Improved performance and consistency of deep learning 3D liver segmentation with heterogeneous cancer stages in magnetic resonance imaging

Moritz Gross; Michael Spektor; Ariel Jaffe; Ahmet S. Kucukkaya; Simon Iseke; Stefan P. Haider; Mario Strazzabosco; Julius Chapiro; John A. Onofrey

doi:10.1371/journal.pone.0260630

Peer Review History

Original SubmissionJune 4, 2021
13 Jul 2021 Decision Letter - Yan Chai Hum, Editor PONE-D-21-18482 Improved performance and consistency of deep learning 3D liver segmentation with heterogenous cancer stages in magnetic resonance imaging PLOS ONE Dear Dr. Onofrey, 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 revise according to reviewers' comments especially the comment to compare the proposed techniques with the state-of-arts to further demonstrate the contributions of the research work. Please submit your revised manuscript by Aug 27 2021 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. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Yan Chai Hum Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: [Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number P30 KD034989 and the National Institutes of Health Grant Award Number DDRCC DK034989-36 for the Clinical Translational Core of the Yale Liver Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Nation Institutes of Health. M.G. was supported by a travel grant by the Rolf W. Günther Foundation for Radiological Sciences for travel to Yale University.] We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: [J.O. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number P30 KD034989 and M.S. the National Institutes of Health Grant Award Number DDRCC DK034989-36 for the Clinical Translational Core of the Yale Liver Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Nation Institutes of Health. M.G. was supported by a travel grant by the Rolf W. Günther Foundation for Radiological Sciences for travel to Yale University.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.] Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. 4. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option. 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. 6. We note that Figures 1, 3 and 4 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a) You may seek permission from the original copyright holder of Figures 1, 3 and 4 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b) If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. [Note: HTML markup is below. Please do not edit.] 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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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: No ****** 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: Well written article. The presented works are reproducible, proposed methodology writing is clear and easy to follow. The writing content demonstrated a high technically sound piece of research works. Presented outcome is convincing with enough simulated samples. Reviewer #2: In this research, authors wish to assess the ability of state-of-the-art deep learning 3D liver segmentation algorithms to generalize across different BCLC liver cancer stages. The research is interesting, however, the proposed methodology existed in the literature and thus the novelty of the research is not sufficient to be published in PLOS ONE. Furthermore, the discussions and also the analysis of the manuscript need to be further improve in order to be published in PLOS ONE. So I suggest reject the article and giving the author a chance to submit after doing additional research to improve the contributions of the research work. Authors may also consider the following comments for the revision work: 1. The writing of the manuscript need to be further improve. The sections and sub sections need to be change. E.g. there should be sections like Literature review, Methodology, Results and Discussions etc. There are some crucial sections missing in the manuscript. The flow is a bit difficult to follow. 2. The format of the references and citations need to be improve. For the literature review, authors should refer to more recent research, i.e. year 2019-2020. Currently there is only 1 2020 reference which is not sufficient. 3. Authors need to identify the research gap and highlight the contribution(s) of the research work in the manuscript to shows the novelty of the research. 4. Authors should compare the proposed techniques with the state-of-arts to further prove the contribution(s)/novelty of the research work. 5. More scientific reasoning should be added in the experimental results' explanations. 6. The format of the tables need to be improved. The current one is a bit difficult to read. ****** 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. 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. https://doi.org/10.1371/journal.pone.0260630.r001
Revision 1
27 Aug 2021 Author Response We thank the reviewers and editor for their time spent reading our manuscript and for their thoughtful comments. We have prepared detailed responses to each comment and have incorporated changes into our revised manuscript using Track Changes (with changes highlighted in blue text). We provide here a summary of major changes made to this revised manuscript. Detailed responses to individual comments can be found in our Response to Reviewers. Summary of Major Changes The revised version of our manuscript includes the following major changes: 1. In response to Reviewer 2, we have revised the manuscript to highlight the contributions and significance: a. We have elaborated on the challenges of distributional shift in machine learning in both the Introduction and the Discussion. Our results demonstrate the problem of distributional shift in liver segmentation and how training across the distribution clinical liver cancer imaging data can make model performance more robust by reducing this shift. b. We have provided additional references to recent liver segmentation approaches to make our manuscript more comprehensive in both the Introduction and the Discussion sections. 2. Addressed specific journal requirements for submission that include: a. Ensured that the manuscript meets PLOS ONE’s style requirements. b. Removal of all funding-related text from the manuscript’s Acknowledgements section. c. Updated the Data Availability statement. d. Moved the Ethics Statement to appear within the Methods section. e. All figures are available under the CC BY 4.0 license. Attachments Attachment Submitted filename: PONE-D-21-18482_response_final.docx https://doi.org/10.1371/journal.pone.0260630.r002
4 Oct 2021 Decision Letter - Yan Chai Hum, Editor PONE-D-21-18482R1Improved performance and consistency of deep learning 3D liver segmentation with heterogenous cancer stages in magnetic resonance imagingPLOS ONE Dear Dr. Onofrey, 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 improve each caption of figure and title for table to assure that take-home message was incorporated into the caption or title so that the figure can be standalone without requiring readers to read the text to understand the gist of the figure/table. In other words, highlight the findings of the figure/table using caption/title to facilitate reading. Besides, please assure that the Github link can be accessed,. Lastly, you are advised to revise your conclusion based on the result acquired from the experiment; reiterate and specify the critical findings based on experimental result and then only explain the implication of these findings to the field of study. Please submit your revised manuscript by Nov 18 2021 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Yan Chai Hum Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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. https://doi.org/10.1371/journal.pone.0260630.r003
Revision 2
5 Nov 2021 Author Response We thank the reviewers and editor for their time spent reading our manuscript and for their thoughtful comments. We have prepared detailed responses to each comment and have incorporated changes into our revised manuscript using Track Changes (with changes highlighted in blue text). Reviewers' Comments: 1. Please improve each caption of figure and title for table to assure that take-home message was incorporated into the caption or title so that the figure can be standalone without requiring readers to read the text to understand the gist of the figure/table. In other words, highlight the findings of the figure/table using caption/title to facilitate reading. We have changed the figure captions and table titles so that they contain and highlight the main message and can be understood without reading the text. 2. Besides, please assure that the Github link can be accessed,. The Github link can now be accessed through the following link: https://github.com/OnofreyLab/liver-segm 3. Lastly, you are advised to revise your conclusion based on the result acquired from the experiment; reiterate and specify the critical findings based on experimental result and then only explain the implication of these findings to the field of study. We have revised our conclusion and made it more specific to our study and field of research. Attachments Attachment Submitted filename: PONE-D-21-18482_R2_response_final.docx https://doi.org/10.1371/journal.pone.0260630.r004
15 Nov 2021 Decision Letter - Yan Chai Hum, Editor Improved performance and consistency of deep learning 3D liver segmentation with heterogenous cancer stages in magnetic resonance imaging PONE-D-21-18482R2 Dear Dr. Onofrey, 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, Yan Chai Hum Academic Editor PLOS ONE Additional Editor Comments (optional): All concerns have been addressed. Reviewers' comments: https://doi.org/10.1371/journal.pone.0260630.r005
Formally Accepted
19 Nov 2021 Acceptance Letter - Yan Chai Hum, Editor PONE-D-21-18482R2 Improved performance and consistency of deep learning 3D liver segmentation with heterogenous cancer stages in magnetic resonance imaging Dear Dr. Onofrey: 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Yan Chai Hum Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260630.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .