Microwave-Assisted Chemical Ablation (MA-CA): A Novel Microwave-Assisted Tissue Ablation Procedure—Preliminary Assessment of Efficiency

Round 1

Reviewer 1 Report

In this contribution, the authors propose a new approach for tumor treatment based on both MW and chemical ablation. In particular, a chemical agent, say ethanol, is used in junction with the well-known and used MW thermal ablation. Results obtained by the authors for different applied heat rates - at equal delivered energy, for ex-vivo bovine liver - look promising. The reviewer thinks that the procedure here shown is novel and interesting, and could be helpful for surgeons that want to improve the performances of tumor thermal ablation procedures. Therefore, it is suggested to consider the present paper for publication after addressing the following points

·        Even if novelty is quite clear, the introduction must be improved by the authors. There are too many references that have been collected in brackets, with no clear explanation about what has been done in each specific paper. Furthermore, from the state-of-art review, the importance of induced heating for tumor treatment is not clear at all. For instance, the authors forgot to mention that time-variable heating (doi.org/10.1016/j.cmpb.2020.105887; doi.org/10.1115/1.4001029), as well as multiple-antennas (doi.org/10.1080/10407782.2020.1835083; doi.org/10.3390/s22197604), can be applied to improve the target zone within tumor treatment based on thermal ablation. These aspects are important to be included within the state-of-art in order to underline that there are still some potential improvements to be done for tumor thermal ablation, even if this is a widely used technique in medical practice

·        With references to Fig. 1, please report a sketch of how the experimental setup works. Did the authors take care of the uncertainty from the experiments?

·        Experimental conditions are resumed in Table 1. Please report the rationale behind these conditions. Are the authors assuming equal total delivered energy as the product between delivered power and exposure time? Are these values typical of clinical practice?

·        The authors report a sketch of how did they run measurements in Fig. 2. It is suggested to report real images, if available; furthermore, please report why did they use both thermocouples and optic fibers, even if the first might affect the delivered MW electromagnetic field

·        Is it reasonable to assume that the ablation zone is an ellipse (Fig. 2)? It is widely known that the target tissue size might affect the ablation shape (doi.org/10.3109/02656736.2014.997312), so please provide more discussion about this point here

·        Section 3, as well as subsection 3.1, are very poor of comments. For instance, please report more comments about Table 2. Did the authors find some particular outcomes, like particular lesion shape depending on the delivered power, etc.? Please report more comments about this section that is the core of the work here done

·        In Fig. 3 and similar, could the authors provide a scale on the figure on the left (IR camera)?

·        Just before the conclusions, are the authors able to provide a better description about the impact of the chemical ablation agent on the procedure? Is this impact significant by considering that ablation is independently induced by heating?

Author Response

Question 1:

Even if novelty is quite clear, the introduction must be improved by the authors. There are too many references that have been collected in brackets, with no clear explanation about what has been done in each specific paper. Furthermore, from the state-of-the-art review, the importance of induced heating for tumor treatment is not clear at all. For instance, the authors forgot to mention that time-variable heating (doi.org/10.1016/j.cmpb.2020.105887; doi.org/10.1115/1.4001029); as well as multiple-antennas (doi.org/10.1080/10407782.2020.1835083; doi.org/10.3390/s22197604), can be applied to improve the target zone within tumor treatment based on thermal ablation. These aspects are important to be included within the state-of-art in order to underline that there are still some potential improvements to be done for tumor thermal ablation, even if this is a widely used technique in medical practice.

 

Answer 1:

The introduction has been rewritten; some references were replaced, and explanations were included in the text. Time-variable heating and multiple antennas have been addressed in the introduction and the references suggested by the Referee have been added. Please see manuscript.

 

Question 2:

With references to Fig. 1, please report a sketch of how the experimental setup works.

Did the authors take care of the uncertainty from the experiments?

 

 

Answer 2:

A sketch has been added beside Fig. 1a and labelled Fig.1b. It describes how the experimental setup works.

Standard deviations have been added to Table 2

 

Questions 3a, 3b, 3c:

Experimental conditions are resumed in Table 1. Question 3a) Please report the rationale behind these conditions. Question 3b) Are the authors assuming equal total delivered energy as the product between delivered power and exposure time? Question 3c) Are these values typical of clinical practice?

 

Answer 3a:

The experimental conditions were discussed with practitioners that have experience in microwave-ablation.

Various experiments were carried out by the authors; 100 W is the typical practical value, and the other conditions were to analyse, in the presence or not of ethanol, the impact on the distribution of power in the irradiated zone. The conditions presented in this paper are the optimum ones. We also used a simulation software (Ansys HFSS); the results obtained on ex vivo samples were very similar to the results obtained in simulation software. The modeling results showed, in the presence of ethanol, that the electric field was significantly concentrated around the emitter compared to a situation without ethanol. Explanation included in manuscript lines 286-299.

We wanted to maintain conditions where total Energy remains constant for all conditions used, therefore a power of 100 W with different times were chosen. Our experimental results where more power and less time are used gave better results. Also, since we were to move towards practical animal clinical tests, these were the conditions chosen.

 

Question 3b:

Are the authors assuming equal total delivered energy as the product between delivered power and exposure time?

 

Answer 3b:

That is what we assume, with the caveat that dielectric variations induced by the temperature induce an increase in reflected power back to the generator. We considered this variation negligible to begin with. As stated, for the total energy delivered and the time of exposure within the ablation zone in the presence of ethanol, we observe that the energy is more concentrated near the ablation antenna.

 

Question 3c:

Are these values typical of clinical practice?

 

Answer 3c:

Yes, these values are typical of clinical practice.

Question 4:

The authors report a sketch of how did they run measurements in Fig. 2. It is suggested to report real images, if available; furthermore, please report why did they use both thermocouples and optic fibers, even if the first might affect the delivered MW electromagnetic field.

 

Answer 4:

We are sorry real images are not available. However, we did redraw the diagram for Fig. 2. Please see manuscript.

 

Thermocouples are provided and used with this generator for medical procedures. We verified that they were not interfering with the field. This technique is classical, and we used the expertise of practitioners in the domain who know that it does not perturb the field. Their placement is also important, we took that into account. We also used the optical fiber as a backup to check the consistency of the measurements given by the thermocouples. An explanation is included in the text, see lines 321-323.

 

Question 5:

Is it reasonable to assume that the ablation zone is an ellipse (Fig. 2)? It is widely known that the target tissue size might affect the ablation shape (doi.org/10.3109/02656736.2014.997312), so please provide more discussion about this point here.

 

Answer 5:

We observed that with ethanol the results give a rounder ablation zone which confirms the modeling results. The form of impact mainly depends on the dielectric characteristics of the irradiated zone. These vary according to the density of the tissue, the temperature, and the density of the treated medium. They can also vary depending on the patient. The shape of impact may also depend on the design of the needle. In fact, certain embodiments more or less limit field leakage along the body of the needle, towards the surface of the treated tissue where the antenna is implanted. Explanation also enclosed in the manuscript, please see lines 359-371. We quoted the reference you provided in your review of the manuscript [34]

 

Question 6:

Section 3, as well as subsection 3.1, are very poor of comments. For instance, please report more comments about Table 2. Did the authors find some particular outcomes, like particular lesion shape depending on the delivered power, etc.? Please report more comments about this section that is the core of the work here done.

 

Answer 6:

More comments were included under section 3.1. Please see manuscript lines 359-371.

 

Question 7:

In Fig. 3 and similar, could the authors provide a scale on the figure on the left (IR camera)?

 

Answer 7:

Unfortunately, we cannot provide a scale.

 

Question 8:

Just before the conclusions, are the authors able to provide a better description about the impact of the chemical ablation agent on the procedure? Is this impact significant by considering that ablation is independently induced by heating?

 

Answer 8:

We included comments in manuscript – please see lines 483-489.

 

Yes, the impact is significant, as stated earlier when ethanol is used. The idea is for the ablation antenna to always "see" an area whose dielectric characteristics are kept almost constant. By using ethanol, (an ablation agent), the emitting antenna always sees a mixture, susceptor / malignant tissue, whose dielectric characteristics are maintained approximately stable. This dampens the dielectric variations of the tissues under the temperature increase effect, which itself is limited to the evaporation temperature of the alcohol, which is always higher than the lethal temperature of the cells. This is in the context of developing a “universal ablation method” for any kind of tissue.

Reviewer 2 Report

The manuscript in front of me is dealing with Microwave-Assisted Chemical Ablation (MA-CA). The manuscript is well organized and contains results that could be interesting for some readers. However, there are some concerns that have to be taken into account in the revision.

