Optical Spectral Approach to Breast Tissue Oxygen Saturation Analysis for Mastectomy Perioperative Control
, Anna A. Krivetskaya 1,2, Tatiana A. Savelieva 1,2, Andrey S. Gorbunov 3, Elena P. Kashirina 3, Sergey S. Kharnas 3, Vladimir V. Levkin 3, Vitaly I. Krasnovsky 3, Ekaterina Yu. Anosova 3, Daria V. Momatiuk 3, Ramil S. Ibragimov 3 and Victor B. Loschenov 1,2
Round 1
Reviewer 1 Report
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Reviewer 2 Report
Dear Authors,
Could You change the sentence: “The study of the state of tissue microcirculation is one of the most important problems 15 in experimental and clinical medicine” into valid version?
Could You add more information about in the line 72 about StO2 and could You show different types of tissues that could be checked by NIRS, for instance cerebral tissue oxygen saturation (cStO2) . I recommend to add: PMID: 33030316.
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Reviewer 3 Report
This manuscript is devoted to develop the method of hemoglobin detection, based on the fiber-optic spectral analysis in visible region for determination of the level of blood supply to breast tissues. The optical phantoms of the mammary gland (intralipid diluted with distilled water (as a scattering medium), whole blood of a volunteer mixed with heparin (as a absorbing medium) and silicone transparent tubes filled with blood (as structure of blood vessels)) simulating the subcutaneous adipose tissue of various thicknesses for determination of the effect of its light scattering on the diffuse reflectance spectrum are developed and realized. The experiments with using theses phantoms and clinical experiments were carried out. These results can be interesting for scientific groups in area of spectroscopy of visible range and medical diagnostics.
There are some points to correct or to make the information more clear:
1) It is necessary to explain the abbreviations at first meaning (e.g. MRI for magnetic resonance imaging - 55th line, ICG dye for Indocyanine green– 62nd line, DIEP for deep inferior epigastric perforators – 66th line, NIR for near infrared – 79th line. Besides it is necessary to add the “oxygen” to the explanation of StO2 (it must be a tissue oxygen saturation) – 71st line.
2) Authors write: “The study was carried out using a spectroscopic system (Figure 1) for measuring blood oxygenation in the visible range, which consisted of a broadband light source with sufficient uniformity in the range of 500–600 nm, a spectrometer with optical filters…”. The radiation source is described after Y-shaped fiber bundle, but it is more convenient to begin the setup description with its description. What was the spectrometer? If this device is commercial one, it is necessary to write the model and producer. If the device is developed by authors or their scientific group it is necessary to write its specification.
3) Figure 1. It is necessary to increase the arrows in the distal end of the bundle, because the emitting and receiving fibers are not distinguish in present image. Besides the Figure caption is “The experimental setup, consisting of a source of broadband light radiation (1), a spectrometer (2), an optical Y-shaped fiber bundle (3) and a PC (4). The optical Y-shaped fiber bundle consists of 7 monofibers: 1 fiber for emitting and 6 for receiving light (5)”. But there are only “1”-“3” numbers in this Figure. The “4”and “5” are absent. And “3” is marked the PC in the Figure but the “Y-shaped fiber bundle” in caption.
4) Authors write about character peaks of hemoglobin: “oxyhemoglobin has two absorption peaks at wavelengths of 542 and 576 nm, reduced hemoglobin has an absorption maximum at a wavelength of 556 nm” (113th -114th lines) “When the characteristic absorption peaks of the two forms of hemoglobin were no longer distinguishable, the measurements were stopped” (188th-189th lines). But there are not the Figure illustrated this characteristic picture in manuscript.
5) The Figure 2 illustrated the measurements on an optical phantom present only two fibers (emitting and receiving). Are these fibers same as monofibers in the Y-shaped fiber bundle?
6) Figure 3. There are very small letters in legend in top line of figures. Besides the value of IL (it is the depth probably) is not determined.
7) What does the “T1”-“T8” in the Figure 5 mean? If they are test points of 1-8 as in Figure 4, why are they with “+” and “-“? It is not clear. Besides the letters of legend (name of curves) are small.
8) Authors write “all obtained StO2 values of each patient, measured on key days before and after surgery” in Figure7 caption. Is average value for saturation for all patients presented here? It is not clear from the caption and text.
This manuscript describes with details the results of development of the optical method of hemoglobin detection in breast tissues at preoperative and postoperative periods at breast cancer.
The manuscript can be published after minor revisions.
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Reviewer 4 Report
The manuscript submitted by D.M. Kustova et al. is devoted to the use of fibre optic-based spectrophotometric oxygen saturation measurements in the perioperative monitoring of mastectomy. The issues addressed in the manuscript overlap with the scope of the Photonics journal. The language used in the manuscript should be understandable to a wide range of readers. The selection of literature does not raise any major objections to me. The logical structure and organization of the manuscript have also raised no major concerns. The concept of using the oxygen saturation level examination based on the backscattered light reflectance for characterization the level of blood supply to the breast tissue before and after surgical treatment is interesting, but before publication the extend revision and corrections are necessary.
Comments:
1) There is residual information in the manuscript regarding the number of measurements carried out, their repetitions, etc., which makes one wonder about the statistical significance and representativeness of the results obtained.
