A deep learning framework for the localization of landmarks on the lateral semi circular canals

Zhixuan Wei; Sudanthi Wijewickrema; Bridget Copson; Jean-Marc Gerard; Stephen O’Leary

doi:10.1371/journal.pone.0348976

Peer Review History

Original SubmissionJune 25, 2025
13 Oct 2025 Decision Letter - Catalina I Villamil, Editor -->PONE-D-25-27140-->-->A Deep Learning Framework for the Localization of Landmarks on the Lateral Semi Circular Canals-->-->PLOS ONE Dear Dr. Wei, 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. ============================== Thank you for your patience in awaiting a decision on this manuscript, as it was difficult to obtain reviewers. -->-->Following my own review of the manuscript and reviewer comments, I am requesting Major Revisions on this manuscript. Please see comments below. -->--> -->-->============================== Please submit your revised manuscript by Nov 27 2025 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'. 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Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. 3. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 4 in your text; if accepted, production will need this reference to link the reader to the Table. 4. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Additional Editor Comments: Reviewer 1 provides very helpful advice regarding additional statistical information, tests, and parameters that should be reported. I further agree that, most importantly, the authors need to include an external validation dataset, as the original dataset contains only n =20 patients and was further subdivided for training and testing. [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: Partly Reviewer #2: Yes ******** -->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: No 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: Yes ****** -->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: This manuscript presents a deep learning framework for the localization of landmarks in the lateral semicircular canals using cone-beam CT data. The study addresses a clinically relevant and technically challenging task, and the authors demonstrate promising results showing that their system achieves accuracy comparable to expert performance and within surgical tolerance levels. The work is well structured, generally well written, and of potential value to the medical imaging and surgical planning communities. Strengths: 1.The study focuses on an important clinical application with direct translational potential for skull base surgery. 2.The methodology is clear and logical, employing a stepwise multi-stage approach that balances computational efficiency with accuracy. 3.Comparative evaluation of several neural network architectures is a strong feature, providing a broader assessment of performance. 4.Use of multiple expert annotations for ground truth increases reliability. 5.The manuscript is clearly written and technically accessible. Limitations and Points for Improvement: 1.Sample Size and Generalizability: The dataset consists of only 20 patients, all with normal anatomy. Even with augmentation, this raises concerns about robustness and generalizability. Inclusion of a larger and more heterogeneous dataset, ideally with pathological cases, would significantly strengthen the study. 2.External Validation: The absence of an external validation cohort is a major limitation. Testing on independent datasets is essential to demonstrate clinical applicability. 3.Statistical Rigor: While mean and standard deviation values are reported, the statistical analysis could be improved. Confidence intervals, hypothesis testing, or Bland–Altman plots would better substantiate the claim of equivalence to human experts. 4.ROI Determination: The exhaustive crop-size approach is functional but inefficient. Alternative approaches (e.g., attention mechanisms, transformer-based localization, or adaptive ROI detection) could be considered to modernize the framework. 5.Interpretability and Clinical Workflow: The manuscript would benefit from visualization of errors, attention maps, or examples of both successes and failures. Furthermore, details such as runtime per scan and workflow integration into surgical planning should be elaborated. 6.Data Availability: The dataset is not publicly available due to ethical restrictions, which limits reproducibility. While this is understandable, stronger justification or provision of anonymized subsets would help align with open science practices. Reviewer #2: The precision the systems achieved to localize three-dimensional landmark coordinates of the semicircular canals is worthy of high praise. According to the data shown in “[8]:Copson B, Wijewickrema S, Slinger C, Youssef D, Gerard JM, O’Leary S. Definition of a coordinate system for multi-modal images of the temporal bone and inner ear. Plos one. 2024”, intra and inter rater (experts) variation is very low. This means that it is an easy and consistent task for the “experts”. How do the authors see the value of this system. ****** -->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: Yes: Parisa Kaviani 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.0348976.r001
Revision 1
8 Dec 2025 Author Response Academic Editor’s comments Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found here and here. We have ensured that the manuscript uses the PLOS ONE template and meets the style requirements. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see here. Before we proceed with your manuscript, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. The data collected is owned by the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. The ethics under which the data was collected by the University of Melbourne researchers restricts its public sharing. However, anonymised data can be shared on request. Please contact Prof Stephen O'Leary (sjoleary@unimelb.edu.au) the head of the Department of Otolaryngology in the University of Melbourne and also the owner of the ethics (#08/796H/18) of the data. Researchers can also contact Kerryn Baker (kerryn.baker@eyeandear.org.au), Education Precinct Manager of the Royal Victorian Eye and Ear Hospital, about the ethics. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 4 in your text; if accepted, production will need this reference to link the reader to the Table. Thank you for noticing this oversight. We have corrected this. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. We feel that the reviewers’ comments are very constructive and neither has requested us to cite references that are not relevant. Additional Editor Comments: Reviewer 1 provides very helpful advice regarding additional statistical information, tests, and parameters that should be reported. I further agree that, most importantly, the authors need to include an external validation dataset, as the original dataset contains only n =20 patients and was further subdivided for training and testing. We admit that n=20 is small. We have however taken steps (such as augmentation and cross validation) to address this. Also, please note that Reference #21 of the paper in the field have used similar (or lesser) number of patients. However, we have done further validation on 14 new patients. Please note that due to practical considerations such as data collection, labelling by experts and time constraints for the first author who is a PhD student in his final year, we have limited the external validation to 14 patients. Please note that we have called this ‘additional validation’ as the dataset was drawn from the same population as the training and test sets. The changes to the manuscript are in lines 296-316. We agree that the additional statistical tests suggested will add value and have conducted them (lines 305–315, figures 13, 14 tables 4). Reviewer 1’s comments 1. Sample Size and Generalizability: The dataset consists of only 20 patients, all with normal anatomy. Even with augmentation, this raises concerns about robustness and generalizability. Inclusion of a larger and more heterogeneous dataset, ideally with pathological cases, would significantly strengthen the study. Thank you for the comments. We agree with the reviewer. Unfortunately, we have been limited in the number of patients due to practical issues in collecting and labelling data. We have taken measures such as augmentation to overcome issues of over-fitting and cross validation. However, as per your suggestion, we have further conducted an external validation that addresses the issue of generalizability. Please note that we have called this ‘additional validation’ as the dataset was drawn from the same population as the training and test sets. Please see Section Additional Validation of the manuscript. This patient cohort for this study were cochlear implant patients. As such, it is rare for any abnormalities and pathologies in and around the lateral semi-circular canals (where the landmarks are located) to be present. We plan to extend the method to include pathological cases in the future. This has been added as a limitation in the discussion (lines 342-345). 2.External Validation: The absence of an external validation cohort is a major limitation. Testing on independent datasets is essential to demonstrate clinical applicability. Thank you. We acknowledge this is an issue and have conducted an additional validation (Section Additional Validation, Table 4 etc). 3.Statistical Rigor: While mean and standard deviation values are reported, the statistical analysis could be improved. Confidence intervals, hypothesis testing, or Bland–Altman plots would better substantiate the claim of equivalence to human experts. Thank you for this suggestion. We have conducted these statistical analyses. Lines 305-315 and table 4, figures 13, 14 in the manuscript reflect these changes. Please note that we have used non-parametric statistics for this analysis as the number of patients in the additional validation set was 14 with no augmentations. This leads to the violation of the normality assumption required to conduct parametrics statistics. 4.ROI Determination: The exhaustive crop-size approach is functional but inefficient. Alternative approaches (e.g., attention mechanisms, transformer-based localization, or adaptive ROI detection) could be considered to modernize the framework. We agree that this approach of crop size detection is not the most optimal. We will conduct more efficient crop size detection methods such as those suggested by the reviewer in future work (lines 356-357). 5.Interpretability and Clinical Workflow: The manuscript would benefit from visualization of errors, attention maps, or examples of both successes and failures. Furthermore, details such as runtime per scan and workflow integration into surgical planning should be elaborated. We have added figures to visualise results including errors (Figures 15). We did not include run time per scan as it is a subjective measure depending on factors such as processing power and memory capacity of the computer. Automating the identification of landmarks enables patient scans to be transformed into a standardized coordinate system, improving the clinical workflow by (1) facilitating automation of downstream tasks such as multi-modal registration, surgical planning, and pathology identification, and (2) minimizing the need for human intervention. This has been added to the manuscript (lines 318-322). 6.Data Availability: The dataset is not publicly available due to ethical restrictions, which limits reproducibility. While this is understandable, stronger justification or provision of anonymized subsets would help align with open science practices. The data collected is owned by the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. The ethics under which the data was collected by the University of Melbourne researchers restricts its public sharing. However, anonymised data can be shared on request. Please contact Prof Stephen O'Leary (sjoleary@unimelb.edu.au) the head of the Department of Otolaryngology in the University of Melbourne and also the owner of the ethics (#08/796H/18) of the data. Researchers can also contact Kerryn Baker (kerryn.baker@eyeandear.org.au), Education Precinct Manager of the Royal Victorian Eye and Ear Hospital, about the ethics. Reviewer 2’s comments According to the data shown in “[8]:Copson B, Wijewickrema S, Slinger C, Youssef D, Gerard JM, O’Leary S. Definition of a coordinate system for multi-modal images of the temporal bone and inner ear. Plos one. 2024”, intra and inter rater (experts) variation is very low. This means that it is an easy and consistent task for the “experts”. How do the authors see the value of this system? Automating the identification of landmarks enables patient scans to be transformed into a standardized coordinate system, improving the clinical workflow by (1) facilitating automation of downstream tasks such as multi-modal registration, surgical planning, and pathology identification, and (2) minimizing the need for human intervention. This has been added to the manuscript (lines 318-322). Attachments Attachment Submitted filename: Rebuttal.pdf https://doi.org/10.1371/journal.pone.0348976.r002
17 Mar 2026 Decision Letter - Catalina I Villamil, Editor -->PONE-D-25-27140R1-->-->A Deep Learning Framework for the Localization of Landmarks on the Lateral Semi Circular Canals-->-->PLOS One Dear Dr. Wei, Thank you for submitting your revised manuscript to PLOS ONE and thank you for your patience. I was able to obtain a review from one additional reviewer. I concur with the reviewer that the major issues with this manuscript (lack of external validation) was addressed. However, there are some minor comments to be addressed that will improve clarity of the figures and manuscript. 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 May 01 2026 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 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, Catalina I Villamil Academic Editor PLOS One Journal Requirements: 1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 2. 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. Additional Editor Comments: I would note that in Fig. 15 it is quite difficult to see the landmarks that are being shown. I would suggest making the dot that designates the landmark(s) bigger. I also suggest making this figure colorblind friendly (e.g. red and blue instead of red and green). 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 #3: (No Response) ******** -->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 #3: Yes ****** -->3. Has the statistical analysis been performed appropriately and rigorously? --> 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 #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 #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 #3: Thank you for the opportunity to review the manuscript entitled “A Deep Learning Framework for the Localization of Landmarks on the Lateral Semicircular Canals.” This study presents an innovative application of deep learning to a longstanding challenge in otologic and vestibular research. Automated and reproducible localization of canal landmarks has potential to advance both clinical and morphometric investigations of the inner ear. Visualizing the detailed morphology of the endosseous and membranous labyrinths remain one of the biggest