Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia

AbstractIdentifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.

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4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

Neurosurgical FOCUS ◽

10.3171/2015.6.focus1590 ◽

2015 ◽

Vol 39 (3) ◽

pp. E9 ◽

Cited By ~ 25

Author(s):

Richard B. Boyer ◽

Nathaniel D. Kelm ◽

D. Colton Riley ◽

Kevin W. Sexton ◽

Alonda C. Pollins ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

High Resolution ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Diffusion Tensor ◽

Ex Vivo ◽

Nerve Fibers ◽

Nerve Transection ◽

Nerve Injuries

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

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Contiguous-slice zonally oblique multislice (CO-ZOOM) diffusion tensor imaging: Examples of in vivo spinal cord and optic nerve applications

Journal of Magnetic Resonance Imaging ◽

10.1002/jmri.21656 ◽

2009 ◽

Vol 29 (2) ◽

pp. 454-460 ◽

Cited By ~ 39

Author(s):

Nicholas G. Dowell ◽

Thomas M. Jenkins ◽

Olga Ciccarelli ◽

David H. Miller ◽

Claudia A.M. Wheeler-Kingshott

Keyword(s):

Spinal Cord ◽

Diffusion Tensor Imaging ◽

Optic Nerve ◽

Diffusion Tensor ◽

Contiguous Slice

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In vivo diffusion tensor imaging of the human optic nerve: Pilot study in normal controls

Magnetic Resonance in Medicine ◽

10.1002/mrm.20964 ◽

2006 ◽

Vol 56 (2) ◽

pp. 446-451 ◽

Cited By ~ 54

Author(s):

C.A.M. Wheeler-Kingshott ◽

S.A. Trip ◽

M.R. Symms ◽

G.J.M. Parker ◽

G.J. Barker ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Pilot Study ◽

Optic Nerve ◽

Diffusion Tensor ◽

Human Optic Nerve ◽

Normal Controls

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In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy

Epilepsia ◽

10.1111/j.1528-1167.2011.02991.x ◽

2011 ◽

Vol 52 (4) ◽

pp. 841-845 ◽

Cited By ~ 14

Author(s):

Pieter van Eijsden ◽

Wim M. Otte ◽

W. Saskia van der Hel ◽

Onno van Nieuwenhuizen ◽

Rick M. Dijkhuizen ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Status Epilepticus ◽

White Matter ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Diffusion Tensor ◽

Ex Vivo ◽

White Matter Pathology

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Longitudinal In Vivo Imaging of Retinal Ganglion Cells and Retinal Thickness Changes Following Optic Nerve Injury in Mice

PLoS ONE ◽

10.1371/journal.pone.0040352 ◽

2012 ◽

Vol 7 (6) ◽

pp. e40352 ◽

Cited By ~ 35

Author(s):

Balwantray C. Chauhan ◽

Kelly T. Stevens ◽

Julie M. Levesque ◽

Andrea C. Nuschke ◽

Glen P. Sharpe ◽

...

Keyword(s):

Optic Nerve ◽

Nerve Injury ◽

Retinal Ganglion Cells ◽

In Vivo Imaging ◽

Ganglion Cells ◽

Retinal Thickness ◽

Retinal Ganglion ◽

Optic Nerve Injury

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In vivo and ex vivo diffusion tensor imaging of cuprizone-induced demyelination in the mouse corpus callosum

Magnetic Resonance in Medicine ◽

10.1002/mrm.23032 ◽

2011 ◽

Vol 67 (3) ◽

pp. 750-759 ◽

Cited By ~ 54

Author(s):

Jiangyang Zhang ◽

Melina V. Jones ◽

Michael T. McMahon ◽

Susumu Mori ◽

Peter A. Calabresi

Keyword(s):

Diffusion Tensor Imaging ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Ex Vivo

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Mesoscopic cortical network reorganization during recovery of partial optic nerve injury in GCaMP6s mice

10.1101/2020.06.28.173799 ◽

2020 ◽

Author(s):

Marianne Groleau ◽

Mojtaba Nazari-Ahangarkolaee ◽

Matthieu P. Vanni ◽

Jacqueline L. Higgins ◽

Anne-Sophie Vézina Bédard ◽

...

Keyword(s):

Visual Acuity ◽

Optic Nerve ◽

Nerve Injury ◽

Cortical Plasticity ◽

Ganglion Cells ◽

Wide Field ◽

Optic Nerve Injury ◽

Nerve Crush ◽

Correlated Activity

AbstractAs the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 30 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated at the same time points. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 30 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

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