Title: Diagnostic performances of adding transition and hepatobiliary phase to washout in
gadoxetic acid-enhanced MRI for subcentimeter hepatocellular carcinoma
Version: 5 Date: 16 Apr 2025
Reviewer:  Maxim Avanesov
Reviewer's report:
The manuscript presents a detailed investigation of the diagnostic performance of different MRI-
based WO criteria for biopsy-proven subcentimeter HCC lesions using gadoxetic acid-enhanced
MRI as well as a combination of these WO criteria and AFP in a large cohort of 200 patients
with histologically proven HCC lesions.
The authors aim to evaluate the diagnostic yield of different MRI-based WO criteria to increase
the reliability of detecting small (<1cm) HCC lesions beyond the currently published LI-RADS
criteria.
This touches on a relevant and evolving topic, particularly in the context of personalised HCC
management, structural MRI reporting and advances in imaging biomarkers.
The text is well written, logically structured and comprehensive, and uses histology as the ground
truth for HCC diagnosis, which further enhances the value of the work.
The results are accurately reported and supported by extensive tables and figures.
However, there are some issues that need to be addressed to further improve the quality of the
manuscript and add value to the audience.
1. Based on the result, the authors propose to use WO extended to TP instead of WO limited
to PVP for the diagnosis of subcentimeter HCC lesions. However, these results were based on
consensus reading between two readers. Could additional inter- and intra-observer variabilities
of sensitivity, specificity, PPV, NPV, and accuracy be provided to observe possible differences
between the three WO criteria, which might further strengthen the proposal to apply WO
extending to TP in clinical practice?
2. If AFP measurement improves the sensitivity and accuracy of all WO imaging criteria, could
you  please add a decision tree as a figure suggesting the use of AFP as the primary gatekeeper
before MRI? For example: If AFP is elevated -> WO TP as the best trade-off between sensitivity
and specificity with high PPV and accuracy; If AFP is normal -> WO HBP or PVP, depending
on the diagnostic cut-offs used .  As a conclusion for clinical implementation, I would make a
concrete suggestion for MRI analysis.
3. What about centres that do not perform a TP sequence because it reduces scanning time and
is not included in the LI-RADS criteria for the diagnosis of HCC? Do the authors think it is
appropriate to skip the TP phase to shorten the scan time and use only WO HBP despite the
significantly reduced specificity, e.g. more false-positive cases?
4. For clinical purposes, comparing PPV, NPV and accuracy is often more valuable than
comparing sensitivity and specificity. Could you please include these statistical comparisons of
PPV, NPV and accuracy in the results?
5. Figure 2/3: Can you provide the signal intensities within the small lesions within each contrast
phase to further highlight the signal drop between different contrast phases? Due to the small
size of the lesions, it is sometimes difficult to visually distinguish between the portal venous
phase and the transitional phase. I suggest writing the name of the sequence directly on the
corresponding images, as some images look very similar.
6. Page 18/19: "Furthermore, the sensitivity of WO extended to HBP was significantly higher
than that of WO extended to TP, suggesting that the inclusion of HBP in the definition of WO
may provide valuable information for the detection of HCC at a very early stage and improve
the accuracy of MR staging". Why don't you directly compare the accuracy of WO extended to
TP and WO extended to HBP?  Can you explain why the sensitivity of WO extended to HBP
was significantly higher compared to WO extended to TP, while the specificity was significantly
lower and the PPV, NPV and accuracies were comparable?
Title: Diagnostic performances of adding transition and hepatobiliary phase to washout in
gadoxetic acid-enhanced MRI for subcentimeter hepatocellular carcinoma
Version: 5 Date: 16 Apr 2025
Reviewer:  Maxim Avanesov
Reviewer's report:
The manuscript presents a detailed investigation of the diagnostic performance of different MRI-
based WO criteria for biopsy-proven subcentimeter HCC lesions using gadoxetic acid-enhanced
MRI as well as a combination of these WO criteria and AFP in a large cohort of 200 patients
with histologically proven HCC lesions.
The authors aim to evaluate the diagnostic yield of different MRI-based WO criteria to increase
the reliability of detecting small (<1cm) HCC lesions beyond the currently published LI-RADS
criteria.
This touches on a relevant and evolving topic, particularly in the context of personalised HCC
management, structural MRI reporting and advances in imaging biomarkers.
The text is well written, logically structured and comprehensive, and uses histology as the ground
truth for HCC diagnosis, which further enhances the value of the work.
The results are accurately reported and supported by extensive tables and figures.
However, there are some issues that need to be addressed to further improve the quality of the
manuscript and add value to the audience.
1. Based on the result, the authors propose to use WO extended to TP instead of WO limited
to PVP for the diagnosis of subcentimeter HCC lesions. However, these results were based on
consensus reading between two readers. Could additional inter- and intra-observer variabilities
of sensitivity, specificity, PPV, NPV, and accuracy be provided to observe possible differences
between the three WO criteria, which might further strengthen the proposal to apply WO
extending to TP in clinical practice?
