Combined Non-Invasive Optical Oximeter and Flowmeter with Basic Metrological Equipment
Round 1
Reviewer 1 Report
First of all, I would like to thank the authors for the clarifications to my previous comments, but in my opinion the issue of prototype validation is still debatable.
Major comments:
I understand the problems cited by the authors regarding standardisation of performance and uniform calibration procedures for blood oximeters and flow meters by different manufacturers. There are no direct regulations, or ISO norms about this. However, there are several reports in the literature (see examples below) concerning the problem of validation of different tissue oximeters from different manufacturers that characterised the measurement results obtained by different devices as INVOS, OxiplexTS, SenSmart, OxiplexTS systems:
[1] https://doi.org/10.1364/BOE.7.002973
[2] https://doi.org/10.1364/BOE.9.000086
[3] https://doi.org/10.1364/BOE.4.001662
[4] https://doi.org/10.1515/bmt-2017-0116
[5] https://doi.org/10.1007/s10877-017-0015-1
Therefore, I wonder why the authors did not perform such a comparison (even minimally) that would clearly demonstrate the advantages of the proposed system among other systems. According to the authors, the main advantage is its multifunctionality of the prototype, and what about sensitivity, dynamic range? In article [1], mathematical equations were derived to convert StO2 measured by one oximeter to another, allowing the characterization of the dynamic range and sensitivity of these oximeters. As a consequence, it is possible to directly compare these devices and their measurement performance. Why do the authors did not decide to determine any objective parameters as, e.g. sensitivity, SNR etc. of the proposed prototype to characterize its performance with even one alternative?
Moreover, in my opinion, the organization of the manuscript is still not very clear. According to accepted standards and requirements of the journal, the manuscript should be divided into the following: introduction, methods and materials, results, discussion (results&discussion), conclusions. I disregard the fact that the authors do not follow this convention, however, in the present form of the manuscript for the readers it is still the biggest problem to state what is actually the result here: the results of testing the phantoms for calibration of the prototype or the results of realized measurements using this two-channel prototype, because the latter measurement part is very superficially treated? The authors should strongly emphasise this.
Lines 621-622: “For the case of cerebral channels, a reproducibility test was also performed according to the procedure described in Section 6.” - there is no Section 6 in the manuscript. How many measurements were made?
Minor comments:
Please include technical details about Specord M40 according to the journal requirements.
Author Response
We’d like to thank the reviewer again for his comments and time spent.
Despite the fact, two other reviewers approved the article for publication after the 1st round of reviewing, the shortcomings, of course, remain in the manuscript yet. We understand that in one article one always want to find answers to all questions. However, this is not always possible. According to the rules of the journal, authors have only 10 days to revise their article. Therefore, we are not able to perform and present a comparison (even minimally) of our prototype with any commercial oximeters. 10 days is too short for that, sorry. Furthermore, in the absence of standardized and certified techniques and equipment for the instrument calibration (measures, for examples), accepted by a community, such a comparison of readings in terms of StO2, BF, etc. does not make sense, in our opinion. Two devices can be always calibrated in such a way, especially using computers and software as a tool for data processing, when both devices show the same result. We have demonstrated this in [25] on the examples of our IOFF technique and LDF (thus, such a comparison can be considered already as published for the flowmetry channel). This becomes possible because signals from photodiodes of the first and second devices are monotonic functions versus BF or StO2. These functions have one domain of definition, so purely mathematically they have a one-to-one correspondence. According to well-known mathematical theorems, there is always a third function, multiplying by which, for example, the first function, one can get the second function, and vice versa. Thus, the problem is not in comparing readings, but in which readings are considered correct.
Another thing is the sensitivity and signal-to noise ratio (SNR). In this point we agree with the reviewer, that it is important and missed in our article. However, again, we have too little time to fully measure and compare all this with other devices, but we added some of results that we had previously to the article (marked by green). Thanks for the comments.
