Title: Ultrasonographic scores for ileal Crohn’s disease assessment: better, worse or the same
as contrast-enhanced ultrasound?
Version: 1 Date: 28 Jan 2022
Reviewer's report:
Intestinal ultrasound has an increasing impact on the management of Crohn´s disease as a non-
invasive imaging modality to guide patients´ treatment.
In contrast to ileocolonoscopy that solely evaluated mucosal inflammatory activity of CD,
ultrasound imaging be it B-Mode imaging or CEUS, is more a cross sectional imaging that
evaluates “transmural activity”.  This may contribute to a more comprehensive evaluation of
intestinal inflammatory load.
In their manuscript, the authors evaluate two different ultrasound activity scores (SUS-CD and
IBUS-SAS) and CEUS peak intensity in relation to different disease parameters, e.g., endoscopic
inflammatory activity, Calprotectin- or CRP-levels.
In their findings, peak intensity in CEUS correlates to endoscopic and clinical activity, but
not to biochemistry activity. They calculate a “cut-off peak intensity” for their correlations.
This number is irrelevant and doesn´t help anybody: it can´t be transferred to other machines/
investigations/investigators because this is an machine- and investigator-individual parameter .
In addition, SUS-SD and IBUS-SAS had a poor correlation to endoscopic and no correlation to
biochemistry disease activity in their study.
Inflammatory activity evaluated in ileocolonosopy does not correspond necessarily to disease
activity and should not be clearly distinguished by an adequate and uniformly uses expression
from overall disease activity. Therefore, the authors should use a consistent  nomenclature
through their whole manuscript, e.g. inflammatory endoscopic  activity (e.g. refer to table 5 “CD
inflammatory activity”) when referring to endoscopic scores/SES-CD.
Because this is a retrospective study, the expression “predict”  e.g., in conclusion of the abstract,
is not adequate. Please use other expressions like “correlate/relate/etc.”.
In the material and method section, there are several questions for the reviewer:
Major:
Could the authors comment on the issue if the ultrasound operator was blinded to the results
of the ileocolonoscopy?
The authors describe that ileocolonoscopy and ultrasound have been done up to one month apart
and they point out that there haven´t be any changes in therapy in this relatively long period
between the two examinations. This doesn´t sound realistic. The authors should comment on
this issue
Minor
Specification of the built-in software of the ultrasound machine is lacking.
SUS-SD had a poor correlation to predict endoscopic activity in contrast to the validation cohort
in the publication that introduce the SUS-SD The authors may discuss this point.
In the context that the authors pointed out that there is a need for studies on the role of CEUS in
active CD detection that would help in introducing the method into everyday practice, it seems to
be contractionary that one sentence earlier, they call for routine integration of CEUS in CD. The
authors should solve this contradiction. In this contex, the reviewers feels, that the conclusion
drawn in the abstract (“CEUS…should be routinely integrated in the US evaluation of CD.” )
seems to be too exaggerated.
Description to Figure 1B: it looks more like a colour doppler acquisitions than CEUS? In
addition, Figure 1  doesn´t really support any information in the manuscript and is therefore
dispensible.
Title: Ultrasonographic scores for ileal Crohn’s disease assessment: better, worse or the same
as contrast-enhanced ultrasound?
Version: 1 Date: 28 Jan 2022
Reviewer's report:
Intestinal ultrasound has an increasing impact on the management of Crohn´s disease as a non-
invasive imaging modality to guide patients´ treatment.
In contrast to ileocolonoscopy that solely evaluated mucosal inflammatory activity of CD,
ultrasound imaging be it B-Mode imaging or CEUS, is more a cross sectional imaging that
evaluates “transmural activity”.  This may contribute to a more comprehensive evaluation of
intestinal inflammatory load.
In their manuscript, the authors evaluate two different ultrasound activity scores (SUS-CD and
IBUS-SAS) and CEUS peak intensity in relation to different disease parameters, e.g., endoscopic
inflammatory activity, Calprotectin- or CRP-levels.
In their findings, peak intensity in CEUS correlates to endoscopic and clinical activity, but
not to biochemistry activity. They calculate a “cut-off peak intensity” for their correlations.
This number is irrelevant and doesn´t help anybody: it can´t be transferred to other machines/
investigations/investigators because this is an machine- and investigator-individual parameter .
In addition, SUS-SD and IBUS-SAS had a poor correlation to endoscopic and no correlation to
biochemistry disease activity in their study.
Inflammatory activity evaluated in ileocolonosopy does not correspond necessarily to disease
activity and should not be clearly distinguished by an adequate and uniformly uses expression
from overall disease activity. Therefore, the authors should use a consistent  nomenclature
through their whole manuscript, e.g. inflammatory endoscopic  activity (e.g. refer to table 5 “CD
inflammatory activity”) when referring to endoscopic scores/SES-CD.
