title: Diffusion tensor imaging detects retinal ganglion cell axon damage in the mouse model of optic nerve crush.
abstract: OBJECTIVE
  Diffusion tensor imaging (DTI) measures the random motion of water molecules reflecting central nervous system tissue integrity and pathology. Glaucoma damages retinal ganglion cells (RGCs) and their axons. The authors hypothesized that DTI-derived axonal and myelin injury biomarkers may be used to detect early axonal damage and may be correlated with RGC loss in the mouse model of optic nerve crush (ONC).
  
  
  METHODS
  The progression of RGC axon degeneration was quantitatively assessed with DTI in vivo, corroborated with axon/myelin immunohistochemical staining and retrograde fluorogold labeling in mice after ONC.
  
  
  RESULTS
  Decreased axial diffusivity (λ(‖)) and relative anisotropy (RA) of damaged axons were observed from 6 hours to 14 days, reflecting axonal injury. DTI detected axonal injury at 6 hours after ONC when SMI-31 did not detect axonal abnormality. Both decreased λ(‖), and SMI-31 identified axon damage at 3 days after ONC. Decreased λ(‖) correlated with reduced SMI-31-positive axon counts from 3 days after ONC. In contrast, the increased λ(⊥) was seen only in the distal segment of optic nerve whereas decreased myelin basic protein-positive axon counts were seen in all segments 3 days after ONC. The number of retrograde-labeled RGCs did not decline significantly until 7 days after ONC. There was a significant correlation between RGC loss and optic nerve axon damage.
  
  
  CONCLUSIONS
  The authors demonstrated that in vivo DTI detected axonal injury earlier than SMI-31. Results suggest that in vivo DTI of optic nerve injury may be used as a noninvasive tool for assessing the pathogenesis of RGC axonal injury.
authors.affiliation: Department of Radiology, Washington University, St. Louis, Missouri, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000175:diagnosis / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000175:diagnosis* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013266:Stilbamidines
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D015415:Biomarkers; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D013266:Stilbamidines