2) In the section on materials and methods, the authors did not directly describe how they determine the oxygen saturation level, either for measurements on a phantom or on living tissue.
3) For preliminary studies on a phantom, the authors use a laser source of radiation with a wavelength of 532 nm, and for studies on patients, they use an LED source that emits polychromatic light. Therefore, I do not understand how these results can be compared?
4) Why do the authors use a broadband source in the developed system described in Section 2.1 and not strictly tailored to the 2 absorbance maxima of oxyhaemoglobin in the range 500-600 nm? On the absorbance at what wavelength is the saturation level determined? This is not clearly described or justified in the manuscript.
5) Have the oxygen saturation measurements obtained with the proposed technique been validated with another reference technique to compare the results and their validity? If not, then the measurements obtained using the authors' method can be correlated with the actual results, i.e. used to assess degrees of saturation, but not necessarily its actual level.
6) The manuscript lacks precise technical specifications and information (model, manufacturer, etc.) of the components (light source, detector, fiber-probe, PC etc.) of the developed measurement system, which is a requirement of any scientific journal, including Photonics. The authors are requested to complete the Materials and methods section and provide an accurate description of the measurement system.
7) When measuring over time, was the same area of tissue analysed each time? How was the position of the probe determined each time?
8) Please include the emission spectrum of the used LED lamp on Fig.1
9) Lines 147-149: The authors are asked to provide precise information on what they used as a reference surface in the spectrophotometric measurements. This information was not included in the manuscript.
10) Lines 162-163: On what basis was the distance between the adjacent fibers determined? The authors are asked to provide detailed information.
11) Lines 168-169: Provide an explanation why such concentration of the intralipid was used in the proposed examination.
12) Lines 176-177: Why authors are using the laser light with wavelength equal to 532 nm for measurements on optical phantom, if in lines 145-149 they are describing the LED lamp as a light source used in the proposed measurement system for tissue? The authors chose to use a wavelength of 532 nm close to the first maximum of oxyhemoglobin and not the wavelength relating to the second maximum of absorbance, which corresponds to a longer wavelength. After all, the longer the wavelength, the greater the depth of penetration of light.
13) Lines 245-246: In my opinion, taking only 3 replicate measurements is not sufficient to obtain representative data. How do the authors obtain histograms from only 3 measurements? Provide an explanation in text how the oxygen saturation St02 was determined? The measurements were validated by another reference/conventional method?
14) Was the skin phenotype of all patients the same? Melanin concentration can influence the reflectance spectra. This issue is not discussed by the authors at all.
15) Lines 283-291: How many repetitions of measurements on patients were performed. From how many measurements were the results averaged? What was the measurement uncertainty?
16) Figure 5 is hardly intuitive to read. I would suggest a different presentation of the results, which would allow a comparison of the values at the corresponding points on both sides of the wound. What is the meaning of T1-8? What about the results for measurements points 9-11 indicated in Fig.4?
17) Fig.6: From how many measurements were the attenuation coefficients averaged? What is the meaning of the black dots in the nipple area?
18) Fig.7: For the sake of clarity and better reception by the readers, please explain directly in text how the oxygen saturation value was determined.
19) The scope of the research carried out and its purpose are not clearly defined and presented in the Introduction section.
20) Some of their research has been carried out in patients; therefore, according to the guidelines of the Declaration of Helsinki, authors can provide approval from the bioethics/ethics committee.
21) Authors are requested to explain all abbreviations used in the text ( e.g., DEIP).
22) Figure 2 does not have the markings (a, b) used in its caption.
23) For the sake of clarity for the readers, please explain the abbreviations used in Fig.2.
24) Can the authors provide any information on the research group: age etc.?
25) When writing what diameter of optical fibre do the authors think of the diameter of the core, diameter of the core and cladding, or the diameter of the core, cladding, and coating?
26) The fibre-optic reflection probe used was created and prepared by the authors; is it commercially available? The authors are requested to complete this information.
27) Line 208: Provide the values of the irradiance (W/cm2) and dose of light energy (J/cm2).
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Reviewer 5 Report
The authors try to study the ability of hemoglobin detection, based on the fiber-optic spectral analysis in visible region, to determine the level of blood supply to breast tissues before surgical treatment, intraoperatively and during observation of the patient in the postoperative period, when breast tissue is healing.
The manuscript is well presented and has good significance regarding the effect of subcutaneous adipose tissue on the shape of diffuse reflectance spectra. However, the authors should address the following comments;
1. regarding the constructed optical phantoms, the authors should point out to the readers that photonic nanojet can be utilized for better and accurate future analysis. "Photonic nanojet analysis by spectral element method" IEEE 2014
2. The data for each day corresponds to the average saturation value for all patients participating in the selected day. The authors should address how the average can be the key of stating this. what about the nature of all data?!
3. in the lines from 331 to 334, don't the authors think that there might be other parameters (Factors) that led the collected data or at least affected on the data and hence on the conclusions drawn in the study?!!
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Round 2
Reviewer 1 Report
The authors answered my concerns.
Reviewer 4 Report
Thank you for the information and clarification provided. In my opinion, the manuscript is suitable for publication.
