Diffusion kurtosis imaging of optic nerve integrity upon chronic intraocular pressure elevation

Abstract

Purpose : Intraocular pressure (IOP) is the only clinically modifiable risk factor for glaucoma, yet the mechanisms through which IOP contributes to glaucomatous damage remain unknown. Here, we aimed to determine the role of mild chronic IOP elevation in structural integrity in the visual pathway using a hydrogel-induced experimental glaucoma model and diffusion kurtosis imaging (DKI).

Methods : Eleven adult C57BL/6J mice received unilateral intracameral injection of an optically clear hydrogel to obstruct aqueous outflow leading to chronic IOP elevation. Another 5 mice received a unilateral intracameral injection of phosphate-buffered saline only. Sustained IOP elevation (19.98 ±4.30 mmHg) in hydrogel-injected eye was confirmed after 4 weeks of injection, followed by in vivo whole-brain diffusion-weighted MRI at b= 1000 and 2000 s/mm² in 30 directions each in a 7-Tesla Bruker MRI scanner using a cryocoil. Conventional diffusion tensor imaging (DTI) parametric maps including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD); DKI maps including axial kurtosis (AK), radial kurtosis (RK), and mean kurtosis (MK); and the extended DKI models for intra-axonal space axial diffusivity (IAS_DA), extra-axonal space (EAS) axial diffusivity (EAS_DE_AXIAL), EAS perpendicular diffusivity (EAS_DE_PERP), tortuosity of EAS, and axonal water fraction (AWF) were derived (PMID: 33018335). Bilateral regions-of-interests (ROIs) were manually delineated for the optic nerve (ON) and anterior commissure (AC) on each map (Fig. 1A). The measured values were analyzed using ANOVA and post-hoc tests.

Results : In the ON projected from the hydrogel-injected eye, lower FA, RK, IAS_DA, and AWF, and higher AD, RD, MD, EAS_DE_AXIAL, EAS_DE_PERP, and EAS tortuosity were observed relative to the contralateral ON or sham control ONs (p<0.05) (Fig. 1B and 2). There was also a decrease in EAS_DE_AXIAL in ON contralateral to the hydrogel-injected eye as compared to the sham control (p<0.05). No significant group difference was observed in AC for any diffusion MRI parameters (p>0.05).

Conclusions : Chronic elevation in IOP led to changes in diffusion parameters not only in IAS but also EAS of the corresponding ON, suggestive of axonal injury, inflammation, and demyelination. DKI may offer a more specific imaging approach than conventional DTI for assessing white matter tract integrity in glaucoma.

This abstract was presented at the 2023 ARVO Imaging in the Eye Conference, held in New Orleans, LA, April 21-22, 2023.