Peer Review History

Original SubmissionJanuary 13, 2020
Decision Letter - Pew-Thian Yap, Editor

PONE-D-20-01149

Registration-free Distortion Correction of Diffusion Weighted MRI

PLOS ONE

Dear Mr. Schilling,

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We look forward to receiving your revised manuscript.

Kind regards,

Pew-Thian Yap

Academic Editor

PLOS ONE

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"This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was supported by the National Institutes of Health under award numbers R01EB017230, and T32EB001628, and in part by ViSE/VICTR VR3029 and the National Center for Research Resources, Grant UL1 RR024975-01, and Department of Defense award number W81XWH-17-2-055. This research was conducted with the support from Intramural Research Program, National Institute on Aging, NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Titan Xp GPU used for this research."

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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: No

Reviewer #2: Partly

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

Reviewer #1: No

Reviewer #2: N/A

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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: No

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 describes a learning-based distortion correction framework, where the structural T1 and distorted single-blip B0 images are used to synthesize undistorted B0 images. Later, the synthesized and distorted B0 images are fed into TOPUP for further correction. Lastly, FSL's eddy tool is used to do complete pre-processing of the DWIs.

Primary flaws of the paper are 1) presentation of the method, 2) novelty & technical soundness.

In Section 1, the authors highlighted the limitations of their previous work (Synb0-DisCo) but didn't show how these limitations are addressed by the proposed approach.

The title of the paper is misleading ("Registration-free"..), as the method relies on TOPUP and it is not truly registration-free. Also, I really don't get the idea of using TOPUP on top of B0 synthesis. If the synthetic undistorted B0 image is good enough then why run TOPUP?

It is difficult to understand the loss functions in textual form, so it would be better if the authors formulate all the loss functions mathematically.

All the figures are of poor quality. The text in the boxes of Fig. 4 is illegible. There is no network architecture shown. The surface overlays in Fig. 6 & 8 are also not clear.

Reviewer #2: The authors propose a novel method to predict an undistorted b0 from a distorted b0 and a structural image using deep learning (U-nets). This undistorted b0 is then used as a reference in FSL's topup to estimate the susceptibility field (i.e., fieldmap), which allows legacy data acquired without an alternative way to estimate the fieldmap to still be analysed. It's a well-presented and very promising approach to this problem.

My only issue is whether the algorithm will be useful in legacy datasets as this does require the U-net to generalise to other datasets. The authors claim in the abstract: "we show generalizability of the proposed approach to datasets that were not in the original training / validation / testing datasets". However, in the paper they only show 3 selected examples from 3 datasets, where the algorithm does indeed do a decent job. A more quantitative comparison of this claim could be easily produced from for example the distribution of the MI with the T1 (similar to what was used in the withheld dataset in the left panel in Figure 7). This would allow the authors to show whether the algorithm reliably generalizes to other dataset, which would be required before applying it to legacy datasets.

Minor issues:

1. Please give the units of the reconstructed voxel size in the BLSA dataset (page 3).

2. When mentioning the coregestration from b0 to T1 using epi_reg, it would be good to mention that this is a rigid-body transformation (6 degrees of freedom).

3. Was the T1 image registered to the standard after intensity normalization (implied by the text) or before intensity normalization (implied by Figure 3)?

4. There are many arrows missing and misplace in Figure 4. The ones I spotted are:

- There should be an arrow from b0_d_MNI_1 to the upper U-net (top part).

- There should be an arrow from b0_u_MNI to the top MSE (top part).

- There should be an arrow from b0_m_MNI_2 to middle MSE (top part).

- Why is there an arrow going upwards from T1_norm_MNI (top part)?

- In the lower part the arrow between b0_d_MNI_1 and the U-net is shifted upwards.

5. In the caption of Figure 6 there is no mention of which outline in the right panels is the distorted b0 and which is the undistored b0. This information is in the caption of Figure 8, but there it is the wrong way around (red is hopefully the outline of the undistorted b0). Also, in Figure 6, there are two typos, namely "With-held" should be "Withheld" and "let" should be "left".

6. What is the legacy synthetic distortion correction (S.D.) approach mentioned in the caption of Figure 7. It might be good to mention this in the results section when discussion Figure 7.

7. When discussing the timings in the discussion, it would be good to mention that the full pipeline of Synb0 still involves running topup, so the total runtime of Synb0 is much more than 2 minutes.

8. The mention of Figure 4 in the discussion should actually refer to Figure 6.

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Reviewer #1: No

Reviewer #2: No

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Revision 1
Decision Letter - Pew-Thian Yap, Editor

PONE-D-20-01149R1

Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps

PLOS ONE

Dear Dr. Schilling,

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.

Please submit your revised manuscript by Aug 16 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

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). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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

We look forward to receiving your revised manuscript.

Kind regards,

Pew-Thian Yap

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 #1: (No Response)

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: Partly

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

**********

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

**********

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: No

Reviewer #2: 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 #1: 1) Check if the statement is correct: "To account for this, the median value of the masked undistorted b0 was scaled such that it matched the masked median value of the undistorted b0". Distorted should be matched to undistorted B0 image?

2) In Fig. 7, what do different colored markers represent?

3) In Fig. 4, no input is mentioned at the beginning.

4) Language of the paper needs significant improvement. There are many grammatical errors, such as:

"Figure 8 shows that these can correct distortions on datasets that may differ from those the networks were trained on." 'These' should be changed to 'this'.

"The inverse transforms were used to convert the generated undistorted b0 back into subject space." Geometric transforms do not "convert" images; transforms deform/warp images.

Reviewer #2: The authors have addressed all my concerns.

I just have two minor comments:

1. In the intro of section 2 the authors state: "in order to provide topup the information necessary to perfectly correct the distorted diffusion data." The word "perfectly" is a bit of an overstatement (no tool is perfect), so I would suggest to remove it.

2. In the right panel in Figure 5 the dots are grey, not green as stated in the caption of Figure 5.

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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: 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.]

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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Please see Response to Reviewers document attached.

Attachments
Attachment
Submitted filename: R1_Response2Reviewers.docx
Revision 2

See Response to Reviewers document.

Attachments
Attachment
Submitted filename: R2_Response2Reviewers.docx
Decision Letter - Pew-Thian Yap, Editor

Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps

PONE-D-20-01149R2

Dear Dr. Schilling,

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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Kind regards,

Pew-Thian Yap

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Pew-Thian Yap, Editor

PONE-D-20-01149R2

Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps

Dear Dr. Schilling:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Pew-Thian Yap

Academic Editor

PLOS ONE

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