Review for 10.1186/s12876-024-03523-1 (2024)

Title: The Diagnostic Value of Dynamic Contrast-Enhanced Ultrasound for Evaluation of
Tissue Oxygen Status in Rat Hepatoma Model
Version: 1 Date: 12 Oct 2024
Reviewer's report:
The present study aimed to explore the contrast-enhanced ultrasound (CEUS) quantitative
parameters for the evaluation of oxygen status in two rat hepatoma models. The authors
concluded that quantitative CEUS parameters correlated with the oxygen status of the tumor,
and they could be utilized to predict the tumor tissue pO2.
Comments
1. Dynamic contrast-enhanced ultrasound (DCE-US) is already clinically used to assess the
microvascular changes in HCC, particularly for monitoring treatment response to systemic and
locoregional therapies like sorafenib, TACE, and immunotherapies. In contrast, the present study
focuses on animal models and does not adequately address the current clinical application of
DCE-US. This creates a gap in the clinical relevance of the study. It should have integrated more
discussions about its potential translational application for human clinical practice, particularly
since DCE-US is used to monitor early treatment responses in HCC patients.
2. DCE-US, which overcomes subjectivity in contrast-enhanced ultrasound (CEUS), is
increasingly used alongside CT and MRI to assess tumor perfusion changes early in treatment.
The present study, however, focuses primarily on CEUS and omits DCE-US, which is
quantitatively more reliable. Since DCE-US is more advanced and has demonstrated earlier
prediction of treatment outcomes, the present study is at a disadvantage by not including a
discussion or comparison of DCE-US as a potential tool for enhancing their findings.
3. DCE-US has been applied in human clinical trials and offers quantifiable results to predict
treatment outcomes in HCC patients. The present study is limited to rat models, and the results
may not reflect the clinical context of human HCC. The authors should have better justified
the relevance of these animal models and discussed the limitations in translating these results
to human patients, where tumor size, vascularization, and response to treatment can differ
significantly.
4. The study lacks longitudinal data, instead it presents a snapshot of hypoxia and perfusion
at one time point. Without monitoring changes in perfusion over time, the study misses an
opportunity to align more closely with clinical practice, where repeated evaluations provide
critical information on treatment efficacy.
5. The study used pO2 polarography to measure tissue oxygenation, a method not as commonly
employed in current clinical practice as imaging modalities like DCE-US and MRI, which can
evaluate perfusion non-invasively. In the clinical context, pO2 polarography has limitations in
spatial resolution and range. The paper does not adequately compare pO2 polarography with
imaging techniques, nor does it address why polarography was chosen over DCE-US, which is
already providing quantitative data on oxygenation changes in clinical settings.
6. The study's key finding is that there is no significant hypoxia in the tumor compared to the
peritumoral liver parenchyma. However, the reason why tumor oxygenation levels were found
to be similar to peritumoral tissue should be better explained. The authors mention that the
tumor was still in its growth stage and necrosis was rare. This should be further explained in the
discussion, as tumor necrosis is usually associated with hypoxia.
7. The Discussion would benefit from a comparison of their findings with the results from early
response assessments in clinical studies, as this would give more weight to their conclusions.
8. While tables are included to present results, graphical representation would help improve the
accessibility and visualization of complex quantitative data.