title: Vascular Dysfunction in Leukoaraiosis.
abstract: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis.
  
  
  
  Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25).
  
  
  
  When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03).
  
  
  
  Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.
authors: From the Departments of Physiology (K.S., J.D., J.A.F.).|Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: K
authors: 0000-0002-1030-752X
authors: K
authors: Sam
authors: Medical Imaging (A.P.C., D.J.M.), University of Toronto, Toronto, Ontario, Canada.|Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: A P
authors: 0000-0003-4578-7110
authors: AP
authors: Crawley
authors: Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: J
authors: 0000-0001-8377-9846
authors: J
authors: Poublanc
authors: Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: J
authors: 0000-0001-9921-2086
authors: J
authors: Conklin
authors: Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: O
authors: 0000-0001-8983-1043
authors: O
authors: Sobczyk
authors: Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: D M
authors: 0000-0001-8007-4947
authors: DM
authors: Mandell
authors: From the Departments of Physiology (K.S., J.D., J.A.F.).|Department of Anesthesiology (J.D., L.V., J.A.F.), University Health Network and The University of Toronto, Toronto, Ontario, Canada.
authors: J
authors: 0000-0003-2270-7392
authors: J
authors: Duffin
authors: Department of Anesthesiology (J.D., L.V., J.A.F.), University Health Network and The University of Toronto, Toronto, Ontario, Canada.
authors: L
authors: L
authors: Venkatraghavan
authors: From the Departments of Physiology (K.S., J.D., J.A.F.).|Department of Anesthesiology (J.D., L.V., J.A.F.), University Health Network and The University of Toronto, Toronto, Ontario, Canada.
authors: J A
authors: 0000-0001-8911-3543
authors: JA
authors: Fisher
authors: L.C. Campbell Cognitive Neurology Research Unit (S.E.B.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors: S E
authors: 0000-0001-7093-8289
authors: SE
authors: Black
authors: Medical Imaging (A.P.C., D.J.M.), University of Toronto, Toronto, Ontario, Canada mikulis@uhnres.utoronto.ca.|Division of Neuroradiology (K.S., A.P.C., J.P., J.C., O.S., D.M.M., D.J.M.), Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors: D J
authors: 0000-0003-3956-0892
authors: DJ
authors: Mikulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D049292:Leukoaraiosis / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000098:blood supply* / Q000503:physiopathology