Manganese‐enhanced MRI of the optic visual pathway and optic nerve injury in adult rats

Abstract

Purpose: To evaluate manganese (Mn 2ϩ )-enhanced MRI in a longitudinal study of normal and injured rat visual projections. Materials and Methods:MRI was performed 24 hours after unilateral intravitreal injection of MnCl 2 (150 nmol) into adult Fischer rats that were divided into four groups: 1) controls (N ϭ 5), 2) dose-response (N ϭ 10, 0.2-200 nmol), 3) time-response with repeated MRI during 24 -168 hours post injection (N ϭ 4), and 4) optic nerve crush (ONC) immediately preceding the MnCl 2 injection (N ϭ 7). Control and ONC animals were reinjected with MnCl 2 20 days after the first injection, and MRI was performed 24 hours later. Results:In the control group, the optic projection was visualized from the retina to the superior colliculus, with indications of transsynaptic transport to the cortex. There was a semilogarithmic relationship between the Mn 2ϩ dose and Mn 2ϩ enhancement from 4 to 200 nmol, and the enhancement decayed gradually to 0 by 168 hours. No Mn 2ϩ -enhanced signal was detected distal to the ON crush site. In the control group, similar enhancement was obtained after the first and second MnCl 2 injections, while in the ONC group the enhancement proximal to the crush site was reduced 20 days post lesion (20dpl). Conclusion:Mn 2ϩ -enhanced MRI is a viable method for temporospatial visualization of normal and injured ON in the adult rat. The observed reduction in the Mn 2ϩ signal proximal to the ONC is probably a result of retrograde damage to the retinal ganglion cells, and not of Mn 2ϩ toxicity.

Manganese transport in the rat optic nerve evaluated with spatial‐ and time‐resolved magnetic resonance imaging

“…This conclusion is supported both by the model fitting to the experimental data in this study and the simulations of the dose-concentration relationship. A semilogarithmic relationship between intravitreal Mn 2þ dose and ON CNR has earlier been reported from in vivo MEMRI of the rat visual system (20) and correspond well with our simulations with a rate-dependent input function (Fig. 8).…”

“…The response of ON contrast to various intravitreal Mn 2þ doses has been reported earlier (20) and a semilogarithmic relationship between intravitreal Mn 2þ dose and ON contrast to noise ratio (CNR) has been found. However, the transport mechanisms governing this semilogarithmic relationship are unknown.…”

Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI)

“…The minimal dose of MnCl 2 that produced reversible toxicity and MR signal Previous tracing with MEMRI in the visual system has typically used volumes of 1-3 μl and MnCl 2 concentrations up to 1.0 M for injection into either the anterior chamber of the mouse eye (Lindsey et al, 2007) or the posterior chamber of the rat eye (Thuen et al, 2005). We noted that the eyes of animals so injected turned gray, and physical exam suggested that they could no longer see.…”

“…Injection of radioactive tracers into the posterior chamber of the eye demonstrates rapid anterograde transit (2mm/hr) from the eye along the optic nerve towards the brain (Grafstein and Forman, 1980). Replicating these experiments by intravitreous injection of Mn 2+ followed by MR imaging demonstrated that Mn 2+ is also transported, possibly at the same rate (Pautler et al, 1998), along the optic nerve and crosses synapses to reach the visual cortex (Pautler, 1999;Pautler et al, 1998;Thuen et al, 2005;Watanabe et al, 2001;Watanabe et al, 2004).…”

“…Mn 2+ injection into the eye results in tracing of the visual system across at least two synapses: first, retinal ganglion cell projections onto the midbrain, and second, midbrain neurons onto the visual cortex (Lindsey et al, 2007;Murayama et al, 2006;Pautler et al, 1998;Thuen et al, 2005;Watanabe et al, 2001). The amount of transfer across synapses appears to correlate with axonal caliber (Murayama et al, 2006).…”