PONE-D-21-02788

Geometrical model of lobular structure and its importance for the liver perfusion analysis

PLOS ONE

Dear Dr. Rohan,

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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Adélia Sequeira, Ph.D

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: Partly

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

Reviewer #1: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

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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 manuscript is concerned with the modelling of blood circulation

in the liver tissue. The liver has fundamental units (the lobules),

the structure of which has been considered in various models of liver

blood perfusion. In the present manuscript the authors propose the use

of a smaller unit, which they call representative periodic cell

(LRPC). They discuss how this enables to use homogenisation methods

to derive macroscopic liver perfusion properties.

The paper is quite well written but, in my view, many parts are

unnecessarily over complicated. This makes it reading the manuscript

more difficult that it ought to be and, ultimately, makes it hard to

grasp some of the key features of the work. I would recommend that the

authors simplify the exposition, which does not necessarily imply that

the presentation needs to be less formal and rigorous.

Having said this, I have some fundamental doubts about the work that I

explain in the following.

- To my knowledge most of the resistance to the flow occurs at the

level of the microcirculation, which means in the sinusoids. The

authors' approach allows one to compute the permeability of small

portal and hepatic veins, but obviously not of the sinusoids. If it

is true that flow resistance is concentrated in the sinusoids, this

spoils the usefulness of determining the permeability of larger

vessels.

- I also ave some doubts about the fact that the authors' approach

allows one to model macroscopic variations of the perfusion of liver

tissue. Blood is delivered to microscopic structures through large

vessels, within which the resistance is relatively small. Thus the

view of a macroscopic percolation through a porous medium

constituted by a large number of LRPCs is not very realistic, in my

opinion. Blood is transported to "groups" of LRPCs through large

vessels and only locally at the microscale blood flow can be thought

of as the flow in a porous medium. In order to understand possible

perfusion depletion of certain tissue regions one has to study blood

flow in relatively large vessels.

I think the authors should carefully consider the above points before

the manuscript can be considered for publication on PLOS ONE.

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Reviewer #1: No

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Geometrical model of lobular structure and its importance for the liver perfusion analysis

PONE-D-21-02788R1

Dear Dr. Rohan

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,

Adélia Sequeira, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The new version of the manuscript has been significantly improved and I suggest its acceptance in the present form.

We deeply apologize for the delay that certainly was partially due to the COVID-19 pandemic.

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

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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

**********

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

Reviewer #1: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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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

**********

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 carefully read the revised version of the manuscript, perusing in

particular the changes with respect to the original submission. The

authors have replied competently and accurately to my comments and

have changed the manuscript accordingly. In my opinion the manuscript

has improved with respect to the original version; this being

particularly true for the Discussion section.

Overall, I think that the paper is carefully written and I suggest

that it is published in the present form.

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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