Purpose High-resolution magnetic resonance imaging (HR-MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can evaluate the integrity of the blood-brain barrier. In this paper, the result of 3.0T HR-MRI and 3.0T DCE-MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events. Methods Thirty-six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR-MRI and 3.0T DCE-MRI has been applied. Results Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR-MRI showed diffuse thickening and enhanced stenosis. TheK(trans)value of 10/23 patients with acute-subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and theK(trans)value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. TheK(trans)value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. TheK(trans)value of patients with acute-subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 +/- 0.038 vs. 0.007 +/- 0.001,p = .000), and there was no significant difference betweenK(trans)in the chronic infarction group and the other two groups (0.098 +/- 0.038 vs. 0.044 +/- 0.012,p = .058; 0.044 +/- 0.012 vs. 0.007 +/- 0.001,p = .057). Conclusion HR-MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE-MRI could be an effective way to evaluate and monitor blood-brain barrier to prevent clinical ischemic stroke.
Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis
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2020/06/0707-Jun-2020
Dear Dr. Feng:
It is a pleasure to accept your manuscript entitled "Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis" in its current form for publication in Brain and Behavior. If there were further comments from the reviewer(s) who read your manuscript, they will be included at the foot of this letter.
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Author Response
2020/05/27Dear Editor,
Thank you for your helpful comments concerning our manuscript entitled “Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis” (ID: BRB3-2019-12-0760.R2). Those comments are all valuable and very helpful for revising and improving our manuscript, as well as the important guiding significance to our researches. Thank you very much for your approval of our last modification. We have also studied comments carefully and have made correction at this time. Revised portion are marked in red in the “Revised Manuscript”, and uploaded the file " Response letter to reviewers ". The main corrections in the paper and the responds to the reviewer’s comments are list below.
Sincerely,
Ping-Yong FengAssociate Editor Comments to Author:
The manuscript is much improved, and the authors were responsive to the reviewer comments. However, as noted by the reviewer, the first paragraph of the introduction is long, covers multiple topics, and is difficult to follow. Please reorganize and consider reducing material to make clear.
Response: Thank you very much for your patience and careful comments. We have revised the Introduction section according to your suggestions. We hope to get your understanding and satisfaction.We appreciate for Editors and Reviewers’ warm work earnestly, and hope that the correction will meet with approval.
Once again, thank you very much for your comments and suggestions.Author response by
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- pre-publication peer review (ROUND 3)
Decision Letter
2020/05/2424-May-2020
We recognise that the impact of the COVID-19 pandemic may affect your ability to return your revised manuscript to us within the requested timeframe. If this is the case, please let us know.
Dear Dr. Feng:
Manuscript ID BRB3-2019-12-0760.R2 entitled "Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis" which you submitted to Brain and Behavior, has been reviewed very favorably and minor revisions have been requested. I invite you to respond to the comments appended below and revise your manuscript.
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agrethe@ucsd.eduAssociate Editor Comments to Author:
The manuscript is much improved, and the authors were responsive to the reviewer comments. However, as noted by the reviewer, the first paragraph of the introduction is long, covers multiple topics, and is difficult to follow. Please reorganize and consider reducing material to make clear.Reviewer(s)' Comments to Author:
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Author Response
2020/05/12Dear Editor,
Thank you for your helpful comments concerning our manuscript entitled “Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis” (ID: BRB3-2019-12-0760.R1). Those comments are all valuable and very helpful for revising and improving our manuscript, as well as the important guiding significance to our researches. Thank you very much for your approval of our last modification. We have also studied comments carefully and have made correction at this time. Revised portion are marked in red in the “Revised Manuscript”, and uploaded the file " Response letter to reviewers ". The main corrections in the paper and the responds to the reviewer’s comments are list below.
Sincerely,
Ping-Yong FengReviewer: 1
Comments to the Author
The authors have been responsive to Reviewer suggestions, and the manuscript much improved, although a few concerns remain:
1.) Regarding #1 in the authors’ response: The additional information and direction added to the Introduction is very useful. The first paragraph, however, in its current form seems quite long and could be made more concise and perhaps, if useful, divided into separate component paragraphs – consider that the first paragraph now seems to covers definition of vasculitis and description of classification approaches; diagnostic criteria; common causes; MRI characterization; comparison to atherosclerosis; and common treatment.