challenges in ontological research. In this context, the authors’ effort to develop a computational framework for landmark detection is both appropriate and potentially impactful. While the deep learning architecture and training procedures fall outside my primary area of expertise, I am happy to provide some feedback on the morphometric study of the LSCC. Below, I offer several suggestions focused on the morphometric and anatomical aspects of the study. • In your “Landmarks of the LSCC” section, you need a clearer definition of where each landmark was placed in reference to anatomical features (e.g., “middle of the bony ampulla and point at which the slender LSCC joins the vestibule”). Please add in this description of the features. • Line 215: “Fi” should be “Fig”. • Line 298: What is meant by the word “annotated”? • Lines 300 and 313: You say the upper boundary for the clinically significant distance threshold is 0.5mm and cite Mueller et al., 2021. That paper reported ~0.5mm as the maximum distance found between the facial recess trajectory orientation to the facial nerve and osseous spiral lamina. However, the average distances they report are 0.44mm, and 0.35mm, respectively. I would recommend elaborating here on why exactly 0.5mm is the best fit for establishing your upper boundary? • Line 331: What is meant by “ground truth”? • Line 332: “…coordinates selected by human experts (citation needed)” • Figure 13. It seems the greater variability in the posterior landmark is driven by one individual. Can you elaborate on why this may be? It might be worth doubling checking the scan to see what is going on here. ****** -->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 #3: Yes: Christopher M Smith ******** [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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. --> https://doi.org/10.1371/journal.pone.0348976.r003
Revision 2
22 Apr 2026 Author Response Dear Editor, Thank you for giving us the opportunity to submit a revised version of our manuscript titled “A Deep Learning Framework for the Localization of Landmarks on the Lateral Semi Circular Canals” to PlosONE. We appreciate the time and effort that you and the reviewers have dedicated to providing feedback on our manuscript. We have modified the manuscript to reflect the suggestions provided. We have highlighted the changes within the manuscript. The manuscript has also been updated with the new LaTeX template available on the PlosONE website. Here is a point-by-point response to the reviewers’ comments and concerns. All the responses are in italic and the corresponding changes in the manuscript are referred to in this rebuttal letter using line numbers. Journal Requirements: 1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Not relevant 2. 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. Thank you for the reviewer’s point, we have added a new reference to elaborate why we chose 0.5mm as the upper boundary for the statistical comparison. The new reference is: Schneider D, Hermann J, Mueller F, Braga GO'TB, Anschuetz L, Caversaccio M, Nolte L, Weber S, Klenzner T. Evolution and Stagnation of Image Guidance for Surgery in the Lateral Skull: A Systematic Review 1989–2020. Front Surg. 2021;7:604362. (line 308) Additional Editor Comments: I would note that in Fig. 15 it is quite difficult to see the landmarks that are being shown. I would suggest making the dot that designates the landmark(s) bigger. I also suggest making this figure colorblind friendly (e.g. red and blue instead of red and green). Thank you for pointing this out. We have updated Fig 15 using bigger landmarks with the colors red and blue. (Fig 15) Reviewer 3’s comments Thank you for the opportunity to review the manuscript entitled “A Deep Learning Framework for the Localization of Landmarks on the Lateral Semicircular Canals.” This study presents an innovative application of deep learning to a longstanding challenge in otologic and vestibular research. Automated and reproducible localization of canal landmarks has potential to advance both clinical and morphometric investigations of the inner ear. Visualizing the detailed morphology of the endosseous and membranous labyrinths remain one of the biggest challenges in ontological research. In this context, the authors’ effort to develop a computational framework for landmark detection is both appropriate and potentially impactful. While the deep learning architecture and training procedures fall outside my primary area of expertise, I am happy to provide some feedback on the morphometric study of the LSCC. Below, I offer several suggestions focused on the morphometric and anatomical aspects of the study. • In your “Landmarks of the LSCC” section, you need a clearer definition of where each landmark was placed in reference to anatomical features (e.g., “middle of the bony ampulla and point at which the slender LSCC joins the vestibule”). Please add in this description of the features. Thank you for your comment. We have added a clearer definition in the section “Landmarks of the LSCC”. The Anterior Landmark was defined as the centre-point of the junction between the anterior aspect of the LSCC, and the utricle - that is, the point at which the slender bony canal opens into the vestibule anteriorly - confirmed in all three imaging planes. The Posterior Landmark was defined equivalently at the posterior junction of the LSCC and the utricle, where the canal re-enters the vestibule posteriorly, again confirmed in all three planes. (line 104 to 109) • Line 215: “Fi” should be “Fig”. Fixed, thank you. (line 220) • Line 298: What is meant by the word “annotated”? Thank you for asking, it is a term used in deep learning which represents the process used to label the ground truth. For example, in our automatic landmarks detection task, it means the ground truth landmarks of the 14 additional patients’ scans were manually identified by expert clinicians. (No change in the manuscript) • Lines 300 and 313: You say the upper boundary for the clinically significant distance threshold is 0.5mm and cite Mueller et al., 2021. That paper reported ~0.5mm as the maximum distance found between the facial recess trajectory orientation to the facial nerve and osseous spiral lamina. However, the average distances they report are 0.44mm, and 0.35mm, respectively. I would recommend elaborating here on why exactly 0.5mm is the best fit for establishing your upper boundary? Thank you for pointing this out. We agree that the literature Mueller et al., 2021 is insufficient for the choice of the upper boundary 0.5mm. We have cited another paper Schneider et. al., which clearly suggested it as the threshold for lateral skull based image guidance. The elaboration has been added in the manuscript: Accuracy requirements in image guided surgery and image registration using landmarks are not standardised, and reasonable thresholds depend on the precision required by the surgical technique. For lateral skull base image guidance, a value of 0.5mm has been suggested (Schneider et. al.), and we adopted this as the predefined upper boundary for evaluating the clinical acceptability of our landmark detection results. (line 305 to 309; line 321; line 350) The reference added: Schneider D, Hermann J, Mueller F, Braga GO'TB, Anschuetz L, Caversaccio M, Nolte L, Weber S, Klenzner T. Evolution and Stagnation of Image Guidance for Surgery in the Lateral Skull: A Systematic Review 1989–2020. Front Surg. 2021;7:604362. • Line 331: What is meant by “ground truth”? Thank you for asking, “ground truth” is a term used in supervised deep learning which represents the target of the model’s optimization direction. In our task it is the median of the landmarks coordinates picked by the experts. The model’s training process is the optimization to minimize the distance between the predicated landmarks and the ground truth landmarks. (No change in the manuscript) • Line 332: “…coordinates selected by human experts (citation needed)” Thanks for the comment. We have added the citation. (line 336) • Figure 13. It seems the greater variability in the posterior landmark is driven by one individual. Can you elaborate on why this may be? It might be worth doubling checking the scan to see what is going on here. Thank you for pointing this out. We have checked the scans of the greatest difference shown in Figure 13’s posterior landmarks. The scans are not from a single patient, they come from three different patients. As far as we can see, there is no obvious pattern in these three cases. We have also observed the slightly higher variation in the posterior landmark coordinates. This is likely because of higher variations in the human landmark detections which were used as ground truth for training our models. We have already addressed this in the discussion. The reason behind the differences in human landmarks detections for anterior and posterior points may be the higher anatomical complexity around posterior points, as when manually annotated, the point where the lateral semicircular canal enters the vestibule is on an oblique plane. In addition, there is variation in the anatomic location of the confluence with the posterior semicircular canal, which can make this landmark susceptible to inter-observer variability. We have added this to the discussion for clarification (line 340 to 345). Attachments Attachment Submitted filename: Rebuttal_auresp_2.pdf https://doi.org/10.1371/journal.pone.0348976.r004
24 Apr 2026 Decision Letter - Catalina I Villamil, Editor A Deep Learning Framework for the Localization of Landmarks on the Lateral Semi Circular Canals PONE-D-25-27140R2 Dear Dr. Wei, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support. 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, Catalina I Villamil Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0348976.r005
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Acceptance Letter - Catalina I Villamil, Editor PONE-D-25-27140R2 PLOS One Dear Dr. Wei, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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. Catalina I Villamil Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0348976.r006

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