A Review of Monitoring Methods for Cerebral Blood Oxygen Saturation

Round 1

Reviewer 1 Report

In this review, the authors reviewed three clinical methods for cerebral blood oxygen saturation monitoring. The present study is of major relevance and of great interest for clinical practice.

I will summarize some points that may increase the quality of the manuscript.

Comments:

1. The manuscript requires English revision regarding grammar and style.
2. The text is frequently redundant and is too long.
3. When discussing methods that measure saturation of hemoglobin, the authors should include inhalatory intoxication (i.e. carbon monoxide) as a possible confounding factor and a limitation of the cerebral blood oxygen saturation method.
4. Information in Table 1, particularly the scope of indications of each method, should be reviewed in light of recent medical guidelines.
5. Very few references (less than 10%) are from the last two years. Therefore, the authors should update the references. Furthermore, the authors have to revise reference citation, one had no date.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

This paper is very well structured and well written. However, many statements need proper citations. The authors should carefully read and proper cite the statements where applicable.

The following are minor comments.

1) On page 1, lines 25-29, lines 42-44: The authors should provide references for this data.

2) Figures 1-3: Do the authors have the approval of this figure for reproduction?

3) On page 3, line 92:  Add reference for “The normal range of SjvO2 is approximately 55–75%.”

4) Caption of The table can be improved. The current caption does not give any information.

Author Response

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Author Response File: Author Response.docx

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

A nice read - good review. 

Some minor points:

Check spelling of haem / ischaemia etc. US or UK spelling for, check throughout.

Table 3 - make gaps between rows for clarity of read.

Lots of hyphenation on words split between lines - spoils the read.

A few spelling mistakes. (e.g., sugery?)

INTRO - lines 1 and 2: reword "The majority of life activities are controlled and governed by the brain.

Figure 5 could be bigger and and a lot clearer.

Title could be changed to ... "A review of ..."

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

This review is quite intriguing for monitoring of SjvO2, PbtO2 and rSO2 with a good amount of
suevey results.

1) Section 3: This section is not well organized. The contents of discussion and the proposed method seem to be mixed up. It would be better that the authors pose an open discussion after the comparison of monitoring methods introduced in the previous section.

2) Section 3.2 would need to be a new section as Section 4 if the authors aims to propose a new method and system using the four near-infrared wavelengths, because the system presented in this review itself is interesting for its potential applications.

3) On the other hand in section 3.2, any evaluation results are not shown (Figure 6?) to understand the effects of the four near-infrared wavelengths before the conclusion.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

The authors of the manuscript claim to review the three most extensively used methods for cerebral blood oxygen saturation monitoring from different aspects: working principles, relevant parameters, current situation of research, commonly used equipment, and advantages and disadvantages. The authors also propose an improvement of the NIRS technique for the measurement of rSO2 by integrating a self-developed non-invasive hardware platform with four light sources instead of two, in order to eliminate the effect of absorption by melanin.

The combining of a review and description of a new technique in one manuscript, is not accepted, in particular where both are presented unclearly, with many inaccuracies in the scientific terms. The different aspects of the review are mixed and are therefore unclear, and the different scientific terms are not always accurate. The second item, the improvement of the NIRS technique, is called a predictive model, while it is not model at all. There is no proof for the improvement of the new technique.

The English language is not good. It seems that it was translated from a foreign language, by a person that translated the text without understanding the context of some words.

Some specific comments.

1. Line 39. “The commonly used cerebral blood oxygen saturation monitoring methods in hospitals include jugular venous oxygen saturation (SjvO2) monitoring, electroencephalogram (EEG), event-related potentials (ERPs), and transcranial doppler ultrasonography (TCD).“

Comment. EEG, ERP and TCD are not oxygen saturation monitoring methods.

2. Line 72. “In some literature reports, SjvO2 is also known as jugular bulb oxygen saturation.”

Comment. The jugular bulb oxygen saturation is designated by SjvO2.

3. Line 80. “SjvO2 monitoring is based on the percentage of oxygen carried by hemoglobin (Hb) and the dynamic changes in whole-brain oxygen supply and consumption”

Comment. SjvO2 is the percentage of oxygenated hemoglobin, and is related to the whole-brain oxygen supply and consumption.

