Abstract
Purpose: :
Diffusion tensor imaging (DTI) is a recently developed imaging technique that measures the random motion of water molecules reflecting integrity and pathology of central nervous system tissues. We have developed quantitative DTI parameters that are sensitive to acute and chronic retina and axon injury. Glaucoma damages retinal ganglion cells (RGCs) and their axons. We hypothesize that DTI derived axonal and myelin injury biomarker may be used to early detect axonal damage and correlating with RGC loss. The utility of DTI in imaging RGC axon degeneration in a glaucoma model was examined.
Methods: :
A mouse model of optic nerve crush (ONC) was used in this study. The progression of RGC axon degeneration was quantitatively assessed with DTI in vivo, corroborated using axon/myelin immunohistochemical staining, and retrograde fluorogold labeling.
Results: :
Optic nerves were readily recognized in DTI maps. Decreased axial diffusivity (||) and relative anisotropy (RA) of damaged axon were observed from 6 hrs to 14 days after axonal injury correlated with immunohistochemistry marker (SMI-31). The elevation of radial diffusivity () was observed distally from 7 days after ONC, also correlated with immunohistochemistry. The number of retrograde-labeled RGCs did not decline significantly until day 7, but DTI detected axon injury at 6hrs and SMI31 identified axon damage at 3 days after ONC. There was a significant correlation between RGC loss and optic nerve axon damage after crush.
Conclusions: :
We show evidence of RGC axon degeneration prior to the ganglion cell body loss using in vivo derived axial diffusivity to quantify optic nerve axonal damage. These results suggest that DTI of optic nerve injury may be used as a noninvasive tool for assessing the pathogenesis of RGC axon injury.
Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • neuroprotection