Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis

Abstract

Background: Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation.

Objective: The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI.

Methods: An advanced, isotropic T2-weighted turbo spin echo MRI was applied to 29 MS patients with (14 patients ON+) or without (15 patients ON-) history of ON and 42 healthy volunteers. An automated tool was used to estimate and compare whole optic nerve and surrounding cerebrospinal fluid radii along the length of the nerve.

Results and conclusion: Only ON+ MS patients had a significantly reduced optic nerve radius compared to healthy controls in the central segment of the optic nerve. Using clinically available MRI methods, we show and quantify ON volume loss for the first time in MS patients.

Keywords: MRI; atrophy; axonal loss; multiple sclerosis.

Figure 1.

Healthy control scanned with: current clinical standard of care T2w MRI axial view (a) and coronal view approximately 10 mm posterior to the globe (b), as well as high-resolution isotropic T2w research imaging axial view (c) and coronal view approximately 10 mm posterior to the globe (d). One can appreciate the superior optic nerve:CSF contrast and benefits of isotropic resolution in visualizing optic nerve morphology in three dimensions. (e) and (f) show axial and coronal views of a 40-year-old RRMS patient with bilateral history of optic neuritis one year post-diagnosis. The regions indicated are enlarged in the yellow inlaid boxes for clarity. T2w: T2-weighted; MRI: magnetic resonance imaging; CSF: cerebrospinal fluid; RRMS: relapsing–remitting multiple sclerosis.

Figure 2.

Renderings of the segmented eye globes (green) and optic chiasm (purple) along with the measured optic nerves for a healthy control ((a)–(c)) and a 47-year-old relapsing–remitting multiple sclerosis patient 15.5 years post-diagnosis with a history of optic neuritis in the left eye ((d)–(f)). Color of the optic nerve corresponds to estimated optic nerve radius in all panels according to the color bar in (d). Optic nerve atrophy can be clearly seen in ((d)–(f)) as compared to ((a)–(c)). (b), (c), (e) and (f) are enlarged in the yellow inlaid boxes for clarity.

Figure 3.

Comparison of volumes of optic nerves never affected by optic neuritis (ON) (left) and optic nerves with a previous history of ON (right) to healthy controls. The upper distribution is the diameter of the sub-arachnoid cerebrospinal fluid while the lower line is the radius of the optic nerve. The shaded blue region indicates one standard deviation of the healthy control population. The shaded region (right) illustrates the region of 15 consecutive measurements (9 mm) where the patients’ nerves are significantly smaller than healthy nerves (Wilcoxon rank-sum; p < 0.05 Bonferroni corrected). The nerves from patients with a negative history of ON were not significantly different from healthy controls.