Title: Evaluating the diagnostic significance of the R2* value on 3.0T MRI for assessing the
severity of warm hepatic ischemia-reperfusion injury
Version: 1 Date: 12 Mar 2025
Reviewer:  Ivan A. Ryzhkov
Reviewer's report:
The manuscript by Xu S. et al. describes an experimental animal study designed to assess
the diagnostic utility of the R2* parameter derived from BOLD MRI for the non-invasive
detection of liver ischemia-reperfusion injury of varying severity. To achieve this goal, the
authors used a robust, well-validated experimental model of warm hepatic ischemia-reperfusion
injury (WHIRI). Several biochemical markers (serum and tissue) and histological examination
of the liver were used to confirm ischaemia-reperfusion liver injury after ischaemia of varying
duration (from 10 to 40 minutes). This is undoubtedly a strong point of the study.
The revisions made to the manuscript after the first round of peer review have significantly
improved its quality. The paper is technically sound and well structured. The study results are
appropriately discussed in the context of previous literature.
However, several issues arose during the review process that require clarification. I present them
below, along with suggestions for improving the presentation of the results.
Major issue:
1) The conclusion formulated at the end of the Discussion is very general and does not answer
the question of the purpose of the study (the diagnostic utility of R2* values on BOLD MRI for
the early detection and assessment of hepatic WHIRI). In my opinion, the results presented in
Table 4 and in the section "Diagnostic efficacy of R2* values for WHIRI" (lines 223-228) are
the most important in terms of novelty and impact of the study.
In this regard, I propose to take the Conclusion of the Abstract as a basis and expand it by
providing key findings on the sensitivity and specificity of the studied parameter in the diagnosis
of WHIRI of varying severity.
Minor issues:
1) Despite the corrections made earlier, the information regarding the anesthesia of the animals
needs to be clarified:
Lines 98-99 “… the rabbits received intravenous anesthesia with 5% pentobarbital at a dose of
1 ml/kg via the marginal ear vein.”
Lines 114-115 “The rabbits continued to receive intravenous anesthesia with 5% pentobarbital
at a dose of 1 ml/kg via the marginal ear vein for euthanasia.”
Lines 124-125 “MRI scans were performed … 6 h after surgery. The animals received
intramuscular anesthesia with Lumianning…”
It appears that repeated injections of pentobarbital after surgery were used not only for
subsequent euthanasia at the end of the experiment, but also to maintain general anesthesia for
6 hours prior to MRI. If so, were there any serious anesthetic complications or mortality among
the animals?
2) Lines 180-181 “A correlation coefficient (r)>0.5 was considered statistically significant…”
The size of the correlation coefficient (r) usually determines the strength of the relationship
between variables (weak, moderate, strong), and not statistical significance.
3) Lines 284-285 “Despite the promising findings, our study had limitations.”
This is a repetition (already stated in line 279)
4) Figure 2. Apparently, the data (box plots) are presented as medians, quartiles and Max/Min
values. If so, this should be indicated in a note or figure legend, since the Materials and Methods
section states “Measurements are expressed as the mean ± standard deviation” (lines 169-170). It
is also unclear to which comparison the p-value in the figure footnote refers (line 428, P=0.000).
5) Figure 3. There may be a typo in the caption for section E (40 minutes?).
The manuscript is recommended for publication after minor revisions.
Title: Evaluating the diagnostic significance of the R2* value on 3.0T MRI for assessing the
severity of warm hepatic ischemia-reperfusion injury
Version: 1 Date: 12 Mar 2025
Reviewer:  Ivan A. Ryzhkov
Reviewer's report:
The manuscript by Xu S. et al. describes an experimental animal study designed to assess
the diagnostic utility of the R2* parameter derived from BOLD MRI for the non-invasive
detection of liver ischemia-reperfusion injury of varying severity. To achieve this goal, the
authors used a robust, well-validated experimental model of warm hepatic ischemia-reperfusion
injury (WHIRI). Several biochemical markers (serum and tissue) and histological examination
of the liver were used to confirm ischaemia-reperfusion liver injury after ischaemia of varying
duration (from 10 to 40 minutes). This is undoubtedly a strong point of the study.
The revisions made to the manuscript after the first round of peer review have significantly
improved its quality. The paper is technically sound and well structured. The study results are
appropriately discussed in the context of previous literature.
However, several issues arose during the review process that require clarification. I present them
below, along with suggestions for improving the presentation of the results.
Major issue:
1) The conclusion formulated at the end of the Discussion is very general and does not answer
the question of the purpose of the study (the diagnostic utility of R2* values on BOLD MRI for
the early detection and assessment of hepatic WHIRI). In my opinion, the results presented in
Table 4 and in the section "Diagnostic efficacy of R2* values for WHIRI" (lines 223-228) are
the most important in terms of novelty and impact of the study.
In this regard, I propose to take the Conclusion of the Abstract as a basis and expand it by
providing key findings on the sensitivity and specificity of the studied parameter in the diagnosis
of WHIRI of varying severity.
