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

• Published in: Journal of magnetic resonance imaging 2008-10, Vol.28 (4), p.855-865
• Main Authors: Thuen, Marte, Berry, Martin, Pedersen, Tina Bugge, Goa, Pål Erik, Summerfield, Mike, Haraldseth, Olav, Sandvig, Axel, Brekken, Christian
• Format: Article
• Language: English
• Subjects: manganese; MEMRI; MRI; toxicity; transport; visual pathway
• ISSN: 1053-1807; 1522-2586
• DOI: 10.1002/jmri.21504

Purpose To provide dose‐response data for the safe and effective use of MnCl2 for manganese (Mn2+) ‐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 Mn2+ from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl2, 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 Mn2+ by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl2. Results There were no changes in RGC density after ivit MnCl2 ≤ 150 nmol, and reductions of 12%, 57%, and 94% occurred after 300, 1500, and 3000 nmol MnCl2. CNR increased in the visual pathway with MnCl2 ≤ 300 nmol, and decreased when the dose was raised further. Minimum detectable ON axon densities were 125,000/mm2. After 200 nmol ion MnCl2, 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 MnCl2. Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn2+ enhancement throughout the visual pathway. Mn2+ traffic within RGC axons is mediated mainly by anterograde transport. J. Magn. Reson. Imaging 2008;28:855–865. © 2008 Wiley‐Liss, Inc.