title: Identifying Significant Changes in Cerebrovascular Reactivity to Carbon Dioxide.
abstract: Changes in cerebrovascular reactivity can be used to assess disease progression and response to therapy but require discrimination of pathology from normal test-to-test variability. Such variability is due to variations in methodology, technology, and physiology with time. With uniform test conditions, our aim was to determine the test-to-test variability of cerebrovascular reactivity in healthy subjects and in patients with known cerebrovascular disease.
  
  
  
  Cerebrovascular reactivity was the ratio of the blood oxygen level-dependent MR imaging response divided by the change in carbon dioxide stimulus. Two standardized cerebrovascular reactivity tests were conducted at 3T in 15 healthy men (36.7 ± 16.1 years of age) within a 4-month period and were coregistered into standard space to yield voxelwise mean cerebrovascular reactivity interval difference measures, composing a reference interval difference atlas. Cerebrovascular reactivity interval difference maps were prepared for 11 male patients. For each patient, the test-retest difference of each voxel was scored statistically as z-values of the corresponding voxel mean difference in the reference atlas and then color-coded and superimposed on the anatomic images to create cerebrovascular reactivity interval difference z-maps.
  
  
  
  There were no significant test-to-test differences in cerebrovascular reactivity in either gray or white matter (mean gray matter, P = .431; mean white matter, P = .857; paired t test) in the healthy cohort. The patient cerebrovascular reactivity interval difference z-maps indicated regions where cerebrovascular reactivity increased or decreased and the probability that the changes were significant.
  
  
  
  Accounting for normal test-to-test differences in cerebrovascular reactivity enables the assessment of significant changes in disease status (stability, progression, or regression) in patients with time.
authors: From the Institute of Medical Science (O.S., D.J.M., J.A.F.) o.pucci@mail.utoronto.ca.
authors: O
authors: 0000-0001-8983-1043
authors: O
authors: Sobczyk
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory (A.P.C., J.P., K.S., D.M.M., D.J.M.).
authors: A P
authors: 0000-0003-4578-7110
authors: AP
authors: Crawley
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory (A.P.C., J.P., K.S., D.M.M., D.J.M.).
authors: J
authors: 0000-0001-8377-9846
authors: J
authors: Poublanc
authors: Department of Physiology (K.S., J.D., J.A.F.), University of Toronto, Toronto, Canada Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory (A.P.C., J.P., K.S., D.M.M., D.J.M.).
authors: K
authors: 0000-0002-1030-752X
authors: K
authors: Sam
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory (A.P.C., J.P., K.S., D.M.M., D.J.M.).
authors: D M
authors: 0000-0001-8007-4947
authors: DM
authors: Mandell
authors: From the Institute of Medical Science (O.S., D.J.M., J.A.F.) Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory (A.P.C., J.P., K.S., D.M.M., D.J.M.).
authors: D J
authors: 0000-0003-3956-0892
authors: DJ
authors: Mikulis
authors: Department of Physiology (K.S., J.D., J.A.F.), University of Toronto, Toronto, Canada Department of Anaesthesia and Pain Management (J.D., J.A.F.), University Health Network, Toronto, Canada.
authors: J
authors: 0000-0003-2270-7392
authors: J
authors: Duffin
authors: From the Institute of Medical Science (O.S., D.J.M., J.A.F.) Department of Physiology (K.S., J.D., J.A.F.), University of Toronto, Toronto, Canada Department of Anaesthesia and Pain Management (J.D., J.A.F.), University Health Network, Toronto, Canada.
authors: J A
authors: 0000-0001-8911-3543
authors: JA
authors: Fisher
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D002245:Carbon Dioxide