusing in the target points. To minimize the number of unwanted interferences, each input phase was calculated to satisfy the in-phase condition in the target tumors, and the phase compensation technique was applied to allow destructive interference to occur between the sub-arrays, as shown in Appl. Sci. 2021, 11, 5972 9 of 15

Figure8a. In the calculated input phase of sub-array #2, the modiﬁed phase ϕm was added to antennas #7–#12 to compensate for phase ϕn2 in Equation (10):

∗ ϕn2 = ϕn2 + ϕm (10)

∗ where ϕn2 is the modified phase applied to sub-array #2. The input phases depending on the different values of the modified phases are reported in Table3, and the SAR distributions with phase compensation depending on the modified phase values are presented ◦ ◦ ◦ ◦ in Figure9 . The added modified phases ϕm are 0 , 60 , 120 , and 180 , respectively. In Figure9 , the modified phase is insufficient for achieving destructive interference in the unwanted spot, and inaccurate E-field synthesis is still observed. However, when the ◦ modified phase ϕm is 180 , sub-arrays #1 and #2 are out-of-phase, so destructive inter- Appl. Sci. 2021, 11, 5972 ference occurs outside the cancer spots, and maximum SAR occurs at (15,10)9 of mm 15 and

(−15,−10) mm, as shown in Figure9d. In this condition, the E-ﬁelds are well concentrated on the desired positions, leading to successful thermal therapeutic effects.

(a) (b)

FigureFigure 8. (a) 8. Two (a) Two breast breast tumor tumor locations locations at at (15,10) (15,10) mm mm andand ((−15,15,−−10)10) mm, mm, and and (b) (theb) the2D section 2D section of SAR of distribution SAR distribution with with inaccurateinaccurate E-ﬁeld E-field synthesis. synthesis.

3.3. Phase Compensation Technique for Multiple Focusing Table 3. Calculated input phases with a modified phase for two different breast tumors. As mentioned in the previous section, unwanted E-field focusing occurred due to the Modified Phase, interactions between the sub-arrays.Antenna In circular Number antenna arrays, the interferences between the antennas on opposite sides are most severe. An inaccurate synthesis of the E-field in- ϕm 1 2 3 4 5 6 7 8 9 10 11 12 side the breast phantom can degrade the success of the hyperthermia treatment. There- ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ 0 71.5 18.3fore, in0 this 29.2section, the86.9 phase148.6 compensation71.5 technique18.3 is applied0 to 29.2enhance the86.9 SAR fo-148.6 ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ 60 71.5 18.3cusing0 in the29.2 target points.86.9 148.6 131.5 78.3 60 89.2 146.9 208.6 ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ 120 71.5 18.3 To0 minimize29.2 the86.9 number148.6 of unwanted191.5 interferences,138.3 each120 input 149.2phase was206.9 calculated268.6 ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ 180 71.5 18.3to satisfy0 the29.2 in-phase86.9 condition148.6 in the 251.5target tumors,198.3 and the180 phase209.2 compensation266.9 tech-328.6 nique was applied to allow destructive interference to occur between the sub-arrays, as shownTo confirm in Figure the 8a. out-of–phaseIn the calculated condition input phase between of sub-array sub-array #2, the #1modified and #2, phase the modified휑m was added to a◦ntennas #7–#12 to compensate for phase 휑푛2 in Equation (10): phase ϕm = 180 is applied in sub-array #2 for two other cases of tumor locations: case ∗ 1—two tumors are at (−10, 20) mm and휑푛2 (15,= 휑−푛10)2 + mm;휑m case 2—two tumors are at (20,0)(10) mm and (−15,−∗ 15) mm. The input phases for case 1 and 2 are shown in Table4. In Figure 10a,b, where 휑푛2 is the modified phase applied to sub-array #2. The input phases depending theon SAR the different distributions values in of accordancethe modified withphases the are input reported phases in Table in Table 3, and4 arethe presented.SAR distri- As a result,butions the with maximum phase compensation SARs are presented depending at on (− the10, modified 20) mm andphase (15, values−10) are mm presented in Figure 10a, andin (20,0)Figure mm9. The and added (−15, modified−15) mm phases in Figure 휑m are 10 b,0°, respectively.60°, 120°, and By180 applying°, respectively. the modified In ◦ phase,Figureϕm 9,= the 180 modifiedin sub-array phase is #2, insufficient the out-of-phase for achieving condition destructive is achieved interference between in sub-arraythe #1unwanted and #2 and spot, the and EM inaccurate energy is well-focusedE-field synthesis in the is still target observed. areas. However, when the modified phase 휑m is 180°, sub-arrays #1 and #2 are out-of-phase, so destructive interference occurs outside the cancer spots, and maximum SAR occurs at (15,10) mm and (−15,−10) mm, as shown in Figure 9d. In this condition, the E-fields are well concentrated on the desired positions, leading to successful thermal therapeutic effects. To confirm the out-of–phase condition between sub-array #1 and #2, the modified phase 휑m = 180° is applied in sub-array #2 for two other cases of tumor locations: case 1—two tumors are at (−10, 20) mm and (15,−10) mm; case 2—two tumors are at (20,0) mm and (−15,−15) mm. The input phases for case 1 and 2 are shown in Table 4. In Figure 10a,b, the SAR distributions in accordance with the input phases in Table 4 are presented. As a result, the maximum SARs are presented at (−10, 20) mm and (15,−10) mm in Figure 10a, and (20,0) mm and (−15,−15) mm in Figure 10b, respectively. By applying the modified Appl. Sci. 2021, 11, 5972 10 of 15

