Study of the Effects of Wall Thickness and Size Variations on the Rupture Risk of Cerebral Aneurysms Using FSI Simulations

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this article, the authors aimed to study the effects of wall thickness and size on the hemodynamics and structural stress in 3 ruptured and 3 unruptured intracranial aneurysms (IAs). They manually altered the aneurysm geometry using T-splines to simulate aneurysm growth at different stages. They also performed a grid convergence study to optimize the mesh density. They found that the aneurysm wall thickness has no effect on the wall shear stress values but could alter the wall displacement as well as the von-mises stress. They also found that the average value of WSS, wall displacement and von-Mises stress change considerably with varying aspect-ratio. Although the methods are robust, the article lacks clear motivation. These are my comments:

Major comments:

·         There are numerous articles that investigate in detail the relationship between morphology and hemodynamics and the current article also has similar if not the same qualitative findings. I fail to see the novelty in this small cohort analysis.

·         Artificial geometry modification is a major disadvantage. Please justify how this is similar to IA growth in a clinical setting.

·         Since stress is inversely proportional to the thickness, thinner walls would give rise to higher stress.

·         Please also consider calculating other hemodynamic metrics like OSI, RRT, WSS divergence etc.

·         Studies have shown that arteries could remodel after IA formation and growth. How do you justify using the same arterial geometry but remove the aneurysm?

Comments on the Quality of English Language

Quality of english is good

Author Response

Response to reviewers

 

First, we want to thank you for reviewing our work. Your comments will help us to improve our manuscript. Please find the detailed responses below and the corresponding revisions and corrections highlighted in track changes in the re-submitted file.

Thank you so much.

 

 

Review 1

Comments and Suggestions for Authors

In this article, the authors aimed to study the effects of wall thickness and size on the hemodynamics and structural stress in 3 ruptured and 3 unruptured intracranial aneurysms (IAs). They manually altered the aneurysm geometry using T-splines to simulate aneurysm growth at different stages. They also performed a grid convergence study to optimize the mesh density. They found that the aneurysm wall thickness has no effect on the wall shear stress values but could alter the wall displacement as well as the von-mises stress. They also found that the average value of WSS, wall displacement and von-Mises stress change considerably with varying aspect-ratio. Although the methods are robust, the article lacks clear motivation.

These are my comments:

Major comments:

There are numerous articles that investigate in detail the relationship between morphology and hemodynamics and the current article also has similar if not the same qualitative findings. I fail to see the novelty in this small cohort analysis.

This is correct, there are several works that investigate the relationships between morphology and hemodynamics, but FSI simulations are few.

For example:

Blood flow dynamics in patient-specific cerebral aneurysm models: The relationship between wall shear stress and aneurysm area index, Alvaro Valencia, Medical Engineering & Physics 30 (2008) 329–340.

Correlated the WSS with the morphology for 34 patient-specific models of saccular aneurysms, but the correlation index was not high.

In the present investigation the effect of size can be in detail reported, because is the same aneurysm that change this size, and other parameter as arterial morphology, and aneurysm ubication does not influences the results.

The novelty is that we investigate the size and wall thickness separately. The size changes will alter the fluid dynamics and the structural stress in the aneurysms, but the reduction of the aneurysm wall thickness will modify the structural stress, we are interested in both phenomena. We additionally studied the WSS between the pre-aneurysm and aneurysm stated in lateral aneurysms.

But the reviewer is correct, mode definitive conclusions will be possible in a future work using more unruptured and ruptured aneurysms.

• Artificial geometry modification is a major disadvantage. Please justify how this is similar to IA growth in a clinical setting.

Since there is no definitive method to predict an aneurysm growth due to the several factors that can affect the growing process, in this study, a method found in the literature is used.

In the investigation: Hemodynamic changes after intracranial aneurysm Growth Bart M. W. Cornelissen, et al. Neurosurg 136:1738–1744, 2022. DOI: 10.3171/2021.6.JNS204155

Aneurysms for 4 year were clinically studies and the growth were reported, the next figure from this investigations show qualitative similar geometries changes as in our investigations:

 

The WSS decreases after growth. For other hemodynamic characteristics, a large variability in assessed changes between aneurysms has been observed in the population.

• Since stress is inversely proportional to the thickness, thinner walls would give rise to higher stress.

This is correct and our results showed this tendence, see Figure 9: The evolution of the average Von Mises stress at the aneurysm with respect to the aneurysm wall thickness.

• Please also consider calculating other hemodynamic metrics like OSI, RRT, WSS divergence etc.

We used the WSS as hemodynamic factor for rupture risks as reported in several publications, [7-9]. WSS is defined as the key parameter to calculate grow and rupture of cerebral aneurysms, [12].

During our investigations we have calculated the OSI, as is showed in these figures:

  

However, the average OSI on the aneurysm did not show a relationship with the size better than the WSS, for this reason we do not report the OSI. The study of other parameters was out of scope of this study and were not investigated.

 

 Studies have shown that arteries could remodel after IA formation and growth. How do you justify using the same arterial geometry but remove the aneurysm?

It is important to note that is very likely for the parent vessel to suffer from geometrical changes after the aneurysm formation and growth, however, that information is not available, and there is no method to retrieve that previous geometry from the available data, therefore, for this study the comparison is done using the same parent vessel.

 

Comments on the Quality of English Language

Quality of english is good

 

The new version has been reviewed by the MDPI English Service.

 

thanks

 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

 

This is an inquiring paper and sheds an essential perspective on the the effects of wall thickness and size variations on the rupture risk of cerebral aneurysms. There is little literature on this topic. I have a few concerns that I would like to point out.

Introduction.
Background information provided is not enough. Please consider writing more about aneurysm in general. In my opinion, the authors have omitted an important factor that has a major impact on the outcome, namely blood viscosity. This should be supplemented. Some factors, such as the width of the aneurysm neck, the size ratio of an aneurysm, the aspect ratio, the presence of atherosclerotic plaque, have also not been discussed. It should be noted that all the aneurysms studied are saccular aneurysms, and fusiform aneurysms were not studied in the study.

Line 54: Instead of „aneurysm is thinner than the artery” I suggest writing "the wall of the aneurysm is thinner than the wall of the parent artery".

Material and Methods

To avoid misunderstanding, it is important to clearly distinguish and use the terms "wall thickness" of an artery or aneurysm and "diameter" of an aneurysm, blood vessel, or artery.

(see line 172- 176, 179, 222, 223, 357 Fig 5, Fig 9, Tab 3, Tab 4 etc),

 

Conclusion

Line 569: Instead of „the lateral vessel” I suggest writing „the parent vessels ” (like in line 402).

Author Response

Response to reviewers

 

First, we want to thank you for reviewing our work. Your comments will help us to improve our manuscript. Please find the detailed responses below and the corresponding revisions and corrections highlighted in track changes in the re-submitted file.

Thank you so much.

 

 

Review 2

Introduction.
Background information provided is not enough. Please consider writing more about aneurysm in general. In my opinion, the authors have omitted an important factor that has a major impact on the outcome, namely blood viscosity. This should be supplemented. Some factors, such as the width of the aneurysm neck, the size ratio of an aneurysm, the aspect ratio, the presence of atherosclerotic plaque, have also not been discussed. It should be noted that all the aneurysms studied are saccular aneurysms, and fusiform aneurysms were not studied in the study.

Thank you for pointing this out. We agree with this comment. Therefore, we have changed the introduction of our work. Please see the new introduction.

Line 54: Instead of „aneurysm is thinner than the artery” I suggest writing "the wall of the aneurysm is thinner than the wall of the parent artery".

Changed

Material and Methods

To avoid misunderstanding, it is important to clearly distinguish and use the terms "wall thickness" of an artery or aneurysm and "diameter" of an aneurysm, blood vessel, or artery.

(see line 172- 176, 179, 222, 223, 357 Fig 5, Fig 9, Tab 3, Tab 4 etc),

We have changed the manuscript according to this suggestion

Conclusion

Line 569: Instead of „the lateral vessel” I suggest writing „the parent vessels ” (like in line 402).

We changed according to your suggestions

 

The new version has been reviewed by the MDPI English Service.

 

thanks

 

 

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

Authors presented a study assessing wall thickness and size variations of cerebral aneurysm using numerical simulations. Authors reported six patient-specific simulation and concluded that wall thickness could be considered as biomarker of rupture risk. Please consider following comments and suggestions:

1) In general, introduction could be shorten.

2) Hypothesis and aims could be better stated. It most be clear and precise.

3) The transition from the WSS rational to wall thickness relevance need to be improved. As presented the rational transition seems weak.

4) No inclusion and exclusion criteria were stated. No ethics approval or consent was mentioned.

5) No details in the acquisition process was reported.

6) No rational was given for the selection of the six reported cases.

7) The rational for case selection for thickness testing is not well justified.

8) Section 2.2. is well described but some aspects remained incomplete or unjustified.

