PONE-D-19-21636

Comprehensive Multimodality Characterization of Hemodynamically Significant and Non-Significant Coronary Lesion using Invasive and Noninvasive Measures

PLOS ONE

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2. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. "Some patients included in this study were also part of the patient cohort of the study "Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques Using Molecular 3-T CMR Imaging With an Albumin-Binding Probe" where - unlike the current study - CMR results were correlated to optical coherence tomography and which was published in JACC cardiovasc imaging in Feb 2019. "  Please clarify whether this [c publication was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.

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Reviewer #1: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

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Reviewer #1: No

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: Authors presents results on the important topic of the analysis of atherosclerotic malformation in coronaries. The methodology based on validation of the result of contrast enhanced MRI using the albumin-bind extra-vascular contrast media by the measurements of QFR is technically sound. Yet the approach used by the authors in terms of MRI techniques does not look fully adequate to the problem.

The physical spatial resolution of the GRE-based sequence used by authors is above is 1.3 mm /pixel. Additionally , authors use a non-selective single inversion recovery (for 3D sequence)with fat suppression and breath-free navigation for the full-heart vessel -wall imaging. This approach is know for introducing significant quantitative bias in results based on signal intensity analysis due to incomplete suppression of fat signal and related problems of identification vessel wall and especially adequate segmenting of the wall malformation. For this reason, number of researches introduced double and even quadruple IR methods for separation of signal from blood, tissue , fat and contrast media in order to make quantitative analysis more reliable. In this work when relatively simple approach is used it would be important to demonstrate clearly the adequate quality of CMR images for two considered cases ( QFR>0.8 and QFR<0.8) especially the quality of blood and fat suppression and to show the example of identified lesion segments images along with non-lesion vessel wall. This would support the capability of methodology to provide conclusive and diagnostically relevant results. Currently paper contains only single CMR image with relatively low spatial resolution and quality of blood suppression. The methodology of data processing on this point should be uncovered in more details. The same is for the quality of the respiratory gating which is known to be drastic problem for the CMR and demands at least demonstration of reliability and comparison with breath-hold technique to be able to estimate the severity of introduced artifacts.

Paper has relative broad Discussion in which however is difficult to identify own result of author from the results from literature. On the other hand Introduction to very concise and no adequate overview of the existing works on coronary vessel wall MRI and existing problems of analysis and quantification is given whereas this topic is covered by numerous publication in the specialized MRI journals ( Magnetic Resonance in Medicine in particular). Most part of the discussion would be reasonable to transfer to the Introduction and update the later one with more references to the key works in vessel wall MR-imaging and especially its technical challenges.

The Conclusion is short, but fussy and does not really match to the formulated objectives of the paper. With limited amount of scanned patients and being a pilot study the focus should be given to the workflow and technical details of the approach to prove the feasibility of methods and evaluate reasoning for the further patient recruitment or necessity to work on technical side.

Some specific remarks

Line 63 – 65 abbriviation CMR, OCT, CAD are not defined.

Line 81 - What does it mean “more advanced” . “Conclusion” does not really match to the goal formulated in “Objective”. Which experimentally measured parameters _parameters_ and values allows or does not allow do make conclusions regarding significance of lesions ?

Line 104. Why the role of CMR measurements is not mentioned in Introduction ? Why it is mentioned in Abstract but no details on the capabilities of MRI for atherosclerosis detection are given here and very little overview of the existing methods of atherosclerotic plaques detection and analysis ( especially contrast enhanced vessel wall imaging). The same is about role MR-angiography and MR-based flow quantification – no or very poor literature overview for the Introduction for paper where CMR supposed to provide the key results.

Line 166 „T2-prepared“ ?

Line 170 : 340mm FOV at matrix 256x256 provides resolution (physical )1.3mm. 0.65mm is interpolated resolution.

169: What was the interslice gap ? Was it 2D ( slice selective RF-pulses) or 3D-encoded sequence ?

170: 3.5ms TR time is quite short and hardware demanding. Was it a standard vendor -provided protocol ( e.g TWIST or VIBE ) or any inhouse-developed sequence ?

182: What means “navigator gating window” in “mm”. Usually “window” for the navigator is time available for measurements the same as cardiac trigger window. Proper adjustment of navigator position is essential part of such measurements – some data demonstrating the navigation quality ( as shown by scanner) and dependence of image quality on the position of navigator “pencil” would be very helpful for the illustration of method robustness and role of motion artifacts in the results.

Line 211: The scheme illustrating the segmenting of coronary is key point of data processing. It would be helpful to demonstrate 1 or 2 examples with significant and non-significant lesion for understanding of the methodology and it reliability.

278: The statistics of quantitative results does not look very reliable for CMR. The standard deviation of enhancement is close or even exceeds ( for native T1) the mean value. What is explanation of such a major variation. How reliable is this data and are they reproducible within single patient ?

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Reviewer #1: No

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Comprehensive Multimodality Characterization of Hemodynamically Significant and Non-Significant Coronary Lesions using Invasive and Noninvasive Measures

PONE-D-19-21636R1

Dear Dr. Engel,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Wolfgang Rudolf Bauer, M.D., Ph.D.

Academic Editor

PLOS ONE