title: Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures.
abstract: OBJECTIVE
  White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up.
  
  
  METHODS
  Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI.
  
  
  RESULTS
  CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time.
  
  
  CONCLUSIONS
  A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: N
authors.initials: N
authors.lastname: Promjunyakul
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lahna
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA ; Department of Neurology, Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kaye
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Dodge
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA ; Department of Neurology, Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: D
authors.initials: D
authors.lastname: Erten-Lyons
authors.affiliation: Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Rooney
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA ; Department of Neurology, Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Silbert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013113:Spin Labels; D066127:White Matter / Q000098:blood supply / Q000473:pathology*
chemical_list: D013113:Spin Labels
keywords: Arterial spin labeling (ASL); CASL, continuous arterial spin labeling; CBF, cerebral blood flow; Cerebral blood flow (CBF) penumbra; Cognitive aging; DWMH, deep white matter hyperintensity; M0, the initial ASL datasets; NAWM L1, normal appearing white matter layer 1; NAWM L15, normal appearing white matter layer 15; NAWM, normal appearing white matter; PASL, pulsed arterial spin labeling; PCASL, pseudo-continuous arterial spin labeling; PVWMH, periventricular white matter hyperintensity; Vascular dementia; WMH, white matter hyperintensity; White matter hyperintensity (WMH)