Dependence of the Registered Blood Flow in Incoherent Optical Fluctuation Flowmetry on the Mean Photon Path Length in a Tissue

Round 1

Reviewer 1 Report

please see the attachment

Comments for author File: Comments.pdf

Author Response

We thank all reviewers. Please, see our response in the pdf-file attached.

Author Response File: Author Response.pdf

Reviewer 2 Report

The paper submitted for review by Denis Lapitan, Andrey Tarasov and Dmitry Rogatkin “Dependence of the registered blood flow in incoherent optical fluctuation flowmetry on the mean photon path length in a tissue” is devoted to the topical problem of the development of optical non-invasive methods of live tissues. The subject of the work corresponds to the subject of the Special Issue of "Photonics, Section Biophotonics and Biomedical Optics"Journal.
The reviewer has several key questions and comments that need to be clarified before publishing this article:

• 1) There is no diagram indicating the parameters used in the simulation. It is necessary to indicate the location of the radiation source and receiver on the skin and designate the SDD parameter.
  2) In the Introduction, the purpose of the work is explicitly stated only on the second page of the article, line 94. Why is the focus and the beginning of the introduction devoted to the comparison of the IOFF method with a low coherence source and LDF with a coherent illumination? In my opinion, it is correct to compare IOFF, for example, with the diffuse reflection method in the mode of recording the dynamics of changes in the reflected radiation intensity at one wavelength. I suggest to focus on the stated goal of the work at the beginning of the article, especially since Monte Carlo simulation was carried out only for IOFF.
  3) Line 36-37 contains the statement "One of the significant limitations of the method (LDF, reviewer's note) is a small diagnostic volume in a tissue, which makes it possible to explore only superficial skin vessels." In Bernjak, Alan, Stefanovska, Aneta, McClintock, Peter, Owen-Lynch, P., Clarkson, Peter article (2022), 10.1142/9789811252143_0033 Studies of coherence between fluctuations in blood flow and oxygen saturation are presented by the combined LDF method and optical reflectance spectroscopy. Page 1240013-2 notes "The exact measurement depth depends on tissue properties but the shallow recording (fiber separation = 2 mm) reaches to around 1 mm in the skin (typical for LDF devices) while the deeper recording (fiber separation = 8 mm) can reach several mm deep". Explain why you claim that under the same experimental conditions, radiation from a source with a low degree of coherence penetrates deeper into the biological tissue than radiation with a high degree of coherence? Provide additional references from other authors to your own article [13].
  
  4) Line 37-38, "As a result (highlighted by reviewer), the method has a low reproducibility of basal skin BF recorded at rest [5]." Basal skin blood flow is studied mainly in so-called “biological zero” studies, see for example Humeau-Heurtier A, Abraham P, Mahe G. Linguistic Analysis of Laser Speckle Contrast Images Recorded at Rest and During Biological Zero: Comparison With Laser Doppler Flowmetry data. IEEE Trans Med Imaging. 2013 Dec;32(12):2311-21. doi: 10.1109/TMI.2013.2281620. The LDF method is widely used to analyze the dynamics of changes in the state of biological tissues during provocative tests, for example, an occlusion or heating test, see, for example, the fundamental studies of Aneta Stefanofska group and many other authors. The statement requires correction or exclusion from the text.
  5) Does the team of authors have a license for Matlab 2022 Software?
  6) According to Figure 1, the MPL value corresponds to an SDD of approximately 0.06 cm, in Figure 3, the MPL=0 value corresponds to SDD=0, based on the figure caption. Is it correct? Show the axis with SDD values ​​in Figure 3.
  7) It is necessary to prove the homoscedasticity of the data presented on Figure 3. Otherwise, the comparison of the residual sum (line 211-212) is incorrect.
  8) It is necessary to analyze the data nonlinearity and evaluate the residual sum without taking into account the point (0,0) in Figure 3, since it was not obtained as a result of simulation and has no physical meaning in a real device.
  9) Is it possible to achieve less than 4 mm SDD in a real device without using fiber sensors? For SDD greater than 5 mm, the relationship between BF and MPL may be linear (according to Figure 3) and there is no need to correct the results.
• 10) Use different dot markers on Figure 1 similar to Figure 2. Change the caption to match the changes.
  11) I suggest to exclude from the text the statement on lines 249 - 251, as not related to the purpose of the work.
  12) There are spelling errors in the text, lines 61 and 74. Line 256 "From the point of view of IOFF measurements' standardization..." is better.

