First application of extremely high-resolution magnetic resonance imaging to study microscopic features of normal and LHON human 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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Supported by NIH Grant #1RO1 EY11396 to 01 and RR13625, the National MS Society RG3071A1, and the RPB Senior Scientific Investigators Award.