title: Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients.
abstract: Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38-0.45) compared to controls (interquartile range = 0.29-0.38), similar to participants with SCA (interquartile range = 0.37-0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Watchmaker
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Meher R
authors.initials: MR
authors.lastname: Juttukonda
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Larry T
authors.initials: LT
authors.lastname: Davis
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Allison O
authors.initials: AO
authors.lastname: Scott
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Faraco
authors.affiliation: 2 Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Gindville
authors.affiliation: 2 Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Jordan
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Petrice M
authors.initials: PM
authors.lastname: Cogswell
authors.affiliation: 3 Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, USA.|4 Department of Neurology, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Jefferson
authors.affiliation: 4 Department of Neurology, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Kirshner
authors.affiliation: 1 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA.|4 Department of Neurology, Vanderbilt University Medical Center, Nashville, USA.|5 Department of Psychiatry, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D010100:Oxygen
keywords: MRI; Oxygen extraction fraction; moyamoya; neurophysiology; stroke