title: Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis.
abstract: OBJECTIVE
  To assess the correlation between cognitive impairment and overall vs regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI tractography in multiple sclerosis (MS).
  
  
  METHODS
  Brain dual-echo, T1-weighted, and DT MRI data were acquired from 82 patients with MS. DT tractography was used to produce maps of white matter (WM) tracts involved in cognition. The sensory thalamocortical projections and optic radiations were studied as "control" WM tracts. The contribution of global brain damage (T2 lesion volume, normalized brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal-appearing WM and GM damage) and damage to selected WM tracts to overall cognitive impairment and to impairment at individual neuropsychological tests was assessed using a random forest (RF) analysis.
  
  
  RESULTS
  Thirty-three patients had cognitive impairment. The majority of MRI measures differed significantly between cognitively impaired and cognitively preserved (CP) patients. Significant correlations were found between performance in the majority of neuropsychological tests and global or regional brain damage (r ranging from -0.60 to 0.57). The RF analysis showed a high performance in classifying cognitively impaired vs CP patients, with a classification (C)-index = 76.8, as well as in classifying patients' impairment in individual neuropsychological tests (C-index between 75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather than measures of normal-appearing WM damage in the same tracts or global brain/WM/GM damage, resulted in the highest classification accuracy.
  
  
  CONCLUSIONS
  Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. m.filippi@hsr.it
authors.forename: S
authors.initials: S
authors.lastname: Mesaros
authors.forename: M A
authors.initials: MA
authors.lastname: Rocca
authors.forename: K
authors.initials: K
authors.lastname: Kacar
authors.forename: J
authors.initials: J
authors.lastname: Kostic
authors.forename: M
authors.initials: M
authors.lastname: Copetti
authors.forename: T
authors.initials: T
authors.lastname: Stosic-Opincal
authors.forename: P
authors.initials: P
authors.lastname: Preziosa
authors.forename: S
authors.initials: S
authors.lastname: Sala
authors.forename: G
authors.initials: G
authors.lastname: Riccitelli
authors.forename: M A
authors.initials: MA
authors.lastname: Horsfield
authors.forename: J
authors.initials: J
authors.lastname: Drulovic
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D009483:Neuropsychological Tests; D013577:Syndrome; D055815:Young Adult