title: Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities.
abstract: To evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease.
  
  
  
  Blood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50-90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The τ corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and τ were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs).
  
  
  
  In comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher τ values by 31.9 (9.6)% (both P < 0.01).
  
  
  
  Vascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH.
authors.affiliation: Department of Physiology, The University of Toronto, Toronto, ON, Canada; Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sam
authors.affiliation: Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Conklin
authors.affiliation: Institute of Medical Sciences, The University of Toronto, Toronto, ON, Canada.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Holmes
authors.affiliation: Institute of Medical Sciences, The University of Toronto, Toronto, ON, Canada.
authors.forename: Olivia
authors.initials: O
authors.lastname: Sobczyk
authors.affiliation: Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Poublanc
authors.affiliation: Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Crawley
authors.affiliation: Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Mandell
authors.affiliation: Department of Anaesthesia, University Health Network, Toronto, ON, Canada.
authors.forename: Lakshmikumar
authors.initials: L
authors.lastname: Venkatraghavan
authors.affiliation: Department of Physiology, The University of Toronto, Toronto, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Duffin
authors.affiliation: Department of Physiology, The University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, The University of Toronto, Toronto, ON, Canada.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Fisher
authors.affiliation: L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada. Electronic address: mikulis@uhnres.utoronto.ca.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mikulis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure
chemical_list: D010100:Oxygen
keywords: BOLD signal; Carbon dioxide; Cerebrovascular Reactivity; Dynamic response; white matter hyperintensity