Responds: Thank you very much for reading and commenting on our manuscript. We appreciate for your constructive suggestions, and your opinions make a great sense. We have tried our best to make betterment on our manuscript according to you advices, and the content of the first paragraph has been simplified and reedited now.
2.) Regarding #5 in the authors’ response: The additions made to the Results section were helpful, however, in addition, the statistical analysis plan and hypothesis testing could be specifically laid out in the Statistical Analysis section as well, so the reader knows what to expect in the Results section.
Responds: Thank you very much for your kind reminding, and we have added the necessary content in the Statistical Analysis section now.
3.) Regarding #6 in authors’ response: The Results section #1 which describes the patient characteristics doesn’t completely explain what is reported in Table 1 – for example, although both the section text and the table note 23 CNSv cases, the text does not refer to the 10 atheroscl or the 3 Moyamoya disease patients, why they are in the Table, and their relevance. Adding that to the Results section 1 description of the CNSv cases and their origins would be useful. In fact it doesn’t seem that Moyamoya is mentioned elsewhere just in the Table 1 and in the discussion, and if so, it will not be clear to the reader why the patients are being studied? Please clarify why the Atherosclerosis and Moyamoya cases are relevant earlier in the manuscript (intro and methods).
Responds: Thank you very much for commenting on our manuscript and constructive suggestions. I am sorry for the inconvenience caused by our mistakes. We have added the relevant background of Moyamoya in our manuscript now, and also the 10 atheroscl and the 3 Moyamoya disease patients characteristics in the Results section.
4.) Regarding #7 in the authors’ response, adding these comparisons is of course fine, but please describe in the methods/statistical analysis section that these comparisons were made and why each group comparison was relevant (the rationale).
Responds: Thank you for your carefully reading and commenting on our manuscript, and it must have cost you time and energy. I'm really sorry that I didn't understand your meaning better in my last reply. Thank you for the constructive suggestion, and we have added the related description in the methods/statistical analysis section now(see the section in red).
5.) The Discussion has been improved, and the addition of a conclusions section very useful.
Responds: Thank you very much for the constructive suggestions. We have added the conclusion section in our manuscript according to you advices now.We appreciate for Editors and Reviewers’ warm work earnestly, and hope that the correction will meet with approval.
Once again, thank you very much for your comments and suggestions.Author response by
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- pre-publication peer review (ROUND 2)
Decision Letter
2020/04/2222-Apr-2020
We recognise that the impact of the COVID-19 pandemic may affect your ability to return your revised manuscript to us within the requested timeframe. If this is the case, please let us know.
Dear Dr. Feng:
Manuscript ID BRB3-2019-12-0760.R1 entitled "Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis" which you submitted to Brain and Behavior, has been reviewed very favorably and minor revisions have been requested. I invite you to respond to the comments appended below and revise your manuscript.
Before submitting your revisions:
Prepare a response to the reviewer comments appended below in point-by-point fashion. In order to expedite the processing of the revised manuscript, please be as specific as possible in your response and indicate the page numbers in the manuscript where you have addressed each comment.
Prepare a revised manuscript (word document), highlighting the changes you’ve made. Save this new document on your computer as you will be asked to upload it during the revision submission process. NOTE: Please be sure to keep in mind reviewer comments and incorporate your responses within the manuscript. There may well be areas where you disagree; for example, you may want to write, "A reviewer suggests that... However, I disagree because...". In any case, please try to address all of the concerns that are raised within the manuscript.
In addition to your revised manuscript with changes highlighted, please also save a “clean” copy where the changes are not marked.
To submit your revised manuscript:
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*** PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. ***
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Log into https://mc.manuscriptcentral.com/brainandbehavior and click on Author Center. Under author resources, use the button “Click here to submit a revision”. PLEASE DO NOT SUBMIT YOUR REVISIONS AS A NEW MANUSCRIPT.
Follow the on-screen instructions. First you will be asked to provide your “Response to Decision Letter”—this is the response to reviewer comments that you prepared earlier.
Click through the next few screens to verify that all previously provided information is correct.
File Upload: Delete any files that you will be replacing (this includes your old manuscript). Upload your new revised manuscript file with changes highlighted, a “clean” copy of your revised manuscript file, any replacement figures/tables, or any new files. Once this is complete, the list of files in the “My Files” section should ONLY contain the final versions of everything. REMEMBER: figures/tables should be in jpeg, tiff, or eps format. We hope that you will designate one of the figures in your paper to be considered for our online covers and potential publication on our blog.
