title: Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.
abstract: OBJECTIVE
  In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations.
  
  
  METHODS
  Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High-resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multigradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated with R2* values.
  
  
  RESULTS
  T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen, whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages.
  
  
  CONCLUSIONS
  T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits.
authors.affiliation: Institute of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany.|Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital in Prague, Charles University in Prague, Praha, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Dusek
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bahn
authors.affiliation: 2nd Department of Neurology, Institute Psychiatry and Neurology, Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Litwin
authors.affiliation: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Jabłonka-Salach
authors.affiliation: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Łuciuk
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Huelnhagen
authors.affiliation: Department of Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: V I
authors.initials: VI
authors.lastname: Madai
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.|Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin and Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Dieringer
authors.affiliation: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Bulska
authors.affiliation: Institute of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Knauth
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.|Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin and Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Niendorf
authors.affiliation: Department of Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany.|Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin and Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sobesky
authors.affiliation: Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin and Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.|NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Paul
authors.affiliation: Neurology Department, University of Kiel, Kiel, Germany.|Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: S A
authors.initials: SA
authors.lastname: Schneider
authors.affiliation: 2nd Department of Neurology, Institute Psychiatry and Neurology, Warsaw, Poland.|Department of Experimental and Clinical Pharmacology, Medical University, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Czlonkowska
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Brück
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wegner
authors.affiliation: Institute of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany.|NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin, Berlin, Germany.|Medical Imaging Analysis Center AG, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Wuerfel
mesh_terms: D000328:Adult; D001253:Astrocytes; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D003300:Copper / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005260:Female; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D003300:Copper; D007501:Iron
keywords: Wilson disease; brain; iron accumulation; pathology; post mortem 7T MRI