Noninvasive topical loading for manganese-enhanced MRI of the mouse visual system

Purpose. To evaluate topical loading as an alternative to intravitreal injection for Mn ²⁺-enhanced magnetic resonance imaging (MEMRI) of the visual system. Methods. Topical administration of 0.5 to 1.5 M MnCl ₂ and intravitreal injections with 0.5 μL 100 mM and Mn ²⁺ μL 1 M MnCl ₂ for mouse MEMRI were conducted, followed by immunohistochemistry. In another mouse group, two topical administrations of 1 M Mn ²⁺ were applied to the same animals 7 days apart, to evaluate the use of MEMRI in a time course study. Dynamic imaging was also conducted to reveal how Mn ²⁺ travels to the retina. MEMRI with topically loaded MnCl ₂ was also conducted in eyes with retinal ischemia, to evaluate whether the enhancements required healthy neurons. Results. After 1 day, topical administration of 1 M and 1.5 M MnCl ₂ rendered significant signal enhancement (up to Mn ²⁺0%) in the superior colliculus (P < 0.05) that was equivalent to that of the Mn ²⁺-μL 1 M injection. Repeated exposure to Mn ²⁺ showed reproduced enhancement. Dynamic imaging showed significant enhancement in the iris, retina, and lens boundary, but not in the vitreous space. In retinal ischemic eyes, no enhancement of MEMRI was detected in the optic nerves. The immunohistochemistry of the optic nerve (1.5 mm anterior to the chiasm) and retina showed no injury 1 week after Mn ²⁺ topical administrations to each mouse. Conclusions. The results demonstrated the feasibility of using topical administration of Mn ²⁺ for MEMRI. Topically loaded Mn ²⁺ did not diffuse into the vitreous space, but was it may have been absorbed into the iris to diffuse or travel via the capillary circulation to reach the retina.