NDLI: In Vivo Evaluation of White Matter Integrity and Anterograde Transport in Visual System After Excitotoxic Retinal Injury With Multimodal MRI and OCT.

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In Vivo Evaluation of White Matter Integrity and Anterograde Transport in Visual System After Excitotoxic Retinal Injury With Multimodal MRI and OCT.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Bo Sigal, Ian A. Schuman, Joel S. Bilonick, Richard A. Kim, Seong-Gi Wu, Ed X. Conner, Ian P. Chan, Kevin C. Ho, Leon C. Wollstein, Gadi Van Der Merwe, Yolandi
Description	Author Affiliation: Ho LC ( 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.); Wang B ( 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.); Conner IP ( 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.); van der Merwe Y ( 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.); Bilonick RA ( 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.); Kim SG ( 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.); Wu EX ( Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.); Sigal IA ( 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.); Wollstein G ( 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.); Schuman JS ( 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.); Chan KC ( 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.)
Abstract	PURPOSE: 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.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.14-15552
Journal	Investigative Opthalmology & Visual Science
Issue Number	6
Volume Number	56
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2015-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Magnetic Resonance Imaging Multimodal Imaging Optic Nerve Diseases Pathology Retinal Diseases Tomography, Optical Coherence Visual Pathways White Matter Animals Mice Mice, Inbred C57bl N-methylaspartate Administration & Dosage Rats, Sprague-dawley Chemically Induced Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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