Appl. Sci. 2021, 11, 5972 phase, 휑m = 180° in sub-array #2, the out-of-phase condition is achieved between sub10- of 15 array #1 and #2 and the EM energy is well-focused in the target areas.

Appl. Sci. 2021, 11, 5972 10 of 15

phase, 휑m = 180° in sub-array #2, the out-of-phase condition is achieved between sub- array #1 and #2 and the EM energy is well-focused in the target areas.

(a) (b)

FigureFigure 9. The 9. The 2D section2D section of SARof SAR distributions distributions with with thethe phasephase compensation technique technique depending depending on the on thevalues values of the of the modified phase (black circles: tumor position): (a) 휑푚 = 0°◦, (b) 휑푚 = 60°, (◦c) 휑푚 = 120° and◦ (d) 휑푚 = 180°. ◦ modiﬁed phase (black circles: tumor position): (a) ϕm = 0 ,(b) ϕm = 60 ,(c) ϕm = 120 and (d) ϕm = 180 .

◦ Table 4. Calculated input phases for multifocal breast cancer for ϕm = 180 .

Position of Multiple Antenna Number Tumors (xt1,yt1), (xt2,yt2) 1 2 3 4 5 6 7 8 9 10 11 12 − Case 1—( 10,20) mm, 199.5◦ 148.6(c) ◦ 86.8◦ 29.2◦ 0◦ 18.3◦ 467.72◦ 429.9◦ (d) 369.2◦ 293.8◦ 219.9◦ 180◦ (15, −10) mm Case 2—(20,0)Figure mm, 9. The 2D159.6 section◦ 90.9of SAR◦ distributions27.9◦ 0 with◦ the27.9 phase◦ compensation90.9◦ 233.9 technique◦ 180 depending◦ 180 ◦on the233.9 values◦ of 307the ◦ 374.9◦ (–15, −15) mm modified phase (black circles: tumor position): (a) 휑푚 = 0°, (b) 휑푚 = 60°, (c) 휑푚 = 120° and (d) 휑푚 = 180°.

(a) (b)

Figure 10. The 2D section of SAR distributions with the phase compensation technique (modified phase, 휑m = 180°): (a) two breast tumors located at (−10,20) mm and (15,−10) mm, (b) two breast tumors located at (20,0) mm and (−15,−15) mm.

(a) (b) Figure 10. The 2D section of SAR distributions with the phase compensation technique (modified phase, 휑 = 180°): (a) ◦ Figure 10. The 2D section of SAR distributions with the phase compensation technique (modiﬁed phase,m ϕm = 180 ): two breast tumors located at (−10,20) mm and (15,−10) mm, (b) two breast tumors located at (20,0) mm and (−15,−15) mm. (a) two breast tumors located at (−10,20) mm and (15,−10) mm, (b) two breast tumors located at (20,0) mm and (−15,−15) mm.

Appl. Sci. 2021, 11, 5972 11 of 15

4. Thermal Experiment Results To verify the thermal effects, the temperature measurement setup and block diagram of the temperature measuring system are presented in Figure 11a,b, respectively. At the boundaries of the phantom in simulation, the initial temperature was set to 0 ◦C for a clear Appl. Sci. 2021, 11, 5972 comparison of the measured temperature increase. The thermal experiments consisted12 of 15 of four stages of radio frequency (RF) signal generation and amplification, RF energy excitation, an experiment on the fabricated phantom, an experiment on the thermal effect, tumandor an cell evaluation positions of and the area effectss, thereby of the temperature leading to effective rise [19]. Thethermal thermal therapeutic effects on effect tumors. necrosis were verified by analyzing the effective treatment area (ETA) [8], which was The inducing power, simulated SAR, and thermal effects achieved with the proposed TSA regarded as a region in which the tumor satisfies the temperature increase requirement of antenna array are summarized in Table 5. 7–10 °C.

(a) (b)

FigureFigure 11. 11. (a()a Configuration) Conﬁguration of of the the temperature temperature measurement measurement setup, setup, and and (b (b) )block block diagram diagram of of the the temperature temperature measuring measuring systemsystem [25 [25].]. To verify the heating effect on both a single tumor and on multiple tumors, the thermal measurements were conducted as follows: two for single tumor cases and one for a double tumor case. The ﬁrst and second cases were conducted on a single tumor located at (0,0) mm and (20,0) mm, respectively, and the third case was conducted on two tumors located at (15,10) mm and (−15,10) mm. The phases of each antenna array were applied to the delay lines based on the calculated input phases. The thermal increase that occurred inside the cylindrical breast phantom was measured using a multi-channel thermometer with 12 probes and a data logger to manage the real time temperature data. The probe was set to detect the middle of the cylindrical phantom in the vertical axis. The simulated and measured results of the thermal effects on a single tumor cell and two tumor cells are shown in Figure 12a–f. The target positions of the tumor cells are marked with a black circle. To achieve an optimum temperature increase during a 1-h period heating, the total input powers of the array antenna were decided by the bio-heat equation supported by the CST Studio Suite [27]. The total input powers for the single tumor cells at (0,0) mm and (20,0) mm were 7.1 W and 6 W, respectively. The simulated and measured (a)maximum temperature increases were 8.4 °C and 8.3 °C for(b the) single tumor cell at (0,0) mm, and 8.5 °C and 8.3 °C for the single tumor cell at (20,0) mm, respectively. The target therapeutic areas of the multifocal breast cancer were at (15,10) mm and (−15,−10) mm, as shown in Figure 12e,f. To provide a heating effect on two targets simultaneously, phase compensation was applied in sub-array #2, and the input phases were controlled with delay lines. The induced total RF power was 7.1 W for 1-h treatment. The simulated and measured maximum temperature increases were 7.8 °C and 7.7 °C, respectively. The temperature transient distribution over time and the simulation and measurement results are shown in Figure 12a–c, where a single tumor was present at (0,0) mm and (20,0) mm, and two tumors at (10,15) mm and (−10,−15) mm. All the temperature results were post- processed using MATLAB. As shown in Figure 13, the temperature increased gradually

tumor cell positions and areas, thereby leading to effective thermal therapeutic effects. The inducing power, simulated SAR, and thermal effects achieved with the proposed TSA antenna array are summarized in Table 5.

Appl. Sci. 2021, 11, 5972 12 of 15

over time. When comparing the simulation and measurement results, the hot spots were (a) well-formed, and the results were well-matched. Moreover,(b) the ETAs covered the target tumor cell positions and areas, thereby leading to effective thermal therapeutic effects. Figure 11. (a) ConfigurationThe of the inducing temperature power, measurement simulated setup, SAR, and and (b thermal) block diagram effects of achieved the temperature with the measuring proposed TSA system [25]. antenna array are summarized in Table5.

(a) (b)

Appl. Sci. 2021, 11, 5972 13 of 15

(e) (f)

FigureFigure 12. 12.The The 2D 2D sections sections of of temperature temperature distributiondistribution after after the the 1 1-h-h heating heating on on a asingle single tumor tumor at at(0,0) (0,0) mm: mm: (a) (simulationa) simulation result and (b) measurement result. Temperature distribution after 1-h heating on a single tumor at (20,0) mm: (c) simula- result and (b) measurement result. Temperature distribution after 1-h heating on a single tumor at (20,0) mm: (c) simulation tion result and (d) measurement result. Temperature distribution for 1-h heating on multiple tumors with phase compen- result and (d) measurement result. Temperature distribution for 1-h heating on multiple tumors with phase compensation sation at (15,10) mm and (−15,−10) mm: (e) simulation result and (f) measurement result. at (15,10) mm and (−15,−10) mm: (e) simulation result and (f) measurement result.

(a) (b) (c) Figure 13. The transient temperature distribution at the tumor center: (a) single tumor at (0,0) mm, (b) single tumor at (20,0) mm, and (c) two tumors at (15,10) mm and (−15,−10) mm.