4. Line 81. “SjvO2 offers an indirect evaluation of brain tissue oxygen metabolism”

Comment. SjvO2, together with other parameters, can offer an indirect evaluation of brain tissue oxygen metabolism.

5. Line 84. “Based on these measurements, Fick's formula is used to calculate the brain tissue oxygen metabolism to represent the whole-brain oxygen saturation. SjvO2 monitoring is a non-qualitative monitoring technique for cerebral perfusion.”

Comment. The brain tissue oxygen metabolism represents the whole-brain oxygen saturation? What is non-qualitative? Is it quantitative? SjvO2 monitoring is a quantitative monitoring technique for cerebral perfusion?

6. Line 101. “According to Fick's law, the parameters related to cerebral oxygen metabolism in SjvO2 monitoring can be calculated using the following formulas:……”

Comment. Not all parameters require the Fick’s Law, and it is not clear why these parameters and equations are required in this section.

7. Line 170. “At present, the two most commonly used equipments are the Abbott Labs Oximetrix 3 SO2/CO monitor and the Edslab by Baxter Healthcare Corporation [4].”

Comment. The reference 4, is from 2002, and it cannot provide information on commonly used equipment at present.

8. Line 177. “light absorption varies under different concentrations of Hb in the blood.

Comment. In the context of SjvO2 monitoring light absorption varies under different concentrations of HbO2 in the blood.

9. Line 202. “This method (PbtO2) monitors brain tissue partial pressure of oxygen, temperature, and pH.

Comment. PbtO2 only monitors brain tissue partial pressure of oxygen.

10. Line 373. “An appropriate wavelength is chosen to estimate the light intensity attenuation at two or more wavelengths.

Comment. Appropriate wavelengths are chosen to estimate cerebral blood oxygen saturation from the light intensity attenuation at two or more wavelengths.

11. Line 622. “Based on the self-developed non-invasive rSO2 monitoring hardware platform shown in Figure 6, we propose a new rSO2 predictive model. A self-developed four-wavelength front-end sensor”

Comment. As was commented above, the self-developed non-invasive rSO2 monitoring hardware platform is not a rSO2 predictive model.  What is “front-end sensor”?

12. Line 625. “In this way, we can achieve continuous non-invasive monitoring and hope to offer a new solution for the NIRS-based monitoring of rSO2.

Comment. It is not enough to hope. You have to show some improvement of the modified and more complex technique.

13. Line 643. “ In Figure 7(b), the near-infrared absorption ability of HbR and HbO2 is alternately higher.

Comment. What is absorption ability and what is alternately higher?

14. What are the absorption units in Figure 7a? The relative absorption of melanin and hemoglobin depends on the relative concentrations of the melanin and hemoglobin. The absorption curve of water seems to be different in Figs 7a and 7b. What is the oxygen saturation of the hemoglobin in Fig. 7a?
15. Line 668. “As shown in Figure 7(a), the melanin in the monitoring area of the brain has a far larger absorption coefficient for 700 nm red light than does hemoglobin. Thus, when constructing the non-invasive rSO2 predictive model, we roughly considered the variation in the optical density of the 700 nm emergent light to be caused by absorption in melanin.

Comment. The assumption is not reasonable. You have to support is quantitatively from a reliable data.

14. Line 675. “That is, the variation in the OD of melanin at a wavelength of 700 nm replaces the light absorption of melanin at wave- lengths of 760 nm and 850 nm during modeling, so as to reduce the complexity of modeling.

Comment. The new assumption should be supported by numbers.

