Chronic injury visualization of regenerating axons in vivo in hamster optic tract transection utilizing a 7 tesla FMRI and a nano contrast agent

Purpose:: A tissue gap caused by deep transections of the optic tract (OT) in the midbrain can completely block the re-innervation of the superior colliculus (SC) by the retina, even when done at young ages when the axons have regenerative potential. Previously we demonstrated 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. Methods:: 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. Results:: Imaging revealed that the first transection was complete. Imaging after the second treatment revealed regenerated axons in the SC of the SAPNS-treated animals. Conclusions:: 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