PONE-D-20-10274

MRI Based Patient Specific Urinary Flow Dynamics Simulation

PLOS ONE

Dear Dr. Roldán-Alzate,

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Additional Editor Comments (if provided):

As editor, I concur completely with the review as presented. At present it is a case report. In order for this to be useful to the field, additional data need to be obtained. I also feel comfortable with a single review, given that the paper is premature at this point. Some difficulties in obtaining reviewers was experienced due to the highly technical nature of the methodology. Most urologists are unfamiliar with the technical details of MRI, and I did not wish to cause further delays in returning the manuscript. I do not see an additional review changing my assessment of the manuscript.

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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

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

Reviewer #1: 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: No

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Reviewer #1: 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 an interesting paper that has applied cardiac wall movement analysis using MRI to assess bladder voiding. The data presented is a bit premature, as the technique was only assessed on one healthy volunteer. There is no statistical analyses to support their hypothesis that most of the bladder wall movement occurs in the dome region. Although the application of the MRI methodology is new for bladder voiding, the approach to measure cardiac wall movement is well documented. I applaud the investigators for attempting to use the methodology in the bladder, which requires such approaches to non-invasively assess its function. Although, the approach is not entirely non-invasive, as the placement of the catheter and voiding approach described seems like it would be cumbersome for patients with bladder disorders.

At the very least, this method needs to be assessed in multiple individuals to support the outcome that there are regional differences in bladder wall movement during voiding. Individuals with bladder voiding issues should have also been included, which would have been more relevant to the urology community.

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Reviewer #1: No

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PONE-D-20-10274R1

A Pilot Study of Bladder Voiding with Real-Time MRI and Computational Fluid Dynamics

PLOS ONE

Dear Dr. Roldán-Alzate,

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 carefully address the issues raised by Reviewer 2. 

==============================

Please submit your revised manuscript by Nov 28 2020 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

We look forward to receiving your revised manuscript.

Kind regards,

Robert Evan Hurst, PhD

Academic Editor

PLOS ONE

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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 #1: All comments have been addressed

Reviewer #2: (No Response)

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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: Partly

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

Reviewer #1: N/A

Reviewer #2: N/A

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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

**********

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: The authors have expanded the study, which has improved the overall quality of the study. Although it would have been ideal to include more patients and conduct statistical analyses, I think the study still warrants being considered for publication.

Reviewer #2: Methods:

1. Authors should include how they documented patients in control group were asymptomatic (e.g. International Prostate Symptom Score or AUA symptom score).

2. How were the 3 BPH/LUTS patients selected from the urology clinic? (Randomly?, IPSS?, Traditional Urodynamics?)

3. Patient selection did not specifically exclude those with neurologic diseases that are known to effect bladder function, such as, diabetes, parkinsonism, etc., even though the control group showed no symptoms. The group with BPH/LUTS could also have complicating neurologic disorders. Therefore, I suggest that the authors specifically state that there were no histories of such diseases.

4. It would have been nice to have Total Prostatic Volumes and Transition zone volumes on at least the BPH/LUTS group.

5. Examination with patients in the supine position in not very physiologic and represents a distinct limitation of the experiment. (Unlike with cardiac CFD.) The potential effect of positioning should be brought up in the DISCUSSION section.

6. The models rely on many assumptions, some of which the authors accurately report

Results:

1. P9,line1 Statement should insert the words “may be” before “due” or amend to say “there is an association between wall displacement and increased flow velocity in the bladder”, since they have not done a large cohort to provide proof.

2. Fig. 6 Caption The authors might have provided more information on how to interpret “streaming lines” and “time points.” Engineers may be familiar with these concepts, but urologists, radiologists imagers and other readers probably need assistance. Also, “velocity magnitude” should be defined here or in the text of the manuscript.

3. Fig. 7 Caption Insert “likely” before “due”.

Discussion:

1. P10,line 3 The authors are “profoundly startled” by dome movement, but I would expect that because the base of the inferior detrusor is limited in movement by the thicker and stiffer stiffer overlying trigone. This would be expected to be exaggerated by gravity if the subject voids in the usual upright posture. A few examples of this are listed below:

[Assessment of movements of the different anatomic portions of the bladder, implications for image-guided radiation therapy for bladder cancer]. [French]

Evaluation des mouvements des differentes portions anatomiques de la vessie, implications pour la radiotherapie guidee par l'image pour les cancers de vessie.