2. If AFP measurement improves the sensitivity and accuracy of all WO imaging criteria, could
you  please add a decision tree as a figure suggesting the use of AFP as the primary gatekeeper
before MRI? For example: If AFP is elevated -> WO TP as the best trade-off between sensitivity
and specificity with high PPV and accuracy; If AFP is normal -> WO HBP or PVP, depending
on the diagnostic cut-offs used .  As a conclusion for clinical implementation, I would make a
concrete suggestion for MRI analysis.
3. What about centres that do not perform a TP sequence because it reduces scanning time and
is not included in the LI-RADS criteria for the diagnosis of HCC? Do the authors think it is
appropriate to skip the TP phase to shorten the scan time and use only WO HBP despite the
significantly reduced specificity, e.g. more false-positive cases?
4. For clinical purposes, comparing PPV, NPV and accuracy is often more valuable than
comparing sensitivity and specificity. Could you please include these statistical comparisons of
PPV, NPV and accuracy in the results?
5. Figure 2/3: Can you provide the signal intensities within the small lesions within each contrast
phase to further highlight the signal drop between different contrast phases? Due to the small
size of the lesions, it is sometimes difficult to visually distinguish between the portal venous
phase and the transitional phase. I suggest writing the name of the sequence directly on the
corresponding images, as some images look very similar.
6. Page 18/19: "Furthermore, the sensitivity of WO extended to HBP was significantly higher
than that of WO extended to TP, suggesting that the inclusion of HBP in the definition of WO
may provide valuable information for the detection of HCC at a very early stage and improve
the accuracy of MR staging". Why don't you directly compare the accuracy of WO extended to
TP and WO extended to HBP?  Can you explain why the sensitivity of WO extended to HBP
was significantly higher compared to WO extended to TP, while the specificity was significantly
lower and the PPV, NPV and accuracies were comparable?
Please review this paper.
user
Title: Diagnostic performances of adding transition and hepatobiliary phase to washout in
gadoxetic acid-enhanced MRI for subcentimeter hepatocellular carcinoma
Version: 5 Date: 16 Apr 2025
Reviewer:  Maxim Avanesov
Reviewer's report:
The manuscript presents a detailed investigation of the diagnostic performance of different MRI-
based WO criteria for biopsy-proven subcentimeter HCC lesions using gadoxetic acid-enhanced
MRI as well as a combination of these WO criteria and AFP in a large cohort of 200 patients
with histologically proven HCC lesions.
The authors aim to evaluate the diagnostic yield of different MRI-based WO criteria to increase
the reliability of detecting small (<1cm) HCC lesions beyond the currently published LI-RADS
criteria.
This touches on a relevant and evolving topic, particularly in the context of personalised HCC
management, structural MRI reporting and advances in imaging biomarkers.
The text is well written, logically structured and comprehensive, and uses histology as the ground
truth for HCC diagnosis, which further enhances the value of the work.
The results are accurately reported and supported by extensive tables and figures.
However, there are some issues that need to be addressed to further improve the quality of the
manuscript and add value to the audience.
1. Based on the result, the authors propose to use WO extended to TP instead of WO limited
to PVP for the diagnosis of subcentimeter HCC lesions. However, these results were based on
consensus reading between two readers. Could additional inter- and intra-observer variabilities
of sensitivity, specificity, PPV, NPV, and accuracy be provided to observe possible differences
between the three WO criteria, which might further strengthen the proposal to apply WO
extending to TP in clinical practice?
2. If AFP measurement improves the sensitivity and accuracy of all WO imaging criteria, could
you  please add a decision tree as a figure suggesting the use of AFP as the primary gatekeeper
before MRI? For example: If AFP is elevated -> WO TP as the best trade-off between sensitivity
and specificity with high PPV and accuracy; If AFP is normal -> WO HBP or PVP, depending
on the diagnostic cut-offs used .  As a conclusion for clinical implementation, I would make a
concrete suggestion for MRI analysis.
3. What about centres that do not perform a TP sequence because it reduces scanning time and
is not included in the LI-RADS criteria for the diagnosis of HCC? Do the authors think it is
appropriate to skip the TP phase to shorten the scan time and use only WO HBP despite the
significantly reduced specificity, e.g. more false-positive cases?
4. For clinical purposes, comparing PPV, NPV and accuracy is often more valuable than
comparing sensitivity and specificity. Could you please include these statistical comparisons of
PPV, NPV and accuracy in the results?
5. Figure 2/3: Can you provide the signal intensities within the small lesions within each contrast
phase to further highlight the signal drop between different contrast phases? Due to the small
size of the lesions, it is sometimes difficult to visually distinguish between the portal venous
phase and the transitional phase. I suggest writing the name of the sequence directly on the
corresponding images, as some images look very similar.
6. Page 18/19: "Furthermore, the sensitivity of WO extended to HBP was significantly higher
than that of WO extended to TP, suggesting that the inclusion of HBP in the definition of WO
may provide valuable information for the detection of HCC at a very early stage and improve
the accuracy of MR staging". Why don't you directly compare the accuracy of WO extended to
TP and WO extended to HBP?  Can you explain why the sensitivity of WO extended to HBP
was significantly higher compared to WO extended to TP, while the specificity was significantly
lower and the PPV, NPV and accuracies were comparable?
assistant