Anterograde-propagation of axonal degeneration in the visual system of wlds mice characterized by diffusion tensor imaging

Purpose: To evaluate the feasibility of using diffusion tensor imaging (DTI) to characterize the temporospatial profile of axonal degeneration and its relation to blood–brain barrier (BBB) permeability. Materials and Methods: Longitudinal DTI was performed in Wallerian degeneration slow (WldS) mice following retinal ischemia. In parallel, gadolinium (Gd)-enhanced T₁-weighted imaging (Gd-T₁WI) was performed to evaluate BBB permeability in white matter during axonal degeneration. To confirm the in vivo findings, immunohistochemistry using SMI-31 and myelin basic protein (MBP) was performed to examine the axons and myelin, respectively, and Evans blue was used to evaluate the permeability of the BBB. Results: Reduced axial diffusivity was found in the optic nerve (ON, –15%, P = 0.0063) 1 week and optic tact (OT, –18%, P = 0.0077) 2 weeks after retinal ischemia, which were respectively associated with an 11% (P = 0.0116) and 25% (P = 0.0001) axonal loss. Increased radial diffusivity was found 1–2 weeks after the colocated decrease of axial diffusivity (35% increase, P = 0.0388 in the ON at week 2 and an 80% increase, P = 0.0015 in the OT at week 4). No significant changes were observed using Gd-T₁WI (P = 0.13–0.75), although an approximately 1-fold increase in Evans blue staining intensity was found in the injured ON and OT starting 1 week after retinal ischemia. Conclusion: We demonstrated the utility of DTI to characterize anterograde-propagating axonal degeneration through the ON and OT following retinal damage. Evans blue staining revealed serum albumin accumulation at injured sites, although there was no BBB leakage detectable using Gd-T₁WI. Level of Evidence: 2. J. Magn. Reson. Imaging 2017;45:482–491.