MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve

Wu, Qisong; Butzkueven, Helmut; Gresle, Melissa; Kirchhoff, Frank; Friedhuber, Anna; Yang, Qing; Wang, Hong; Fang, Ke; Lei, Hao; Egan, Gary F.; Kilpatrick, Trevor J.

doi:10.1016/j.neuroimage.2007.06.029

Cited by 78 publications

(84 citation statements)

References 42 publications

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“…White matter injury reduces in the mouse ON (28,44,46,49), and our value of approximately 1 m 2 /msec measured at the ONC site is in agreement with previous findings (28,44,46,49). The reduced at the ONC site is not unexpected, as all longitudinal structures, such as microtubule, neurofilaments, axonal membranes, and myelin sheaths, are disrupted by the ON transection.…”

Section: Memri and Dti Used To Detect On Injury And Regenerationsupporting

confidence: 92%

Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

Thuen

Olsen

Berry

et al. 2008

Magnetic Resonance Imaging

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Purpose:To evaluate manganese (Mn 2ϩ )-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) as tools for detection of axonal injury and regeneration after intravitreal peripheral nerve graft (PNG) implantation in the rat optic nerve (ON). Materials and Methods:In adult Fischer rats, retinal ganglion cell (RGC) survival was evaluated in Flurogold (FG) back-filled retinal whole mounts after ON crush (ONC), intravitreal PNG, and intravitreal MnCl 2 injection (150 nmol) at 0 and 20 days post lesion (dpl). MEMRI and echoplanar DTI (DTI-EPI) was obtained of noninjured ON one day after intravitreal MnCl 2 injection, and at 1 and 21 dpl after ONC, intravitreal PNG, and intravitreal MnCl 2 injections given at 0 and 20 dpl. GAP-43 immunohistochemistry was performed after the last MRI.Results: ONC reduced RGC density in retina by 94% at 21 dpl compared to noninjured ON without MnCl 2 injections. Both intravitreal PNG and intravitreal MnCl 2 injections improved RGC survival in retina, which was reduced by 90% (ONCϩMnCl 2 ), 82% (ONCϩPNG), and 74% (ONCϩPNGϩMnCl 2 ) compared to noninjured ON. DTIderived parameters (fractional anisotropy [FA], mean diffusivity, axial diffusivity , and radial diffusivity Ќ ) were unaffected by the presence of Mn 2ϩ in the ON. At 1 dpl, CNR MEMRI and were reduced at the injury site, while at 21 dpl they were increased at the injury site compared to values measured at 1 dpl. GAP-43 immunoreactive axons were present in the ON distal to the ONC injury site. Conclusion:MEMRI and DTI enabled detection of functional and structural degradation after rat ON injury, and there was correlation between the MRI-derived and immunohistochemical measures of axon regeneration. UNLIKE AXONS IN THE PERIPHERAL NERVOUS SYS-TEM, those in the central nervous system (CNS) of adult mammals do not regenerate after injury (1,2). Failure to regenerate is attributed to a combination of axon growth arrest by myelin-associated and scar-derived inhibitory molecules (3,4), and to the absence of growth-promoting neurotrophic factors in the adult CNS (5). Several therapeutic interventions have been tested in animal models to try to promote axon regeneration in the adult mammalian CNS, including neutralizing inhibitory molecules by bacterial enzyme chondroitinase ABC (6) and administration of growthpromoting factors released, for example, from olfactory ensheathing cells and stem cells (7,8). One method that has been shown to have an effect in an optic nerve (ON) animal model is the intravitreal implantation of a peripheral nerve graft (PNG) after ON transection. Schwann cells in the PNG produce trophic factors that promote both retinal ganglion cell (RGC) survival and axon growth through the putative inhibitory environment of the injured ON, as documented in several studies (9 -11). Most studies detect regenerating axons in the CNS using traditional axon tracing techniques (e.g.,

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Section: Memri and Dti Used To Detect On Injury And Regenerationsupporting

confidence: 92%

Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

Thuen

Olsen

Berry

et al. 2008

Magnetic Resonance Imaging

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“…Various DTI-histology correlations in animal models have demonstrated relationships of diffusion anisotropy with axonal density and extra-axonal fraction (Takahashi et al, 2002;Schwartz et al, 2005;Wu et al, 2007), although we only found trends with these parameters in our small sample of in vivo results in the fimbria-fornix of humans with TLE (Table 3, Fig. 4).…”

Section: Discussionmentioning

confidence: 59%

In VivoDiffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy

Concha¹,

Livy²,

Beaulieu³

et al. 2010

J. Neurosci.

198

165

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While diffusion tensor imaging (DTI) has been extensively used to infer micro-structural characteristics of cerebral white matter in human conditions, correlations between human in vivo DTI and histology have not been performed. Temporal lobe epilepsy (TLE) patients with mesial temporal sclerosis (MTS) have abnormal DTI parameters of the fimbria-fornix (relative to TLE patients without MTS) which are presumed to represent differences in axonal/myelin integrity. Medically intractable TLE patients who undergo temporal lobe resection including the fimbria-fornix provide a unique opportunity to study the anatomical correlates of water diffusion abnormalities in freshly excised tissue. Eleven patients with medically intractable TLE were recruited (six with and five without MTS) for presurgical DTI followed by surgical excision of a small specimen of the fimbria-fornix which was processed for electron microscopy. Blinded quantitative analysis of the microphotographs included axonal diameter, density and area, cumulative axon membrane circumference, and myelin thickness and area. As predicted by DTI the fimbria-fornix of TLE patients with MTS had increased extra-axonal fraction, and reduced cumulative axonal membrane circumference and myelin area. Consistent with the animal literature, water diffusion anisotropy over the crus of the fimbria-fornix was strongly correlated with axonal membranes (cumulative membrane circumference) within the surgical specimen (ϳ15% of what was analyzed with DTI). The demonstration of a correlation between histology and human in vivo DTI, in combination with the observation that in vivo DTI accurately predicted white matter abnormalities in a human disease condition, provides strong validation of the application of DTI as a noninvasive marker of white matter pathology.

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“…Although axonal organization and packing may underpin the observed changes, the increase in the proportion of myelinated fibers within the measured region may also have contributed to the trend towards an increase in mean diffusivity and axial diffusivity. Consistent with this idea, demyelination of the corpus callosum has been shown to result in decreased axial diffusivity with no change in radial diffusivity (Wu et al, 2007). In this study we used a highorder tractography model to detect differences between groups; however the small animal numbers in each group limited the power of our analysis.…”

Section: Discussionmentioning

confidence: 81%

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

et al. 2013

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AbbreviationsChAT: Choline acetyl transferase dMRI: diffusion MRI FA: fractional anisotropy MCI: mild cognitive impairment MRI: magnetic resonance imaging p75 NTR : p75 neurotrophin receptor PB: phosphate buffer PBS: phosphate buffered saline ROI: region of interest SAP: saporin KeywordsCholinergic basal forebrain, tractography, p75 neurotrophin receptor, MRI, diffusion weighted imaging, neurodegeneration 3

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MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve

Cited by 78 publications

References 42 publications

Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

In VivoDiffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

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MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve

Cited by 78 publications

References 42 publications

Combination of Mn2+‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

Combination of Mn2+‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

In VivoDiffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

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Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve

Combination of Mn²⁺‐enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve