PONE-D-21-07115

Development of a Standardized MRI Protocol for Pancreas Assessment in Humans

PLOS ONE

Dear Dr. Virostko,

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Mingwu Jin, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

The manuscript represents an important and well-organized work for standardizing the MRI protocol for pancreas assessment. Addressing the issues raised by the reviewers could further strengthen its impact.

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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: The authors proposed a non-contrast quantitative MR imaging protocol for pancreas, including DWI, T1, MTR and PDFF (liver & pancreas). The purpose of this protocol is to provide quantitative matrix for diagnosing and monitoring pancreatic abnormalities caused by chronic or acute pancreatitis, NAFLD, diabetes, and pancreatic cancer. Since obesity and NAFLD are risk factors in the development of diabetes, evaluation of adipose tissue and the liver would strengthen this protocol. In the quantitative imaging field, MRE is also an important method to detect tissue abnormalities (inflammation and fibrosis) via mechanical response against applied vibration. It has been well-established that liver stiffness can be a reliable alternative to biopsy for assessing hepatic fibrosis and providing prognostic value as well. There are many publications about pancreatic MRE from Dr. Yu Shi in this field. The author could make a complete imaging characterization by adding this imaging method.

1. Methods: what’s the time range for phantom scan between locations? According to Ref 23, there was little change in a longitudinal study of 25days for the ice water phantom, but no mention of longer time. In Ref 24, they used 5% and 10% BSA, no mention of 15%, or any dynamic changes. Will the reference value change during time? If not, any other reference?

2. Methods: how big are the ROIs for calculating fat fraction, pancreas and liver, respectively? And where are the ROIs located, since the fat fraction varies much between locations.

3. Results: the hepatic fat fraction of Volunteers 5, is over 5%, which is diagnosed as fatty liver. In that case, it might influence the measurements of pancreas.

4. Discussion: the measurements of fat fraction are all missing in Denver, is there any reason?

5. Figure 1: the figure and descriptions in manuscript should be consistent. eg, in the manuscript Methods_Phantom Studies, it was described as T1, MTR, and fat fraction, in the figure it showed “T1/MTR/Fat” in the top row , but the bottom row indicate Canola oil, BSA, and Gadolinium, which are used for fat fraction, MTR, and T1, respectively. Besides, it is also really confusing with three same color pattern and no unit or label at all.

6. Figure 4A, please indicate all the measurements, it is difficult to tell changes from the color.

Reviewer #2: This manuscript presents a standardized MRI protocol for pancreas assessment in humans and define the reproducibility of all kind of measurements, such as pancreas size, shape, ADC, T1 relaxation time, MTR and fat fractions. These quantitative MRI matrixes of the pancreas were performed at multiple sites. Physics phantoms were constructed for protocol standardization including pancreas volume, ADC, T1, MTR, and fat fractions. Also, the same 5 healthy volunteers with no known pancreas pathology or diabetes traveled to multiple sites to standardize the protocols. In addition to these scanning technique standardizations, images of the phantoms and human volunteers were analyzed using the same methodology. The reproducibility was quantified for phantoms across different MRI scanners and for healthy volunteers across four MRI scanners. These techniques are very helpful for standardize the protocols. The authors provided very meaningful data to support the conclusions. The manuscripts were written and structured very well. Because the choice of protocol standardization in multiple vendors and different locations impacts image quality in pancreas MRI studies, this study is a useful topic for radiologists and clinicians to know about. Overall, a very comprehensive pancreas MRI protocol optimizing study that has the potential to serve as a good reference/resource for the readers. There are some concerns listed below:

1. In MRI Scanning Protocol section, list in a table of scanner vendors, model and software version will be helpful for understanding the results.

2. In Table 1, can it include the bandwidth? b vectors for DWI? Regarding to T1 mapping, what does “5 acquisitions: 5 flip angles”? 5 series?

3. In table 2, it seems the quantitative T1 values in via ,2,3,4 in Melbourne is lower than these in other sites? Is it the system bias?

4. Could you please comment on that if we can normalize the data with standardized phantom data for the quantitative measurements in humans/individuals?

5. How many radiologists were involved in for outlining pancreas volume? Were the same radiologists involved in doing the same work for all sites’ studies? If not, any bias?

6. More volunteer’s data will be better.

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Reviewer #1: No

Reviewer #2: No

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Development of a Standardized MRI Protocol for Pancreas Assessment in Humans

PONE-D-21-07115R1

Dear Dr. Virostko,

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,

Mingwu Jin, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Please improve Fig. 1 and Fig. 4 suggested by Reviewer 1 for the final version.

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: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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: (No Response)

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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: (No Response)

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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: Figure 1, numbers along the colorbar are too small to read. Please try less labels and large font size

Figure 4, a color scale without unit for both T1 and ADC does not help. Please make horizontal one for each modality.

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