What Changes Occur in the Brain of Veteran? A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study

Round 1

Reviewer 1 Report

Interesting paper. Corrections and elaborations are required in the MR spectroscopy method description and results presentation. Specifically,

1. line 79: mention that 4 single voxel spectroscopy measurements were performed (or was it multivoxel chemical shift imaging?), 2. Table 1: correct errors: apparently TE was 35 ms and TR 1500 ms (mix-up) and NEX 8 would amount to 12 sec acquisition time in SVS (impossible) or maybe 8x refers to the number of phase encode steps in CSI x 8? 3. line 91-: how was absolute concentration of Cr determined, perhaps relative to unsaturated water signal after correction for T1 and T2 saturation? Detail needed! 4. Sorely missing is an example showing the spectra for the four voxels quantified. 5. A brief description must be provided of the SAGE software used for spectroscopy analysis. Is it frequency domain processing with automated phasing, base line correction and curve fitting to minimize operator input?

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

This paper “What changes occur in the brain of veteran? A magnetic resonance imaging and proton magnetic resonance spectroscopy study”, aims to assess common anomalies in soldiers’ head MRI and to compare the relative concentration of magnetic resonance spectroscopy metabolites in the brain of soldiers and healthy age-matched controls. Overall, 54 male professional soldiers have been included in the study group, and 46 healthy, age-matched males were in the control group. Relative values of N- acetyl aspartate (NAA), choline (Cho), and myoinositol (mI) to creatine (Cr) were assessed. Mean relative concentrations of metabolites were compared between the study and control group, separately for frontal and occipital lobes as well as between sides in the study group. The most frequent findings in head MRIs of soldiers are sinus disease, asymmetric lateral ventricles, and dilated perivascular spaces. In the frontal lobes, mI/Cr ratio was significantly higher (p=0.005), while NAA/Cr ratio was low (p=0.001) in the group of soldiers. Moreover, the authors claimed that in occipital lobes, NAA/Cr ratio was significantly lower (p=0.005) in military personnel and there was a tendency to a higher mI/Cr ratio in soldiers’ occipital lobes (p=0.056). Comparing between sides, significantly higher mI/Cr (p.

The topic is justified. The paper is not well written, it could be further improved if the following remarks are taken into consideration:

1-ABSTRACT: this needs to be more concise.

2-Several grammatical mistakes including punctuation etc. are found in the whole draft of the article, which needs to be fixed.

3- The introduction section lacks, proper justification, rationale, and contribution of the study.

4. Materials and Methods (Study group). Although 54 controls are sufficient for this study, if more controls are possible to be part of the study, would enable findings robust. The same is the case with Materials and Methods (Control group).

5. Materials and Methods (MRI examination protocol). Seems a “GENERAL ELECTRIC” MRI scanner is used with 1.5T, but the authors did not mention it.

6. Results (Findings in MRI of the head of soldiers) findings are clear based on Analysis of MRI and HMRS data. The main point is, did these metabolites in the brain of soldiers, i.e., NAA, Cho, and mI to to Cr bear these ranges permanently as discussed in the study report? Did the authors verify these, from the analysis of MRI and HMRS data after the assignment of soft jobs? What was the gap between the disposal of their last hard assignment and the day of scanning?

7- Discussion sections seem fruitful.

8. Can these findings, i.e., Sinusitis, Paranasal sinus retention cyst, Sinonasal polyps, etc. be correlated with stress, depression, etc.?

9- The conclusion section should be more comprehensive.

10- The motivation is not clear. Please specify the importance of the proposed solution.

11- In my opinion, this is not a research paper, but a clinical report.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

In this revision one issue remains unsolved. Absolute quantification should correct for the unsuppressed water signal per SV measurement, the number of protons per spectral peak and differential saturation per peak (T1,T2). There is no indication that the authors did any of this. However, all results are reported as metabolite/Cr ratios and the paper becomes acceptable as soon as any reference to absulute quantification is removed from the paper.

Author Response

Reviewer #1: In this revision one issue remains unsolved. Absolute quantification should correct for the unsuppressed water signal per SV measurement, the number of protons per spectral peak and differential saturation per peak (T1,T2). There is no indication that the authors did any of this. However, all results are reported as metabolite/Cr ratios and the paper becomes acceptable as soon as any reference to absulute quantification is removed from the paper.

Authors’ response: We removed mentions regarding absolute quantification of metabolites from section 2.4.

Reviewer 2 Report

The authors addressed comments convincingly.

Author Response

Thank you for your remarks and help in the improvement of the manuscript.