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

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 Fluro-Gold (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 does was raised further. Minimum detectable ON axon densities were 125,000/mm(2). 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 does 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.