title: White Matter Tract Injury is Associated with Deep Gray Matter Iron Deposition in Multiple Sclerosis.
abstract: With respect to healthy controls (HCs), increased iron concentrations in the deep gray matter (GM) and decreased white matter (WM) integrity are common findings in multiple sclerosis (MS) patients. The association between these features of the disease remains poorly understood. We investigated the relationship between deep iron deposition in the deep GM and WM injury in associated fiber tracts in MS patients.
  
  
  
  Sixty-six MS patients (mean age 50.0 years, median Expanded Disability Status Scale 5.25, mean disease duration 19.1 years) and 29 HCs, group matched for age and sex were imaged on a 1.5T scanner. Susceptibility-weighted imaging and diffusion tensor imaging (DTI) were used for assessing high-pass filtered phase values in the deep GM and normal appearing WM (NAWM) integrity in associated fiber tracts, respectively. Correlation analyses investigated the associations between filtered phase values (suggestive of iron content) and WM damage.
  
  
  
  Areas indicative of increased iron levels were found in the left and right caudates as well as in the left thalamus. MS patients presented with decreased DTI-derived measures of tissue integrity in the associated WM tracts. Greater mean, axial and radial diffusivities were associated with increased iron levels in all three GM areas (r values .393 to .514 with corresponding P values .003 to <.0001). Global NAWM diffusivity measures were not related to mean filtered phase values within the deep GM.
  
  
  
  Increased iron concentration in the deep GM is associated with decreased tissue integrity of the connected WM in MS patients.
authors.affiliation: MR Research Laboratory, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.|Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.|Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tavazzi
authors.affiliation: MR Research Laboratory, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Maria Marcella
authors.initials: MM
authors.lastname: Laganà
authors.affiliation: MR Research Laboratory, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baglio
authors.affiliation: MR Research Laboratory, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cecconi
authors.affiliation: MR Research Laboratory, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Viotti
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.|MRI Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Baselli
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, IRCCS, Don Gnocchi Foundation ONLUS, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
mesh_terms: D000328:Adult; D005260:Female; D066128:Gray Matter / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging* / Q000293:injuries / Q000473:pathology
chemical_list: D007501:Iron
keywords: MRI; Multiple sclerosis; diffusion tensor imaging; iron deposition; tractography