In Vivo Assessment of Nerve Degeneration and Regeneration by Gadofluorine M Enhanced MRI

Abstract

Nerve injury represents a major cause of disability. In the peripheral nervous system nerves have the capacity to regrow, but within weeks after injury it is impossible to clarify whether proper regeneration is under way, or fails. In the present experimental study we report on a novel tool to assess nerve outgrowth in vivo. After systemic application, the novel gadolinium-based magnetic resonance (MR) contrast agent Gadofluorine M (Gf) selectively accumulated and persisted in nerve fibres undergoing Wallerian degeneration giving rise to bright contrast on T1-weighted MR images. Gf enhancement on MRI was present already at 48 hours within the entire nerve segments undergoing Wallerian degeneration, and subsequently disappeared from proximal to distal parts in parallel to regrowth of nerve fibres. Most importantly, Gf enhancement persisted in non-regenerating, permanently transected nerves. Our novel Gf-based MRI methodology holds promise for clinical use to bridge the diagnostic gap between nerve injury and completed nerve regeneration, and to determine the necessity for neurolysis and engraftment if spontaneous regeneration fails.