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March 27, 2018; 90 (13) Article

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease

Melanie E. Fields, Kristin P. Guilliams, Dustin K. Ragan, Michael M. Binkley, Cihat Eldeniz, Yasheng Chen, Monica L. Hulbert, Robert C. McKinstry, Joshua S. Shimony, Katie D. Vo, Allan Doctor, Hongyu An, Andria L. Ford, Jin-Moo Lee
First published March 2, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005194
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Article Information

vol. 90 no. 13 e1134-e1142
DOI: 
https://doi.org/10.1212/WNL.0000000000005194
PubMed: 
29500287
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received March 23, 2017
  • Accepted in final form December 5, 2017
  • First Published March 2, 2018.

Article Versions

Copyright & Usage: 
© 2018 American Academy of Neurology

Author Disclosures

    1. Melanie E. Fields, MD, MSCI*,
    2. Kristin P. Guilliams, MD, MSCI*,
    3. Dustin K. Ragan, PhD,
    4. Michael M. Binkley, MS,
    5. Cihat Eldeniz, PhD,
    6. Yasheng Chen, DSc,
    7. Monica L. Hulbert, MD,
    8. Robert C. McKinstry, MD, PhD,
    9. Joshua S. Shimony, MD, PhD,
    10. Katie D. Vo, MD,
    11. Allan Doctor, MD,
    12. Hongyu An, DSc,
    13. Andria L. Ford, MD, MSCI† and
    14. Jin-Moo Lee, MD, PhD†
  1. Melanie E. Fields, MD, MSCI*,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. 1. NIH NHLBI, K12 5K12HL087107, Scholar, 8/1/2014- 5/31/2017 2. NIH NHLBI, 1K23HL136904-01, PI, 6/1/2017- 5/31/2021 3. NIH NCATS UL1TR000448, PI - Research Forum for Child Health Supplemental Funding Award, 04/01/2013 - 03/31/2017 4. NIH NHCHD U54 HD087011, PI - Washington University Intellectual and Developmental Disabilities Research Center, 5/15/2016- 11/15/2017 5. NIH NCATS UL1TR000448, PI - Foundation for Barnes-Jewish Hospital and Washington University Institute of Clinical and Translational Sciences, 7/1/2017- 6/30/2018

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1. Mallinckrodt Institute of Radiology Pilot Study Award, 2/1/2015- 3/31/2016 2. American Society of Hematology Fellow Scholar Award, 7/1/2017- 6/30/2019 Stock/Stock Options, Medical Equipment & Materials: 1. Equity ownership in Proclara Biosciences.

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Kristin P. Guilliams, MD, MSCI*,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Asian and Oceanian Congress of Child Neurology, funding for travel to speak at conference

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Dustin K. Ragan, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Michael M. Binkley, MS,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. My Ph.D. fellowship is sponsored by the NIH using the training program for a separate project in pulmonary medicine for the development of a microfluidic diagnostic test for COPD. Grant T32HL007317-39, graduate student trainee, 1 year, National Institutes of Health

    Research Support, Academic Entities:

    1. Washington University in St. Louis, Department of Mechanical Engineering and Material Science

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Cihat Eldeniz, PhD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. (1) [Purpose: Obtaining images without motion blurring at multiple respiratory phases.] Free-breathing and self-navigated MRI method for deformable motion derivation US provisional application # 62/446,193 (2) [Purpose: Obtaining an attenuation correction map for simultaneous PET/MR.] Dual Flip Angle Multi-Echo Ultra-Short Echo Time (DUFA- MUTE) Magnetic Resonance Imaging (MRI) Systems and Methods US provisional application # 62/445,817

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. National Institute of Health, P30 NS098577, PI: Hongyu An, Role: Postdoctoral Research Associate, Years: 2 years [perhaps ???]

