title: Decreased frontal lobe gray matter perfusion in cognitively impaired patients with secondary-progressive multiple sclerosis detected by the bookend technique.
abstract: OBJECTIVE
  There is increasing evidence implicating microvascular impairment in MS pathogenesis. Perfusion imaging offers a unique opportunity to investigate the functional impact of GM pathology. We sought to quantify differences in MR imaging-based bookend-derived cerebral perfusion between cognitively impaired and nonimpaired patients with SPMS.
  
  
  METHODS
  Patients were prospectively recruited and assessed using MR imaging and the standard cognitive battery called the Minimal Assessment of Cognitive Function in MS. Patients exhibiting impairment on ≥ 2 individual tests were classified as cognitively impaired. Healthy controls were prospectively recruited and assessed using MR imaging to validate bookend assumptions. Structural and perfusion scans were coregistered and partitioned into anatomic brain regions and tissue compartments. Clinical and radiologic characteristics were compared between patients with and without impairment to identify potential confounders. A Bonferroni adjusted P value threshold (P < .005) was used for lobar and sublobar level analyses to correct for multiple comparisons.
  
  
  RESULTS
  Thirty-seven patients with SPMS (age 56 ± 9 years; 23 women, 14 men) and 10 age- and sex-matched healthy controls were recruited. Bookend assumptions were found to be valid in MS. GM and WM qCBV were all globally reduced in impaired patients. After adjusting for potential confounders while examining sublobar level perfusion, only GM qCBV was significantly different between cognitive groups, and this hypoperfusion localized to the bilateral medial superior frontal regions and left inferior, middle, and superior frontal regions (P < .005) of impaired patients compared with nonimpaired patients. GM qCBV accounted for 22.5% of the model variance compared with a model including only confounders (P = .0007).
  
  
  CONCLUSIONS
  Bookend-derived GM qCBV was significantly reduced in cognitively impaired patients with SPMS in functionally relevant brain regions.
authors.affiliation: Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. richard.aviv@sunnybrook.ca
authors.forename: R I
authors.initials: RI
authors.lastname: Aviv
authors.forename: P L
authors.initials: PL
authors.lastname: Francis
authors.forename: R
authors.initials: R
authors.lastname: Tenenbein
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Eilaghi
authors.forename: L
authors.initials: L
authors.lastname: Lee
authors.forename: T J
authors.initials: TJ
authors.lastname: Carroll
authors.forename: J
authors.initials: J
authors.lastname: Mouannes-Srour
authors.forename: A
authors.initials: A
authors.lastname: Feinstein
mesh_terms: D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity