title: Diffusion imaging of nigral alterations in early Parkinson's disease with dopaminergic deficits.
abstract: BACKGROUND
  This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits.
  
  
  METHODS
  Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ((123) I)ioflupane dopamine transporter (DAT) single-photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra.
  
  
  RESULTS
  A repeated-measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD.
  
  
  CONCLUSIONS
  Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality.
authors.affiliation: Department of Veteran Affairs Medical Center, San Francisco, California, USA.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuff
authors.affiliation: Department of Veteran Affairs Medical Center, San Francisco, California, USA.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Wu
authors.affiliation: Department of Veteran Affairs Medical Center, San Francisco, California, USA.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Buckley
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Foster
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Coffey
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Gitelman
authors.affiliation: Institute for Neurodegenerative Disorders (IND) and Molecular Neuroimaging, LLC (MNI), New Haven, Connecticut, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Mendick
authors.affiliation: Institute for Neurodegenerative Disorders (IND) and Molecular Neuroimaging, LLC (MNI), New Haven, Connecticut, USA.
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Simuni
authors.affiliation: Department of Veteran Affairs Medical Center, San Francisco, California, USA.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Hunter
authors.affiliation: Department of Veteran Affairs Medical Center, San Francisco, California, USA.|Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.affiliation: Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Rees
authors.affiliation: Emory University, Atlanta, Georgia, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Factor
authors.affiliation: University of Tuebingen, Tuebingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.affiliation: University of Tuebingen, Tuebingen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Wurster
authors.affiliation: University of Tuebingen, Tuebingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gauss
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Sprenger
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Paracelsus-Elena Klinik, Kassel, Germany.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: Paracelsus-Elena Klinik, Kassel, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Mari
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Arita
authors.initials: A
authors.lastname: McCoy
authors.affiliation: Macquarie University, Sydney, Australia.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Ranola
authors.affiliation: Institute for Neurodegenerative Disorders (IND) and Molecular Neuroimaging, LLC (MNI), New Haven, Connecticut, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
mesh_terms: D000368:Aged; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004298:Dopamine
keywords: dopamine; fractional anisotropy; neuroimaging; substantia nigra