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J. D. Lindsey, M. Scadeng, C. K. S. Leung, R. N. Weinreb; Evaluation of Mouse Optic Tract Damage in vivo Using Anatomical and Diffusion Tensor Magnetic Resonance Imaging. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4060.
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Non-invasive strategies to directly assess the integrity of retinal ganglion cell (RGC) axons could facilitate longitudinal assessment of progression in animal models of glaucoma. Diffusion tensor (DT) imaging is a modality of magnetic resonance (MR) imaging of biological tissues in which image signal is a function of local microstructural characteristics of water diffusion. This study evaluates DT MR imaging to assess structural changes in mouse brain following optic nerve damage.
Four mice carrying a transgene for cyan fluorescent protein (CFP) driven by the promoter for Thy-1 received unilateral optic nerve crush. Loss of RGCs expressing CFP was confirmed by weekly imaging of the cells for 3 weeks using blue-light confocal scanning laser ophthalmoscopy (bCSLO). One year later, the mice were anesthetized with isofluorane and imaged in a 7-Tesla MR scanner using T1-weighted anatomical imaging (3D FLASH MRI) and DT MR imaging. Image intensity in ipsilateral and contralateral optic tract profiles, as well as in control white matter and gray matter regions, were analyzed using AMIRA and evaluated statistically.
Loss of CFP-expressing RGCs occurred by exponential decay over three weeks and then stabilized. In both FLASH and DT MR images, normal optic tracts appeared as dark bands on the ventrolateral surface of the thalamus between the chiasm and the lateral geniculate. Image intensity in the optic tract corresponding to the control nerve was the same as white matter (P>0.05, both FLASH and DT modes), but markedly differed from gray matter (FLASH control optic tract 11819±741 vs. FLASH gray matter 17718±1534, P<0.05; DT control optic tract 11960±248 vs. DT gray matter 21166±1766, P<0.05). Conversely, image intensity in the optic tract of the crushed nerve differed from white matter (FLASH crushed nerve optic tract 16554±1172 vs. FLASH white matter 11627±391, P<0.05; DT crushed nerve optic tract 20600±2526 vs. DT white matter 11687±451, P<0.05), but was the same as gray matter (P>0.05, both modes). The ratio of the control and crushed nerve optic tract image intensities was greater when obtained by DT MR imaging (1.72±0.20) than by FLASH MR imaging (1.40±0.12; P=0.02).
These data are consistent with the elimination of RGC axons from the optic tract following optic nerve crush. Thus, FLASH and DT MR imaging are promising for in vivo assessment of the optic tract axon loss. Moreover, DT MR imaging may have greater dynamic range for this purpose than FLASH MR imaging.
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