PONE-D-21-06747

In-silico study of accuracy and precision of left-ventricular strain quantification from 3D tagged MRI

PLOS ONE

Dear Dr. Genet,

I am the new AE for this paper.  It seems one review indicated that this version is a revision.  Anyway,  this is the first time Reviewer 2 saw this.  Please read the comments and respond carefully.

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

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We look forward to receiving your revised manuscript.

Kind regards,

Dalin Tang

Academic Editor

PLOS ONE

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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: No

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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: The authors did a very good job of revision that greatly improved the overall quality of this manuscript.

They answered all my questions point by point and they are to be congratulated for the quality of this revision.

This work seems to me sufficiently improved to be published.

Reviewer #2: The present manuscript evaluates a finite-element method for strain quantization using an in-silico phantom. The approach of using an in-silico phantom is likely of interest to investigators in the field and the analysis of how parameters like tag distance and pixel size affect the accuracy of the strain quantification is important. The manuscript does not open completely new ground in the field, but it could make a useful contribution to the field, and the results are important for expanding our current knowledge about the limits of strain quantification with current MRI methods and post-processing techniques. This comment is also not meant to the play down the indisputable technical sophistication of the work. The manuscript could be improved by avoiding some errors like the use of terms or abbreviations before they are properly defined, providing some more information about the in-silico phantom, and in general helping the reader gain an easier intuitive understanding of the results and the fundamental limits to reducing strain error.

1) In-silico phantom: it would be useful to have some basic information about the phantom in terms of ES and ED cavity volume, mean wall thickness at ED and ES. In particular the relation between mean wall thickness and tag-line spacing is of some relevance for understanding when increased tag-line distance impacts on the accuracy of radial strain estimation. In fact, in the case of radial strains it may be useful to not only assess strain quantification as a function of TPR but also as a function of the tag-line-distance to mean wall-thickness ratio. It should be made clearer to the reader that for radial strain quantification it is important that at least two intersection points/lines fall within the wall thickness when moving in the radial direction. This limitation is much less of a constraint for the circumferential and longitudinal components.

2) Page 4: it may be better to use different symbols for the functional J in equation 6 and the quantity J in equation 7, as they apparently represent different things.

3) Equation 4: Generally, with regularization the primary quantity that is to be minimized - in this case the similarity metric - is not weighted by the regularization parameter. Why did the authors choose in this case to use a (1-beta) factor to weigh the similarity metric, in addition to the customary weighing of the regularization term by beta? Is there any logic behind requiring that the two weighting factors to sum to one, i.e. choosing weighting factors of (1-beta) and beta?

4) Page 4, choice of regularization parameter value: for practical application of the proposed method the regularization parameter would have to be chosen without recourse to the ground truth, which in practice means using some heuristic like the L-curve criterion or similar. Could the authors please comment on this and also relate this to the question why they weighed both terms in equation 6 by (1-beta) and beta, respectively. How does this affect the choice of optimal regularization parameter when the ground truth is not known?

5) TPR (Tag distance to Pixel size Ratio) is first defined in Results, but the abbreviation is used beforehand in Methods. The authors should define new symbols or abbreviation at first use in the manuscript.

6) The nature of the shifts that were applied to analyze the effects of varying degrees of geometric inconsistencies are not clear. In what direction where shifts applied to the images? Would a shift applied in one direction not result in different degrees of accuracy depending on the location of a myocardial segment relative to the center of the LV and the direction of the shift? This is rather confusing, and the authors need to make a better effort in explaining their method of evaluating geometric inconsistencies!

7) Could the authors indicate in which cases (figures) the change of strain parameter or error is significant? It looks like in many cases the change of one parameter (e.g. SNR in the case of Figure 8) has little effect on the quantification error! I think that indicating which changes are statistically significant is better than just speaking of “a considerable increase” of quantity X or similar.

8) The figures are appended in the manuscript PDF in reverse order (in terms of the numbering).

9) Equation 1: The image-related quantity X_i is not explained.

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Reviewer #1: No

Reviewer #2: Yes: Michael Jerosch-Herold

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PONE-D-21-06747R1

In-silico study of accuracy and precision of left-ventricular strain quantification from 3D tagged MRI

PLOS ONE

Dear Dr. Genet,

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 Oct 09 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,

Dalin Tang

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

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

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 #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 #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 #2: The manuscript has been skillfully revised by the authors. After examining the revised manuscript I still have two queries for the authors, but these should only require very minor changes to the manuscript.

1) Equation 1 implies a very simply preparation for spatial modulation of magnetization, while in practice e.g. a binomial scheme is going to result in sharper tag lines. The authors could point out that in this sense there are potentially looking at a worst case scenario in terms of tag line contrast.

2) The authors state in the legend for the new figure S1: "The tracking algorithm requires a higher regularization strength as image resolution and SNR decrease." Could the authors clarify if image resolution causes an increase of the regularization weight independent of the SNR, or if the effect of image resolution is through the natural decrease of SNR? It would make sense that higher image resolution does require stronger regularization, as the higher image resolution is likely increasing how ill-posed the inverse problem is. I am also not sure if what they call a "decrease" of image resolution is correct terminology, because if pixel size decreases I would call this "higher resolution" and not a decrease of resolution. The authors should consult with a native speaker.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Michael Jerosch-Herold

[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.

In-silico study of accuracy and precision of left-ventricular strain quantification from 3D tagged MRI

PONE-D-21-06747R2

Dear Dr. Genet,

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,

Dalin Tang

Academic Editor

PLOS ONE

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