Common Carotid Artery Volume Flow: A Comparison Study between Ultrasound Vector Flow Imaging and Phase Contrast Magnetic Resonance Imaging

Round 1

Reviewer 1 Report

This is a very nicely written and discussed manuscript which provides some clarification to the use of different techniques to evaluate blood flow. 

The data is well controlled and the authors clearly state and address some of the limitations of the study. 

Overall, it was a pleasure to read this manuscript. Well done.

Author Response

To the reviewers and the editor

We would like to thank the reviewers for the useful and constructive comments on our paper. Our reply to each comment is given below. In addition, the changes in the manuscript are highlighted in red

Reviewers 1

Thank you for your positive comments and feedback. The manuscript has been reviewed and corrected for misspellings and grammatical errors. 

Reviewer 2

 “It is an interesting study. VFI was good evaluation of hemodynamics. The performance of MRI was better than VFI. The correlation was higher between VFI and MRA”

Reply:

Thank you for the positive feedback. MRA is regarded the gold standard for non-invasive cerebral blood flow measurement as stated in the introduction. While the results indicated that the precision estimates for VFI and MRA (19.2% and 31.9%) were not significantly different though with a trend towards an improved precision of VFI compared to MRA (p<0.061), the VFI volume flow was significantly lower than MRA (p<0.017). Hence, from the results can be extracted that VFI underestimates compared to MRA, but may be more precise.

The following has been added to the conclusion as suggested by the reviewer.

In healthy volunteers, VFI and MRA volume flow estimates of the CCA were strongly correlated, though VFI significantly underestimated the volume flow estimates. VFI had superior precision compared to MRA and was after correction of the systematic bias interchangeable with MRA. VFI may be a useful alternative for volume flow estimation in the CCA with bedside availability and lower operational cost compared to MRA.

“The intimal-medial thickness in common carotid artery has been widely used as one of the parameters of atherosclerosis. The peak systolic velocity more than 125 cm/s means 50 % stenosis and 200 cm/sec mean 70% stenosis in internal carotid artery. What’s the clinical application for VFI in common carotid artery”

Reply:

It is correct that intima thickness is used for atherosclerosis, and peak systolic velocity is used as parameter in the carotid artery for stenosis assessment.  However, volume flow may play a role in stenosis assessment.

First, the stenosis will reduce the volume flow. This can result in cerebral hypoperfusion as shown by (Khan AA, Patel J, Desikan S, Chrencik M, Martinez-Delcid J, Caraballo B, Yokemick J, Gray VL, Sorkin JD, Cebral J, Sikdar S, Lal BK. Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion. J Vasc Surg. 2021 May;73(5):1611-1621.e2.) leading to cognitive impairment, which is not fully assessed by peak systolic velocity estimation.

Second, peak systolic velocity is normally measured within the stenosis for severity assessment. This can be cumbersome due to calcifications showed by (Morales MM, Anacleto A, Filho CM, Ledesma S, Aldrovani M, Wolosker N. Peak Systolic Velocity for Calcified Plaques Fails to Estimate Carotid Stenosis Degree. Ann Vasc Surg. 2019 Aug;59:1-4.) With volume flow assessment using VFI, the carotid artery can be evaluated downstream of the stenosis. Thus, the measurement can be assessed in a vessel segment without shadowing calcifications though affected by a stenosis upstream.

Future studies are needed to investigate VFI for stenosis assessment.

The following has been added to the discussion:

In diseased vessels with stenotic segments, the velocity will increase and the volume flow decrease [33, 34]. While, the intima-media thickness in the common carotid artery has been used as a surrogate marker for atherosclerosis [35], the preferred method for stenosis assessment using ultrasound is velocity evaluation within the stenotic vessel segment [36]. However, due to calcified plaques, the stenosis degree from velocity assessment can be difficult to estimate in some patients, and volume flow estimation with VFI downstream of the stenosis could be an alternative measure [37].

The complexity of the flow will also be increased with stenoses, and can be assessed with spectral Doppler US by estimating spectral broadening or evaluating mosaic patterns with color Doppler [38, 39].

The following papers have been added to the reference list:

Grant, E.G.; Benson, C.B.; Moneta, G.L.; Alexandrov, A.V.; Baker, J.D.; Bluth E.I.; Carroll, B.A.; Eliasziw, M.; Gocke, J.; Hertzberg, B.S.; Katanick, S.; Needleman, L., Pellerito, J.; Polak, J.F.; Rholl, K.S.; Wooster, D.L.; Zierler, R.E. Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology 2003 229,2, 340-346.

Ackroyd, N.; Gill, R.; Griffiths, K.; Kossoff, G.; Appleberg, M. Quantitative common carotid artery blood flow: prediction of internal carotid artery stenosis. J Vasc Surg 1986, 3, 846-853. 

Nezu, T.; Hosomi, N.; Aoki, S.; Matsumoto, M.; Carotid Intima-Media Thickness for Atherosclerosis. J Atheroscler Thromb 2016 23, 18-31.

Mortimer, R.; Nachiappan, S.; Howlett, D.C. Carotid artery stenosis screening: where are we now?. Br J Radiol 2018, 90, 20170380.

Morales, M.M.; Anacleto, A.; Filho, C.M., Ledesma, S.; Aldrovani, M.; Wolosker, N. Peak Systolic Velocity for Calcified Plaques Fails to Estimate Carotid Stenosis Degree. Ann Vasc Surg 2019, 59, 1-4. 

Abstract: p<0.061 in line 18, p<0.017 in line 19, after p were =not<?

Reply:

The reviewer is correct, the p-values are equal to and not below the numbers given. This has been corrected in the paper.