Pan Q; Thariat J; Bogalhas F; Lagrange JL.

Cancer Radiotherapie. 16(3):167-78, 2012 May.

[Journal Article]

UI: 22365260

Authors Full Name

Pan, Q; Thariat, J; Bogalhas, F; Lagrange, J-L.

Cite My Projects Annotate

AB PURPOSE: To assess interfraction and intrafraction bladder wall movements in the different anatomic portions of the bladder. PATIENTS AND METHODS: Six patients were treated for prostate cancer with conformal irradiation. Daily online cone beam computed tomography was performed for repositioning and an additional one was performed following irradiation once weekly. Four craniocaudal levels were defined to calculate movements amplitudes compared to the scanner tracking: level 1 at the bladder neck, level 2 at mid-height of the bladder, level 3 at mid-height of the dome, level 4 at the apex in a distended bladder. Bladder height was also measured. RESULTS: On 198 daily cone beam computed tomographies, radial bladder right/left/anterior/posterior wall displacements at level 2 were 0.08 +/- 0.24, 0.11 +/- 0.33, 0.16 +/- 0.45 and 0.14 +/- 0.50 cm and at level 3 0.07 +/- 0.78, 0.18 +/- 0.98, 0.43 +/- 0.94 and 0.04 +/- 1.02 cm. Dome and neck displacements were 0.08 +/- 1.41 cm and 0.08 +/- 0.64 cm. Seventeen cone beam computed tomographies were done following irradiation. Radial bladder right/left/anterior/halfway up the trine wall displacements at level 2 before and after irradiation were 0.02+/-0.18, 0.01+/-0.30, 0.09 +/- 0.32 and 0.22 +/- 0.42 cm and at level 3 0.27 +/- 0.60, 0.37 +/- 1.15, 0.18 +/- 0.87 and 0.54 +/- 1.68 cm. CONCLUSION: Significant bladder wall displacements were observed on the anterior wall and upper portion of the bladder. Isotropic margins may not be sufficient to account for inter- and intrafraction bladder wall displacements at the latter levels. Tailored bladder anatomy-based anisotropic margins may be necessary to optimally spare the small intestine and to guaranty proper tumour coverage in case of bladder cancer. For upper bladder tumours, margins of over 2 cm would be necessary, which make them less adequate for external beam irradiation.

Assessment of Bladder Motion for Clinical Radiotherapy Practice Using Cine–Magnetic Resonance Imaging

Catherine A McBain;Vincent S Khoo;David L Buckley;Jonathan S Sykes;Melanie M Green;Richard A Cowan;Charles E Hutchinson;Christopher J Moore;Patricia M Price

ISSN: 0360-3016; DOI: 10.1016/j.ijrobp.2008.11.040

International journal of radiation oncology, biology, physics. , 2009, Vol.75(3),

2. p10 line 7 “thatt” typo

3. p10,l para 7 The authors might consider that CFD may also show vesicoureteral reflux, although it is not demonstrated in this study cohort.

REFERENCES: There are several incomplete or mistaken references

#13 Busse R incomplete reference

#28 Turkiye “Klinikleri” J Med Sci

SUMMARY

Pilot feasibility studies require a lesser level of evidence than more determinative research. The authors conceive of an image-based non-invasive technique that may substitute for traditional multichannel urodynamics. I would offer that their studies may provide different information rather than fully replace pressure-flow studies. The results of this study can make no conclusions other than proof of concept which it adequately does. I would recommend the authors re-phrase the final paragraph to say that the findings “in men with BPH/LUTS “suggest asymmetric bladder wall motion compared to healthy men…….”

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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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A Pilot Study of Bladder Voiding with Real-Time MRI and Computational Fluid Dynamics

PONE-D-20-10274R2

Dear Dr. Roldán-Alzate,

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.

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Kind regards,

Robert Evan Hurst, PhD

Academic Editor

PLOS ONE

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