Manganese-enhanced MRI of the rat visual pathway: Acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn2+

✍ Scribed by Marte Thuen; Martin Berry; Tina Bugge Pedersen; Pål Erik Goa; Mike Summerfield; Olav Haraldseth; Axel Sandvig; Christian Brekken

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 828 KB
• Volume: 28
• Category: Article
• ISSN: 1053-1807
• DOI: 10.1002/jmri.21504

✦ Synopsis

Abstract

Purpose

To provide dose‐response data for the safe and effective use of MnCl~2~ for manganese (Mn^2+^) ‐enhanced MRI (MEMRI) of the visual pathway.

Materials and Methods

Retinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density resolution for MEMRI, mode of axonal transport and clearance of Mn^2+^ from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl~2~, neural toxicity was measured by counting surviving RGC back‐filled with FluroGold (FG), CNR of the vitreous body and visual pathway by three‐dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with axon density, and axonal transport of Mn^2+^ by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl~2~.

Results

There were no changes in RGC density after ivit MnCl~2~ ≤ 150 nmol, and reductions of 12%, 57%, and 94% occurred after 300, 1500, and 3000 nmol MnCl~2~. CNR increased in the visual pathway with MnCl~2~ ≤ 300 nmol, and decreased when the dose was raised further. Minimum detectable ON axon densities were 125,000/mm^2^. After 200 nmol ion MnCl~2~, CNR>0 were recorded distally from the ion site, but there was no signal in the retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired.

Conclusion

The optimal dose for MEMRI of the rat visual pathway was found to be 150–300 nmol ivit MnCl~2~. Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn^2+^ enhancement throughout the visual pathway. Mn^2+^ traffic within RGC axons is mediated mainly by anterograde transport. J. Magn. Reson. Imaging 2008;28:855–865. © 2008 Wiley‐Liss, Inc.