9) For all figures, quality and presentation need to be improved. All details most be given in the figure legends to get a clear understanding without the need of looking in them main document.

10) Table 1. Define all abbreviations.

11) In general, careful with punctuation and typos.

12) Please give full details in all figures.

13) Be consistent in figure labels.

14) For figure 7 use a better selection of line type. It is hard to read the three plots.

15) Careful with color bar legends. Values most be easy to read.

16) Careful with use of space in the document.

17) When comparing cases please use same representation range.

18) Conclusion most be framed in the context of presented results. Considering current # of cases it is difficult to have strong statements in the conclusion. This study is most a pilot study. Avoid reporting values in the conclusion move it to discussion.

 

Comments on the Quality of English Language

Please consider a general language revision from a native speaker.

Author Response

Response to reviewers

 

First, we want to thank you for reviewing our work. Your comments will help us to improve our manuscript. Please find the detailed responses below and the corresponding revisions and corrections highlighted in track changes in the re-submitted file.

Thank you so much.

 

 

Review 3

Authors presented a study assessing wall thickness and size variations of cerebral aneurysm using numerical simulations. Authors reported six patient-specific simulation and concluded that wall thickness could be considered as biomarker of rupture risk. Please consider following comments and suggestions:

1) In general, introduction could be shorten.

Our introduction is short, and the other reviewer need more explanation, so please accept it as is informed.

2) Hypothesis and aims could be better stated. It most be clear and precise.

The size changes will alter the fluid dynamics and the structural stress in the aneurysms, but a reduction of the aneurysm wall thickness will modify the structural stress, we are interested in both phenomena. We additionally studied the WSS between the pre aneurysm and aneurysm stated in lateral aneurysms.

3) The transition from the WSS rational to wall thickness relevance need to be improved. As presented the rational transition seems weak.

The changes in wall thickness produce wall deformation and therefore changes the fluid dynamics in the aneurysms and finally a change in WSS, and it can be a trigger for increases the rupture risk, [23].

4) No inclusion and exclusion criteria were stated. No ethics approval or consent was mentioned.

Two lateral and one terminal ruptured and unruptured geometries were chosen for the data base considering different size and forms. Geometries with small aneurysms and geometries with blebs in the aneurysms were discarded as candidate

The acquisition process was reported in detail in [29]. All the patients for this investigation gave their informed consent, that the image data of 3D angiography can be used for numerical investigation of fluid dynamics, for the investigation reported in [29], and no new geometry is reconstructed for this present study.

5) No details in the acquisition process was reported.

The acquisition process was reported in detail in [29].

6) No rational was given for the selection of the six reported cases.

Two lateral and one terminal ruptured and unruptured geometries were chosen for the data base considering different size and forms.

7) The rational for case selection for thickness testing is not well justified.

The wall thickness in an aneurysm dome can be characterized as a thick wall, transition and thin wall, [23], the wall thickness variation in this study included the thick and transition aneurysms wall thickness.

8) Section 2.2. is well described but some aspects remained incomplete or unjustified.

The section was completed with new information

9) For all figures, quality and presentation need to be improved. All details most be given in the figure legends to get a clear understanding without the need of looking in them main document.

Some figures were changes (figure 8 and 9) and other were enlarged

10) Table 1. Define all abbreviations.

Defined in the text and table

11) In general, careful with punctuation and typos.

We have revised the text

12) Please give full details in all figures.

The details in Figure 22 were modified.

13) Be consistent in figure labels.

We have revised the labels

14) For figure 7 use a better selection of line type. It is hard to read the three plots.

Figure 7 was enlarged, but we want to show that the results are similar.

15) Careful with color bar legends. Values most be easy to read.

We have checked our figures and in all you can read the values

16) Careful with use of space in the document.

We have revised

17) When comparing cases please use same representation range.

The ranges in the figures were choose property for each case

18) Conclusion most be framed in the context of presented results. Considering current # of cases it is difficult to have strong statements in the conclusion. This study is most a pilot study. Avoid reporting values in the conclusion move it to discussion.

The conclusions were changed according with your comments

19) Comments on the Quality of English Language

Please consider a general language revision from a native speaker.

The new version has been reviewed by the MDPI English Service.

 

 

thanks

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

All comments have been addressed.

Author Response

We thank the reviewer who helped us improve our work.

 

Best

 

Alvaro Valencia

Reviewer 3 Report

Comments and Suggestions for Authors

NA

Comments on the Quality of English Language

NA

Author Response

We thank the reviewer who helped us improve our work.

 

Best

 

Alvaro Valencia