Assessing optic nerve microstructural integrity in asymmetric glaucoma using diffusion MRI

Abstract

Purpose : Recent optic nerve (ON) diffusion magnetic resonance imaging (dMRI) studies show promise to quantify ON tissue microstructural integrity in open angle glaucoma (OAG), with ON diffusion tensor imaging (DTI) measures correlating with retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT). Nevertheless, the effect size of such relationship remains small to moderate, due to the technical challenges in achieving reliable human ON dMRI. Here, we quantify ON microstructural integrity in asymmetric OAG patients with our improved ON dMRI acquisition and analysis protocol.

Methods : Asymmetric OAG patients underwent complete eye exams including intraocular pressure (IOP), dilated fundus exam, automated visual fields, stereo disc photography, and RNFL OCT imaging; and 3T inner-volume oblique axial ON dMRI at 1.3 mm isotropic resolution (Fig. 1). The dMRI data were processed using our recently optimized ON dMRI registration scheme with nonlinear dMRI volume alignment and automated ON center region-of-interest (ROI) definition. After DTI modeling with free water elimination (FWE), radial diffusivity (RD) and fractional anisotropy (FA) of each nerve was measured in the ROI of each nerve.

Results : 8 patients, 6 females, with (mean±SD) age 66 ± 4 years, IOP 10.1 ± 3.1, 12.1 ± 3.2 mmHg, PSD 9.3 ± 2.2, 2.5 ± 2.0 db, global RNFL thickness 57.0 ± 7.1 μm, 73.1 ± 10.2 μm (Fig. 2A) in the more and less affected eyes, respectively. RD was higher in the more affected (0.52 ± 0.13 μm²/ms), than the less affected (0.37 ± 0.08 μm²/ms) eyes (Fig. 2B, reflecting increased extra-axonal space due to axonal loss. RNFL thickness strongly correlated with RD (Pearson’s r = -0.7, Fig. 2C) and FA (r = 0.7). PSD moderately correlated with RD (r = 0.45) and FA (r = -0.45).

Conclusions : The strong correlation between FWE-DTI RD with RNFL thickness even in a small cohort of OAG suggests a large effect size of our improved ON dMRI measures of microstructural integrity.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Figure 1. Representative RNFL OCT results (A,B and D,E) and the corresponding FWE-DTI RD overlaid on b0 images of the ON (C,F) of less (top) and more (bottom) affected eyes.

 

Figure 2. Line (left in A/B) and estimation plots (right in A/B) show the difference in RNFL thickness and FWE-DTI RD between the less and more affected eyes. RD strongly correlated with RNFL thickness (C, gray = regression line). Each color represents a subject.