Abstract
Glaucoma is a disorder causing visual field loss as a result of retinal ganglion cell damage. Previous diffusion-weighted MRI (dMRI) studies demonstrated that retinal ganglion cell damage affects tissues in the optic tract and optic radiation (Nuzzi et al., 2018). However, since previous studies used the diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. Here, we used a multi-contrast MRI approach to clarify the type of microstructural damage occurring in glaucoma patients. We collected multi-shell dMRI data from 17 glaucoma patients (mean age = 56.6, 8 females) and 30 controls (mean age = 51.4 years, 14 females) using a 3T SIEMENS MRI scanner. We also collected quantitative T1 (qT1) data (Mezer et al., 2013), which are considered to be relatively specific to myelin, from all participants. We analyzed dMRI data using neurite orientation dispersion and density imaging (Zhang et al., 2012) to estimate three types of tissue property metrics (intra-cellular volume fraction, [ICVF]; orientation dispersion index, [ODI]; isotropic volume fraction, [ISoV]). We identified the optic tract and optic radiation using tractography (Sherbondy et al., 2008). In the optic tract, we found significant differences between glaucoma patients and controls for all metrics (d’ = -0.99, 1.40, -1.71, and 1.40 for qT1, ICVF, ODI, and ISoV; P < .005 in all cases). In the optic radiation, we only found significant inter-group differences in ICVF (d’ = 1.13; P < .001), not in others (d’= -0.06, -0.42, 0.19 for qT1, ODI, and ISoV; P > .1 in all cases). ICVF in the optic radiation significantly correlated with the visual field test (R = 0.50, P = 0.04). Our results suggest that tissue changes in the optic radiation might be explained by axonal damage affecting intracellular diffusion signals, rather than myelin damage.