Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese‐enhanced MRI (MEMRI)

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. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.