title: Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome.
abstract: OBJECTIVE
  To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects.
  
  
  METHODS
  We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar).
  
  
  RESULTS
  Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus (p = < 0.01), putamen (p < 0.01), globus pallidus (p < 0.01) and pulvinar (p < 0.05). We found no significant nor consistent trends in the relationship between susceptibility and age for either the study controls or CIS patients, in any ROI (r(2) < 0.5; p > 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI (r(2) < 0.5; p > 0.05); however, a moderate correlation (r(2) = 0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility of the caudate nucleus.
  
  
  CONCLUSIONS
  CIS patients showed an increased iron accumulation, as measured using susceptibility mapping of the deep grey matter, suggesting that iron changes did occur at the earlier stages of CIS disease.
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, UK.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Al-Radaideh
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Wharton
authors.forename: Su-Yin
authors.initials: SY
authors.lastname: Lim
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Tench
authors.forename: Paul S
authors.initials: PS
authors.lastname: Morgan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Bowtell
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.forename: Penny A
authors.initials: PA
authors.lastname: Gowland
mesh_terms: D000328:Adult; D001923:Brain Chemistry; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007501:Iron
keywords: Clinically Isolated Syndrome; Deep grey matter; brain regions; demyelinating disease; early MS; iron; magnetic resonance imaging; susceptibility mapping; ultra-high field