MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve.
Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used to investigate central nervous system (CNS) white matter structure and pathology. Changes in principal diffusivities parallel and perpendicular to nerve fibers or axonal tracts have been associated with axonal pathology and de/dysmyelination respectively. However, the ultra-structural properties and the pathological alterations of white matter responsible for diffusivity changes have not been fully elucidated. We examined the relationship between the directional diffusivities and ultra-structural properties in mouse optic nerve using healthy animals, and mice with optic neuritis (ON) that exhibited marked inflammatory changes and moderately severe axonal pathology. Progressive axonal degeneration in ON resulted in a 23% reduction of parallel diffusivity as detected by diffusion MRI (P<10(-5)), but no change in perpendicular diffusivity. Parallel diffusion changes were highly correlated with the total axolemmal cross-sectional area in the pre-chiasmal portion of the optic nerve (r=0.86, P<0.001). This study provides quantitative evidence that reduced parallel diffusivity in the optic nerve correlates significantly with axolemmal cross-sectional area reductions. MRI-based assessment of axonal degeneration in murine ON is feasible and potentially useful for monitoring of neuro-protective therapies in preclinical trials in animals.
Wu
Qizhu
Q
Howard Florey Institute, University of Melbourne, VIC 3010, Australia.
Butzkueven
Helmut
H
Gresle
Melissa
M
Kirchhoff
Frank
F
Friedhuber
Anna
A
Yang
Qing
Q
Wang
Hong
H
Fang
Ke
K
Lei
Hao
H
Egan
Gary F
GF
Kilpatrick
Trevor J
TJ
D000465:Algorithms; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure*; D003627:Data Interpretation, Statistical; D038524:Diffusion Magnetic Resonance Imaging; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D006023:Glycoproteins / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology; D009901:Optic Nerve Diseases / Q000473:pathology*
D006023:Glycoproteins