PONE-D-19-18726

4D MRI: Robust sorting of free breathing MRI slices for use in interventional settings

PLOS ONE

Dear Mr. Gulamhussene,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

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Enrico Grisan

Academic Editor

PLOS ONE

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'This study was supported by funding from the Investitionsbank Sachsen-Anhalt (https://www.ib-sachsen-anhalt.de/) to GG with the grant number 1704/00038. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of this manuscript.'

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Additional Editor Comments (if provided):

Dear Authors,

the reviewers' have found scientific merit on your work and we are requesting a minor revision to address the point raised in their comments.

However, PLOS-ONE request the data to be made available, and it is not clear how anonymized MRI data can pose ethical challenges (just thinking about the many repositories targeting variuos diseases). In order to allow the publications, you should provide strong reasons why MRI data can not be shared and clarify the criteria for access.

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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: No

Reviewer #2: No

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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: The paper presents a method for the reconstruction of 4D MRI sequences accounting for many states of respiratory motion. It finds that the proposed method, compared to a baseline, reconstructs sequences more often, more quickly, and to a higher perceived quality. Overall, while the method is a fairly incremental improvement over existing work, the paper is clearly written and the experiments well conceived.

I think there are a few minor issues with the paper which should be corrected in revisions.

- The two similarity measures used are referenced by their names in OpenCV - TM_CCORR_NORMED and TM_CCOEFF_NORMED.These measures should be described (mathematically) in the text. They are a key part of the method and discussed at length, but a reader who is unfamiliar with OpenCV software would have no idea what they are. Their exact implementations in OpenCV may even change in the future.

- There are a number of grammatical / spelling errors in the text which should be corrected. For example,

-- the sentence beginning on line 5 should read "Our application scenario[s] are ... where the challenge of a moving target exist[s] ... but none satisfy all [the] needs ..." (corrections in [])

-- the sentence beginning on line 108 seems to have had some words cut out of it

-- the caption for Figure 6 misspells 'contrast'

- Regarding the data availability, it is reasonable to withhold the actual MRI image data - the journal suggests though that the numerical scores used to generate the summary statistics in, for example, tables 2 and 3 could be provided.

Reviewer #2: The authors describe a method for reconstructing four-dimensional volumes (three spatial + one temporal) from multiple 2D acquisitions. Navigator images are interleaved with imaging frames to provide a method for assigning 2D slices to the 4D volume. The work is built upon a method from Siebenthal et al and describes a minor improvement by constraining the search space for the navigator tracking. The data are not publicly available but the authors do note it is available upon reasonable request.

Please find minor comments below:

1). Please contextualize the imaging time (40 to 80 minutes) for interventional imaging. For non-interventionists, this seems like a very long acquisition time.

2). Please comment on why only healthy volunteers were scanned and speculate on what limitations the method may face in the presence of irregular breathing that is more likely in a patient population.

3). Please briefly describe TM CCOEFF NORMED and TM CCORR NORMED

4). Please comment on the limitations of manual steps such as ROI selection in the scanner environment. Could such steps be automated?

5). Please provide reconstruction times in the body of the paper.

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6. 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.

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Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-18726R1

4D MRI: Robust sorting of free breathing MRI slices for use in interventional settings

PLOS ONE

Dear Mr. Gulamhussene,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Both reviewers are enthusiastic for the manuscript. However, there are few minor comments to be addressed. Please respond all carefully. 

We would appreciate receiving your revised manuscript by May 21 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Haydar Celik, PhD

Academic Editor

PLOS ONE

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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 #2: All comments have been addressed

Reviewer #3: 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 #2: Yes

Reviewer #3: Partly

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

Reviewer #2: Yes

Reviewer #3: No

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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 #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: (No Response)

Reviewer #3: The manuscript titled “4D MRI: Robust sorting of free breathing MRI slices for use in interventional settings” presents a modification of a previously published technique for respiratory motion extraction and 4D image volume generation as pre-procedural imaging for MR-guided interventions. The manuscript is well written, and the results presented in a clear manner. Nevertheless, the manuscript could benefit from direct and succinct clarification as to what are the differences between “their method” and the “reference method” since their method builds upon the reference one. The Methods section clarifies the method, but it is not clear where the original ends and where the new one begins. This should be crystal clear for any reader without having to read the entirety of the work.

General Comments

1) Treatments of individual subjects: The authors acquire multiple datasets from some subjects (“One subject was imaged three times, four subjects were imaged twice…”). These repeated acquisitions are treated as independent measurements and it appears there is no distinction when calculating metrics and averages or in any of the statistical analysis. Yet, these samples are not statistically independent measures. It is clear that in MRI some volunteers naturally provide excellent images and others are simply less photogenic (usually move more in the scanner). Hence, acquiring images from one subject 3 times and treating those values as independent can bias the measurement. Any data from a single subject should be averaged/combined into a single point before statistical consideration (e.g. ANOVA, binomial test). Similarly, when constructing the cases for review by the 10 radiologists, the number of slices included from a given volunteer should be equal. Ultimately, in most of these analyses there are only 13 subjects, not 19.

2) Matched pairs and image quality: Please clarify in the text if the “slice pairs” shown to radiologists for evaluation where of the same slice on the same subject. This is implied in the text but not made explicit. If it is the case, then the analysis made sense. If it isn’t then the comparison analysis does not make sense at all and is probably the incorrect approach. Also, please clarify why there is no pathway for the radiologist to grade images in terms of quality? T

The current analysis allows an observer to pick one or the other image (or both), but it does not assess how many times the reconstruction produced images that were inadequate for interventional guidance either due to incoherent data or residual image artifact. That result is simply hidden by the observer choosing the alternative (especially since there is no “neither” option). In other words, though proposed technique may receive more “points” that the reference technique, if it fails to reconstruct an adequate image within the 4D volume, then it may not be worth pursuing. To claim superiority, the authors need to demonstrate that the images that are reconstructed are not junk any more than those reconstructed in the original method.

3) Scan time: The acquisition time for the proposed method is clearly an issue. I recommend the authors discuss potential techniques for speeding up acquisition. I would suggest that the authors should include the use of phased array coils which would allow for the use of parallel imaging for in plane acceleration, or even more aptly suited, the use of SMS (simultaneous multislice imaging) which is ideal for this approach. I have yet to see a single interventional MRI procedure in which phased array coils were not used during pre-procedural imaging and I believe that in an effort to increase breadth of applicability by relying only on the body coil for signal, the authors are hurting their actual applicability due prohibitively long scan times.

Specific Comments

Page 3/13, Methods, first paragraph: “TR = 40.0 ms” is manufacturer specific term since no modern TRUFI sequence can run with this TR successfully (especially at 3T). The parameters that should be reported in this section but aren’t include: (1) real repetition time (TR) which in Siemens-speak is referred to as echo spacing (likely 2*TE), (2) the actual number of ky-lines acquired within the matrix of 140 phase encodes and descriptions of whether partial Fourier sampling in ky (or assymetric echo in kx) is applied, (3) the readout bandwidth, (4) the min,max and average number of slices acquired per subject (assume 38-57 but average should be reported). In the current description, if 140 lines of k-space were acquired in 200 ms (ignoring start/stop subsequences), then each line would take 1.43 ms, not a feasible number given the matrix size. Hence, the authors need to specify the acquisition more correctly to ensure reproducibility for the reader to understand the current acquisition strategy since it has great impact on temporal resolution.

Page 3/13, Methods, first paragraph: “… body coil…” Clarifying terminology about body coils as there may be some confusion here. The term “body coil” is used to describe the large-bore fixed birdcage coil used for homogeneous RF transmission, rarely used for imaging in diagnostic MRI due to extremely low SNR. A body array (a coil composed of multiple elements) represents the standard surface coils arrays with multiple receive channels that are standard in diagnostic MRI. It is not clear which was used for imaging here, though by the description the authors used no body arrays and used only the body coil for imaging. If this is correct, please clarify the terminology.

Page 4/13: “localisators” is not MR terminology or standard English. The typically used term is "localizer(s)" or "localiser(s)".

Page 6/13: The phrase "well trackable" is awkward in English. Maybe "easily trackable" or "robustly trackable"? Also, since the term is inherently subjective, it may be helpful to display a figure/panel with several patterns that do meet the criteria and maybe even some patterns that do not meet the desired criteria. This is central to the paper as in the end, the authors are using cross correlation on a vessel pattern to estimate respiratory state.

Figure 10: There should be error bars for each point? If my understanding is correct, each point represents averages across all subjects?

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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 #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

4D MRI: Robust sorting of free breathing MRI slices for use in interventional settings

PONE-D-19-18726R2

Dear Dr. Gulamhussene,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Haydar Celik, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

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 #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: Yes

**********

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 #2: Yes

Reviewer #3: Yes

**********

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 #2: Yes

Reviewer #3: Yes

**********

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 #2: I believe the authors have addressed all of the concerns of the reviewers in their revised manuscript.

Reviewer #3: The majority of my comments have been addressed appropriately.

The majority of my comments have been addressed appropriately.

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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 #2: No

Reviewer #3: No