First application of extremely high-resolution magnetic resonance imaging to study microscopic features of normal and LHON human optic nerve

Abstract

Purpose To apply new methods in magnetic resonance imaging (MRI) in resolving the histoarchitecture of the human optic nerve obtained from normal individuals and a Leber’s hereditary optic neuropathy (LHON) case. Design Small case series—clinicopathologic correlation. Method Three optic nerves were obtained from two normal subjects, aged 69 and 70, and a LHON/3460 patient, aged 75. The posterior pole of the eye with attached optic nerves was fixed in buffered paraformaldehyde and placed into a 10-mm quartz tube. Images were acquired in a Bruker AMX500 12 Tesla microimaging system. The three-dimensional data were acquired with 512 × 256 × 256 points, yielding a final isotopic resolution of 30 μm. Results The sclera, choroids, and retina were easily distinguished. The nerve fiber layer was seen to enter the optic disc and traverse the lamina cribrosa (LC). The resolution of the image of the optic nerve head was such that the LC was visualized as multiple stacked plates. The fibers emerged from glial columns in the LC as distinct fascicles and could be made out to change appearance as they became myelinated and expanded in the more posterior nerve. The ophthalmic artery and vein were visualized, as were the optic nerve arachnoid and dural sheaths. In the Leber’s case, the LC plates seemed collapsed or compressed. The axonal bundles were atrophic and the pial-collagen septae markedly thickened. The entire nerve had shrunk, creating space under the arachnoid, down and around the central ophthalmic artery and vein. Conclusions These results demonstrate the feasibility of using extremely high-resolution magnetic resonance imaging (μMRI) to examine the three-dimensional (30 μm) images of the human optic nerve. Several atrophic lesions, normally visible only by histopathologic examination, were visualized in the Leber’s optic nerve. μMRI may eventually permit the in vivo visualization of lesions in or about the optic nerve.