Combination of Mn(2+)-enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Thuen
Marte
M
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. marte.thuen@ntnu.no
Olsen
Oystein
O
Berry
Martin
M
Pedersen
Tina Bugge
TB
Kristoffersen
Anders
A
Haraldseth
Olav
O
Sandvig
Axel
A
Brekken
Christian
C
D000818:Animals; D002712:Chlorides; D003287:Contrast Media; D020833:Diffuse Axonal Injury / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D007089:Image Enhancement / Q000379:methods*; D017895:Manganese Compounds; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012680:Sensitivity and Specificity
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride