Title: Multi-parametric Magnetic Resonance Imaging of Liver Regeneration in a Standardized
Partial Hepatectomy Rat Model
Version: 1 Date: 15 Jun 2022
Reviewer's report:
Caixin Qiu and collaborators evaluate the role of „Multi-parametric Magnetic Resonance
Imaging of Liver Regeneration in a Standardized Partial Hepatectomy Rat Model”. This is
an important study further establishing the role of small animal imaging techniques on liver
regeneration. However, several experimental aspects raise concerns.
Major issues:
1.       Lack of novelty. The main findings of the study were the following: “PH induced liver
changes that can be observed on MRI.” However, there are numerous preclinical researches,
which proved that micro-MRI is a suitable method to follow liver regeneration after various
surgical interventions (PH, PVL, ALPPS, etc).
2.       Ki67 index showed that the mitotic activity of hepatocytes reached the peak on
postoperative day 2 in the present study. According to literature data the peak of cell division
is somewhat earlier (24-30hour). Therefore, it is a need to validate the animal model used in
the current experiments and assess the possibility that technical elements accounted for this
deviation from literature results.
3.       In the pathological analysis groups the author did not measure the weight (or volume)
of the liver. By these measurements the validation of the model would be possible. In addition
these data could be compared with the volumetric alterations measured by MRI (giving some
additional information of the reliability of the used methods).
4.       The authors speculated that the significant increase in T2 values after PH results from
an increase in fat and water content of the residual liver. However, these alterations were not
analyzed completely in the pathological group. The wet, and dry weight of the liver lobes
were not measured. The wet/dry ratio of the liver was not calculated (edema formation). In
addition, to measure the fat content of the hepatocyte the authors used a simple semiquantitative
score on H&E slides. There is no information about the type/location of steatosis (macro-, or
microsteatotis/periportal, centrolobular), and the authors did not use special staining (e.g. Oil
red O).
5.       “The D value of tissues is affected by cell perimeter length, cell density, size, and
permeability, and a study showed that the cell perimeter length is the most important factor.
[…] K values are a measure of the complexity and heterogeneity of the cell microenvironment.”
However, the author did not analyze the micro-architectural alterations in regenerating liver
lobes, only measured the size of the hepatocyte on H&E stained slides (not reliable). By
immunohistochemical staining for cytokeratins - outline the cell membranes of the hepatocytes
– the determination is cell area and surface is more accurate. In addition, architectural changes of
the liver lobules and the alterations in connective tissue content could have also been evaluated.
This manuscript is not suitable for publication in the present form.
Title: Multi-parametric Magnetic Resonance Imaging of Liver Regeneration in a Standardized
Partial Hepatectomy Rat Model
Version: 1 Date: 15 Jun 2022
Reviewer's report:
Caixin Qiu and collaborators evaluate the role of „Multi-parametric Magnetic Resonance
Imaging of Liver Regeneration in a Standardized Partial Hepatectomy Rat Model”. This is
an important study further establishing the role of small animal imaging techniques on liver
regeneration. However, several experimental aspects raise concerns.
Major issues:
1.       Lack of novelty. The main findings of the study were the following: “PH induced liver
changes that can be observed on MRI.” However, there are numerous preclinical researches,
which proved that micro-MRI is a suitable method to follow liver regeneration after various
surgical interventions (PH, PVL, ALPPS, etc).
2.       Ki67 index showed that the mitotic activity of hepatocytes reached the peak on
postoperative day 2 in the present study. According to literature data the peak of cell division
is somewhat earlier (24-30hour). Therefore, it is a need to validate the animal model used in
the current experiments and assess the possibility that technical elements accounted for this
deviation from literature results.
3.       In the pathological analysis groups the author did not measure the weight (or volume)
of the liver. By these measurements the validation of the model would be possible. In addition
these data could be compared with the volumetric alterations measured by MRI (giving some
additional information of the reliability of the used methods).
4.       The authors speculated that the significant increase in T2 values after PH results from
an increase in fat and water content of the residual liver. However, these alterations were not
analyzed completely in the pathological group. The wet, and dry weight of the liver lobes
were not measured. The wet/dry ratio of the liver was not calculated (edema formation). In
addition, to measure the fat content of the hepatocyte the authors used a simple semiquantitative
score on H&E slides. There is no information about the type/location of steatosis (macro-, or
microsteatotis/periportal, centrolobular), and the authors did not use special staining (e.g. Oil
red O).
5.       “The D value of tissues is affected by cell perimeter length, cell density, size, and
permeability, and a study showed that the cell perimeter length is the most important factor.
[…] K values are a measure of the complexity and heterogeneity of the cell microenvironment.”
However, the author did not analyze the micro-architectural alterations in regenerating liver
lobes, only measured the size of the hepatocyte on H&E stained slides (not reliable). By
immunohistochemical staining for cytokeratins - outline the cell membranes of the hepatocytes
– the determination is cell area and surface is more accurate. In addition, architectural changes of
the liver lobules and the alterations in connective tissue content could have also been evaluated.
This manuscript is not suitable for publication in the present form.
Please review this paper.
user
Title: Multi-parametric Magnetic Resonance Imaging of Liver Regeneration in a Standardized
Partial Hepatectomy Rat Model
Version: 1 Date: 15 Jun 2022
Reviewer's report:
Caixin Qiu and collaborators evaluate the role of „Multi-parametric Magnetic Resonance
Imaging of Liver Regeneration in a Standardized Partial Hepatectomy Rat Model”. This is
an important study further establishing the role of small animal imaging techniques on liver
regeneration. However, several experimental aspects raise concerns.
Major issues:
1.       Lack of novelty. The main findings of the study were the following: “PH induced liver
changes that can be observed on MRI.” However, there are numerous preclinical researches,
which proved that micro-MRI is a suitable method to follow liver regeneration after various
surgical interventions (PH, PVL, ALPPS, etc).
2.       Ki67 index showed that the mitotic activity of hepatocytes reached the peak on
postoperative day 2 in the present study. According to literature data the peak of cell division
is somewhat earlier (24-30hour). Therefore, it is a need to validate the animal model used in
the current experiments and assess the possibility that technical elements accounted for this
deviation from literature results.
3.       In the pathological analysis groups the author did not measure the weight (or volume)
of the liver. By these measurements the validation of the model would be possible. In addition
these data could be compared with the volumetric alterations measured by MRI (giving some
additional information of the reliability of the used methods).
4.       The authors speculated that the significant increase in T2 values after PH results from
an increase in fat and water content of the residual liver. However, these alterations were not
analyzed completely in the pathological group. The wet, and dry weight of the liver lobes
were not measured. The wet/dry ratio of the liver was not calculated (edema formation). In
addition, to measure the fat content of the hepatocyte the authors used a simple semiquantitative
score on H&E slides. There is no information about the type/location of steatosis (macro-, or
microsteatotis/periportal, centrolobular), and the authors did not use special staining (e.g. Oil
red O).
5.       “The D value of tissues is affected by cell perimeter length, cell density, size, and
permeability, and a study showed that the cell perimeter length is the most important factor.
[…] K values are a measure of the complexity and heterogeneity of the cell microenvironment.”
However, the author did not analyze the micro-architectural alterations in regenerating liver
lobes, only measured the size of the hepatocyte on H&E stained slides (not reliable). By
immunohistochemical staining for cytokeratins - outline the cell membranes of the hepatocytes
– the determination is cell area and surface is more accurate. In addition, architectural changes of
the liver lobules and the alterations in connective tissue content could have also been evaluated.
This manuscript is not suitable for publication in the present form.
assistant