title: Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease.
abstract: Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect >50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p<0.005) and decreased fractional anisotropy (p<0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p < or = 0.002) and correlated with the numbers of SN dopaminergic neurons (r=-0.75, p=0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-1045, USA. mboska@unmc.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.forename: Khader M
authors.initials: KM
authors.lastname: Hasan
authors.forename: Danette
authors.initials: D
authors.lastname: Kibuule
authors.forename: Rebecca
authors.initials: R
authors.lastname: Banerjee
authors.forename: Erin
authors.initials: E
authors.lastname: McIntyre
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Theresa
authors.initials: T
authors.lastname: Hahn
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
mesh_terms: D000818:Animals; D016880:Anisotropy; D001931:Brain Mapping / Q000379:methods; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D004298:Dopamine