Heat distribution improvement with the implementation of polyethylene-covered water bolus into breast cancer hyperthermia

This paper presents the implementation of polyethylene-covered water bolus into a non-invasive breast cancer hyperthermia applicator. This modified hyperthermia applicator is introduced to improve the performance of hyperthermia by reducing or removing unwanted hotspots during hyperthermia treatment. This simulation-based experiment is carried out to observe the heating distribution of hyperthermia with water bolus coated by three different thicknesses of polyethylene cover or layer, which are 0.5mm, 0.8mm and 1.0mm. The solvent used in the water bolus is distilled water. The 915MHz microstrip antenna as a hyperthermia applicator and stage 2 breast cancer with a cancer depth of 28.6 mm to 73.6 mm is selected for this study. Based on the results, with the modified HTP integrated by water bolus, the heat pattern of hyperthermia simulation becomes more concentrated into the targeted cancer region, and unwanted hotspots nearby the skin area of breast tissue are removed. The 0.5mm thick polyethylene cover showed the best results with a focusing region between 29.4mm to 69.4mm compared with the result of hyperthermia without implemented water bolus, which heated the 26.6mm to 67.3mm region.


Introduction
Hyperthermia is an alternative treatment for cancer treatment procedures by inducing heat to form a biological effect towards the treated tissue [1].The hyperthermia procedure is used to elevate the temperature of the cancerous tissue to 41 °C-45 °C without affecting the surrounding healthy tissue [2].Hyperthermia treatment procedure (HTP) has been proven to increase the efficacy of conventional cancer treatment.Currently, successful therapy method in a combination of HTP with radiation therapy and/or chemotherapy has increased [3], [4].This is due to HTP complex effects on cancer, which are significantly disrupted the ability of tumour cells to divide and lead to the shrinkage of tumours.HTP is also able to prevent cancer cell repair after adjuvant therapy with chemotherapy or radiotherapy as it is able to coagulate the cancer tissue to necrotic tissue and then destroy it by the human antibody system [5], [6].
However, several limitations, such as poor penetration depth, difficulty in controlling focus position distance, and massive skin burn problems, need to be improved, especially when non-invasive hyperthermia is concerned [7], [8].
There are numerous research studies that have recently been focusing on improving the efficiency of HTP.For example, Rahpeima & Lin introduced magnetic fluid hyperthermia with an external AC magnetic field [6].Yusri & Muldarisnur designed complementary split-ring resonator metamaterial with gaps from 0.5 to 3.5 mm to increase the heat concentration of HTP [9].Various HTP antenna slot designs such as Y-slot, C-shaped slot, and multi-arrayed circular slot are proposed to improve the radiating path and focus position distance of HTP [10]- [12].
Besides the above research on HTP, water bolus (WB) is another element in HTP that was proven to be able to reduce skin burn issues during the treatment [13], [14].It is often used as a cooling material with the proposed HTP applicators [15], [16].The implementation of WB in HTP was observed to improve the effective field size (EFS) of the EMF in the targeted tissue [17].
Therefore, this research was an enhancement or further development of the research team's previous research with the implementation of polyethylene-covered WB into breast cancer HTP [10], [18].This research was further developing the breast-shaped WB discussed in [10] with polyethylene layer as the container of WB.
The antenna design and breast phantom used in this research were proposed and introduced in another previous research of the research team published in the year 2021 [18].Thus, the main purpose of this research is to investigate the addition of polyethylene-covered WB to improve the efficiency of a 915 MHz microstrip antenna in stage 2 breast cancer treatment through EM simulation.

Methodology
This section will discuss the research type, microstrip antenna and breast phantom development and WB designs in subsections 2.1, 2.2 and 2.3, respectively.

Research type
The research approach in this study is a quantitative experimental approach.According to John W. Creswell, this approach is used to determine how a specific treatment affects an outcome [19].This approach figures out how different designs of water bolus will affect the HTP efficiency.
This research focuses on experimentation by simulation type of research.A simulation study is important as it is an initial step before further experiments are conducted.The simulation also allows concepts and ideas to be more easily verified, communicated and understood.Therefore, the performance of the HTP applicator can be measured through this simulation study, and the resulting radiation distribution can be observed via Specific Absorption Rate (SAR) measurement parameter.
The simulator software used in this experimental investigation is called SEMCAD X 14.8.4,which is produced by SPEAG.The SEMCAD X software is a highly specialised full-wave EMF solver used to design an HTP applicator, as well as to obtain the radiation distribution, which presents the EM energy penetration depth and its energy focus distance.This software is a thermal simulation platform and 3D full-wave electromagnetic simulation based on the FEM and FDTD methods.

