title: Parkinson Disease: Diffusion MR Imaging to Detect Nigrostriatal Pathway Loss in a Marmoset Model Treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
abstract: OBJECTIVE
  To investigate the use of diffusion-tensor imaging (DTI) to detect denervation of the nigrostriatal pathway in a nonhuman primate model of Parkinson disease (PD) after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
  
  
  METHODS
  This study was approved by the institutional committee for animal experiments. DTI was performed in marmosets (n = 6) by using a 7-T magnetic resonance (MR) imager before and 10 weeks after administration of MPTP. Fixed brains of a normal marmoset and a marmoset model of PD (n = 1) were analyzed by using microscopic tractography. Tyrosine-hydroxylase staining of dopaminergic neurons and three-dimensional histologic analysis also were performed in normal marmosets (n = 2) and a PD marmoset model (n = 2) to validate the course of the nigrostriatal pathway revealed at tractography. Statistical analysis of voxel-based and post hoc region-of-interest analyses of DTI maps was performed by using a paired t test.
  
  
  RESULTS
  At voxel-based analysis of DTI before and after treatment, MPTP-treated marmoset brains showed significantly increased axial and radial diffusivity in the bilateral nigrostriatal pathway (P < .05, false discovery rate corrected). The largest area of significantly increased diffusivity was an area of axial diffusivity in the right hemispere (177 mm(3)) that corresponded to the location of dopaminergic neurodegeneration at histologic evaluation. Region-of-interest analysis revealed a 27% increase in axial diffusivity in the right hemisphere (1.198 mm(2)/sec ± 0.111 to 1.522 mm(2)/sec ± 0.118; P = .002). Three-dimensional histologic analysis with tyrosine-hydroxylase staining showed the course of the nigrostriatal pathway and degeneration in the PD marmoset model as the absence of a tyrosine-hydroxylase stained region. Microscopic tractography showed that the connection of the substantia nigra to the striatum followed the same course as the nigrostriatal pathway and fewer fiber tracts in the PD marmoset model.
  
  
  CONCLUSIONS
  DTI and microscopic tractography showed the loss of fiber structures of the nigrostriatal pathway in the marmoset model of PD. The results of this study provide a potential basis for the use of DTI in the clinical diagnosis of PD.
authors.affiliation: From the Departments of Physiology (K.H., R.Y., Y.K., H.O.) and Diagnostic Radiology (S.M.), Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Central Institute for Experimental Animals, Kawasaki, Japan (K.H., K.A., R.Y., K.K., Y.K., T. Inoue, T. Itoh); Faculty of Radiological Technology, Fujita Health University School of Health Sciences, Toyoake, Japan (M.Y.); Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan (H.J.O.); and Laboratory for Marmoset Neural Architecture, RIKEN Brain Science Institute, Wako, Japan (H.O.).
authors.forename: Keigo
authors.initials: K
authors.lastname: Hikishima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yano
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Komaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshio
authors.initials: T
authors.lastname: Itoh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamada
authors.forename: Suketaka
authors.initials: S
authors.lastname: Momoshima
authors.forename: Hirotaka J
authors.initials: HJ
authors.lastname: Okano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D002144:Callithrix; D003342:Corpus Striatum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D008297:Male; D009434:Neural Pathways / Q000473:pathology*; D010300:Parkinson Disease / Q000175:diagnosis*; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine