PONE-D-22-32958INSPIRE: Intensity and spatial information-based deformable image registrationPLOS ONE

Dear Dr. Öfverstedt,

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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: 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: 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: This is a very nice paper on intensity and geometry based deformable registration of images. The main advantage of the contribution is the general-purpose nature of the proposed method for deformable image registration. The theoretical and algorithmic solutions aim at computational efficiency in two scenarios. The method on a 2D dataset created from retinal images, characterised by presence of networks of thin structures.The authors provide the source code of their implementation.

I find that the literature is sufficiently cited, the method is technically sound and clearly formulated. The English also reads very well.

I only the following relatively minor issues:

- In the experiments with the retinal images, authors had to resort into synthetically deforming the images, in order to simulate deformable distortions. However, open datasets for registration of retinal images, that exhibit these properties, already exist (e.g. the FIRE dataset).

- There is no visual demonstration of the method. Of course the quantitative evaluation of the approach is a significant and valuable benchmark. Nevertheless, it does not provide a qualitative demonstration of the effect of the deformable transformation in the resultant images. The images provided in Figures 1 & 2 are rather unclear and do not suffice for such a demonstration.

Reviewer #2: The authors present a method for deformable image registration, combining intensity and spatial information, utilizing elastic B-splines and incorporating inverse inconsistency penalization. Such method can be utilized for performing both 2D and 3D registration.

The introduction and related work sections provide enough relevant information to locate the proposed work within the current state of the art. They also provide good background about the math behind key elements of the method

The method section provides a very detail and supported description of the method

Evaluation section does an adequate job, providing metrics and comparisons both for 2D and 3D registrations. My biggest gripe here is that for the 2D registration, the authors perform registration of retinal images, but they create their own synthetic dataset instead of utilizing the publicly available FIRE dataset, which is widely utilized in this domain and that would also allow for easy comparison with domain specific registration methods, not only with general methods. Analysis of performance for 3D registration on brain MRI scans i good

Dataset:

- FIRE: Fundus Image Registration dataset

- https://projects.ics.forth.gr/cvrl/fire/

- https://doi.org/10.35119/maio.v1i4.42

Some interesting methods utilizing the FIRE dataset that could be used to compare with

- Semi-supervised Keypoint Detector and Descriptor for Retinal Image Matching https://doi.org/10.1007/978-3-031-19803-8_35

- Retinal fundus image registration framework using Bayesian integration and asymmetric Gaussian mixture model https://doi.org/10.1002/ima.22789

- Color fundus image registration using a learning-based domain-specific landmark detection methodology https://doi.org/10.1016/j.compbiomed.2021.105101

- REMPE: Registration of Retinal Images Through Eye Modelling and Pose Estimation https://doi.org/10.1109/JBHI.2020.2984483

- Unsupervised Deep Learning Network for Deformable Fundus Image Registration https://doi.org/10.1109/ICASSP43922.2022.9747686

Discussion and conclusion are succinct, but complete

In conclusion, this is an interesting work, with a very detailed manuscript. I would only request the authors to provide results for retinal image registration utilizing the mentioned dataset, to enable comparing their method with domain specific methods.

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Reviewer #1: No

Reviewer #2: No

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INSPIRE: Intensity and spatial information-based deformable image registration

PONE-D-22-32958R1

Dear Dr. Öfverstedt,

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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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,

Gulistan Raja

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 #1: All comments have been addressed

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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: 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 #1: I find that the reviewers sufficiently addresses both comments raised by the reviewers and the paper merits publication.

Reviewer #2: (No Response)

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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

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