Using a 7 Tesla fMRI and a nano contrast agent to visualize axon regeneration in vivo after chronic optic tract injury in hamsters

Abstract

Deep transections in the optic tract (OT) cause tissue gaps in the midbrain, completely blocking the re-innervation of the superior colliculus (SC) by the retina, even when done at young ages when the axons have regenerative potential. We previously showed that a self-assembling peptide nanofiber scaffold (SAPNS) facilitated the reconstruction of a tissue substrate that supports regeneration across the tissue disruption, even if treated 3 months after the original lesion. Here we show that by using a nano contrast agent (NCA) optic tract regeneration can be visualized in vivo in a mammalian chronic injury model. In a group of young adult hamsters (8 wk), the OT at the brachium of the SC was completely severed with a deep knife wound, extending 1-2 mm below the surface from the midline to a point beyond the lateral margin of SC. Following the transection of the optic tract at the brachium of the SC, the eyes were injected with a NCA and imaged in a 7 Tesla fMRI. This was repeated 3 more times just before the second surgery and SAPNS treatment, then twice following the treatment. During the second OT surgery the animals had a partial scar resection and were injected with 100 ul of 1% SAPNS into the site of injury. The contralateral side of the same animal served as the control. Imaging revealed that the first transection was complete. Imaging after the second treatment revealed regenerated axons in the SC of the SAPNS-treated animals. A 7 Tesla fMRI is able to detect axons in the optic tract in hamsters before, during and after regeneration in a chronic injury treatment model.