Author Response

We thank all reviewers. Please, see our response in the pdf-file attached.

Author Response File: Author Response.pdf

Reviewer 3 Report

The paper is devoted to the important question of the development the technique the microcirculation registration. They provide novel technique, which has a potential interest. 

I have several comments on it:

1. What physical value exactly the authors try to measure. Please give the definition of the blood flow. In the line 32 authors mention that BF, velocity and or concentraiont of moving rbc. 

2. The authors mainly refer on papers of 2005-2008 describing PPG. At the moment this topic is extensively developed and new works are published. I highy recommend to observe several papers written by prof. Kamshillin's group.  

3. I reccomend to add the scheme of the light source and detector location.

4. Fig.1 Please provide the plot desigh which can be understood in the gray scale presentaion. 

5. The authors should in detail describe the calculation procedure. How many realization they provided. At which parameters (SSD) exactly the calculations were carried out. Why the distance 1.6 cm was chosen. I suppose that studiing MLP of 2 cm bones should be included. This is interesting mathematical trick to study such distances. What is physical meaning of such simulations. 

6. Please provide all error bars on the plots.

7. The most serious remark. Have you calculated the point wich coordinates (0,0).  In case this is only theoretic point please add points for other MLP, namely 0.1, 0.2, ..05 cm.  What is the error bar? Revise your conclusions (line 249-255) according to the real results. 

8. I suppose, that conclusion lines 250-251 looks to be to strong.

Minor comments

1. Line 35 is it important that the surface of the photodetector is quadratic. 

2. Line 42 The word "capricious" can be changed to proper one. 

3. Line 45-line 52. It is enough to write one fluctuations (pulsations).

4. Line 52. "One more" is not appropiate

5. Line 61 "propotionally" - mistake

6. Line 74. "isobestic" - mistake

Please revise English language more proper. 

 

Author Response

We thank all reviewers. Please, see our response in the pdf-file attached.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I have carefully read the authors answers. I consider that the manuscript has been improved. All my remarks have been revised. I suppose the article “Dependence of the registered blood flow in incoherent optical fluctuation flowmetry on the mean photon path length in a tissue” should be recommended for publication in the journal Photonics.

Author Response

We thank the reviewer for his/her time and for the approval of our article.

Reviewer 3 Report

First of all I would like to thank the author for the detailed answer on reviewers questions. Now let me know to discuss them carefully.

1.       The authors write “BF is proportional to the rate of the blood volume increment in a tissue per unit time”. Can it be negative? It is not quite the same as authors rewritten from the cited paper “The term perfusion describes the amount of blood delivered to the capillary beds of a block of tissue in a certain period of time.” Also in the plots the authors use “flux”, but not BF. What is the difference?

2.       ok

3.       The scheme in the Fig.1 is very confusing. The geometrical scale of the dermis, accordingly to the paper, is 0.7 mm. Looking at the scheme one can conclude that the probe scale is approximately 0.2 mm, which does not correspond to the real size of the probe – 1 mm².

4.       Ok

5.       OK

6.        Please estimate the level of the error of your simulations. 

7.       The main result is obtained by the fitting data obtained from the numerical calculations. As authors do not show the error of their oscillations, they cannot estimate the error of the fitting. Another question concerning Fig.4 is as follows. The maximum MPL considered in the paper is 3.5 cm. The authors do not show the optical path in the tissue, so here the reader shall imagine it, basing on his own knowledge of the light propagation in the tissue. Concerning known “banana” form we obtain that penetration depth is close to 1 cm. Please clarify which anatomic location exactly describes this model.

8.        Ок.

9.       The authors use direct translation of professional  slang of their native language, namely in different parts of the paper they write “square detector, quadratic photodetector, square law detector”. I suppose that it should be written in the proper English term. It is not easy to understand what the authors keep in their mind writing “square detectors” (line 150).

 Minor comments:

1.       The units shold be carefully checked for every number in the paper.

 

Author Response

We partially revised the manuscript and answered all questions in the attached file.

Author Response File: Author Response.pdf