Because this is a retrospective study, the expression “predict”  e.g., in conclusion of the abstract,
is not adequate. Please use other expressions like “correlate/relate/etc.”.
In the material and method section, there are several questions for the reviewer:
Major:
Could the authors comment on the issue if the ultrasound operator was blinded to the results
of the ileocolonoscopy?
The authors describe that ileocolonoscopy and ultrasound have been done up to one month apart
and they point out that there haven´t be any changes in therapy in this relatively long period
between the two examinations. This doesn´t sound realistic. The authors should comment on
this issue
Minor
Specification of the built-in software of the ultrasound machine is lacking.
SUS-SD had a poor correlation to predict endoscopic activity in contrast to the validation cohort
in the publication that introduce the SUS-SD The authors may discuss this point.
In the context that the authors pointed out that there is a need for studies on the role of CEUS in
active CD detection that would help in introducing the method into everyday practice, it seems to
be contractionary that one sentence earlier, they call for routine integration of CEUS in CD. The
authors should solve this contradiction. In this contex, the reviewers feels, that the conclusion
drawn in the abstract (“CEUS…should be routinely integrated in the US evaluation of CD.” )
seems to be too exaggerated.
Description to Figure 1B: it looks more like a colour doppler acquisitions than CEUS? In
addition, Figure 1  doesn´t really support any information in the manuscript and is therefore
dispensible.
Please review this paper.
user
Title: Ultrasonographic scores for ileal Crohn’s disease assessment: better, worse or the same
as contrast-enhanced ultrasound?
Version: 1 Date: 28 Jan 2022
Reviewer's report:
Intestinal ultrasound has an increasing impact on the management of Crohn´s disease as a non-
invasive imaging modality to guide patients´ treatment.
In contrast to ileocolonoscopy that solely evaluated mucosal inflammatory activity of CD,
ultrasound imaging be it B-Mode imaging or CEUS, is more a cross sectional imaging that
evaluates “transmural activity”.  This may contribute to a more comprehensive evaluation of
intestinal inflammatory load.
In their manuscript, the authors evaluate two different ultrasound activity scores (SUS-CD and
IBUS-SAS) and CEUS peak intensity in relation to different disease parameters, e.g., endoscopic
inflammatory activity, Calprotectin- or CRP-levels.
In their findings, peak intensity in CEUS correlates to endoscopic and clinical activity, but
not to biochemistry activity. They calculate a “cut-off peak intensity” for their correlations.
This number is irrelevant and doesn´t help anybody: it can´t be transferred to other machines/
investigations/investigators because this is an machine- and investigator-individual parameter .
In addition, SUS-SD and IBUS-SAS had a poor correlation to endoscopic and no correlation to
biochemistry disease activity in their study.
Inflammatory activity evaluated in ileocolonosopy does not correspond necessarily to disease
activity and should not be clearly distinguished by an adequate and uniformly uses expression
from overall disease activity. Therefore, the authors should use a consistent  nomenclature
through their whole manuscript, e.g. inflammatory endoscopic  activity (e.g. refer to table 5 “CD
inflammatory activity”) when referring to endoscopic scores/SES-CD.
Because this is a retrospective study, the expression “predict”  e.g., in conclusion of the abstract,
is not adequate. Please use other expressions like “correlate/relate/etc.”.
In the material and method section, there are several questions for the reviewer:
Major:
Could the authors comment on the issue if the ultrasound operator was blinded to the results
of the ileocolonoscopy?
The authors describe that ileocolonoscopy and ultrasound have been done up to one month apart
and they point out that there haven´t be any changes in therapy in this relatively long period
between the two examinations. This doesn´t sound realistic. The authors should comment on
this issue
Minor
Specification of the built-in software of the ultrasound machine is lacking.
SUS-SD had a poor correlation to predict endoscopic activity in contrast to the validation cohort
in the publication that introduce the SUS-SD The authors may discuss this point.
In the context that the authors pointed out that there is a need for studies on the role of CEUS in
active CD detection that would help in introducing the method into everyday practice, it seems to
be contractionary that one sentence earlier, they call for routine integration of CEUS in CD. The
authors should solve this contradiction. In this contex, the reviewers feels, that the conclusion
drawn in the abstract (“CEUS…should be routinely integrated in the US evaluation of CD.” )
seems to be too exaggerated.
Description to Figure 1B: it looks more like a colour doppler acquisitions than CEUS? In
addition, Figure 1  doesn´t really support any information in the manuscript and is therefore
dispensible.
assistant