Anatomic and hemodynamic characterization of vertebral artery duplication via color doppler ultrasonography

Xue Han; Wenbo Duan; Wanling Wen; Tian Lin; Dongxu Lu; Juan Du; Li Liu

doi:10.1371/journal.pone.0336216

Peer Review History

Original SubmissionApril 5, 2025
3 Sep 2025 Decision Letter - Priti Chaudhary, Editor Dear Dr. Liu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Oct 18 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: The manuscript was interesting and good written and discussed. Introduction was good written. Materials and method were good designed. Results were good described and illustrated Discussion was good written. Reviewer #2: 1) the patient selection criteria are unclear to me. I am not aware of a disease that is named VA-cervical spondylosis. Please make it clear to the reader what is the indication for these patients to have underwent the ultrasound examination? Is it VA compression syndrome symptoms? If so, clarify. 2) The clinical relevance of duplicate VA is not at all explored further in the sample set, while the manuscipt would be substantially improved in valor if the authors would substantiate the claim in their dataset that these duplications are associated with other vascular malformations? 3) The clinical relevance of just a comparison of the two limbs in 1 patient compared to the other VA is in my opinion unclear if the readers has no idea of the other parameters that are relevant to cerebral perfusion. 4) The methodology of measurement of PSV in the vertebral artery may be dependent of the insonation angle. There is no reference of the way that this was controlled for between the duplicate arteries. How sure can we be that differences in flow are not based on technical flaws? Please clarify. ****** what does this mean? ). If published, this will include your full peer review and any attached files. 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Revision 1
17 Oct 2025 Author Response Additional Editor Comments: Authors are required to reply all the queries, raised by Reviewer 2. Methodology is not clear. 1. How the patients were selected. The study included patients who had undergone Color Doppler Ultrasonography of VA in suspicion of VA compression syndrome or ischemic cerebral vascular diseases. 2. How sample size calculation done. Kindly clarify. First of all, this is a retrospective study, and the incidence of VA duplication was not quite clear, so that sample size was not rigidly calculated. This had been pointed out in limitation part. Secondly, to get our study subjects, we screened all VA ultrasound examination records in our center during January 2019 to December 2022. And indications for VA ultrasound examination were patients with complains of dizziness or vertigo that in suspicion of VA compression syndrome and patients with evidence or risk of ischemic cerebral vascular disease including but not limited to acute ischemic stroke or transient ischemic attack. All patients we found had been included. For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. Comments to the Author Review Comments to the Author Reviewer #1: The manuscript was interesting and good written and discussed. Introduction was good written. Materials and method were good designed. Results were good described and illustrated Discussion was good written. Reviewer #2: 1) the patient selection criteria are unclear to me. I am not aware of a disease that is named VA-cervical spondylosis. Please make it clear to the reader what is the indication for these patients to have underwent the ultrasound examination? Is it VA compression syndrome symptoms? If so, clarify. Response to reviewer: The indications for VA ultrasound examination were patients with complains of dizziness or vertigo that in suspicion of VA compression syndrome and patients with risks or evidence of ischemic cerebral vascular disease including acute ischemic stroke or transient ischemic attack. 2) The clinical relevance of duplicate VA is not at all explored further in the sample set, while the manuscript would be substantially improved in valor if the authors would substantiate the claim in their dataset that these duplications are associated with other vascular malformations? Response to reviewer: Thank you for the suggestion. We totally agree with you on the importance of investigation about the relevance between VA duplication and other vascular malformations, however, within our limited sample size, we found only 4 of 18 subjects underwent head and neck CTA examination and 2 other patients had brain MRA examination, all of them reported no other vascular malformations. And we have put this in the limitation part. Further study with prospective design might offer a better answer to this question. 3) The clinical relevance of just a comparison of the two limbs in 1 patient compared to the other VA is in my opinion unclear if the readers has no idea of the other parameters that are relevant to cerebral perfusion. Response to reviewer: We agree that direct correlation with cerebral perfusion parameters would provide a more comprehensive picture. PSV is the cornerstone parameter for diagnosing arterial stenosis in Doppler ultrasonography. The main hypothesis of our study was that the two stems of duplicated vertebral artery, which potentially having different embryological origins, may exhibit inherent hemodynamic differences. So the primary clinical significance of our data lies in reporting the hemodynamic features of this specific anatomical variant. By comparing the PSV of each stem to that of a normal, single VA, we aim to answer a critical clinical question: What constitutes a 'normal' versus 'pathologically elevated' PSV in this variant? This is directly relevant to the sonographer or vascular neurologist in daily practice. Without such reference data, there is a risk of either over-diagnosing stenosis in a high-flow but normal stem, or under-diagnosing a true stenosis. Identifying a stem with significantly elevated PSV can signal the need for closer monitoring or further investigation with cross-sectional imaging (e.g., CTA or MRA) to rule out clinically significant stenosis that could impact posterior circulation perfusion. We also added the following paragraph into the limitation part: “One limitation of this study is the lack of correlation between our PSV measurements and cerebral perfusion parameters.” 4) The methodology of measurement of PSV in the vertebral artery may be dependent of the insonation angle. There is no reference of the way that this was controlled for between the duplicate arteries. How sure can we be that differences in flow are not based on technical flaws? Please clarify. Response to reviewer: During the PSV measurement procedure, standardized device parameters were ensured and preset optimizations were applied. A unified preset condition for the vertebral artery was used. The Doppler gain was adjusted to clearly display the spectral waveform outline while avoiding background “snowy” noise. Insufficient gain may result in incomplete spectral filling, whereas excessive gain introduces noise. The wall filter was adjusted to retain true low-velocity flow signals while adequately filtering low-frequency signals caused by vessel wall motion. Excessive filtering may truncate diastolic flow and lead to measurement errors. Doppler angle correction was consistently performed, with the correction line aligned parallel to the vessel wall. For the V2 segment of the vertebral artery, the straight portion between transverse foramina was generally used as a reference. The Doppler angle θ was maintained at ≤ 60°. The sample volume size was set to cover most of the vessel lumen without extending beyond the vessel wall (typically 1.5–2.0 mm). It was positioned in the center of the vessel, away from near-wall regions, to obtain core flow velocities representative of laminar flow. This content has been included in the Methods section. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0336216.r002
23 Oct 2025 Decision Letter - Priti Chaudhary, Editor Anatomic and Hemodynamic Characterization of Vertebral Artery Duplication via Color Doppler Ultrasonography PONE-D-25-15044R1 Dear Dr. Li Liu, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Priti Chaudhary, M.S. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0336216.r003
Formally Accepted
Acceptance Letter - Priti Chaudhary, Editor PONE-D-25-15044R1 PLOS ONE Dear Dr. Liu, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Priti Chaudhary Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0336216.r004

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