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Yasheng Chen, DSc,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. The NIH HL129241, R01NS085419, R01NS082561, P30NS098577

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Monica L. Hulbert, MD,
    8. Scientific Advisory Boards:

    1. Sickle Cell Transplant Alliance for Research

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Pediatric Blood and Cancer, editorial board member, 20116-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. My husband is employed at Pfizer, Inc as a quality control scientist; 2012- present

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. State of Missouri, grant # C3143345003, PI, 2012-2018 HRSA, 2U1EMC278650400, co-investigator, 2014-2017 NIH, R01 HL129241-02, co-investigator, 2015-2020 NIH, 5U1EMC278650300, co-infestigator, 2017-2022 Stock/Stock Options, Medical Equipment & Materials: stock in Pfizer, Inc as part of my husband's employment/retirement plan

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Robert C. McKinstry, MD, PhD,
    9. Scientific Advisory Boards:

    1. Guerbet, LLC

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Siemens Healthcare - travel, meals and honoraria. Philips - travel and meals.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH 2R01HD055741-11 Investigator 07/01/2007 ? 7/31/2022 NIH 2UL1TR000448-06 Core Director 09/17/2007 ? 05/31/2017 NIH 1UL1TR002345-01 Core Director 01/19/2017 - 02/28/2022 NIH 1U01NS092764-01A1 Investigator 09/30/2016 ? 06/30/2021

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. March of Dimes Investigator 11/01/2014 ? 10/31/2019

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Joshua S. Shimony, MD, PhD,
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) NIH R01 CA203861 PI (2) NIH R01 MH114970 PI (3) NIH U54 HD087011 Co-I

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. I routinely testify in legal cases, mostly related to Traumatic brain injury or Injured infant cases. These do not relate to the current manuscript.

  10. Katie D. Vo, MD,
    11. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Allan Doctor, MD,
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. Biogen, Inc.

    Funding for travel or speaker honoraria:

    1. Biogen, Inc.

    Editorial Boards:

    1. Pediatric Critical Care Medicine (past 5Y) (editorial board)

    Patents:

    1. 2005 U.S. Patent # 7,763,472. Methods for Identifying and Measuring S-Nitrosothiol Bonds in Heme-containing Cells and Molecules. 2016 U.S. Patent # 9,486,508. Blood Substitute Composition and Method of Use (NanoCrit). Also filed in: Europe, Australia, Canada, Japan and South Africa.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Entegrion, Inc. Terumo, BCT KaloCyte, Inc.

    Research Support, Government Entities:

    1. NIH/NIGMS/NHLBI 1R01GM113838; PI 2015-20 NIH/NHLBI 1R42HL135965-01A1; PI 2017-20 DoD GRANT12234110; PI 2017-20

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Children?s Discovery Institute, CH-LI-2013-420; PI 2013-17

    Stock/Stock Options/Board of Directors Compensation:

    1. KaloCyte, Inc.

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. KaloCyte, Inc. Stock/Stock Options, Medical Equipment & Materials: KaloCyte, Inc.

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Hongyu An, DSc,
    13. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH, R01NS082561, PI, 04/01/14-03/31/19 NIH, 1P30NS098577, PI, 07/01/16-06/30/20 NIH, 1R01HL129241-01, Co-I, 08/01/15-05/31/19

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  13. Andria L. Ford, MD, MSCI† and
    14. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH NHLBI, R01HL129241, PI, 2015-2020 NIH UL1 TR000448, Washington University Institute of Clinical and Translational Science, Project PI, 2015-2016

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  14. Jin-Moo Lee, MD, PhD†
    15. Scientific Advisory Boards:

    1. DSMB for the CN-105 CATCH Trial, AegisCN LLC

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Translational Stroke Research, Editorial Board, 2012- present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) NIH NINDS R01NS084028 PI 7/17/13-6/30/18 (2) NIH NINDS R01NS085419 PI 4/1/14-3/31/19 (3) NIH NIA R21AG055333 PI 3/15/17-2/28/19 (4) NIH NINDS R01NS094692 PI 8/1/17-5/31/22

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Barnes-Jewish Hospital Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Division of Pediatric Hematology/Oncology (M.E.F., M.L.H.), Division of Pediatric Neurology (K.P.G.), Division of Pediatric Critical Care Medicine (K.P.G., A.D.), Department of Neurology (D.K.R., Y.C., A.L.F., J.-M.L.), and Mallinckrodt Institute of Radiology (C.E., R.C.M., J.S.S., K.D.V., H.A., J.-M.L.), Washington University School of Medicine; and Department of Biomedical Engineering (M.B.M., J.-M.L.), Washington University, St. Louis, MO.
  1. Correspondence
    Dr. Lee leejm{at}neuro.wustl.edu or Dr. Ford forda{at}wustl.edu
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