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Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species., Materials and Methods: The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl(2) injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl)., Results: Signal intensity profiles of the Mn(2+)-enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn(2+)-enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration., Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To evaluate manganese (Mn(2+))-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 echo-planar 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% (ONC+MnCl(2)), 82% (ONC+PNG), and 74% (ONC+PNG+MnCl(2)) compared to noninjured ON. DTI-derived parameters (fractional anisotropy [FA], mean diffusivity, axial diffusivity lambda( parallel), and radial diffusivity lambda( perpendicular)) were unaffected by the presence of Mn(2+) in the ON. At 1 dpl, CNR(MEMRI) and lambda( parallel) 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.

Purpose: To provide dose-response data for the safe and effective use of MnCl(2) for manganese (Mn(2+)) -enhanced MRI (MEMRI) of the visual pathway., Materials and Methods: Retinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density resolution for MEMRI, mode of axonal transport and clearance of Mn(2+) from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl(2), neural toxicity was measured by counting surviving RGC back-filled with FluroGold (FG), CNR of the vitreous body and visual pathway by three-dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with axon density, and axonal transport of Mn(2+) by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl(2)., Results: There were no changes in RGC density after ivit MnCl(2) 0 were recorded distally from the ion site, but there was no signal in the retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired., Conclusion: The optimal dose for MEMRI of the rat visual pathway was found to be 150-300 nmol ivit MnCl(2). Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn(2+) enhancement throughout the visual pathway. Mn(2+) traffic within RGC axons is mediated mainly by anterograde transport., ((c) 2008 Wiley-Liss, Inc.)

Purpose: To evaluate manganese (Mn2+)-enhanced MRI in a longitudinal study of normal and injured rat visual projections., Materials and Methods: MRI was performed 24 hours after unilateral intravitreal injection of MnCl2 (150 nmol) into adult Fischer rats that were divided into four groups: 1) controls (N = 5), 2) dose-response (N = 10, 0.2-200 nmol), 3) time-response with repeated MRI during 24-168 hours post injection (N = 4), and 4) optic nerve crush (ONC) immediately preceding the MnCl2 injection (N = 7). Control and ONC animals were reinjected with MnCl2 20 days after the first injection, and MRI was performed 24 hours later., Results: In the control group, the optic projection was visualized from the retina to the superior colliculus, with indications of transsynaptic transport to the cortex. There was a semilogarithmic relationship between the Mn2+ dose and Mn2+ enhancement from 4 to 200 nmol, and the enhancement decayed gradually to 0 by 168 hours. No Mn2+-enhanced signal was detected distal to the ON crush site. In the control group, similar enhancement was obtained after the first and second MnCl2 injections, while in the ONC group the enhancement proximal to the crush site was reduced 20 days post lesion (20 dpl)., Conclusion: Mn2+-enhanced MRI is a viable method for temporospatial visualization of normal and injured ON in the adult rat. The observed reduction in the Mn2+ signal proximal to the ONC is probably a result of retrograde damage to the retinal ganglion cells, and not of Mn2+ toxicity., ((c) 2005 Wiley-Liss, Inc.)