Phase Compensation Technique for Effective Heat Focusing in Microwave Hyperthermia Systems

Round 1

Reviewer 1 Report

Manuscript ID: applsci-1230667

Reviewer Comments:

The manuscript deals with EM energy focusing for an 12-element array of phase-compensated TSA antennas used in microwave hyperthermia of a female breast tumor. All antennas, operating on the 2.4 GHz frequency, form a circle around the treated tissue. The input phases of the TSA antennas are set individually for each tumor and for multiple tumors locations using sub-array beam focusing with the phase compensation technique. Accurate phase control of the antennas in the array enables the accumulation of the specific absorption rate (SAR) and thus temperature in the target tissue. At the same time, thermal damage to healthy cells is minimized. The calculations were verified with the measurements. The proposed array system and phase compensation technique provide the enhance therapeutic capabilities for breast cancer hyperthermia treatment planning.

In my opinion the obtained results are interesting and may be worth publishing in this journal after major revision.

The manuscript is written with poor English. Authors have used many repetitions. The work requires language proofreading by a English native speaker.

All manuscript text and references should be rewritten in Applied Sciences journal template style:

https://www.mdpi.com/journal/applsci/instructions

Use abbreviations for all journal names.

The most of cited literature are appropriate but most of the cited literature is very old. Some items are even 30 years old. To improve the paper I recommend referring the following abroad papers from last couple years:

• Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, DOI: 10.3322/caac.21660|
• Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models, DOI:10.3390/ijms21176270
• In Silico Study on Tumor-Size-Dependent Thermal Profiles inside an Anthropomorphic Female Breast Phantom Subjected to Multi-Dipole Antenna Array, DOI: 10.3390/ijms21228597
• Quantitative Interpretation of UWB Radar Images for Non-Invasive Tissue Temperature Estimation during Hyperthermia, DOI:10.3390/diagnostics11050818
• Numerical Analysis of Human Cancer Therapy Using Microwave Ablation, DOI: 10.3390/app10010211
• SAR distribution of non-invasive hyperthermia with microstrip applicators on different breast cancer stages, DOI: 10.11591/ijeecs.v22.i1.pp232-240
• SAR optimization for multi-dipole antenna array with regard to local hyperthermia, DOI: 10.15199/48.2019.01.05
• Analysis of Interaction Scattering Cross Sections and Their Physical Bounds for Multiple-Dipole Stimulation of a Three-Dimensional Layered Medium, DOI: 10.1109/OJAP.2021.3070199
• Optimal control of hyperthermia thermal damage based on tumor configuration, DOI: 10.1016/j.rinp.2021.103992
• Breast cancer hyperthermia using a grid array applicator, DOI: 10.1109/SoutheastCon44009.2020.9249686
• Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors, DOI: 10.3390/pharmaceutics12111007
• Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy, DOI: :10.3390/ijms21155187
• Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice, DOI: 10.1039/C9NR06730B
• Microwave Diathermy for Deep Heating Therapy of Knee Joint, DOI: 10.2528/PIERC19110604
• Essential Facts on the History of Hyperthermia and their Connections with Electromedicine

 Please, check if the referencing literature is adequate for the given content! Especially in reference [16] (line 86) and others.

 In my opinion, in the Introduction section the authors should better describe, and not just list, existing hyperthermia systems based on phased antennas array including the optimal constrained power focusing, the time reversal method for power absorption focusing, E-field focusing, SAR focusing, and similar ones. Moreover, the authors should describe give some statistics of breast cancer based on current cancer reports.

 The authors should explain whether the proposed phase compensation technique for microwave hyperthermia is their own proposal or taken from the literature. This is not apparent from the information provided in lines 56–57 and 67–68.

 The authors did not provide the basic equations of the electromagnetic field and temperature field used in the simulation. It is also not known what numerical method was used in the calculations. This should be clarified.

 Please, provide the full name of the CST Studio Suite program used in the simulation.

 In my opinion, the derivation of Equations (3)–(5) is not needed. Equation (5) may be included in Equation (2) for SAR factor, namely SAR = C ∆T/∆t.

 The authors should clearly state whether they simulate a 3D model (as shown in Figure 4) or 2D model as shown in Figures 6, 8, 9 and 11.

 The drawings presented in Figures 1 and 10 have been used in previous author's paper [15]. What about copy permissions? Ref. [15] should be cited in figure captions and information about copy permission should be included there.

 Why is the power given in dBm and not in W (wats)? It should be clarified.

There is no information for which moments of time the comparisons of temperature distributions in Figure 11 were made? Are they the same in simulation and measurements? How did the authors measure temperature in the 2D space? This should be clarified.

 I strongly recommend comparing the temperature transient distributions in tumor centre for simulations and measurements in all analysed cases.

What were the tumors radii?

The quality of drawings is good enough.

Drawing in Figure 2 should be limited to the frequency in the range 1–5 GHz.

The phase designation should be standardized. Please, choose one notation φ or ϕ. See at Figure 5 and whole manuscript text.

Please, indicate tumors positions in Figure 9 (circled the tumors).

Moreover, the revised manuscript needs some editorial improvements:

In Keywords section the authors should add the keyword: female breast phantom.

For multiple citations use long dash: –, e.g. [2–4].

All variable parameters should be written in italic style, e.g. σ, δ, x, y, z, T, t, n.

Non-variable indexes should be written in non-italic style, e.g. ε_r, y_t, λ_eff, ϕ_min, ϕ_PL, ϕ_m.

All constants should be written in non italic style, e.g. π.

Add missing dots at the end of figure and table captions.

Table captions should be written in non-capitalized style.

Remove unnecessary tabs.

Add missing units after tumor positions, e.g. (20,0) mm.

All drawings should be referenced in the text by the word Figure. X.

In tables 1 and 2 one word centred is enough: Antenna number.

 

Detailed remarks and suggested corrections are included in the attached pdf file with notes.

 Please, answer the reviewer's comments in details and mark all changes in the manuscript text.

 

Summarizing, the manuscript may be interesting but it needs some improvements before it will be accepted to print in this journal. In my opinion, the manuscript may deserves to be published in the Applied Sciences journal after major revision and author's corrections taking into account the recommendations indicated by the reviewers.

Comments for author File: Comments.pdf

Author Response

We appreciate your careful review and suggestions.

We made an attachment to reply all of your comments

We hope and believe that you will be able to observe our effort.

Thank you

Sincerely

Author Response File: Author Response.docx

Reviewer 2 Report

General comment:

 

This works deals with the study and test of a pahse compensation technique for the microwave hyperthermia treatment of breast tumors. 

The paper uses numerical and experimental methods to demonstrate the value of proposed approach.

 

The paper has a relatively low number of references, despite being somehow nee. However, given that the topic is quite conventional, more details, comparison and improvements must be reported in the Introduction section in order to better highlight the need, value and quality of the approach proposed by the authors.

 

The methodology, is interesting, but the numerical scenario is not updated to the state of the art techniques. The limitations of the numerical framework must be compared to other algorithms (in terms of strategy, time, benefits, etc.) and, if modifications are not possible, then a deep but coherent discussion must be provided to highlight the preliminary character of the results, while forecasting the potentialities of the approach.

 

The results can be improved in terms of quality, quantity (different scenarios and case studies taken from the literature) and way of presenting them. 

 

Specific comments:

 

Lines 25-29: Missing references, I suggest the authors to read:

 

https://doi.org/10.1016/j.breast.2015.03.008

 

https://doi.org/10.3389/fonc.2017.00132

 

 

Lines 32: Check the "°C" it seems that a different font has been used.

47°C is an upper temperature bound which is not reported in the literature. Please provide a reference for justifying such high value (at which protein start to coagulate and other irreversible damages occurs), or correct according to the guidelines, and quality assurances recommendations found in:

 

https://doi.org/10.1080/02656736.2016.1277791

 

10.3389/fonc.2020.00819

 

About the state of the art solution about focusing in microwave hypertermia, I expected to find cited the following pivotal, significant and valuable works:

 

10.1109/TMTT.2006.872790

 

10.1109/TAP.2013.2293336

 

10.1109/TAP.2015.2463681

 

10.1109/JERM.2017.2766569

 

10.1109/JERM.2020.3043383

 

Your introduction poorly reflects the current state of the art of microwave hyperthermia. Consider that, at the moment, the status quo and goals of the microwave hyperthermia community are pointing towards multiphysic, full 3d models with algorithm testing in standard conditions, as reported and explained in:

 

https://doi.org/10.1080/02656736.2020.1772996 

 

Other solutions, simplified from a geometrical point of view, reflects a deeper understanding of the physiopathology and the treatment physics, such as this recent and very interesting work:

 

10.1109/JERM.2020.3016890

 

Please, revise the Introduction section to account for all these problems, different approaches and better explain what your job is offering to the community.

 

 

2. 

 

Lines 72-79: No references for these statements, which deserves a more in depth analysis and a detailed presentation of the technical requirements.

I suggest the author to consider:

 

https://doi.org/10.1080/02656736.2017.1337935s

 

10.1109/JERM.2019.2909441

 

10.1109/JERM.2020.3016890

 

https://doi.org/10.1080/02656736.2020.1779357

 

10.1109/TBME.2021.3059869

 

Lines 81-83: Did you optimized your antennas? Have you considered to carry out a (maybe multiphysic) optimization of your design? Discuss this point, to avoid the readers to think that your work is incremental, please rely on:

 

10.1109/JMMCT.2017.2647818

 

Do not disregard the work because it refer to ablation antennas, please try to be inspired by the driving idea of a multiphysic, application-oriented design. 

 

Fig. 1: I think that the authors must provide a summary table of their antenna characteristics and compare to the other antennas of phased array for breast cancer hyperthermia treatment. This would surely add value to their work, and would help to highlight the novelty and quality of their solution. Please, refer to previously reported suggested readings and try to expand the number of cited works.

Note: report in the caption the colors for the metal and the dielectric, it would help some non-technical readers of this multidisciplinary journal to understand.

 

Line 91-95: No reference or justification for these statements, please refer and compare to the literaure. Demonstrate or support your bald phrases with examples taken fro the literature. This is mandatory.

 

Why a matching medium was not considered in your simulations? Consider the several works in breast microwave imaging:

 

10.2528/PIERB12022006

 

10.1109/TMTT.2004.832686

 

Please, provide an explanation (or a numerical demonstration) of the fact that the power transfer from the antenna to the body is (quasi) maximuum, or better, without a matchin medium. 

 

 

The authors must comment and explain why to use a homogenous phantom, while the majority of the work uses 3D geometry which are also freely accessible and portable in several softwares, e.g.:

 

10.1109/TBME.2013.2293839

 

https://doi.org/10.1016/j.cmpb.2020.105606

 

The shape of the phantom is cylindrical, instead of a hemi-sphere, as often assumed in the literature. I don't feel confident about this point. The geometry must be modified.

 

Fig. 2 - THE AUTHORS ARE NOT REPORTING ANY METHODOLOGICAL DETIAL OF THE S11 MEASUREMENT. I believe that the measurements are done with the antenna in free space. If not, please provide the recipe, values and comparison of the phantom dielectric properties used for the measurements. This is a serious fall and lack of your work.

 

Fig. 3 provide normalized or logarithmic plot of the electric field. However, this figure refer to the breast (which is a cylinder and not a hemisphere) without the tumors. This is quite of scarce interest and of help to the aim of your work.  

 

Sec. 2.2 does not even try to face the problem of feeding the array, which is an underestimated aspect. Please comment.

 

 

Sect. 2.3 is very scholastic, nothing new is said about the SAR. This section reflects a superficial analysis of the thermal aspects. Please, refer to:

 

10.1109/JERM.2019.2909441

 

10.1109/JERM.2020.3016890

 

Try to use the physical and mathematical description of these works, or, at least, to try to highlight how your SAR estimation is . 

Furthermore, the authors are not reporting if and how the SAR was volume- and time-averaged. These aspects cannot be neglected in hyperthermia, since SAR can be (but it is not recognized as) a therapeutic predictor, read:

 

https://doi.org/10.1080/02656736.2021.1875060

 

MINNAAR, C. (2020). CHALLENGES ASSOCIATED WITH HYPERTHERMIA. Challenges and Solutions of Oncological Hyperthermia, 1.

 

https://doi.org/10.1080/02656736.2019.1590652

 

Sect. 3

 

When the authors refers to cells, are they trulyreferring to the single (micrometric) cells? Please, this is a multidisciplinary journal, revise these sections by referring to neoplasms, tumor masses or try to use some other taxonomy taken from the more clinical and medical readings I have suggested

 

Section 3 must be compared (even with simulations) other focusing approach. Your work does not demonstrate that this approach is better than the others found in the literature. 

 

Sect. 4

 

The experimental setup used for the temperature assessment is quite different to the more standardized approaches used in this field, such as

 

10.1088/0031-9155/52/11/010

 

Please comment.

 

Note: the authors are never using "temperature difference", which is what they are showing us.

Furthermore, since CST can do it and the authors used it, why the simulations details (boudnary conditions, thermal properties) are not reported? This is another big miss in this work. Please refer to for the thermal part:

 

10.1109/JERM.2020.3016890

 

I think that I am missing something about the temperature sampling and how it seems the same discretization of CST (fIG. 11). I must ask the author to clarify how the measurements and comparison was carried out. 

Author Response

We appreciate your careful review and suggestions.

We made an attachment to reply all of your comments

We hope and believe that you will be able to observe our effort.

Thank you

Sincerely

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Manuscript ID: applsci-1230667-v2

Reviewer Comments:

The manuscript deals with EM energy focusing for an 12-element array of phase-compensated TSA antennas used in microwave hyperthermia of a female breast tumor. The proposed array system and phase compensation technique provide the enhance therapeutic capabilities for breast cancer hyperthermia treatment planning.

Most of reviewer commets are included in the revised manuscript but still it needs some improvements.

In my opinion the obtained results are interesting and may be worth publishing in this journal after major revision.

The manuscript is written with poor English. Authors have used many repetitions. The work requires language proofreading by a English native speaker.

All manuscript text and references should be rewritten in Applied Sciences journal template style.

The most of used references are appropriate. In reference [7] the wrong authors names are given. In [9] the article year should be checked. In [14] author name should be corrected. In [17] add article pages instead of DOI number. References [16] and [18] are duplicated. In [28] the given website is not exist. In [30] correct the journal name.

 Use abbreviations for all journal names.

The authors should clearly state in the text that they created a 3D model and the presented graphs are only 2D planes of this model. Unified notation in whole manuscript – use 2D and 3D.

 It is not known from the manuscript text how the TSA are feeding and how input antenna power was applied to each antenna – the boundary condition should be described or the relevant literature should be provided.

 Whether in the numerical analysis for multifocal breast cancer case, all tumors have the same radii of 5 mm or different? It should be clarified.

 I do not know what is the difference between the results presented in Tables 3 and 4. Why the modified phase φ_m = 180^o was selected in Table 4? This should be better described in the text.

 Why initial temperature of the breast phantom was assumed as 0^oC since the human body temperature is around 37^oC?

Which genetic algorithm was used in CST Studio Suite and what was he based on?

 Which numerical method has been implemented by CST Studio Suite?

 

Moreover, the revised manuscript needs some more improvements:  

Figure 2 and Table 1 should be centred horizontally.

The quality of Figures 4b and 5 should be improved- figure descriptions are not readable.

Vector E in Equation (3) should be written in bold or overlined as in Equation (2). In both equations notation should be unified. In terms “E-field“ I suggest use italic style.

In caption of Table 1 cite appropriate references where mentioned parameters may be found.

Add all necessary symbols used in Table a. I think that the heat capacity should be in J/K/kg.

Given values are measured for phantom liquid? It should be clarified in the text. Are they the same as given in page 3 and next pages?

Check the numbers of tables in whole manuscript and their referring in text.

 

Detailed remarks and suggested corrections are included in the attached pdf file with notes.

Please, answer the reviewer's comments in details and mark all changes in the manuscript text.

Summarizing, the manuscript may be interesting but it needs some improvements before it will be accepted to print in this journal. In my opinion, the manuscript may be published in the Applied Sciences journal after major revision and author's corrections taking into account the recommendations indicated by the reviewers.

Comments for author File: Comments.pdf

Author Response

Dear reviewer 1,

We appreciate your careful review and suggestions. The resubmitted manuscript was revised according to the reviewer’s comment. We hope and believe that you will be able to observe our effort.

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

The paper has been improved, but I suggest the authors increase the introduction , the section results, and check the references of the first revision. The quality of the work has improved a lot.

Author Response

Dear reviewer 2,

We appreciate your careful review and suggestions. The resubmitted manuscript was revised according to the reviewer’s comment. We hope and believe that you will be able to observe our effort.

Please see the attachment.

Author Response File: Author Response.docx