Stenosis Indicators Applied to Patient-Specific Renal Arteries without and with Stenosis
Round 1
Reviewer 1 Report
Major comments
· The introduction is incomplete because the authors do not discuss the state of the art in studying the hemodynamics of the renal vessels or stenosed arteries. This makes it difficult to appreciate the context of the problem and understand why the authors chose the method they did for examination of their research questions.
· More details should be provided about the imaging method for the patient, i.e. image resolution, type of system on which the patients were imaged, etc.
· Some justification should be given for the segmentation method used. How much error is expected due to the choice of segmentation method? Were any others tried? Thresholding is a fairly primitive technique and I would not expect it to perform as accurately as more advanced techniques.
· The authors need to justify the value of the diffusivity coefficient of RBCs quoted in line 125.
· In line 148-150, the authors state their viscosity model may produce complex numbers, but they do not say how they address this problem in the simulation (since obviously the viscosity can’t actually be a complex number.)
· Line 193-197: I find the discussion of relative residence time confusing. The authors do not really define what this parameter means conceptually. Please reword this section.
· Line 209: The choices for parameter values should be justified. Also, it is confusing that the authors use D for both the diffusion coefficient and the “dose term”
· The authors have not adequately motivated their choices to use RRT and PAS to assess stenosis prognosis. They need to distinguish these particular metrics from just any random parameter they could have picked to characterize the flow.
· It seems to me that the outlet flow rates in the various branches are not realistic. You should compare your values to documented literature on flow rates and, if they are significantly different, explain why you chose to apply pressure outlet conditions rather than flow rate outlet conditions.
· It would be helpful to add a plot of the inlet flow rate vs. time, or at the very least state the maximum and average inlet Reynolds numbers.
· The color bars, vectors, and labels on Figures 7-10 are virtually unreadable because they are so small. This urgently needs to be fixed—it is currently impossible for the reader to interpret the data in a meaningful way.
· I find the description of frequency calculations in the shear layer (described around line 462) to be very hand-wavy—please explain exactly what you did and show the calculation (or take this section out.)
· No results are presented on the distribution of red blood cells. I don’t understand why the authors bothered to simulate blood as a two-phase flow if they still solve the incompressible equations and don’t even present the data on the phase separation or discuss what it means.
· I am really unclear about the overall purpose of the paper. The authors say they are looking for a metric that will predict a site of future stenosis, but they have no data showing what happens when the cases they have examined redevelop stenosis. I have a hard time following the conclusions they draw because of this missing piece. The authors must clarify their purpose and explain why what they actually did makes progress in solving the problem they pose.
Minor comments
· Missing apostrophe in line 86: “patient’s”
· The square roots in equation 5 look very strange on my computer. Make sure they are correct in the final version.
· Line 242 should say “represent” not “represents”
· Line 417 should read “the presence OF flow irregularities”
· Line 457 should read “locations” or “another location,” not merely “location”
Author Response
Please see the enclosed PDF-file.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors assessed the usefulness of four different indexes (Time Averaged Wall Shear Stress (TAWSS), the Oscillatory Shear Index (OSI), the Relative Reference Time (RRT) and Endothelium Activation Indicator (EAI)) for determining the risk of new stenosis after revascularization in renal arteries. The authors used CFD models with rigid walls to complete this study. In my opinion their results are very interesting, and may have potential for clinical applications. However, there are several major limitations that may affect their results. These limitation (see below) must be clearly mentioned and discussed in the paper.
Major comments:
This paper has four major limitations:
1- Only three patients have been investigated.
2- Rigid wall assumption: please state this limitation clearly in a separate “Limitations” section and discuss how and why results with compliant wall will (or will not) be different. This must also be reflected in the title of the manuscript as well. Please change the title to something like “Stenosis indicators applied to patient specific renal arteries without and with stenosis with rigid wall assumption”.
3- It is not clear what velocity profile was used at the inlet, Womersley profile, flat velocity profile, or …? The choice of velocity profile must be justified and the shortcomings (if there is any) should be discussed.
4- The compliance of the kidney in patients has not been considered. Discuss how this may affect your finding.
Minor comments:
Line 46: “… found in certain arteries at certain locations” such as….
Line 74-77: briefly describe the markers in this paragraph as well.
Line 209: Give a reference for a,b, and c constant value or provide an explanation.
Line 256: provide a reference for Voronoi scheme.
Section 3.2: show the inflow waveform.
Figures 5-10. The color bar font sizes are very small. Also, please make sure all of them have the same scale.
Line 431: Typo: OSI (9-9) and RRT (9-9) cannot be correct. I think d-f and g-I were dropped.
Line 504-506: create a “Limitations” section and move 504-506 to this section.
Line 525-526: provide a reference for “it has to be noted that it experimentally been found that atherosclerosis may occur in low WSS as well as at high WSS regions.”
Line 593: “ developing clinically appropriate boundary conditions is essential”. There are some, such as:
1- Vignon-Clementel, Irene E., et al. "Outflow boundary conditions for three-dimensional finite element modeling of blood flow and pressure in arteries." Computer methods in applied mechanics and engineering 195.29-32 (2006): 3776-3796.
2- Pahlevan, Niema M., et al. "A physiologically relevant, simple outflow boundary model for truncated vasculature." Annals of biomedical engineering 39.5 (2011): 1470-1481.
3- Attaran, Seyed Hamidreza, Hanieh Niroomand-Oscuii, and Farzan Ghalichi. "A novel, simple 3D/2D outflow boundary model for blood flow simulations in compliant arteries." Computers & Fluids 174 (2018): 229-240.
I think it is appropriate to mention and cite them here.
Author Response
Please see the enclosed PDF-file.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have responded to my comments in a satisfactory matter.
Author Response
The authors have responded to my comments in a satisfactory matter.
- We thank the reviewer for this.
Reviewer 2 Report
1- One of my comment was not addressed correctly. "It is not clear what velocity profile was used at the inlet, Womersley profile, flat velocity profile, or …? The choice of velocity profile must be justified and the shortcomings (if there is any) should be discussed".
I was referring to the spatial velocity profile not temporal. I assumed this is would be clear as Womersley profile is a spatial velocity profile not temporal. Please address this accordingly and justify your assumption.
2- I disagree with the authors that rigid wall assumption is minor. This does not mean the results of this paper is not physiologically correct. However, it must be reflected in the title of the manuscript. The current title is misleading.
3- A reference is missing in line 342.
Author Response
Please see the enclosed PDF file.
Author Response File: Author Response.pdf
Round 3
Reviewer 2 Report
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