Reviewer 2 Report

It is an interesting study. VFI was good for evaluation of hemodynamics. The performance of MRA was better than VFI. The correlation was higher between VFI and MRA.

The intima-medial thickness in common carotid artery has been widely used as one of the parameters of atherosclerosis. The peak systolic velocity more than 125 cm/sec means 50% stenosis and 200 cm/sec mean 70% stenosis in internal carotid artery. What's the clinical application for VFI in common carotid artery.

Abstract: p<0.061 in line 18, p<0.017 in line 19, after p were =not <?

Author Response

To the reviewers and the editor

We would like to thank the reviewers for the useful and constructive comments on our paper. Our reply to each comment is given below. In addition, the changes in the manuscript are highlighted in red

Reviewers 1

Thank you for your positive comments and feedback. The manuscript has been reviewed and corrected for misspellings and grammatical errors. 

Reviewer 2

 “It is an interesting study. VFI was good evaluation of hemodynamics. The performance of MRI was better than VFI. The correlation was higher between VFI and MRA”

Reply:

Thank you for the positive feedback. MRA is regarded the gold standard for non-invasive cerebral blood flow measurement as stated in the introduction. While the results indicated that the precision estimates for VFI and MRA (19.2% and 31.9%) were not significantly different though with a trend towards an improved precision of VFI compared to MRA (p<0.061), the VFI volume flow was significantly lower than MRA (p<0.017). Hence, from the results can be extracted that VFI underestimates compared to MRA, but may be more precise.

The following has been added to the conclusion as suggested by the reviewer.

In healthy volunteers, VFI and MRA volume flow estimates of the CCA were strongly correlated, though VFI significantly underestimated the volume flow estimates. VFI had superior precision compared to MRA and was after correction of the systematic bias interchangeable with MRA. VFI may be a useful alternative for volume flow estimation in the CCA with bedside availability and lower operational cost compared to MRA.

“The intimal-medial thickness in common carotid artery has been widely used as one of the parameters of atherosclerosis. The peak systolic velocity more than 125 cm/s means 50 % stenosis and 200 cm/sec mean 70% stenosis in internal carotid artery. What’s the clinical application for VFI in common carotid artery”

Reply:

It is correct that intima thickness is used for atherosclerosis, and peak systolic velocity is used as parameter in the carotid artery for stenosis assessment.  However, volume flow may play a role in stenosis assessment.

First, the stenosis will reduce the volume flow. This can result in cerebral hypoperfusion as shown by (Khan AA, Patel J, Desikan S, Chrencik M, Martinez-Delcid J, Caraballo B, Yokemick J, Gray VL, Sorkin JD, Cebral J, Sikdar S, Lal BK. Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion. J Vasc Surg. 2021 May;73(5):1611-1621.e2.) leading to cognitive impairment, which is not fully assessed by peak systolic velocity estimation.

Second, peak systolic velocity is normally measured within the stenosis for severity assessment. This can be cumbersome due to calcifications showed by (Morales MM, Anacleto A, Filho CM, Ledesma S, Aldrovani M, Wolosker N. Peak Systolic Velocity for Calcified Plaques Fails to Estimate Carotid Stenosis Degree. Ann Vasc Surg. 2019 Aug;59:1-4.) With volume flow assessment using VFI, the carotid artery can be evaluated downstream of the stenosis. Thus, the measurement can be assessed in a vessel segment without shadowing calcifications though affected by a stenosis upstream.

Future studies are needed to investigate VFI for stenosis assessment.

The following has been added to the discussion:

In diseased vessels with stenotic segments, the velocity will increase and the volume flow decrease [33, 34]. While, the intima-media thickness in the common carotid artery has been used as a surrogate marker for atherosclerosis [35], the preferred method for stenosis assessment using ultrasound is velocity evaluation within the stenotic vessel segment [36]. However, due to calcified plaques, the stenosis degree from velocity assessment can be difficult to estimate in some patients, and volume flow estimation with VFI downstream of the stenosis could be an alternative measure [37].

The complexity of the flow will also be increased with stenoses, and can be assessed with spectral Doppler US by estimating spectral broadening or evaluating mosaic patterns with color Doppler [38, 39].

The following papers have been added to the reference list:

Grant, E.G.; Benson, C.B.; Moneta, G.L.; Alexandrov, A.V.; Baker, J.D.; Bluth E.I.; Carroll, B.A.; Eliasziw, M.; Gocke, J.; Hertzberg, B.S.; Katanick, S.; Needleman, L., Pellerito, J.; Polak, J.F.; Rholl, K.S.; Wooster, D.L.; Zierler, R.E. Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology 2003 229,2, 340-346.

Ackroyd, N.; Gill, R.; Griffiths, K.; Kossoff, G.; Appleberg, M. Quantitative common carotid artery blood flow: prediction of internal carotid artery stenosis. J Vasc Surg 1986, 3, 846-853. 

Nezu, T.; Hosomi, N.; Aoki, S.; Matsumoto, M.; Carotid Intima-Media Thickness for Atherosclerosis. J Atheroscler Thromb 2016 23, 18-31.

Mortimer, R.; Nachiappan, S.; Howlett, D.C. Carotid artery stenosis screening: where are we now?. Br J Radiol 2018, 90, 20170380.

Morales, M.M.; Anacleto, A.; Filho, C.M., Ledesma, S.; Aldrovani, M.; Wolosker, N. Peak Systolic Velocity for Calcified Plaques Fails to Estimate Carotid Stenosis Degree. Ann Vasc Surg 2019, 59, 1-4. 

Abstract: p<0.061 in line 18, p<0.017 in line 19, after p were =not<?

Reply:

The reviewer is correct, the p-values are equal to and not below the numbers given. This has been corrected in the paper.