title: Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson's Disease Stages?
abstract: BACKGROUND
  Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson's disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD.
  
  
  METHODS
  Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients.
  
  
  RESULTS
  The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages.
  
  
  CONCLUSIONS
  Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Hopes
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grolez
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Neuroradiology, Lille University Hospital, Lille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lopes
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ryckewaert
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carrière
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Small Animal Imaging Unit, Lille University, Lille, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Auger
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Medical Pharmacology, Lille University, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Laloux
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Medical Pharmacology, Lille University, Lille, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Petrault
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Medical Pharmacology, Lille University, Lille, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Devedjian
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Medical Pharmacology, Lille University, Lille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Defebvre
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Neuroradiology, Lille University Hospital, Lille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Jissendi
authors.affiliation: INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Neuroradiology, Lille University Hospital, Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delmaire
authors.affiliation: Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.|INSERM U1171, Faculty of Medicine, Lille University, Lille, France.|Department of Medical Pharmacology, Lille University, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Devos
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000208:Acute Disease; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003342:Corpus Striatum / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007501:Iron / Q000032:analysis; D019190:Iron Overload / Q000150:complications; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology*; D010302:Parkinson Disease, Secondary / Q000150:complications / Q000473:pathology; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D015415:Biomarkers; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron