Faculty Collaboration Database

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease. Neurology 2018 Mar 27;90(13):e1134-e1142

Date

03/04/2018

Pubmed ID

29500287

Pubmed Central ID

PMC5880632

DOI

10.1212/WNL.0000000000005194

Scopus ID

2-s2.0-85053904496 (requires institutional sign-in at Scopus site)   77 Citations

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.

Author List

Fields ME, Guilliams KP, Ragan DK, Binkley MM, Eldeniz C, Chen Y, Hulbert ML, McKinstry RC, Shimony JS, Vo KD, Doctor A, An H, Ford AL, Lee JM

Author

Dustin K. Ragan PhD Assistant Professor in the Radiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Anemia, Sickle Cell
Brain
Cerebrovascular Circulation
Child
Child, Preschool
Cohort Studies
Female
Humans
Image Interpretation, Computer-Assisted
Magnetic Resonance Imaging
Male
Oxygen
Oxygen Consumption
Stroke
Young Adult