How to Perform Cardiac Contrast-Enhanced Ultrasound (cCEUS): Part II—Advanced Applications and Interpretation

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This article offers a informative look at the topic, presenting key points in a clear and organized way. The author does a good job of explaining complex ideas and backing them up with relevant sources. The writing is mostly easy to be followed, making it accessible to a broad audience. Overall, it’s a strong piece that makes a positive contribution to the subject.                

Methodological Rigor or Experimental Design: The study is a well-organized, comprehensive evaluation of diagnostic performance in multiple datasets. The methodology is good, and  established performance metrics, as sensitivity,Specificity, accurary,RoC is used. The evaluation protocol is the same through a set of test sets which ensures soundness of comparisons.

Analysis and Interpretation of Data; Validity of the Findings: The authors present their results in a clear and detailed format, using tables and figures as needed to illustrate the main points. For the most part, their inference based on the results is sound and well supported by the data. 

Alignment with Current Literature and Novelty: The literature review is sufficient, highlighting key developments and positioning the work within the broader field. The authors identify relevant gaps, particularly the need for consistent validation across diverse datasets.
 The novelty lies more in the scope of evaluation—testing across multiple datasets—than in the algorithmic design itself. The authors should clearly articulate what distinguishes their approach from similar prior work, especially in practical or clinical implications.                                                          

Author Response

Dear Editors and Reviewers,

 

Thank you for the comments concerning our manuscript “How to Perform Cardiac Contrast-Enhanced Ultrasound (cCEUS): Part II – Advanced Applications and Interpretation diagnostics-3789306”: by Harald Becher, Andreas Helfen, Guido Michels, Nicola Gaibazzi, Roxy Senior, Christoph Frank Dietrich

The comments are important and helpful to improve our paper. Please find our point-to-point reply below. All the changes were highlighted in yellow (green) in our revised manuscript.

We are hoping that after careful revision our paper deserves publication.

Sincerely yours,

 

Prof. Dr. Christoph F Dietrich

Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland.

Email: c.f.dietrich@googlemail.com

Tel: +41765397277

 

Reviewer 1

This article offers an informative look at the topic, presenting key points in a clear and organized way. The author does a good job of explaining complex ideas and backing them up with relevant sources. The writing is mostly easy to be followed, making it accessible to a broad audience. Overall, it’s a strong piece that makes a positive contribution to the subject.  

Methodological Rigor or Experimental Design: The study is a well-organized, comprehensive evaluation of diagnostic performance in multiple datasets. The methodology is good, and established performance metrics, as sensitivity, specificity, accuracy, RoC is used. The evaluation protocol is the same through a set of test sets which ensures soundness of comparisons.

Analysis and Interpretation of Data; Validity of the Findings: The authors present their results in a clear and detailed format, using tables and figures as needed to illustrate the main points. For the most part, their inference based on the results is sound and well supported by the data.

Alignment with Current Literature and Novelty: The literature review is sufficient, highlighting key developments and positioning the work within the broader field. The authors identify relevant gaps, particularly the need for consistent validation across diverse datasets.

 The novelty lies more in the scope of evaluation—testing across multiple datasets—than in the algorithmic design itself. The authors should clearly articulate what distinguishes their approach from similar prior work, especially in practical or clinical implications.

Response: We included in the introduction on page 3, line 39: The growing use of CEUS and recent studies have provided fresh insights on how to perform echocardiography with UEAs in clinical practice. In this article we translate the current knowledge into a comprehensive state-of-the-art compendium for the echocardiographer. We respond to the demands of clinicians for standardized and detailed advice which is specific to each indication. Echocardiographers also have a special need for detailed guidance on how to interpret and report studies with UEAs. However, there has been a lack of practical guidance which we address in this article.

Reviewer 2 Report

Comments and Suggestions for Authors

This review article provides a comprehensive and up-to-date overview of the use of cardiac contrast-enhanced ultrasound (cCEUS), focusing on both procedural techniques and interpretative strategies in accordance with current imaging society guidelines. The authors effectively build upon their previous publication (Part 1), offering a structured and educational approach to the application of ultrasound-enhancing agents (UEAs) in evaluating global and regional left ventricular function, as well as myocardial diseases and perfusion abnormalities. The inclusion of technical considerations, pre-scan evaluation, key scanning planes, and interpretation protocols makes this review especially practical for clinicians and trainees.

Importantly, the article incorporates findings from recent studies and clinical practice recommendations, making it a valuable resource for those implementing CEUS in echocardiographic practice, particularly in complex or critically ill patients. The emphasis on training and quality control is also commendable.

However, the conclusion section is relatively weak compared to the rest of the paper. Rather than simply reiterating the general safety and utility of cCEUS, the conclusion should have more clearly summarized the major findings and clinical implications of the review. Stronger synthesis of the reviewed evidence—highlighting key benefits, limitations, and future directions—would enhance the overall impact and utility of the paper.

Author Response

Dear Editors and Reviewers,

 

Thank you for the comments concerning our manuscript “How to Perform Cardiac Contrast-Enhanced Ultrasound (cCEUS): Part II – Advanced Applications and Interpretation diagnostics-3789306”: by Harald Becher, Andreas Helfen, Guido Michels, Nicola Gaibazzi, Roxy Senior, Christoph Frank Dietrich

The comments are important and helpful to improve our paper. Please find our point-to-point reply below. All the changes were highlighted in yellow (green) in our revised manuscript.

We are hoping that after careful revision our paper deserves publication.

Sincerely yours,

 

Prof. Dr. Christoph F Dietrich

Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland.

Email: c.f.dietrich@googlemail.com

Tel: +41765397277

 

Reviewer 2

This review article provides a comprehensive and up-to-date overview of the use of cardiac contrast-enhanced ultrasound (cCEUS), focusing on both procedural techniques and interpretative strategies in accordance with current imaging society guidelines. The authors effectively build upon their previous publication (Part 1), offering a structured and educational approach to the application of ultrasound-enhancing agents (UEAs) in evaluating global and regional left ventricular function, as well as myocardial diseases and perfusion abnormalities. The inclusion of technical considerations, pre-scan evaluation, key scanning planes, and interpretation protocols makes this review especially practical for clinicians and trainees. Importantly, the article incorporates findings from recent studies and clinical practice recommendations, making it a valuable resource for those implementing CEUS in echocardiographic practice, particularly in complex or critically ill patients. The emphasis on training and quality control is also commendable.

However, the conclusion section is relatively weak compared to the rest of the paper. Rather than simply reiterating the general safety and utility of cCEUS, the conclusion should have more clearly summarized the major findings and clinical implications of the review. Stronger synthesis of the reviewed evidence—highlighting key benefits, limitations, and future directions—would enhance the overall impact and utility of the paper.

Response: We have replaced the conclusion on page 24, line 632: This article elaborates the practical application of CEUS for specific echocardiographic questions when assessing patients for LV thrombi, tumours, myocardial disease and perfusion abnormalities. Systematic pathways have been created with detailed advice for every step of the CEUS procedures as well as for the interpretation and reporting of the findings. This article addresses the needs of echocardiographers who can integrate the pathways in their quality assurance. Standardized interpretation and reporting will improve communication between the echocardiographers with other medical staff. Finally, standardized procedures with adherence to high quality standards will facilitate the application of automated analysis tools and artificial intelligence for recordings with UEAs.

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript serves as a detailed guide on the use of ultrasound enhancing agents (UEAs) for advanced echocardiography. It covers the application of UEAs for assessing left ventricular aneurysms, thrombi, and tumors, as well as for evaluating hypertrophic cardiomyopathy, excessive trabeculation and myocardial perfusion. The document also includes a section on the use in critically ill patients and provides guidelines for education and quality control.

The manuscript is overall well-steructured and provides a detailed, practical guide. The content is logical and goes from basic concepts to more advanced applications. However, a thorough review for grammar, syntax, and typographical errors would significantly improve its readability and professional tone. The language is often a bit too colloquial for a journal article. Please make an extensive proofreading process before resubmission.

Please also revise abbreviations for consistency with the rest of the text.

In terms of originality and literature comparison, the value of this manuscript lies in synthesizing and presenting this information in a practical shape made by experts in the field. It cites many relevant papers and recommendations. The references enclosed relevant and well-selected.

Overall, the manuscript is a valuable resource. The revisions advised above would increase its quality by correcting errors and improving the academic tone and clarity.

Comments on the Quality of English Language

A thorough review for grammar, syntax, and typographical errors would significantly improve its readability and professional tone. The language is often a bit too colloquial for a journal article. Please make an extensive proofreading process before resubmission.

Author Response

Dear Editors and Reviewers,

 

Thank you for the comments concerning our manuscript “How to Perform Cardiac Contrast-Enhanced Ultrasound (cCEUS): Part II – Advanced Applications and Interpretation diagnostics-3789306”: by Harald Becher, Andreas Helfen, Guido Michels, Nicola Gaibazzi, Roxy Senior, Christoph Frank Dietrich

The comments are important and helpful to improve our paper. Please find our point-to-point reply below. All the changes were highlighted in yellow (green) in our revised manuscript.

We are hoping that after careful revision our paper deserves publication.

Sincerely yours,

 

Prof. Dr. Christoph F Dietrich

Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland.

Email: c.f.dietrich@googlemail.com

Tel: +41765397277

 

Reviewer 3

This manuscript serves as a detailed guide on the use of ultrasound enhancing agents (UEAs) for advanced echocardiography. It covers the application of UEAs for assessing left ventricular aneurysms, thrombi, and tumors, as well as for evaluating hypertrophic cardiomyopathy, excessive trabeculation and myocardial perfusion. The document also includes a section on the use in critically ill patients and provides guidelines for education and quality control.

The manuscript is overall well-structured and provides a detailed, practical guide. The content is logical and goes from basic concepts to more advanced applications. However, a thorough review for grammar, syntax, and typographical errors would significantly improve its readability and professional tone. The language is often a bit too colloquial for a journal article. Please make an extensive proofreading process before resubmission.

Please also revise abbreviations for consistency with the rest of the text.

In terms of originality and literature comparison, the value of this manuscript lies in synthesizing and presenting this information in a practical shape made by experts in the field. It cites many relevant papers and recommendations. The references enclosed relevant and well-selected.

Overall, the manuscript is a valuable resource. The revisions advised above would increase its quality by correcting errors and improving the academic tone and clarity.

Comments on the Quality of English Language

A thorough review for grammar, syntax, and typographical errors would significantly improve its readability and professional tone. The language is often a bit too colloquial for a journal article. Please make an extensive proofreading process before resubmission.

Response: Extensive proofreading was performed ad typographical errors, wrong grammar and syntax was corrected. We have replaced several sentences and paragraphs and highlighted in yellow.

Reviewer 4 Report

Comments and Suggestions for Authors

This is a comprehensive and well-structured state-of-the-art review covering advanced applications of cardiac contrast-enhanced ultrasound. The article focuses on advanced interpretation, specific pathologies, Doppler enhancement, myocardial perfusion, and use in critically ill patients. The manuscript is written clearly, well-referenced, and provides practical technical details, figures, and tables that would be highly useful to echocardiographers in both academic and clinical settings.

This review covers a broad range of advanced applications (LV thrombi, aneurysms, hypertrophic cardiomyopathy, trabeculation, myocardial perfusion, Doppler enhancement, and use in ICU patients).

This review serves as a practical guidance: provides clear instructions on settings (low vs. intermediate mechanical index, bolus vs. infusion), pitfalls, and alternative imaging modalities and has a high educational value highlighting training, quality assurance, and competency requirements, which are crucial for broader adoption of cardiac contrast-enhanced ultrasound.

The high-quality figures and tables use to illustrate pitfalls, imaging strategies, and diagnostic criteria greatly improves readability and applicability.

The manuscript is suitable for publication. Its clinical and educational value is very high, and it will serve as an important reference for echocardiographers worldwide.

Author Response

Dear Editors and Reviewers,

 

Thank you for the comments concerning our manuscript “How to Perform Cardiac Contrast-Enhanced Ultrasound (cCEUS): Part II – Advanced Applications and Interpretation diagnostics-3789306”: by Harald Becher, Andreas Helfen, Guido Michels, Nicola Gaibazzi, Roxy Senior, Christoph Frank Dietrich

The comments are important and helpful to improve our paper. Please find our point-to-point reply below. All the changes were highlighted in yellow (green) in our revised manuscript.

We are hoping that after careful revision our paper deserves publication.

Sincerely yours,

 

Prof. Dr. Christoph F Dietrich

Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland.

Email: c.f.dietrich@googlemail.com

Tel: +41765397277

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I think the paper has been well revised.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors adequately addressed my concerns and for me the paper is now suitable for publication.