Dose response and time course of manganese-enhanced magnetic resonance imaging for visual pathway tracing in vivo

Axonal tracing is useful for detecting optic nerve injury and regeneration, but many commonly used methods cannot be used to observe axoplasmic flow and synaptic transmission in vivo. Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) can be used for in vivo longitudinal tracing of the visual pathway. Here, we explored the dose response and time course of an intravitreal injection of MnCl(2) for tracing the visual pathway in rabbits in vivo using MEMRI. We found that 2 mM MnCl(2) enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus, whereas at all other doses tested (5–40 mM), images of the visual pathway from the retina to the contralateral superior colliculus were significantly enhanced. The images were brightest at 24 hours, and then decreased in brightness until the end of the experiment (7 days). No signal enhancement was observed in the visual cortex at any concentration of MnCl(2). These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo. Signal enhancement in MEMRI depends on the dose of MnCl(2), and the strongest signals appear 24 hours after intravitreal injection.