Reviewer ’s report  
 
Title: Liver injury monitoring, fibrosis staging and inflammati on grading using T1rho magnetic 
resonance imaging: An experimental study in rats with carbon tetrachloride intoxication  
 
Version: 2 Date: 25 Sep 2019  
 
Reviewer: Xiaolin Wang  
 
Reviewer's report:  
 
Shuangshuang Xie et al performed an interestin g study to evaluate the merit of T1rho MRI for 
monitoring CCl4 - induced liver injury in rat model. It comes to the conclusion that inflammation 
activity had a greater impact on liver T1rho values than fibrosis. There were some concerns, 
which need to be ad dressed:  
 
1. It showed that liver T1rho values of rats with same inflammation grades showed no 
difference among different fibrosis stages, and only T1rho values of different 
inflammation grades with fibrosis stage 3 had significant difference. Can you pleas e 
show the values of T1rho of different inflammation grades with fibrosis stage 3?  
 
2. As the authors mentioned in the manuscript, a rat model of liver fibrosis may not reflect 
the pathologic changes of the human liver accurately. The authors should discuss  more 
about the merit of T1rho MRI in clinical detection or diagnosis of liver disease according 
to the published literatures and also the new findings in this paper.  
 
3. The authors investigated the impact of liver fibrosis and inflammation on liver T1rho 
values by using CCl4 - induced liver injury in rats. Can T1rho be used as a non -invasive 
imaging technique for evaluating liver fibrosis of inflammation? Can you determine the 
diagnostic accuracy of T1rho for significant fibrosis or inflammation by using RO C 
(receive operating curve) analysis?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additio nal statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptab le 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this  manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied f or patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the a uthors and, if the manuscript is accepted f or publication, my  named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Reviewer ’s report  
 
Title: Liver injury monitoring, fibrosis staging and inflammati on grading using T1rho magnetic 
resonance imaging: An experimental study in rats with carbon tetrachloride intoxication  
 
Version: 2 Date: 25 Sep 2019  
 
Reviewer: Xiaolin Wang  
 
Reviewer's report:  
 
Shuangshuang Xie et al performed an interestin g study to evaluate the merit of T1rho MRI for 
monitoring CCl4 - induced liver injury in rat model. It comes to the conclusion that inflammation 
activity had a greater impact on liver T1rho values than fibrosis. There were some concerns, 
which need to be ad dressed:  
 
1. It showed that liver T1rho values of rats with same inflammation grades showed no 
difference among different fibrosis stages, and only T1rho values of different 
inflammation grades with fibrosis stage 3 had significant difference. Can you pleas e 
show the values of T1rho of different inflammation grades with fibrosis stage 3?  
 
2. As the authors mentioned in the manuscript, a rat model of liver fibrosis may not reflect 
the pathologic changes of the human liver accurately. The authors should discuss  more 
about the merit of T1rho MRI in clinical detection or diagnosis of liver disease according 
to the published literatures and also the new findings in this paper.  
 
3. The authors investigated the impact of liver fibrosis and inflammation on liver T1rho 
values by using CCl4 - induced liver injury in rats. Can T1rho be used as a non -invasive 
imaging technique for evaluating liver fibrosis of inflammation? Can you determine the 
diagnostic accuracy of T1rho for significant fibrosis or inflammation by using RO C 
(receive operating curve) analysis?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additio nal statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptab le 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this  manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied f or patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the a uthors and, if the manuscript is accepted f or publication, my  named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Liver injury monitoring, fibrosis staging and inflammati on grading using T1rho magnetic 
resonance imaging: An experimental study in rats with carbon tetrachloride intoxication  
 
Version: 2 Date: 25 Sep 2019  
 
Reviewer: Xiaolin Wang  
 
Reviewer's report:  
 
Shuangshuang Xie et al performed an interestin g study to evaluate the merit of T1rho MRI for 
monitoring CCl4 - induced liver injury in rat model. It comes to the conclusion that inflammation 
activity had a greater impact on liver T1rho values than fibrosis. There were some concerns, 
which need to be ad dressed:  
 
1. It showed that liver T1rho values of rats with same inflammation grades showed no 
difference among different fibrosis stages, and only T1rho values of different 
inflammation grades with fibrosis stage 3 had significant difference. Can you pleas e 
show the values of T1rho of different inflammation grades with fibrosis stage 3?  
 
2. As the authors mentioned in the manuscript, a rat model of liver fibrosis may not reflect 
the pathologic changes of the human liver accurately. The authors should discuss  more 
about the merit of T1rho MRI in clinical detection or diagnosis of liver disease according 
to the published literatures and also the new findings in this paper.  
 
3. The authors investigated the impact of liver fibrosis and inflammation on liver T1rho 
values by using CCl4 - induced liver injury in rats. Can T1rho be used as a non -invasive 
imaging technique for evaluating liver fibrosis of inflammation? Can you determine the 
diagnostic accuracy of T1rho for significant fibrosis or inflammation by using RO C 
(receive operating curve) analysis?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additio nal statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptab le 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this  manuscript, either now or in the 
future?  
 
3.  Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied f or patents relating to the content of the manuscript?  
 
5.  Do you have any other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the a uthors and, if the manuscript is accepted f or publication, my  named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
assistant