Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn(2+)

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) <or= 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) <or= 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.