Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

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
Melanie E. Fields
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristin P. Guilliams
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dustin K. Ragan
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael M. Binkley
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cihat Eldeniz
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasheng Chen
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monica L. Hulbert
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert C. McKinstry
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua S. Shimony
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katie D. Vo
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allan Doctor
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongyu An
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andria L. Ford
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jin-Moo Lee
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.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
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
Neurology Mar 2018, 90 (13) e1134-e1142; DOI: 10.1212/WNL.0000000000005194

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
253

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Objective To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD.

Methods Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps.

Results Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort.

Conclusions Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

GLOSSARY

CBF=
cerebral blood flow;
CMRO2=
cerebral metabolic rate of oxygen utilization;
FLAIR=
fluid-attenuated inversion recovery;
HbA=
hemoglobin A;
HbS=
hemoglobin S;
HbSβthal0=
hemoglobin S-β thalassemia null;
HbSS=
hemoglobin SS;
MCA=
middle cerebral artery;
MRA=
magnetic resonance angiography;
OEF=
oxygen extraction fraction;
SCD=
sickle cell disease;
SCI=
silent cerebral infarct;
TCD=
transcranial Doppler

Footnotes

  • ↵* Drs. Fields and Guilliams contributed equally and are designated as co–first authors.

  • ↵† Drs. Ford and Lee contributed equally and are designated as co–senior authors.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 585

  • Received March 23, 2017.
  • Accepted in final form December 5, 2017.
  • © 2018 American Academy of Neurology
View Full Text

AAN Members

We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.

Google Safari Microsoft Edge Firefox

Click here to login

AAN Non-Member Subscribers

Click here to login

Purchase access

For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)

Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here 

Purchase
Individual access to articles is available through the Add to Cart option on the article page.  Access for 1 day (from the computer you are currently using) is US$ 39.00.  Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means.  The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use.  Distributing copies (electronic or otherwise) of the article is not allowed.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • GLOSSARY
    • Methods
    • Results
    • Discussion
    • Author contributions
    • Study funding
    • Disclosure
    • Acknowledgment
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study

Dr. Robert Shapiro and Dr. Amynah Pradhan

► Watch

Related Articles

  • The promise of noninvasive cerebral hemodynamic assessment in sickle cell anemia

Topics Discussed

  • All Cerebrovascular disease/Stroke
  • MRI
  • Infarction
  • Hematologic
  • Childhood stroke

Alert Me

  • Alert me when eletters are published
Neurology: 100 (5)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise