title: Iron deposition on SWI-filtered phase in the subcortical deep gray matter of patients with clinically isolated syndrome may precede structure-specific atrophy.
abstract: OBJECTIVE
  Increasing evidence suggests that iron deposition is present in the later stages of MS. In this study we examined abnormal phase values, indicative of increased iron content on SWI-filtered phase images of the SDGM in CIS patients and HC. We also examined the association of abnormal phase with conventional MR imaging outcomes at first clinical onset.
  
  
  METHODS
  Forty-two patients with CIS (31 female, 11 male) and 65 age and sex-matched HC (41 female, 24 male) were scanned on a 3T scanner. Mean age was 40.1 (SD = 10.4) years in patients with CIS, and 42.8 (SD = 14) years in HC, while mean disease duration was 1.2 years (SD = 1.3) in patients with CIS. MP-APT, NPTV, and normalized volume measurements were derived for all SDGM structures. Parametric and nonparametric group-wise comparisons were performed, and associations were determined with other MR imaging  metrics.
  
  
  RESULTS
  Patients with CIS had significantly increased MP-APT (P = .029) and MP-APT volume (P = .045) in the pulvinar nucleus of the thalamus compared with HC. Furthermore, the putamen (P = .004), caudate (P = .035), and total SDGM (P = .048) displayed significant increases in MP-APT volume, while MP-APT was also significantly increased in the putamen (P = .029). No global or regional volumetric MR imaging differences were found between the study groups. Significant correlations were observed between increased MP-APT volumes of total SDGM, caudate, thalamus, hippocampus, and substantia nigra with white matter atrophy and increased T2 lesion volume (P <  .05).
  
  
  CONCLUSIONS
  Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement, in the various SDGM structures, suggesting that iron deposition may precede structure-specific  atrophy.
authors.affiliation: Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, Buffalo, NY 14203, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hagemeier
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: N
authors.initials: N
authors.lastname: Bergsland
authors.forename: M
authors.initials: M
authors.lastname: Heininen-Brown
authors.forename: E
authors.initials: E
authors.lastname: Carl
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
authors.forename: C
authors.initials: C
authors.lastname: Magnano
authors.forename: D
authors.initials: D
authors.lastname: Hojnacki
authors.forename: M G
authors.initials: MG
authors.lastname: Dwyer
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism* / Q000473:pathology
chemical_list: D007501:Iron