1) The abstract should be rewritten to contain some results and major contribution of the manuscript to attract readers.

2) The Introduction is too short. But, the major problem is related to the 1st and 2nd paragraphs that should be linked into one paragraph. 

3) Captions of Figures contain all relevant information, but captions of tables have to contain additional information. 

4) Line spacing in conclusion is not the same as in the rest of manuscript. 

5) The main problem is self-citation. There are only 34 references and the minimum 15 of them are references of  J.R.J. Paré, J.M.R. Bélanger, etc. The authors should add more references of the others, if they want to keep large number of their references. 

Author Response

Question 1:

The abstract should be rewritten to contain some results and major contribution of the manuscript to attract readers.

 

Answer 1:

The abstract was rewritten according to your guidelines. We did include experimental conditions and remarks about results. The limitation is that the abstract should have a maximum of 200 words. Please see manuscript.

 

Question 2:

The introduction is too short. But the major problem is related to the 1^st and 2^nd paragraphs that should be linked into one paragraph.

 

Answer 2:

The introduction has been rewritten; some references were replaced, and explanations were included in the text.

 

Question 3:

Caption of Figures contain all relevant information, but captions of tables have to contain additional information.

Answer 3:

Captions for Tables 1 and 2 were expanded. Please see manuscript.

 

Question 4:

Line spacing in conclusion is not the same as in the rest of manuscript.

 

Answer 4:

This will be taken care of during the editing process.

 

Question 5:

The main problem is self-citation. There are only 34 references and the minimum 15 of them are references of J.RJ. Paré, J.M.R. Bélanger, etc. The authors should add more references of the others, if they want to keep large number of their references.

 

Answer 5:

References from JRJP and JMRB et al. have been reduced to 5; making it 14.7% - which is acceptable to the journal.

Reviewer 3 Report

The paper is well written : However the following points need to be clarified by the authors
The authors have chosen 100 W of MW power for different time instants to record the results. Is it possible to mention the significance of this value of power being used. Is it the maximum peak power available at the transmitter end before saturation or nonlinearity occurs? 

Ablation exposed to other intermediate levels of input power can be an interesting aspect.

 

The labeling of Figures 3 to 6 represents various ablation conditions, whereas  their figures are very subtle to correlate ( map) these stated conditions. For a reader the figures represent a final achieved result.

 

Author Response

Question 1:

The authors have chosen 100 W power for different time instants to record the results. Is it possible to mention the significance of this value of power being used. Is it the maximum peak power available at the transmitter end before saturation or non linearity occurs?

 

Answer 1:

The experimental conditions were discussed with practitioners that have experience in microwave-ablation.

Various experiments were carried out by the authors; 100 W is the typical practical value, and the other conditions were to analyse, in the presence or not of ethanol, the impact on the distribution of power in the irradiated zone. The conditions presented in this paper are the optimum ones. We also used a simulation software (Ansys HFSS); the results obtained on ex vivo samples were very similar to the results obtained in simulation software. The modeling results showed, in the presence of ethanol, that the electric field was significantly concentrated around the emitter compared to a situation without ethanol. Explanation included in manuscript lines 286-299.

We wanted to maintain conditions where total Energy remains constant for all conditions used, therefore a power of 100 W with different times were chosen. Our experimental results where more power and less time are used gave better results. Also, since we were to move towards practical animal clinical tests, these were the conditions chosen.

 

Our generator is in continuous mode; therefore, we cannot consider a “peak power” – we are not in pulse mode.

 

Question 2:

Ablation exposed to other intermediate levels of input power can be an interesting aspect.

 

Answer 2:

Yes, we agree. We have performed multiple experiments with various levels of input. The values chosen for the experiment presented here were chosen as per the rational explained above. Please see answer to your question 1.

 

Question 3:

The labelling of Figures 3 to 6 represents various ablation conditions, whereas their figures are very subtle to correlate (map) these stated conditions. Far a reader the figures represent a final achieved result.

 

Answer 3:

If we understand correctly the referee is asking to provide more details regarding the lesion, shape, color, etc. More comments were included under section 3.1. Please see manuscript lines 359-371.

 

Round 2

Reviewer 1 Report

The reviewer thinks that the paper can be accepted as it is in the revised form

Reviewer 2 Report

The authors addressed all the Referee'c comments. The paper should be accepted for publication.