As to the organization of the manuscript, we can explain, that this article we prepared at the personal invitation of the editor of this special issue Dr. Pavel Subochev. At the stage of discussion, we considered with him various topics and format for the article, for example, the theoretical justification for measurements, clinical trials data, a description of the design of the device, etc. He selected the design of the device. Therefore, the article was born in such a version. Probably, the new result is actually difficult to extract from the text, especially for those who are not an engineer, but a university or academic scientist. Scientists always prefer to see dependencies and data, not a design. We can agree. Nevertheless, we can explain that we believe our new result consists in follows:
- Previously it was not known how to combine flowmetry and oximetry technique in one optical probe; therefore, it was not known how to raise up the diagnostic informativeness of oximeters. We offer the way. However, to do this a number of other problems should be solved. We described it in the manuscript. For example:
- The clear justification for the selected cyclograms for LEDs, the advantages and disadvantages of different cyclograms, especially for the case of a combination of oximetry and flowmetry, was not published (we don’t know such publications). We investigated the problem.
- Solid-state and time-stable measures (not liquid, which are bad reproducible and not time-stable) which can be applicable for both cerebral and peripheral probes were not known. We proposed and tested such measures.
In summary, the result is the demonstrated possibility of the integrated approach to the development of methods and instruments for oximetry. We have not improved the measurement accuracy in comparison with known devices. We did not formulate such a task. We tried to create a more informative and reasonable device through a combination of technologies and the development of the equipment for its subsequent metrological certification. In our opinion, until now, such a complex approach was not known yet in the field of optical noninvasive diagnostics.
We have added some of these explanations to the text in Introduction as well as in Discussion and conclusions. All corrections are marked by green.
With best regards,
Authors
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors addressed all the questions properly.
Author Response
Thank you for approving our article for publication. However, one of the reviewers made more comments, so we finalized and send the article again.
Reviewer 3 Report
The paper has been duly revised according to the Reviewer comments, and is now suitable for publication in "Photonics"
Author Response
Thank you for approving our article for publication. However, one of the reviewers made more comments, so we finalized and send the article again.
Round 2
Reviewer 1 Report
Thank you for the authors' explanations and corrections. In my opinion, the validation of any diagnostic method is a critical condition is applicability, however, I take into account the engineering qualities of the developed solution and the short time provided to improve the manuscript. It is also important to remember that the main audience for this article is the scientific community. And I write this both as an engineer (with 15 years of experience) and as an academic scientist
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
This paper introduced a combined optical oximeter and flowmeter device, for StO2, Vb and BF measurement. The performance of this device is characterized and validated through basic metrological equipment. This paper is well written overall. Some small concerns need to be addressed
- In the beginning of Introduction, optical coherence tomography should be ‘OCT’ instead of OTO.
- The combination of oximetry and flowmetry has been attempted by a couple of other groups (Simultaneous blood flow and blood oxygenation measurements using a combination of diffuse speckle contrast analysis and near-infrared spectroscopy, 2016). The authors should describe the difference and the unique contribution of this work.
- Beyond LDF, there are other flowmetry technologies, such as diffuse correlation spectroscopy (Diffuse correlation spectroscopy (DCS): a diagnostic tool for assessing tissue blood flow in vascular-related diseases and therapies, 2012) and more recent works like diffuse speckle pulsatile flowmetry (Fast pulsatile blood flow measurement in deep tissue through a multimode detection fiber, 2020). The authors should describe the technical difference of the LED based flowmetry.
- No in vivo experiment result is demonstrated in this paper. The authors should consider adding in, and describe more about the significance of this device in medical applications.
Reviewer 2 Report
The paper “Combined non-invasive optical oximeter and flowmeter with basic metrological equipment” presents a step-by-step work on the development of a multifunctional equipment aimed to combine the measurement of different parameters for a cost and time effective assessment of functionality head’s organs. The sequence of experiments, with background for example on optics of tissues to set up of device and calculations to be performed, is completed by convincing results. As from the remarks as stated below, the paper needs a minor revision.
