title: Quantitative Susceptibility Mapping Suggests Altered Brain Iron in Premanifest Huntington Disease.
abstract: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression.
  
  
  
  Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures.
  
  
  
  Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores.
  
  
  
  The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland Jiri.vanbergen@uzh.ch.
authors.forename: J M G
authors.identifier: 0000-0003-4001-6149
authors.initials: JM
authors.lastname: van Bergen
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: J
authors.identifier: 0000-0001-5481-7380
authors.initials: J
authors.lastname: Hua
authors.affiliation: Psychiatry and Behavioral Sciences (P.G.U., R.L.M., C.A.R.) Division of Psychiatry Research and Psychogeriatric Medicine (P.G.U.), University of Zurich, Zurich, Switzerland.
authors.forename: P G
authors.identifier: 0000-0002-6116-3386
authors.initials: PG
authors.lastname: Unschuld
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: I A L
authors.identifier: 0000-0002-0621-5948
authors.initials: IA
authors.lastname: Lim
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: C K
authors.identifier: 0000-0002-0629-3006
authors.initials: CK
authors.lastname: Jones
authors.affiliation: Psychiatry and Behavioral Sciences (P.G.U., R.L.M., C.A.R.) Neurology (R.L.M., C.A.R.), Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: R L
authors.identifier: 0000-0003-3024-8595
authors.initials: RL
authors.lastname: Margolis
authors.affiliation: Psychiatry and Behavioral Sciences (P.G.U., R.L.M., C.A.R.) Neurology (R.L.M., C.A.R.), Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: C A
authors.identifier: 0000-0003-1882-5847
authors.initials: CA
authors.lastname: Ross
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: P C M
authors.identifier: 0000-0002-9706-1066
authors.initials: PC
authors.lastname: van Zijl
authors.affiliation: From the Departments of Radiology and Radiological Sciences (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.) F.M. Kirby Research Center for Functional Brain Imaging (J.M.G.v.B., J.H., I.A.L.L., C.K.J., P.C.M.v.Z., X.L.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: X
authors.identifier: 0000-0002-4350-3375
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*
chemical_list: D007501:Iron