Review and submit: please be sure to double-check everything carefully so that your manuscript can be processed as quickly as possible.
Deadlines:
Because we are trying to facilitate timely publication of manuscripts submitted to Brain and Behavior,your revised manuscript should be uploaded as soon as possible. If it is not possible for you to submit your revision in 2 months, we may have to consider your paper as a new submission. If you feel that you will be unable to submit your revision within the time allowed please contact me to discuss the possibility of extending the revision time.If you would like help with English language editing, or other article preparation support, Wiley Editing Services offers expert help with English Language Editing, as well as translation, manuscript formatting, and figure formatting at www.wileyauthors.com/eeo/preparation. You can also check out our resources for Preparing Your Article for general guidance about writing and preparing your manuscript at www.wileyauthors.com/eeo/prepresources.
Once again, thank you for submitting your manuscript to Brain and Behavior and I look forward to receiving your revision.
Sincerely,
Dr. Amanda Bischoff-Grethe
Editor in Chief, Brain and Behavior
agrethe@ucsd.eduAssociate Editor Comments to Author:
Reviewer(s)' Comments to Author:
Reviewer: 1
Comments to the Author
The authors have been responsive to Reviewer suggestions, and the manuscript much improved, although a few concerns remain:
1.) Regarding #1 in the authors’ response: The additional information and direction added to the Introduction is very useful. The first paragraph, however, in its current form seems quite long and could be made more concise and perhaps, if useful, divided into separate component paragraphs – consider that the first paragraph now seems to covers definition of vasculitis and description of classification approaches; diagnostic criteria; common causes; MRI characterization; comparison to atherosclerosis; and common treatment.
2.) Regarding #5 in the authors’ response: The additions made to the Results section were helpful, however, in addition, the statistical analysis plan and hypothesis testing could be specifically laid out in the Statistical Analysis section as well, so the reader knows what to expect in the Results section.
3.) Regarding #6 in authors’ response: The Results section #1 which describes the patient characteristics doesn’t completely explain what is reported in Table 1 – for example, although both the section text and the table note 23 CNSv cases, the text does not refer to the 10 atheroscl or the 3 Moyamoya disease patients, why they are in the Table, and their relevance. Adding that to the Results section 1 description of the CNSv cases and their origins would be useful. In fact it doesn’t seem that Moyamoya is mentioned elsewhere just in the Table 1 and in the discussion, and if so, it will not be clear to the reader why the patients are being studied? Please clarify why the Atherosclerosis and Moyamoya cases are relevant earlier in the manuscript (intro and methods).
4.) Regarding #7 in the authors’ response, adding these comparisons is of course fine, but please describe in the methods/statistical analysis section that these comparisons were made and why each group comparison was relevant (the rationale).
5.) The Discussion has been improved, and the addition of a conclusions section very useful.Decision letter by
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Reviewer report
2020/04/17The authors have been responsive to Reviewer suggestions, and the manuscript much improved, although a few concerns remain:
1.) Regarding #1 in the authors’ response: The additional information and direction added to the Introduction is very useful. The first paragraph, however, in its current form seems quite long and could be made more concise and perhaps, if useful, divided into separate component paragraphs – consider that the first paragraph now seems to covers definition of vasculitis and description of classification approaches; diagnostic criteria; common causes; MRI characterization; comparison to atherosclerosis; and common treatment.
2.) Regarding #5 in the authors’ response: The additions made to the Results section were helpful, however, in addition, the statistical analysis plan and hypothesis testing could be specifically laid out in the Statistical Analysis section as well, so the reader knows what to expect in the Results section.
3.) Regarding #6 in authors’ response: The Results section #1 which describes the patient characteristics doesn’t completely explain what is reported in Table 1 – for example, although both the section text and the table note 23 CNSv cases, the text does not refer to the 10 atheroscl or the 3 Moyamoya disease patients, why they are in the Table, and their relevance. Adding that to the Results section 1 description of the CNSv cases and their origins would be useful. In fact it doesn’t seem that Moyamoya is mentioned elsewhere just in the Table 1 and in the discussion, and if so, it will not be clear to the reader why the patients are being studied? Please clarify why the Atherosclerosis and Moyamoya cases are relevant earlier in the manuscript (intro and methods).
4.) Regarding #7 in the authors’ response, adding these comparisons is of course fine, but please describe in the methods/statistical analysis section that these comparisons were made and why each group comparison was relevant (the rationale).
5.) The Discussion has been improved, and the addition of a conclusions section very useful.Reviewed by
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Author Response
2020/03/20Dear Editor,
Thank you for your helpful comments concerning our manuscript entitled “Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis” (ID: BRB3-2019-12-0760). Those comments are all valuable and very helpful for revising and improving our manuscript, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the “Revised Manuscript”, and uploaded the file " Response letter to reviewers ". The main corrections in the paper and the responds to the reviewer’s comments are list below.
Sincerely,
Ping-Yong FengReviewer: 1
Comments to the Author
The authors used high resolution and dynamic contrast-enhanced (DCE) MRI to assess vascular wall characteristics (thickening and stenosis) and blood brain barrier integrity in individuals though to have central nervous system vasculitis. Of 36 patients studied, 23 had vasculitis with evidence of thickening and stenosis in the vascular wall and lumen on high resolution MRI. The DCE results were explored in a number of ways across subsets of patients, although a summary of these findings and the direct clinical implications were not clear. The stated goal seems to be distinguishing underlying causes of intracranial stenosis lesions and strokes using these MRI methods, since symptoms are similar yet treatment courses are distinct. As written, the manuscript would benefit from additional methodological detail and clarification of statistical analyses, as well as more direct guidance of how the findings will be use in the clinical setting particularly with respect to DCE-MRI. More detailed comments follow:1) In the first paragraph of the introduction, the authors note that clinical symptoms are quite similar across different causes of arterial stenosis and ischemic stroke, and that different treatments would be necessary depending on the underlying cause. It would be useful to add a) what the symptoms are, and b) what the different treatment routes would be to support the need to differentiate. In the second paragraph, the authors should add specifically what the study explored and how it will answer these needs, with some additional reference citations, to guide the reader of the scientific approach and potential outcomes.
Response: Thank you very much for reading and commenting on our manuscript. We appreciate for your constructive suggestions, and your opinions make a great sense. We have tried our best to make betterment on our manuscript according to you advices, and added the related illustration in the first and second paragraph of our manuscript now(see the section in red).2) In Methods section 1 Patients: the authors include information on the scans acquired, however, this would be better placed in the 2nd paragraph.
Response: Thank you very much for reading and commenting on our manuscript. We have modified our manuscript according to you advices, and have added the detailed illustration in the 2nd paragraph now(see the section in red).3) In Methods section 2 Data acquisitions, please provide details on the scan parameters for the high resolution and DCE MRI sequences acquired. This would be important should anyone wish to replicate the work. The use of “routine” scans should also be defined, since routine may vary quite a bit across sites. In addition, there are a number of subtle differences in methods that readers may be interested in comparing across studies.
Response: Thank you very much for commenting on our manuscript and constructive suggestions. We have added the detailed illustration in the 2nd section of Methods now(see the section in red).4) In Methods section 3 Data analyze (This term ‘analyze’ may be better replaced with ‘analysis’): Please define ADC and MRA and MIP for the reader. Please provide a citation for the vascular measurements, and associated reliability or other statistical information on the measurements. Also it would be very helpful to the reader to clarify sub-sections on vascular measurements and the blood brain integrity measurements, along with a summary for each on what the primary metrics are to be used in the study.
Response: Thank you very much for commenting on our manuscript and constructive suggestions. We have modified our manuscript according to you advices, and have added the detailed illustration in the third section of Methods now(see the section in red).5) In Methods section 4 Statistical analysis and Results comments: Addition of the specific comparisons to be made would strengthen the manuscript and provide the reader with structure for interpreting the results. For example, in the Results section 3 in the last sentence of the paragraph, a relationship analysis is suggested but it is not completely clear what this will tell the reader. Furthermore, in the Results sections 3 and 4, the authors discuss findings within subsets of the patient groups that were not previously mentioned. It is not clear to the reader at this point why these subgroups were explored and what the findings across these different subgroups might imply. There are of course many complexities to the underlying patient differences, however, this has not been conveyed to the reader.
Response: Thank you for your carefully reading and commenting on our manuscript, and it must have cost you time and energy. In Results section 3, we grouped the cases according to the different luminal stenosis degree and extent, and made a statistical analysis of the relationship between cerebral infarction and the two factors respectively. There was no statistical significance in results, thus we come to the conclusion that there was no clear correlation between the extent and degree of vascular stenosis and the occurrence of ischemic cerebral apoplexy. In Results section 4, we grouped the involved cases according to the different stages of cerebral infarction, and made a statistical analysis of the Ktrans value of the groups. Thank you for the constructive suggestion, and we have added the related illustration in the manuscript now(see the section in red).6) In Results Section 1 – please make sure that the verbal description of the participants in this section matches and includes information provided in Table 1. For example, the Table uses terms like “moyamoya disease” and the text on page 7 refers to cytomegalovirus… The general reader may not know how to map the different categories. In addition, clarification of how these risk factors are important for the current study, the findings, and the interpretation is important to provide clearly.
Response: Thank you very much for the constructive suggestion, and we have modified our manuscript now(see the section in red).7) Results section 4: This suggests that the blood brain barrier may only have been examined in participants with acute-subacute phase of cerebral infarction. If this is the case, this should be made clear in the methods and the rationale provided in the introduction. As it currently reads, it would suggest that this was examined in all participants. There is also mention of longitudinal data in this section that was not previously described. The longitudinal approach and reliability of the method should be detailed.
Response: Thank you for your carefully reading and commenting on our manuscript. We appreciate for your constructive suggestions. We have made a statistical analysis of the Ktrans value of the acute-subacute cerebral infarction group, the chronic cerebral infarction group and the non-cerebrovascular events group, and have added the description in Results section 4 now(see the section in red).8) The first and second paragraphs of the Discussion read more like introductory text, it is often best to start the discussion with the primary findings and implications of the study.
Response: Thank you for your constructive suggestions, and we have modified our manuscript now(see the section in red).9) The third paragraph of the Discussion includes some results. Some of these may be in the Results section but not all, and the Discussion would not need to include the numbers since the Results would provide those details. This would make it easier to read through the findings in the Discussion.
Response: Thank you for your constructive suggestions, and we have modified our manuscript now(see the section in red).10) As noted above, it would be helpful to provide a rationale earlier in the manuscript regarding the focus on the 10 patient cases that are discussed on page 11 at the bottom and page 13.
Response: Thank you for your constructive suggestions, and we have modified our manuscript now(see the section in red).11) The Discussion component on page 12 regarding the DCE-MRI provide a great deal of introductory material on DCE, some of which might be useful in the Introduction for the reader.
Response: Thank you for your constructive suggestions, and we have modified our manuscript now(see the section in red).12) It would be useful to have a final conclusions section that brings together the high resolution and DCE findings that will help guide the differentiation of underlying causes of stenosis and stroke to guide treatment.
Response: Thank you for your constructive suggestions, and we have added the final conclusions in the manuscript now(see the section in red). Thank you very much for your carefully reading and commenting on our manuscript again.13) The abstract is somewhat vague on the methods and the results summary is difficult to follow; a more succinct summary with clear implications with respect to the DCE would be very helpful.
Response: Thank you for your constructive suggestions, and we have modified our manuscript now(see the section in red).Reviewer: 2
Comments to the Author
Comments)
1. The diagnosis of CNS vasculitis, atherosclerosis, and MMDs are unclear, and the criteria was not specified in the manuscript. Without a confirmatory diagnosis of each disease category, the comparison is useless.
Response: Thank you for your carefully reading and commenting on our manuscript. We appreciate for your constructive suggestions, and have added the mentioned context in the Introduction section now(see the section in red).I do not find any advantage of DCE-MRI over vessel wall MRA in the differential diagnosis of vessel wall pathology. The authors should have shown at least sensitivity and specificity of DCE-MRI in the diagnosis of CNS vasculitis.
Response: Thank you very much for your comments on our manuscript, and I am sorry for the inconvenience caused by our ambiguous presentation. Actually, DCE-MRI sequence is not used to diagnose CNS vasculitis, it is mainly used to quantitatively measure Ktrans value to reflect the microcirculation of brain tissue. We have modified the description in the manuscript now(see the section in red).Patients with subacute infarction must be excluded.
Response: Thank you very much for your comments on our manuscript, and I am sorry for the inconvenience caused by our ambiguous presentation. In fact, we have already excluded the patients with subacute infarction in our present study.Add figures for ROI selection in the MCA blood supply area.
