PONE-D-24-06602Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevancePLOS ONE

Dear Dr. Harrison,

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Arka Bhowmik, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. Recommendation for acceptance is conditional to adequate responses to specific suggestions.

2. While I believe the manuscript to be statistically sound, I defer final determination of statistical analysis to a reviewer/editor with a stronger basis in statistical assessment

5. I have provided a review/commentary on the subject written by me illustrating where the current manuscript fits in to current knowledge of the topic. This is provided for the editors in case they choose to use it. I reserve the possibility of making minor edits pending authors response to revision suggestions. I also separately provide specific comments and suggestions for authors to address in their manuscript.

Reviewer #2: This paper describes a cross-sectional analysis of leptomeningeal and dural contrast enhancement detected on 3T and 7T MRI compared to healthy controls. The study included 95 MS subjects and 17 controls. The study assessed the detection properties regarding the time of contrast administration. It is found that LME is more common in patients with MS and better detected in 7T scanners with postponed image acquisition.

The study is of high scientific value, because not so many research groups work on methodology of LME detection and scans' acquisition. Specifically, the use of 7 Tesla makes the study of great value due to high resolution of the scan and detection of different types of pathology. The results clearly state that postponed 7 Tesla imaging is more sensitive than the early one.

Several issues are worth to discuss:

1. A surprisingly high amount of LME detected in the control group. These findings are contradicting to another studies on 7 Tesla machine where HC group were positive in 6.7%. I would like the authors to discuss more on these results since they can lead to very forthcoming conclusions regarding the specificity of this biomarker. It is clearly stated, though, that LME may be found in another diseases, e.g. non-inflammatory CNS disorders, and even in healthy controls, so such a high percentage of LME and PDE in the control group would refer to eligibility criteria for controls and to review of their medical history.

2. Several factors may have had the impact of LME prevalence in this study and low difference to the HC group. For example, the a great amount of patients with MS in the study received anti-B-cell therapy and anti-VLA-4 therapy, that may decrease the prevalence of LME (although studies on that are still running). It is worth considering a therapy type or line (1st line and 2nd line) to include in regression models to account for.

Also, this patient group was rather moderately disabled, since the median EDSS score was 2.5. Some studies showed that patients of early stages can show no LME while it's accumulation appears on later stages. It would be interesting to see the numbers of LME in patients with different EDSS scores as a part of this research process. This may also be an interesting topic for further research.

3. Only few MRI Departments have access to 7 Tesla MRI, so, if this biomarker comes to be used routinely, a 3 Tesla will be the main machine used for it. I would like the authors to describe why they didn't use early time 3 Tesla sequence and only used delayed 3 Tesla acquisition. This may be of additional knowledge on the methodology.

It would be also of some importance if the authors would describe why specifically 21 and 23 minutes were selected as timepoints for MRI scans. Other labs use other timeframes and it would great if authors would describe their decision-making process.

Finally, I can conclude that this papers is of high scientific and practical value and requires only minor changes to make several issues more clear.

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Reviewer #1: Yes: David S. Titelbaum, M.D.

Reviewer #2: Yes: Gleb Makshakov

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Attachments

Attachment

Submitted filename: Titelbaum comments and suggestions for Harrison et al.docx

Attachment

Submitted filename: Titelbaum commentary of Harrison et al with refs.docx

Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance

PONE-D-24-06602R1

Dear Dr. Harrison,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Arka Bhowmik, Ph.D.

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: I thank the authors of the paper for their work and suggest the paper to be accepted for publishing.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: David S. Titelbaum, MD

Dept of Radiology

Shields Health Care

Brockton, MA USA

Reviewer #2: Yes: Gleb Makshakov

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