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Thank you for your revised manuscript which has been accepted for publication in Peer J.Please do some minor editing at production, as noted by Reviewer 2
This report was written in clear english and presented clearly.
The authors have addressed my previous queries and comments satisfactory.
I recommend this manuscript for publication in PeerJ.
This paper contributes broadly to MRI research in the areas of white matter pathology and MS model. It has especially tease out the correlation and sensitivity between T1/T2 and DTI parameters to measure changes in WM content.
Additional experimental details have been added as requested.
Additional results and discussion have been added to make this paper clearer.
line 118: delete "also"
Fig 6: delete "Again"
line 520: "known"
Two peer reviewers have mentioned very important comments that your team should take into serious consideration.Please do the necessary revisions and resubmit to PeerJ for re-review when the revisions are completed.
1. cuprizone is demylination and remylination model. You just limited your study to validate demyleination process. It would be interested to study both processe and suggest a validation.
2. I suggest you compare your cuprizone model with other MS model.
3. Your diffusion weighted imaging is so limited and you did not compare it with other imaging approaches.
4. Your sample number is low
This article presents an in-depth MRI study using T1/T2, myelin water fraction and DTI parameters to study demyelination in cuprizone mouse model and supported with myelin and microglia histology.
This paper attempt to address hotly debated topics in MRI, and I would like to see this manuscript published.
The manuscript is in a very good shape. It is very well written and the figures are clear.
This paper aims to test the sensitivity of myelin water fraction imaging using mcDESPOT in cuprizone demyelination model, and compare the results with standard quantitative MR methods.
The experiment is well laid out, but I have a few comments:
Line 101, it is not clear if this total time include DTI. Please add the acquisition time for each modalities, and also for mcDESPOT acquisitions.
What is the b values and the d/D for DTI?
130: What is L-BFGS-B?
151; I don’t understand this sentence “Instead, we synthesized an image from the T1&T2 maps and the TE/TR of the diffusion sequence.” What image?
The data presented is robust, and the control is present.
Line 238: is there any behavioural difference between control and cuprizone mice?
Line 274: Perhaps should add a comment about large areas of changes shown by T2?
Figure 6. Do you still have the samples to do neurofilament axonal staining? Perhaps FA is sensitive to the arrangement of axonal fibre, so if they are intact, then this would be expected.
FA has been used to study embryonic brain development, where they are still completely unmyelinated.
319: Perhaps you use low/mid b-value ~750 and high b-value ~3000 s/mm2 then you can distinguish between inflammation and demyelination components?
414: Something is missing “decreases in FA after . ”
Lines 410-417 and 419-425 are rather confusing. Perhaps it warrants a table to present/summarize it clearly.
Can you add treatment length, the results of microglia, myelin and axonal staining (if available) in this table? Also add their b-values and directions, in vivo/ex vivo.
446: Performance comparison between DTI and relaxometry data. I think you will need to do regression analyses between the MRI parameters and the myelin and microglia histology staining (and axonal staining?) to test for their correlation strengths.
- What is the effect of microglia infiltration and/or demyelination to the MRI data?
- Are there some areas which has demyelination but not so much increase in microglia activation? Do these areas have different MRI parameters to areas with both strong demyelination and microglia activation?
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