title: In Vivo Evaluation of White Matter Integrity and Anterograde Transport in Visual System After Excitotoxic Retinal Injury With Multimodal MRI and OCT.
abstract: OBJECTIVE
  Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. However, their spatiotemporal relationships remain unclear. We hypothesized that the effects of excitotoxic retinal injury (ERI) on the visual system can be revealed in vivo by diffusion tensor magnetic resonance imagining (DTI), manganese-enhanced magnetic resonance imagining (MRI), and optical coherence tomography (OCT).
  
  
  METHODS
  Diffusion tensor MRI was performed at 9.4 Tesla to monitor white matter integrity changes after unilateral N-methyl-D-aspartate (NMDA)-induced ERI in six Sprague-Dawley rats and six C57BL/6J mice. Additionally, four rats and four mice were intravitreally injected with saline to compare with NMDA-injected animals. Optical coherence tomography of the retina and manganese-enhanced MRI of anterograde transport were evaluated and correlated with DTI parameters.
  
  
  RESULTS
  In the rat optic nerve, the largest axial diffusivity decrease and radial diffusivity increase occurred within the first 3 and 7 days post ERI, respectively, suggestive of early axonal degeneration and delayed demyelination. The optic tract showed smaller directional diffusivity changes and weaker DTI correlations with retinal thickness compared with optic nerve, indicative of anterograde degeneration. The splenium of corpus callosum was also reorganized at 4 weeks post ERI. The DTI profiles appeared comparable between rat and mouse models. Furthermore, the NMDA-injured visual pathway showed reduced anterograde manganese transport, which correlated with diffusivity changes along but not perpendicular to optic nerve.
  
  
  CONCLUSIONS
  Diffusion tensor MRI, manganese-enhanced MRI, and OCT provided an in vivo model system for characterizing the spatiotemporal changes in white matter integrity, the eye-brain relationships and structural-physiological relationships in the visual system after ERI.
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 2UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylva.
authors.forename: Leon C
authors.initials: LC
authors.lastname: Ho
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Conner
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 2UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylva.
authors.forename: Yolandi
authors.initials: Y
authors.lastname: van der Merwe
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bilonick
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 6McGowan Institute for Regenerative.
authors.forename: Seong-Gi
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Sigal
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 5Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pi.
authors.forename: Gadi
authors.initials: G
authors.lastname: Wollstein
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Bioengineering, Swanson School of Engineering, University.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 2UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylva.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Chan
mesh_terms: D000818:Animals; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging; D016202:N-Methylaspartate / Q000008:administration & dosage; D009901:Optic Nerve Diseases / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
chemical_list: D016202:N-Methylaspartate