Elsevier

Ophthalmology

Volume 109, Issue 6, June 2002, Pages 1085-1091
Ophthalmology

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

https://doi.org/10.1016/S0161-6420(02)01027-8Get rights and content

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.

Section snippets

Material and methods

Optic nerves were fixed in mixed aldehydes, rinsed in phosphate-buffered solution, and stored at 4° C. Immediately before imaging, specimens were immersed in perfluoropolyether, and then sealed into a 10-mm-diameter quartz tube. The perfluoropolyether used to suspend the specimen in the quartz tube does not show a background proton signal in MR images.

Imaging was performed using a wide-bore (89 mm) Bruker AMX500 microimaging system (Bruker Instruments Inc., Billerica, MA) located at the

Cases

Two control cases were used to establish the normal characteristics of human optic nerve investigated by μMRI. These were compared with a third case, a 75-year-old woman affected with LHON, to investigate pathologic changes.

Both controls were nearly age matched (69-year-old male, 70-year-old woman) with the LHON case and neither had any ocular disease. The LHON proband was from an Italian family carrying the mitochondrial DNA pathogenic mutation at position 3460. Investigation of multiple

Results

The posterior sclera, choroid, and retina were easily distinguished. Sagittal, axial, and coronal sections through all three optic nerves (controls and LHON) provided far more detail and even histoarchitecture than ever before demonstrated on MRI. For example, on sagittal sections of normal optic nerves, one could easily discern the ophthalmic artery as it coursed posteriorly from the lamina cribrosa (Fig 1A, B). The lamina cribrosa could be seen as an extension of the sclera, almost dividing

Discussion

Our results demonstrate that μMRI is an effective tool for explaining the 3D structure of the optic nerve head and is capable of clearly identifying many of the pathologic features associated with LHON.

The reconstructed 3D views afforded an unparalleled opportunity for visualizing and understanding the anatomy of optic nerve structures such as the vascular circle of Zinn-Haller. Although each section demonstrated only a portion of this circle, by having the computer generate a short video that

Acknowledgements

We are grateful for the technical assistance provided by Tony Rodriguez, Ernesto Barron, and Sendhil Velan.

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  • Cited by (0)

    Supported by NIH Grant #1RO1 EY11396 to 01 and RR13625, the National MS Society RG3071A1, and the RPB Senior Scientific Investigators Award.

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