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

Abstract

Purpose: To evaluate manganese (Mn2+)-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) as tools for detection of axonal injury and regeneration after intravit-real 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 MnCl2 injection, and at 1 and 21 dpl after ONC, intravitreal PNG, and intravitreal MnCl2 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 MnCl2 injections. Both intravitreal PNG and intravitreal MnCl2 injections improved RGC survival in retina, which was reduced by 90% (ONC + MnCl 2), 82% (ONC+PNG), and 74% (ONC+PNG+MnCl2) compared to noninjured ON. DTI-derived parameters (fractional anisotropy [FA], mean diffu-sivity, axial diffusivityλ||,and radial diffusivity λ⊥) were unaffected by the presence of Mn2+ in the ON. At 1 dpl, CNRMEMRI and λ||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 immu-nohistochemical measures of axon regeneration. © 2008 Wiley-Liss, Inc.