MRI Assessment of Motor Capabilities in Patients with Duchenne Muscular Dystrophy According to the Motor Function Measure Scale

Round 1

Reviewer 1 Report

The authors of this manuscript use a motor function assessment scale to assess the motor abilities of DMD patients. This is fascinating research on a human disease model. However, there are a few topics that authors could clarify.

Major and minor revisions:

• Are the participants in this study male or female? Please clarify it.
• I recommend making a table for patients that includes information such as age, gender, motor ability (major points) and ethnicity, etc.
• The authors must include a statistic section in the materials and methods part.
• In table 1, the points are not clear so please make it easy to understand for the reader.
• Figures 1 and 2 require the use of statistical significant signs e.g. (*) to indicate statistically significant differences between groups, and the two figures should be remade using GraphPad Prism.
• Please use a star, arrow, or arrowhead to indicate important changes in figures 3-5, and include a scale bar for the photos. Please rewrite all figure legends to include more information.
• Please add the MRI of the healthy subject as a control to compare disease stages. This is critical to understand the major changes in healthy subjects and patients.
• In figures 3-5, what are the major morphological changes in the muscles at different phases? Please make a table as a summary.

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript entitled “MRI assessment of motor capabilities in patients with Duchenne muscular dystrophy according to the Motor Function Measure scale “ investigates the potential use of Motor Function Measure scale to assess the motor capabilities of patients with Duchenne muscular dystrophy at different stages of the disease. These finding were correlated by visualization of fibro-fatty muscle replacement using MRI imaging.

The paper is well written; however the outdated used references and the novelty of this work dampened the reviewer enthusiasm.

The authors used periods to designate decimals.

Demographic Information of the recruited patients are needed.

Reference 9 is an abstract for poster presentation, is this was peer reviewed?

The discussion does not include recently published works on the use of MRI as biomarker for DMD progression.

The conclusion are already known or not supported by the study findings. (i.e. The use of MSM scale MRI sequences with the determination of water T2 values using a three-exponential calculation model makes it possible to effectively quantitatively determine the activity of inflammatory processes in DMD and evaluate the effectiveness of anti-inflammatory therapy.)

Almost all citations are outdated.

The funding (s) from this study should be summarized in the conclusion. Is it not clear if this study is different from previous published wok.

Many recent and interesting publication needs to be included and discussed/compared to this study.

doi: 10.1002/acn3.51417

doi: 10.1212/WNL.0000000000008939

doi: 10.1212/WNL.0000000000009244

doi: 10.1002/ana.24599

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

The authors attempted to correlate the motor functional performance measured by MDM scale and MRI data of the lower extremity muscles. The study is interesting however it needs substantial additional improvements.

1. The method section is not detailed enough. The data on person performing the MFM and MRI evaluation is not given. Were these specialists? Of which speciality? Were they experienced? Were the evaluators of MRI blinded from the MFM score etc. Also the interrater agreement indices should be provided.
2. All MRI images were evaluated semi quantitatively using Mercuri Fibroid Fat Degeneration Scale, why where there no quantitative image analysis performed? For example fat fraction that could be performed using simple or more advanced segmentation methods (e.g. https://doi.org/10.5566/ias.2397 and ) in predetermined ROI. Also average T2 values were shown to be good predictor of future loss of function, therefore this data would be really interesting (https://doi.org/10.1212/WNL.0000000000009012).
3. It would also be interesting to correlate these FF and T2 biomarkers and Mercuri score with morphometric data on studied skeletal muscles, like cross-sectional area at standard positions (DOI: 1016/j.apmr.2010.03.024 and https://doi.org/10.1371/journal.pone.0198200)
4. Since the accessibility of MRI is still limited, do you think US evaluation of skeletal muscles with advanced quantitative image analysis (
   DOI: 5566/ias.2113) could also serve as biomarker to stage or asses the state of muscular system in DMD or other similar conditions ( DOI: 10.1002/mus.24296 ). Please discuss.
5. The limitation section should be moved to discussion section.
6. The introduction section should also summarise what is already known about MRI biomarkers of DMD severity etc. And the results of the study should be more extensively compared to the results of other similar study using skeletal muscle MRI.

Author Response

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Reviewer 4 Report

The manuscript: „MRI assessment of motor capabilities in patients with Duchenne muscular dystrophy according to the Motor Function Measure scale" by Vasily Suslov and colleagues conducted a correlation analysis between the MFM scale and MRI data motor capabilities on the MFM scale in patients with DMD based on MRI assessment of motor capabilities. The authors stress the importance of MFM scale in effectively assessing the motor capabilities of patients with Duchenne muscular dystrophy at different stages of the disease. The study is nicely conducted and despite availability of the MRI data of only 32 patients, the results are convincing.

 After going through the manuscript, I have a minor comment:

1. Was the sample size large enough to draw the statistical conclusions? There is a discrepancy in sizes of two study groups (patients with intact walking ability, n= 32 and patients without the possibility of independent movement, n=7). Please clarify whether this might have influenced a bias in the results?

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

In table 1 what did you mean by 2,5 (points)?

Please remove all full stops (.) from the table heading.

Please check all typing errors.

I strongly recommended English writing editing.

Author Response

Dear reviewer!

We appreciate your work in correcting our manuscript. On the merits of the latest remarks, we report:

1. Technical notes (.) with tables were removed.
2. The manuscript was additionally edited in the department of foreign languages of our university. Highlighted in blue (or removed).

Sincerely, authors

Reviewer 3 Report

The authors claim they performed the quantification of FF (%), T2 and estimation of cross-sectional area and that they will publish them as separate papers. Since these are the results describing the same substrate it is not ethical to publish them twice.

Second, the authors say that the same specialist performed clinical and MRI evaluation. Since both evaluations are subjective, this could cause a substantial bias, making the results described here invalid. Therefore, MRI should be evaluated by a different specialist (preferably 2 or more) blinded to the results of clinical examination, and inter-rater agreement should be reported.

Author Response

Dear reviewer!

We appreciate your work in correcting our manuscript. On the merits of the latest remarks, we report:

1. In order not to mislead the reader, we removed the line about subsequent articles. Although we mean the publication of other materials on this topic, which are not reflected in this manuscript.
2. Added to the text – MRI and clinical assessment were performed and evaluated by one specialist investigator. In addition, MRI data were evaluated by staff radiologists. In a blind comparison, the differences in scores were practically the same.

Sincerely, authors