Diffusion MRI Detects Axonal Loss in Glaucomatous Optic Nerve

Abstract

Purpose : Optic axonopathy in glaucoma can cause irreversible damage of optic nerve (ON) and blindness. We have developed a diffusion basis spectrum imaging (DBSI) to noninvasively assess axonal injury/loss in the presence of coexisting inflammation in ON. The current study aims to assess the relationship between optical coherence tomography (OCT)-detected retinal nerve fiber layer (RNFL) thinning with DBSI-determined axonal loss in glaucoma patients.

Methods : Ten healthy control (CTL) and nineteen patients with glaucoma were recruited. Ophthalmic exams were performed on glaucoma subjects only. DBSI was performed on a 3T Siemens Prisma scanner with 64-channel head coil. Two image slices were adjusted perpendicular to the ON axis (Fig.1A-C). A 31-direction diffusion-weighted (DW) scheme was performed on both ON with single-shot EPI: TR = 2.5 s, TE = 53.8 ms, in-plane resolution=1.1 x1.1 mm², slice thickness=4 mm, max b-value=1,000 s/mm², and total acquisition time=4.5 min for each eye. Diffusion tensor imaging (DTI) and DBSI derived metrics were computed using lab-developed software.

Results : By adding extra radio frequency pulse perpendicular to ON, DW can suppress the surrounding cerebrospinal fluid (CSF) signals more accurately reflecting ON atrophy (Fig.1D,E). The corresponding DBSI metrics (Fig. 2 upper panel) detected coexisting pathologies in ON. In the glaucoma cohort, no change was seen in DBSI restricted fraction (Fig.2A). DBSI detected significant 40% increase of non-restricted fraction (Fig.2B) and 50% decrease of axonal volume (Fig.2C) compared to CTL. Residual axons were not damaged as reflected by insignificant changes in DBSI λ_|| (Fig.2E) and DBSI λ_⊥ (Fig.2G). In contrast, DTI-λ_|| (Fig.2F) and - λ⊥ (Fig.2H) were confounded by surrounding CSF and failed to reflect true ON pathology. The DBSI axonal volume was consistent with OCT (Fig.2D).

Conclusions : In patients with glaucomatous optic neuropathy, DBSI quantifies the extent of axonal loss. Axonal loss correlated with OCT-detected RNFL thinning.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1 Two cross-sectional views (B&C) perpendicular to ON tract in axial view (A). DW of CTL (D) and glaucoma (E) ONs reflected atrophy in glaucoma ON. Red arrows indicate ON.
Scale bar 5 mm

 

Figure 2 Maps (upper panel) and boxplots (A-C, E-H) of DBSI or DTI and correlations of DBSI axonal volume with OCT (D).