Minor issues:
1) Despite the corrections made earlier, the information regarding the anesthesia of the animals
needs to be clarified:
Lines 98-99 “… the rabbits received intravenous anesthesia with 5% pentobarbital at a dose of
1 ml/kg via the marginal ear vein.”
Lines 114-115 “The rabbits continued to receive intravenous anesthesia with 5% pentobarbital
at a dose of 1 ml/kg via the marginal ear vein for euthanasia.”
Lines 124-125 “MRI scans were performed … 6 h after surgery. The animals received
intramuscular anesthesia with Lumianning…”
It appears that repeated injections of pentobarbital after surgery were used not only for
subsequent euthanasia at the end of the experiment, but also to maintain general anesthesia for
6 hours prior to MRI. If so, were there any serious anesthetic complications or mortality among
the animals?
2) Lines 180-181 “A correlation coefficient (r)>0.5 was considered statistically significant…”
The size of the correlation coefficient (r) usually determines the strength of the relationship
between variables (weak, moderate, strong), and not statistical significance.
3) Lines 284-285 “Despite the promising findings, our study had limitations.”
This is a repetition (already stated in line 279)
4) Figure 2. Apparently, the data (box plots) are presented as medians, quartiles and Max/Min
values. If so, this should be indicated in a note or figure legend, since the Materials and Methods
section states “Measurements are expressed as the mean ± standard deviation” (lines 169-170). It
is also unclear to which comparison the p-value in the figure footnote refers (line 428, P=0.000).
5) Figure 3. There may be a typo in the caption for section E (40 minutes?).
The manuscript is recommended for publication after minor revisions.
Please review this paper.
user
Title: Evaluating the diagnostic significance of the R2* value on 3.0T MRI for assessing the
severity of warm hepatic ischemia-reperfusion injury
Version: 1 Date: 12 Mar 2025
Reviewer:  Ivan A. Ryzhkov
Reviewer's report:
The manuscript by Xu S. et al. describes an experimental animal study designed to assess
the diagnostic utility of the R2* parameter derived from BOLD MRI for the non-invasive
detection of liver ischemia-reperfusion injury of varying severity. To achieve this goal, the
authors used a robust, well-validated experimental model of warm hepatic ischemia-reperfusion
injury (WHIRI). Several biochemical markers (serum and tissue) and histological examination
of the liver were used to confirm ischaemia-reperfusion liver injury after ischaemia of varying
duration (from 10 to 40 minutes). This is undoubtedly a strong point of the study.
The revisions made to the manuscript after the first round of peer review have significantly
improved its quality. The paper is technically sound and well structured. The study results are
appropriately discussed in the context of previous literature.
However, several issues arose during the review process that require clarification. I present them
below, along with suggestions for improving the presentation of the results.
Major issue:
1) The conclusion formulated at the end of the Discussion is very general and does not answer
the question of the purpose of the study (the diagnostic utility of R2* values on BOLD MRI for
the early detection and assessment of hepatic WHIRI). In my opinion, the results presented in
Table 4 and in the section "Diagnostic efficacy of R2* values for WHIRI" (lines 223-228) are
the most important in terms of novelty and impact of the study.
In this regard, I propose to take the Conclusion of the Abstract as a basis and expand it by
providing key findings on the sensitivity and specificity of the studied parameter in the diagnosis
of WHIRI of varying severity.
Minor issues:
1) Despite the corrections made earlier, the information regarding the anesthesia of the animals
needs to be clarified:
Lines 98-99 “… the rabbits received intravenous anesthesia with 5% pentobarbital at a dose of
1 ml/kg via the marginal ear vein.”
Lines 114-115 “The rabbits continued to receive intravenous anesthesia with 5% pentobarbital
at a dose of 1 ml/kg via the marginal ear vein for euthanasia.”
Lines 124-125 “MRI scans were performed … 6 h after surgery. The animals received
intramuscular anesthesia with Lumianning…”
It appears that repeated injections of pentobarbital after surgery were used not only for
subsequent euthanasia at the end of the experiment, but also to maintain general anesthesia for
6 hours prior to MRI. If so, were there any serious anesthetic complications or mortality among
the animals?
2) Lines 180-181 “A correlation coefficient (r)>0.5 was considered statistically significant…”
The size of the correlation coefficient (r) usually determines the strength of the relationship
between variables (weak, moderate, strong), and not statistical significance.
3) Lines 284-285 “Despite the promising findings, our study had limitations.”
This is a repetition (already stated in line 279)
4) Figure 2. Apparently, the data (box plots) are presented as medians, quartiles and Max/Min
values. If so, this should be indicated in a note or figure legend, since the Materials and Methods
section states “Measurements are expressed as the mean ± standard deviation” (lines 169-170). It
is also unclear to which comparison the p-value in the figure footnote refers (line 428, P=0.000).
5) Figure 3. There may be a typo in the caption for section E (40 minutes?).
The manuscript is recommended for publication after minor revisions.
assistant