Table 5. Comparison of the simulation and measurement results.

Single Tumor at Single Tumor at Two Tumors at (15,10) mm, Parameters (0,0) mm (20,0) mm (−15,−10) mm Input RF power (W) 7.1 6 7.1 Maximum SAR in the simulation (W/kg) 18.1 23.1 14.1 Maximum temperature increase in simulation (℃) 8.4 8.5 7.8 Maximum temperature increase in measurement (℃) 8.3 8.3 7.7 ETA in simulation (mm2) 226.9 201 153.9 ETA in measurement (mm2) 216.3 195.9 132.7

(e) (f) Figure 12. The 2D sections of temperature distribution after the 1-h heating on a single tumor at (0,0) mm: (a) simulation result and (b) measurement result. Temperature distribution after 1-h heating on a single tumor at (20,0) mm: (c) simula- Appl.tion Sci. 2021result, 11 and, 5972 (d) measurement result. Temperature distribution for 1-h heating on multiple tumors with phase compen- 13 of 15 sation at (15,10) mm and (−15,−10) mm: (e) simulation result and (f) measurement result.

(a) (b) (c)

FigureFigure 13. 13. TThehe transient transient temperature temperature distribution distribution at atthe the tumor tumor center: center: (a) (asingle) single tumor tumor at (0,0) at (0,0) mm, mm, (b) (singleb) single tumor tumor at at (20,0)(20,0) mm, mm, and and (c ()c )two two tumors tumors at at (15,10) (15,10) mm mm and and (− (15,−15,−10)− 10)mm. mm.

Table 5. Comparison of the simulation and measurement results. Table 5. Comparison of the simulation and measurement results. Single Tumor at Single Tumor at Two Tumors at (15,10) mm, Parameters Two Tumors at (0,0)Single mm Tumor at(20,0) Singlemm Tumor at(−15,−10) mm Parameters (15,10) mm, Input RF power (W) 7.1 (0,0) mm 6 (20,0) mm 7.1 (−15,−10) mm Maximum SAR in the simulation (W/kg) 18.1 23.1 14.1 Maximum temperature increase in simulationInput RF power (℃) (W)8.4 7.18.5 67.8 7.1 Maximum SAR in the simulation Maximum temperature increase in measurement (℃) 8.3 18.18.3 23.17.7 14.1 ETA in simulation (mm2) (W/kg) 226.9 201 153.9 Maximum temperature increase ETA in measurement (mm2) 216.3 8.4195.9 8.5132.7 7.8 in simulation (°C) Maximum temperature increase 8.3 8.3 7.7 5. Conclusionin measurements (°C) AnETA antenna in simulation array that (mm uses2) the phase226.9 compensation technique 201 to effectively 153.9 concen- 2 trate ETAEM energy in measurement during microwave (mm ) hyperthermia216.3 treatment for 195.9 deep-seated breast 132.7 cancer

5. Conclusions An antenna array that uses the phase compensation technique to effectively concentrate EM energy during microwave hyperthermia treatment for deep-seated breast cancer was proposed in this paper. The thermal effect was determined based on the E-field absorbed in the therapeutic region. To deliver EM energy inside the human breast, the input phases of each antenna should be controlled based on the location of the tumor cells. Strong constructive interference in the target area can be achieved when each TSA has equal polarization characteristics. Therefore, the direction of each antenna and array configuration was optimized for effective E-field synthesis. Moreover, accurate phase control is needed on the target area to minimize thermal damage to normal cells. The input phase of each antenna in the 12-element array was calculated for single and multiple targets depending on the tumor condition in the breast phantom. For multiple targets in particular, sub-array beam focusing was applied to simultaneously provide therapeutic effects on the multifocal breast cancer. To minimize interference between the sub-arrays, the values of the modified phase for phase compensation were added to the antennas in one of the sub-arrays so that sub-arrays #1 and #2 were out-of-phase. The temperature distribution of the single tumor and multiple tumor cases were simulated and measured to verify the therapeutic performance of the proposed approach. Consequently, the proposed 12-element array system and the phase compensation technique provided enhanced therapeutic capabilities for breast cancer hyperthermia treatment. Appl. Sci. 2021, 11, 5972 14 of 15

Author Contributions: Data curation and writing—original draft preparation, S.L.; writing—review and editing, S.L. and Y.J.Y.; supervision, Y.J.Y. Both authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy restrictions. Acknowledgments: This paper was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2019R1A2C1005764). Conﬂicts of Interest: The authors declare no conﬂict of interest.

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