Evaluation of Mannitol Intervention Effects on Ischemic Cerebral Edema in Mice Using Swept Source Optical Coherence Tomography

Round 1

Reviewer 1 Report

The manuscript is devoted to application of optical coherence tomography angiography and attenuation imaging to evaluate the relieving cerebral edema using mannitol. Article is well written and can be accepted after minor revision.

1) On Figure 7 it looks like first ticks on panels A and C should be "0", not "1".

2) Please add in Figure 8 and figure 10  error bars representing 95% confidence intervals to visualize the statistical significance.

3) The standard deviation in Figures 7 and 9 are bigger then the difference between groups. Namely, in Figure 9A all the red std devs are covered by the blue std devs (especially on 8 and 9 hours). It looks like there are heteroscedasticity or something like this and the statistical inference can be distorted by some statistical artifacts (namely, the observed effect on Fig9A at 9 hours for treatment group can be related to high dispersion of the data; the real significance of this effect is not clear). Please add the rigorous statistical analysis of the presented results to support your conclusions to improve scientific merit. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Overall, the study seems to be interesting and the application of using OCT for assessing cerebral edema is good. But, it is to be noted that the study is performed on a small animal model. This is not stated in the article title or in the abstract. This could be misleading to readers.  Furthermore, the total number of control and treated samples are not mentioned. This is a key drawback of the article. With larger sample size and with statistical analysis performed for the treated and control group can greatly improve the article's scope of attracting readers and will form a base for further research by other research groups. So from a reviewer’s point of view, it is highly advised that the authors clearly state the scope of the article in the title, abstract, and conclusion of the manuscript. The result analysis is extensive, this will be useful for understanding the main aspect of the study. The manuscript can be accepted upon addressing the following comments.

Comments:

1. Title and abstract are misleading, The authors bust clearly state in which specimen the proposed study is done in Manuscript Title, Abstract, and Conclusion, so authors must include the statement "in animal model or mice"
2. In the introduction section, the description and background for use of OCT and its other functional imaging methods like ODT, OCA, MM-ODT , SV-OCT, PS-OCT in use of brain and cerebral imaging should be included with appropriate citations. The current version of the introduction in this aspect is very short and brief.
3. How many specimens were used in each group? Only one specimen per group?
4. If multiple specimens are used, then a statistical analysis should be done and the results must be presented with clear description in results and in the discussion.
5. Authors should consider including a color bar for the intensity OCT images.
6. Can the authors provide a Gif or video file of showing the progression of cerebral blood flow and cerebral edema in time.
7. In figures 3 to 6 a short description of images in each row should be included. Also, the color-bar description should be included.
8. Authors should consider including the cross-sectional of different post-processed images. This can give a depth visualization along with the edema progression region identification and differentiation from nearby structures.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors have addressed all comments and made sufficient modifications as recommended.

The Manuscript can be accepted to publish in its current format.