Response: Thank you for your constructive suggestions, and we have added the figures for ROI selection in the MCA blood supply area as Figure 1 now.The definition of smoke syndrome was not specified. It is not a scientific term and currently not used.
Response: I am very sorry for the undefined description, and thank you for your kind reminding. “Smoke syndrome” has been removed and replaced with “moyamoya disease” in the manuscript now.What is the meaning Infection/immune index? Is it a clinically significant index? How you can identify patients with previous infection or reveal immune compromised state?
Response: Infection/immune index is an important auxiliary index for the diagnosis of secondary vasculitis, which is clinically performed by blood/cerebrospinal fluid (CSF) for infection or immune biochemistry. I am very sorry for the undefined description, and we have modified the illustration now.The discussion part should be shortened. Figures must be reorganized.
Response: Thank you for your carefully reading on our manuscript and precise suggestions. We have modified the discussion and figures now.
We appreciate for Editors and Reviewers’ warm work earnestly, and hope that the correction will meet with approval.
Once again, thank you very much for your comments and suggestions.Author response by
Cite this author response
- pre-publication peer review (ROUND 1)
Decision Letter
2020/01/1616-Jan-2020
Dear Dr. Feng:
Manuscript ID BRB3-2019-12-0760 entitled "Diagnostic value of HR-MRI and DCE-MRI in unilateral middle cerebral artery inflammatory stenosis" which you submitted to Brain and Behavior, has been reviewed. Some revisions to your manuscript have been recommended. Therefore, I invite you to respond to the comments appended below and revise your manuscript.
Before submitting your revisions:
Prepare a response to the reviewer comments appended below in point-by-point fashion. In order to expedite the processing of the revised manuscript, please be as specific as possible in your response and indicate the page numbers in the manuscript where you have addressed each comment.
Prepare a revised manuscript (word document), highlighting the changes you’ve made. Save this new document on your computer as you will be asked to upload it during the revision submission process. NOTE: Please be sure to keep in mind reviewer comments and incorporate your responses within the manuscript. There may well be areas where you disagree; for example, you may want to write, "A reviewer suggests that... However, I disagree because...". In any case, please try to address all of the concerns that are raised within the manuscript.
In addition to your revised manuscript with changes highlighted, please also save a “clean” copy where the changes are not marked.
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agrethe@ucsd.eduAssociate Editor Comments to Author:
Reviewer(s)' Comments to Author:
Reviewer: 1
Comments to the Author
The authors used high resolution and dynamic contrast-enhanced (DCE) MRI to assess vascular wall characteristics (thickening and stenosis) and blood brain barrier integrity in individuals though to have central nervous system vasculitis. Of 36 patients studied, 23 had vasculitis with evidence of thickening and stenosis in the vascular wall and lumen on high resolution MRI. The DCE results were explored in a number of ways across subsets of patients, although a summary of these findings and the direct clinical implications were not clear. The stated goal seems to be distinguishing underlying causes of intracranial stenosis lesions and strokes using these MRI methods, since symptoms are similar yet treatment courses are distinct. As written, the manuscript would benefit from additional methodological detail and clarification of statistical analyses, as well as more direct guidance of how the findings will be use in the clinical setting particularly with respect to DCE-MRI. More detailed comments follow:1) In the first paragraph of the introduction, the authors note that clinical symptoms are quite similar across different causes of arterial stenosis and ischemic stroke, and that different treatments would be necessary depending on the underlying cause. It would be useful to add a) what the symptoms are, and b) what the different treatment routes would be to support the need to differentiate. In the second paragraph, the authors should add specifically what the study explored and how it will answer these needs, with some additional reference citations, to guide the reader of the scientific approach and potential outcomes.
2) In Methods section 1 Patients: the authors include information on the scans acquired, however, this would be better placed in the 2nd paragraph.
3) In Methods section 2 Data acquisitions, please provide details on the scan parameters for the high resolution and DCE MRI sequences acquired. This would be important should anyone wish to replicate the work. The use of “routine” scans should also be defined, since routine may vary quite a bit across sites. In addition, there are a number of subtle differences in methods that readers may be interested in comparing across studies.
4) In Methods section 3 Data analyze (This term ‘analyze’ may be better replaced with ‘analysis’): Please define ADC and MRA and MIP for the reader. Please provide a citation for the vascular measurements, and associated reliability or other statistical information on the measurements. Also it would be very helpful to the reader to clarify sub-sections on vascular measurements and the blood brain integrity measurements, along with a summary for each on what the primary metrics are to be used in the study.
5) In Methods section 4 Statistical analysis and Results comments: Addition of the specific comparisons to be made would strengthen the manuscript and provide the reader with structure for interpreting the results. For example, in the Results section 3 in the last sentence of the paragraph, a relationship analysis is suggested but it is not completely clear what this will tell the reader. Furthermore, in the Results sections 3 and 4, the authors discuss findings within subsets of the patient groups that were not previously mentioned. It is not clear to the reader at this point why these subgroups were explored and what the findings across these different subgroups might imply. There are of course many complexities to the underlying patient differences, however, this has not been conveyed to the reader.
6) In Results Section 1 – please make sure that the verbal description of the participants in this section matches and includes information provided in Table 1. For example, the Table uses terms like “moyamoya disease” and the text on page 7 refers to cytomegalovirus… The general reader may not know how to map the different categories. In addition, clarification of how these risk factors are important for the current study, the findings, and the interpretation is important to provide clearly.
7) Results section 4: This suggests that the blood brain barrier may only have been examined in participants with acute-subacute phase of cerebral infarction. If this is the case, this should be made clear in the methods and the rationale provided in the introduction. As it currently reads, it would suggest that this was examined in all participants. There is also mention of longitudinal data in this section that was not previously described. The longitudinal approach and reliability of the method should be detailed.
8) The first and second paragraphs of the Discussion read more like introductory text, it is often best to start the discussion with the primary findings and implications of the study.
9) The third paragraph of the Discussion includes some results. Some of these may be in the Results section but not all, and the Discussion would not need to include the numbers since the Results would provide those details. This would make it easier to read through the findings in the Discussion.
10) As noted above, it would be helpful to provide a rationale earlier in the manuscript regarding the focus on the 10 patient cases that are discussed on page 11 at the bottom and page 13.
11) The Discussion component on page 12 regarding the DCE-MRI provide a great deal of introductory material on DCE, some of which might be useful in the Introduction for the reader.
12) It would be useful to have a final conclusions section that brings together the high resolution and DCE findings that will help guide the differentiation of underlying causes of stenosis and stroke to guide treatment.
13) The abstract is somewhat vague on the methods and the results summary is difficult to follow; a more succinct summary with clear implications with respect to the DCE would be very helpful.
Reviewer: 2
Comments to the Author
Comments)
1. The diagnosis of CNS vasculitis, atherosclerosis, and MMDs are unclear, and the criteria was not specified in the manuscript. Without a confirmatory diagnosis of each disease category, the comparison is useless.
2. I do not find any advantage of DCE-MRI over vessel wall MRA in the differential diagnosis of vessel wall pathology. The authors should have shown at least sensitivity and specificity of DCE-MRI in the diagnosis of CNS vasculitis.
3. Patients with subacute infarction must be excluded.
4. Add figures for ROI selection in the MCA blood supply area.
5. The definition of smoke syndrome was not specified. It is not a scientific term and currently not used.
6. What is the meaning Infection/immune index? Is it a clinically significant index? How you can identify patients with previous infection or reveal immune compromised state?
7. The discussion part should be shortened. Figures must be reorganized.Decision letter by
Cite this decision letter
Reviewer report
2020/01/15Comments)
1. The diagnosis of CNS vasculitis, atherosclerosis, and MMDs are unclear, and the criteria was not specified in the manuscript. Without a confirmatory diagnosis of each disease category, the comparison is useless.
2. I do not find any advantage of DCE-MRI over vessel wall MRA in the differential diagnosis of vessel wall pathology. The authors should have shown at least sensitivity and specificity of DCE-MRI in the diagnosis of CNS vasculitis.
3. Patients with subacute infarction must be excluded.
4. Add figures for ROI selection in the MCA blood supply area.
5. The definition of smoke syndrome was not specified. It is not a scientific term and currently not used.
6. What is the meaning Infection/immune index? Is it a clinically significant index? How you can identify patients with previous infection or reveal immune compromised state?
7. The discussion part should be shortened. Figures must be reorganized.Reviewed by
Cite this review
Reviewer report
2019/12/26The authors used high resolution and dynamic contrast-enhanced (DCE) MRI to assess vascular wall characteristics (thickening and stenosis) and blood brain barrier integrity in individuals though to have central nervous system vasculitis. Of 36 patients studied, 23 had vasculitis with evidence of thickening and stenosis in the vascular wall and lumen on high resolution MRI. The DCE results were explored in a number of ways across subsets of patients, although a summary of these findings and the direct clinical implications were not clear. The stated goal seems to be distinguishing underlying causes of intracranial stenosis lesions and strokes using these MRI methods, since symptoms are similar yet treatment courses are distinct. As written, the manuscript would benefit from additional methodological detail and clarification of statistical analyses, as well as more direct guidance of how the findings will be use in the clinical setting particularly with respect to DCE-MRI. More detailed comments follow:
1) In the first paragraph of the introduction, the authors note that clinical symptoms are quite similar across different causes of arterial stenosis and ischemic stroke, and that different treatments would be necessary depending on the underlying cause. It would be useful to add a) what the symptoms are, and b) what the different treatment routes would be to support the need to differentiate. In the second paragraph, the authors should add specifically what the study explored and how it will answer these needs, with some additional reference citations, to guide the reader of the scientific approach and potential outcomes.
2) In Methods section 1 Patients: the authors include information on the scans acquired, however, this would be better placed in the 2nd paragraph.
3) In Methods section 2 Data acquisitions, please provide details on the scan parameters for the high resolution and DCE MRI sequences acquired. This would be important should anyone wish to replicate the work. The use of “routine” scans should also be defined, since routine may vary quite a bit across sites. In addition, there are a number of subtle differences in methods that readers may be interested in comparing across studies.
4) In Methods section 3 Data analyze (This term ‘analyze’ may be better replaced with ‘analysis’): Please define ADC and MRA and MIP for the reader. Please provide a citation for the vascular measurements, and associated reliability or other statistical information on the measurements. Also it would be very helpful to the reader to clarify sub-sections on vascular measurements and the blood brain integrity measurements, along with a summary for each on what the primary metrics are to be used in the study.
5) In Methods section 4 Statistical analysis and Results comments: Addition of the specific comparisons to be made would strengthen the manuscript and provide the reader with structure for interpreting the results. For example, in the Results section 3 in the last sentence of the paragraph, a relationship analysis is suggested but it is not completely clear what this will tell the reader. Furthermore, in the Results sections 3 and 4, the authors discuss findings within subsets of the patient groups that were not previously mentioned. It is not clear to the reader at this point why these subgroups were explored and what the findings across these different subgroups might imply. There are of course many complexities to the underlying patient differences, however, this has not been conveyed to the reader.
6) In Results Section 1 – please make sure that the verbal description of the participants in this section matches and includes information provided in Table 1. For example, the Table uses terms like “moyamoya disease” and the text on page 7 refers to cytomegalovirus… The general reader may not know how to map the different categories. In addition, clarification of how these risk factors are important for the current study, the findings, and the interpretation is important to provide clearly.
7) Results section 4: This suggests that the blood brain barrier may only have been examined in participants with acute-subacute phase of cerebral infarction. If this is the case, this should be made clear in the methods and the rationale provided in the introduction. As it currently reads, it would suggest that this was examined in all participants. There is also mention of longitudinal data in this section that was not previously described. The longitudinal approach and reliability of the method should be detailed.
8) The first and second paragraphs of the Discussion read more like introductory text, it is often best to start the discussion with the primary findings and implications of the study.
9) The third paragraph of the Discussion includes some results. Some of these may be in the Results section but not all, and the Discussion would not need to include the numbers since the Results would provide those details. This would make it easier to read through the findings in the Discussion.
10) As noted above, it would be helpful to provide a rationale earlier in the manuscript regarding the focus on the 10 patient cases that are discussed on page 11 at the bottom and page 13.
11) The Discussion component on page 12 regarding the DCE-MRI provide a great deal of introductory material on DCE, some of which might be useful in the Introduction for the reader.
12) It would be useful to have a final conclusions section that brings together the high resolution and DCE findings that will help guide the differentiation of underlying causes of stenosis and stroke to guide treatment.
13) The abstract is somewhat vague on the methods and the results summary is difficult to follow; a more succinct summary with clear implications with respect to the DCE would be very helpful.
Reviewed by
Cite this review