Major remark
In general, the organization of the paper is unlike the common ones, distinguishing “Materials and Methods” from “Results”. Anyway, I understand that the organization as given is more suitable to clearly provide an upward information on background, experimental organization, calculations, and results. So, it would be suggested to add a sentence at the end of “Introduction” to assess the reasons for this text organization.
Page 18 - The sentences “Further experimental research should include testing the idea in clinical trials. We deliberately do not present the results of such tests in this article, because it should be a separate study with its own goals, design and results. This should be a separate article, we believe” could be more conveniently given as:” Further experimental research should include testing the idea in clinical trials. The results of such tests are planned to be given in a next separate study with its own goals, design and results”.
Minor remark
Page 4, line 170, please provide the Ref. Number (n. 27, right?). It is likely correctly given in the References section, but please check.
Reviewer 3 Report
The manuscript describes the idea of a dual-channel device for measurement of saturation and blood flow, issues related to the design of measurement probes, and attempts to verify the operation of this device on phantoms. It is an interesting approach, since multi-channel detection of multiply quantities always enables a more complex diagnosis. However, in my opinion, the manuscript in its current form is not suitable for publication because it contains many methodological shortcomings, and the repeatability of the presented results is debatable. The concept of the device for simultaneous measurement of two values: saturation and blood flow, as well as the constructed sensor, is interesting, however, the presented version of the manuscript and presented results do not allow objectively state the effectiveness and correctness of this sensor.
The manuscript is written in such a way that it is difficult to clearly understand what its main purpose is. Is this manuscript supposed to present the developed measuring device and its validation, issues connected with its construction and design of measuring probes, numerical simulations of its operation, etc.?
The information placed in each article should allow for potential verification, replication of the obtained results by other researchers, which is completely impossible for this manuscript. The main complaint is the lack of detailed description of several important issues:
- Apart from the schematic diagram (Fig.3a), there is no information about the detailed technical specification of the components of the designed device, which should be included used light sources, its wavelengths, powers, detectors, and its sensitivity etc. All necessary dates should be provided if authors are presenting the novel sensing system.
- There is no precise specifications or information about optical properties of the proposed phantoms, which were used in simulation of the real measurement conditions. The authors mention the optical properties ( optical coefficients, parameter) of the tissue, but there is no information on the optical properties of the proposed phantoms, which are designed to simulate the real tissue and real measurements conditions.
- I understand that the used phantoms were proposed by the authors; however, I wonder if the obtained results were validated/ confirmed by other conventional oximeter or blood flow sensor? If not, I have doubts about the correctness of obtained results that can not be validated, which means that they may not be representative.
Furthermore, the authors have not focused on presenting any information regarding the measurement accuracy of the proposed sensor. The only "real" measurement results from the sensor, not simulations, are presented in Fig. 6 and Fig. 10, but it is difficult to assess their repeatability, reliability, because the whole paper lacks information about any measurement uncertainties.
How many measurements have been taken with this sensor at all? There is no information on this at all, again calls into question the representativeness and reproducibility of the results obtained.
Since the authors propose a sensor for dual-channel measurement of saturation and blood flow, why is the validation of its performance presented on the basis of two separate measurements of these two quantities and not simultaneous measurement? After all, the presented results do not allow for verification of the possibility of simultaneous detection of both quantities.
The structure and division of sections are inconsistent with the requirements of the journal. More than 8 pages of introduction to the discussed issue (3 subsections) is, in my opinion, far too much. This part should be significantly shortened.
I do not understand the use of the word measure in this manuscript at all? Can the authors explain what the term refers to in their case, for example, in lines ‘332-339’ and Fig.5a.
Figures and tables should not be divided and placed on separate pages but on one page. Correct this.
Line 170: Missing reference
