The Effects of Energy on the Relationship between the Acoustic Focal Region and Biological Focal Region during Low-Power Cumulative HIFU Ablation
Round 1
Reviewer 1 Report
The effects of energy on the relationship between acoustic focal region and biological focal region during low-power cumulative HIFU ablation
This manuscript discusses the relationship between the acoustic focal region (AFR) and the biological focal region (BFR) with different combinations of power and time in low power cumulative HIFU treatment.
This study demonstrated that in the low power cumulative HIFU treatment, when the lengths of BFRs and the length of AFR were approximately equal, the shape of the BFR induced by ‘High power×Short time’ exposure was closer to that of AFR than the shape of the BFR induced by ‘Low power×Long time’ exposure, and the exposure energy required was significantly reduced.
Line 48: Some studies analyzed the relationship between the shape of BFR
> Please add references.
Line 137-146: peak negative pressure (p-) exceeding 30 MPa
> Please add transducer brand name and model used for the experiments, diameter, radius of curvature, ….
To compare the results the transducer parameters used for the simulation have to be the same of the HIFU transducer used for the experiments.
Line 142-143 In the phantom experiment, because the phantom was semitransparent, the camera (30fps) could monitor the shapes of BFRs of the phantom accurately.
> please reformulate the sentence
Line 147: The experimental system of bovine liver did not need a camera and upper machine.
> Please justify.
Line 165: different tissues and its reliability in clinical tumor hyperthermia.21,22
> wrong way used for references
Line 174-176: For the phantom, when the lengths of BFRs were equal with different acoustic power, the higher the acoustic power, the shorter the widths of BFRs, the more similar the shapes of the BFRs to that of the AFR.
> please reformulate the sentence
Line 189-190: It’s clear that using different combinations of acoustic power and time could produce BFRs with various shapes
> It is obvious, please delete or reformulate the sentence
Line 197-198: In the phantom experiment, the acoustic power was 25W, 50W and 75W respectively and we repeat 3 times for each power
> Did you use the same phantom 3 times? Please specify
Why there are different power level for the experiments with liver (50 W, 100W and 150W) and with phantom (25W, 50 W and 75W)?
Please add comments.
Author Response
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Author Response.docx
Reviewer 2 Report
This article presents a very important research topic.
However, it is necessary to make the following observations regarding the content of the article. The authors must support themselves with textbooks or articles referring to high intensity ultrasound and prefer the concept of acoustic cavitation.
The general content of the article describes the term HIFU and describes the different power parameters. But they do not present the acoustic intensities that they studied and simulated.
Likewise, they do not clarify how it affects the shear stress waves and consequently the shock waves caused by acoustic cavitation.
They present the expressions of the wave equation where they include the losses due to different factors, including the expression of thermal waves. But they omit how the expression of acoustic cavitation influences generating multibubbles.
From figure 4 to figure 9, they should change the word sonication to the word ultrasonication, this because the studies were carried out in the ultrasound spectrum.
Author Response
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Author Response File: Author Response.docx
Reviewer 3 Report
Peer Review
Manuscript ID: Applied Sciences-2273656
Title: The effects of energy on the relationship between acoustic focal region and biological focal region during low-power cumulative HIFU ablation
The Manuscript by Peng et al. entitled “The effects of energy on the relationship between acoustic focal region and biological focal region during low-power cumulative HIFU ablation” lies within the journal’s scope of Applied Sciences. The authors examine the relationship between the acoustic focal region (AFR) of transducer and biological focal region (BFR) for different power and time combinations for a High Intensity Focused Ultrasound (HIFU) therapy. A finite element method approach was used to perform numerical simulations. Pennes Bioheat Equation, Westervelt equation and equivalent thermal dose model was used to compute the temperature distribution, acoustic field, and shape of biological focal regions. Finite difference time domain approach is used to solve Westervelt equation to a second order accuracy.
Please provide rebuttal or a point-by-point reply to all given comments below.
#Comment-1
The equation (7) doesn’t include metabolic heat generation rates. In the second term to the right side of Pennes Bioheat Equation, the authors didn’t include density of blood, which thereby questions the correct implementation of Pennes bioheat equation.
#Comment-2 (Typos)
The authors must carefully proof-read their manuscript.
Line 97: In the formula is the absorption coefficient corresponding to the nth harmonic component.
It should be nth as a superscript.
Line 236-237: In the low-power cumulative HIFU treatment, the shapes of BFRs in phantom and 236 bovine liver was investigated both experimentally and theoreyically.
It should be theoretically.
#Comment-3
Equation 9: Eq 43 is not the correct representation of Cumulative Equivalent Minutes. Consider Replace Eq43 with CEM 43 at all appearances in the manuscript. The manuscript lacks discussion about Cumulative Equivalent Minutes at 43
#Comment-4
For figure 02, also include the actual photo of the experimental set-up.
#Comment-5
Figure 03 shows negative and positive pressure with equal magnitude. Please replot with 0 minimum pressure and maximum as shown and then plot the graph.
#Comment-6 (Major Comment)
The simulation lags the implementation of thermal damage implementation, Table showing important parameters such blood perfusion of tissue. Blood perfusion affects the treatment duration, maximum energy deposition rates, maximum and minimum temperature achieved. The study lags the discussion on temperature distribution and thermal damage within the tissue. It will be difficult to verify the numerical simulation results without the information of temperature distribution computed through Pennes bioheat equation. Also, we will be interested to see the thermal damage coupled with the temperature-time history. These are the minimum results requirements for shown coupled differential equations is expected from this work. Include Temperature, Thermal damage, Modified thermal damage, Cumulative Equivalent Minutes,
#Comment-7 (Major Comment)
The literature review conducted for this work is not enough. Authors haven’t clearly discussed results. The Conclusion section is missing from this piece of work. Conclusion section must be included. Authors should highlight the importance of their numerical simulations as there are multitude of studies available in this regard.
#Comment-8 (Major Comment)
For figures 6 and 8, place your numerical simulations next to it at the same scale.
#Comment-9
There are some issues which were not included and should be discussed either in future scope of work or limitation of present computational work. Also, there are several suggestions for the authors to incorporate before recommending the work for publication such as heating changes the interstitial space and should be discussed in future scope of work [https://doi.org/10.1016/j.icheatmasstransfer.2021.105393]. Regeneration capabilities of healthy tissues near tumor boundaries [https://doi.org/10.1016/j.icheatmasstransfer.2022.106046], Variable blood perfusion and restricting heating to tumor tissues only [https://doi.org/10.1016/j.cmpb.2020.105781], Newer mathematical models in bioheat transfer: temperature dependent time-delay [https://doi.org/10.1115/1.4046967]. Consider including it in limitations section or future scope of work.
#Comment-10
Discuss the validation of present study with any experimental data. Compare and contrast your results.
Comments for author File: 
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Author Response
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Round 2
Reviewer 1 Report
Authors comments accepted.
Author Response
Thanks!
Reviewer 3 Report
The authors have addressed by comments. However, authors should consider including temperature and thermal damage maps to compute these BFR. The authors have updated representation of Eq43 to CEM43 in the text of manuscript. However, they need to correct it in Equation 9. Without the knowledge of temperature distribution, one may not be able to compute the thermal equivalent minutes. Per line 217-219, thermal damage is associated with therapeutic index of 4.0-4.6 computed via Arrhenius equation using kinetic rate coefficients. So, language modification to such instances is recommended in order to avoid the confusion to the readers. It should be replaced with "heating induced changes..." Also, correct the typo in equation 101. It should be "simulation". It is recommended that the authors should consider including information for temperature field distribution for energy deposition rates. You may plot Temperature vs time for 75 W, 100 W, 125 W or include this information in Table and mention volumetric temperature maximum, minimum, average for different wattage of 75, 100, 125. From Abstract section, last lines 23-24 must be deleted as there are several variables which were not considered for it to be recommended for its clinical translation i.e. "This study provides a reference for doctors to determine power, time and movement distance in clinical treatment." Also, the authors needs to be consistent whether they have employed the finite element methods (FEM) or finite-difference time-domain (FDTD) method. It is unclear as from lines 77-79, line 15, line 64. They need to discuss how it was implemented? The focus of manuscript should be experimental and please consider improvising your flow of text at appropriate instances. Also, include appropriate assumptions to your numerical simulations including Pennes bioheat equation, Westervelt equation and the boundary conditions used to compute BFR and AFR. The authors may refer and include to https://doi.org/10.1016/j.ijthermalsci.2022.107996 for correct implementation of Pennes Bioheat equation. Also, cite appropriate assumptions used to compute the BFR and AFR by using information from Pennes Bioheat Equation.
Author Response
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Author Response File: Author Response.docx
