Review for 10.1186/s12876-025-03701-9 (2025)

Title: T1/T2 mapping as a non-invasive method for evaluating liver fibrosis based on
correlation of biomarkers: a preclinical study
Version: 3 Date: 25 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the use of T1 and T2 mapping sequences is explained, the actual MRI pulse sequence
parameters are only mentioned briefly in a supplementary file. For the sake of clarity and
reproducibility, it would be beneficial to include a summary of the key sequence parameters
(e.g., repetition time (TR), echo time (TE), inversion times, etc.) directly in the main text.
-The description of the T1 mapping technique using the Messroghli equation and the nonlinear
fitting algorithm is good, but providing a few more specifics on the fitting process and how this
is handled in terms of potential errors or confounding factors could be helpful for the technical
audience.
-While the use of CCl4-induced fibrosis is well-established, there could be a brief mention of the
limitations of this model. For example, how closely does CCl4-induced fibrosis mimic human
liver fibrosis in terms of inflammation patterns, fibrosis distribution, or progression speed?
Acknowledging these potential limitations would provide nuance and transparency, especially
if these results are to be translated into clinical settings.
-The model's relevance to human liver fibrosis in varying stages (e.g., early vs. advanced
fibrosis) could be expanded upon. Does this model replicate the early stages of fibrosis as seen
in humans, or is it skewed more toward later-stage disease?
-While the use of HYP content for quantifying collagen deposition is appropriate, it might
be helpful to briefly justify why this specific biomarker was selected over other potential
markers of fibrosis. For instance, could other markers (e.g., collagen type I, TIMP-1) provide
complementary information or would they complicate the analysis? A brief mention of this
would give more insight into the rationale behind biomarker selection.
-The inflammatory cytokines (IL-1, IL-6, TNF-#) are important, but the link between these
biomarkers and fibrosis progression could be explored further. Are there particular stages of
fibrosis where these markers are expected to peak, and how does this influence the interpretation
of the MRI data?
-While the animal protocols are clear, there could be additional details on how the mice were
randomized into groups, especially in terms of the timing of MRI scans and histopathological
analysis. How were the three-time points selected, and was there a rationale behind choosing the
2-week interval? The methodology should ideally provide a clear rationale for all experimental
timelines.
-Discuss the lack of significant difference (P > 0.05) in more detail, considering potential factors
such as sample size, disease stage, or model limitations that may have contributed to the result.
A more in-depth explanation would enhance the reader's understanding of this point.
-Expand the discussion on the limitations of the CCl4 model and its relevance to human liver
fibrosis. Address the potential biases introduced by this model and consider discussing how
findings may differ in other models of liver disease.
-Provide more detailed mechanistic insights into how T1/T2 values correlate with HYP content
and inflammatory markers. For example, what specific features of the inflammatory response
influence T2 values, and how might these change across fibrosis stages?