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

The paper reports on several main methods of brain oxygen monitoring in terms of technologies, parameters, applications and the current research results. In the discussion section, the authors suggest a model for prediction of oxygen saturation based on the NIRS. The paper misses on a few major issues for a proper scientific review paper, mainly that the range of technologies covered is restricted to few methods and not extensive enough. My main comments are below:

• The title of the paper indicates the paper to be a review on the available methods for cerebral oxygen saturation measurement. The paper, however, only focuses on the invasive methods, and does not cover the imaging methods in detail. Moreover, the paper includes methods and models proposed by the authors which is not common in a review paper. I suggest some re-structuring of the paper and adaption of the title so it gives a better overview of the paper content.
• The paper structure can be improved, for example, what is the difference between the paragraph starting at line 63 and section 2.1? Lines 63-64, why is the general purpose of oxygen saturation monitoring explained here instead of the introduction? Line 111 is a repetition of earlier descriptions.
• Line 70: Please clarify ‘under conditions not limited to pathological’
• Line 83-84: The Fick’s principle should be elaborated on and related to the equations 1-6. Should be considered that Fick’s principle is used to measure flow and oxygen consumption rate in the first place. Section 2.1.2 can be combined with 2.1.1 to give a better flow to the text.
• Lines 85-86, what is the purpose of mentioning ‘non-qualitative’? Why do the authors state monitoring of perfusion here while the purpose is to discuss the oxygen measurements?
• Line 93: How can the consumption of oxygen be higher than supply? Please clarify.
• Fig 5. The authors should rather include the technical principles and not commercial systems.
• I find section 3.2 more suitable for the NIRS in section 2 instead, where the methods are described. Alternatively, under a separate section before discussion.
• Fig 7. These ‘constituents’ are often referred to ‘chromophores’ or the main ‘absorbing constituents’ and not any constituent.

The mentioned chromophores are commonly cited from the work of Scott Prahl or WG Zijlstra. The authors should check if Ref 69 is using any of these data (or other reference spectra), and if so cite the original work instead.

• There are other optical methods that can be used for oxygen saturation measurement, e.g. diffuse reflectance spectroscopy.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

In the first version of the manuscript the authors tried to review the three most extensively used methods for cerebral blood oxygen saturation monitoring from different aspects: working principles, relevant parameters, current situation of research, commonly used equipment, and advantages and disadvantages (citation from the abstract of the first version). The authors also proposed an improvement of the NIRS technique for the measurement of rSO2 by integrating a self-developed non-invasive hardware platform with four light sources instead of two, in order to eliminate the effect of absorption by melanin. They called it predictive model.

In my review of the first version, I wrote that the combination of a review and description of a new technique in one manuscript, is not accepted, in particular where both are presented unclearly, with many inaccuracies in the scientific terms. In their revised version the authors did not change their basic concept, and the revised manuscript is still a combination of a review of NIRS technique and a description of an improved technique (both presented unclearly). They responded to my comment only by deleting the words “A Review” from the title, but left the manuscript as it was before, with minor corrections.

That can be seen in their revised Abstract:

“  ……The present study discusses the three most extensively used methods for cerebral blood oxygen saturation monitoring from different aspects: working principles, relevant parameters, current situation of research, commonly used equipment, and advantages and disadvantages. Furthermore, we propose a predictive model of rSO2 based on multi-wavelength near-infrared spectroscopy (NIRS) by integrating a self-developed non-invasive hardware platform for rSO2 monitoring to provide a new solution for cerebral blood oxygen saturation monitoring using the NIRS technique.”

An appropriate manuscript, describing an improved technique, should be divided into Introduction, Materials and Methods, Results and Discussion. In the current manuscript, the former review of the NIRS technique would have served as an Introduction, if it is shortened significantly and the contents only include information that is relevant to the new/improved technique. In the Materials and Methods section, only the relevant material should be written. Then should come the Results section, which seems to be absent in the manuscript. In this way the manuscript might be properly reviewed and might properly present an improved NIRS technique.

Regarding comments, the authors properly responded to some specific minor comments and corrected some inaccuracies in the scientific terms, but their response to the basic major comments is not sufficient. In particular, the responses to Points 11-16 cannot be accepted. Furthermore, when properly rewritten they should appear in the text of the manuscript.

Reviewer 4 Report

The authors have tried to answer my comments however not all of the answers are satisfying with only some of them implemented in the manuscript. The changes implemented in the manuscript are minor. The title is still not reflecting on the content of the paper. Anyhow, my major concern with the paper is that it is a mixture of review and research where both the review part and the research study (section 4) need more work and completeness.