Microstrip antenna and breast phantom development
The usage of a microstrip antenna was chosen because it can have its thickness and size altered using different frequencies, a miniaturisation factor, and an improvement in the type of array [20].Microstrip antennas can be built and designed in a variety of ways.
In this study, the rectangular shape was highlighted because, as compared to other shapes, it has the greatest beamwidth.When using different operating frequencies, this rectangular shape is also simpler to modify [21].Moreover, there is a strong correlation between operating frequency and microstrip patch size [22], [23].Equations ( 1) to (7) showed the formula used in microstrip antenna development. (1) W, Co, fo,   ,   , h,   , ΔL, Lg and Wg represent antenna width, speed of light, fundamental frequency, the permittivity of the substrate, effective permittivity, thickness of the substrate, fringing effect, ground plate length and ground plate width, respectively.
The applied frequency for the microstrip antenna selected was 915 MHz, as it showed the greatest results with stage 2 cancer in the previous research [18].The substrate used was RO4350, with a permittivity value of 3.48 and a thickness of 1.524mm [24].RO 4350 was also selected as an antenna substrate in some recent research [18], [25].
Based on Equations ( 1) to ( 7), the microstrip antenna was designed with parameters as shown in Table 1.
The breast phantom with stage 2 cancer was analysed with 25 sets of real patient mammogram data from one of the General Hospitals in Malaysia.As the details of the hospital and raw data were confidential under ethical approval, only the analysed results were presented in this section.Mammogram analysis was done with Digital Imaging and Communications in Medicine (DICOM) software.
With DICOM, the average size of the cancer was determined, while the surface depth and inner depth that HTP targeted to reach for stage 2 breast cancer are 28.6 mm and 73.6 mm, respectively.Analysed data from another stage of cancer can be referred to [18].
The microstrip antenna, a breast phantom with 100.16mm breast fat and stage 2 cancers were developed and presented in Figure 1.

Water bolus development
A water bolus was designed to provide a cooling condition effect.This was because water bolus can reduce the skin burn effects, improve the EFS and reshape the heat pattern during HTP execution.The water bolus developments were referred from the previous related works in the year 2022, which is the breast-shaped water bolus [10].To further investigate the WB designed before, this study developed three 2mm WB (Figure 2) with 0.5mm, 0.8mm and 1mm thickness polyethylene.The modelled polyethylene-covered WB, or in other words, distilled water-filled WB packed with a plastic bag (Polyethylene), was built as illustrated in Figure 3.A few parameters needed to be decided in the SEMCAD X before simulating the developed model.Table 2 presents permittivity (), electrical conductivity (EC, S/m) and specific heat capacity (c, J/kg°C) at frequency 915MHz, which were referred from SEMCAD X build-in Gabriel Database, results by Hussien et al. [7] and typical heat properties which are used in [26]- [28].

Results and discussion
The average mass of the cube of SAR and applied power were chosen as 1 g and 1 W for the simulation environment, respectively.The distance between the antenna and WB is 0.05mm, while gaps between WB and breast phantom were fixed with 0 mm. Figure 4 presents the SAR distribution of the 915 MHz HTP applicator without integration of WB, the SAR value and focus position distance (FPD) were recorded.As shown in Figure 4, the HTP without integration of WB had unwanted hotspots around the healthy tissue (red circled region), while the FPD of heat pattern (26.6mm to 67.3mm) was also observed in the healthy tissue area, compared with the cancer size as discussed in Subsection 2.2, which was 28.6 mm to 73.6 mm.Therefore, the implementation of WB is significantly needed for HTP treatment.
Figures 5, 6 and 7 present the SAR distribution of the 915 MHz HTP applicator with the integration of WB that was covered with polyethylene of 0.5mm, 0.8mm and 1mm thickness, respectively.As shown in Figures 5, 6 and 7, the unwanted hotspot (red circled region) in Figure 4 was removed after the integration of WB into HTP.Furthermore, the heated region or SAR distribution became more even and did not exceed the cancer region, as in Figure 4.This research finding agrees with [17], [29], where the water bolus reduced the heat concentration from the surface tissue.
However, the peak SAR reading decreased after WB was implemented.The value for all three cases after integration WB dropped from 2.0 mW/g to 1.3 mW/g.This causes the HTP treatment time to become longer to reach 41 °C.By using the IEEE/IEC-62704 standard mentioned in [18], the treatment time for 2.0 mW/g and 1.3 mW/g of SAR value to reach 41 °C were 117 minutes and 180 minutes, respectively, which was quite long periods although it still within the common animal test time consumption for HTP [5].To overcome this problem, further research to vary the incoming antenna power is required.
Moreover, the thickness of polyethylene showed some minor differences in terms of FPD observed.Comparing Figures 5, 6 and 7, the thicker the polyethylene layer, the smaller the effective heated area.Therefore, selecting of proper thickness and type of WB covering material is a significant research topic to improve HTP performance.Besides that, solvent or gel for WB and the flow rate of solvent in WB are also the important indicators for WB research [15], [30].

Conclusion
The integration of WB showed a significant effect, especially concern about removing or reducing the unwanted hotspot in HTP.Three different thicknesses of polyethylene layer (0.5mm, 0.8mm and 1.0mm) were developed and simulated in this study.The results determined that with the implementation of polyethylene-covered water bolus into breast cancer hyperthermia, the heat pattern shifted and concentrated into the cancer region.The exceeded heat in the skin surface of the breast phantom was also reduced.
The best simulation resulted with the HTP that integrated with 0.5mm thick polyethylene-covered WB, which performed FPD in the range of 29.4mm to 69.4mm, a significant improvement from HTP without WB (FPD: 26.6mm to 67.3mm).
Despite the significant outcome, there were some limitations of this research, where the application of WB reduced the SAR value, and this may cause the treatment periods to become longer.Lack of variables such as thickness, materials for the solvent or gels, size, shape, and solvent flow rate should be involved and considered in future studies.

Table 1 .
Design of rectangular microstrip antenna under frequency 915 MHz.

Table 2 .
Electrical and Thermal Properties of Elements Used.