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Updated: May 21, 2026
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
Impact of repeated topical-loaded manganese-enhanced MRI on the mouse visual system
Shu-Wei Sun1, Tiffany Thiel, Hsiao-Fang Liang
1Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA. rsun@llu.edu
Purpose:
Optic nerve degeneration in diseases such as glaucoma and multiple sclerosis evolves in months to years. The use of Mn(2+)-Enhanced Magnetic Resonance Imaging (MEMRI) in a time-course study may provide new insights into the disease progression. Previously, we demonstrated the feasibility of using a topical administration for Mn(2+) delivery to the visual system. This study is to evaluate the impact of biweekly or monthly repeated Mn(2+) topical administration and the pH levels of the Mn(2+) solutions for MEMRI on the mouse visual pathway.
Methods:
Using groups of mice, the MEMRI with an acidic or pH neutralized 1 M MnCl(2) solution was performed. To evaluate the feasibility of repeated MEMRIs, topical-loaded MEMRI was conducted biweekly seven times or monthly three times. The enhancement of MEMRI in the visual system was quantified. After repeated MEMRIs, the corneas were examined by optical coherence tomography. The retinal ganglion cells (RGCs) and optic nerves were examined by histology.
Results:
All mice exhibited consistent enhancements along the visual system following repeated MEMRIs. The acidic Mn(2+) solution induced a greater MEMRI enhancement as compared with a neutral pH Mn(2+) solution. Significant 20% RGC loss was found after three biweekly Mn(2+) inductions, but no RGC loss was found after three monthly Mn(2+) treatments. The corneal thickness was found increased after seven biweekly topical-loaded MEMRI.
Conclusions:
Acidic Mn(2+) solutions enhanced the uptake of Mn(2+) observed on the MEMRI. Increasing the time intervals of repeated Mn(2+) topical administration reduced the adverse effects caused by MEMRI.
Insights
Repeated topical manganese (Mn2+) administration for Manganese-Enhanced MRI (MEMRI) in mice showed that acidic solutions enhanced visual pathway imaging. However, biweekly treatments led to retinal ganglion cell loss, while monthly treatments did not.
Area of Science:
- Neuroimaging
- Ophthalmology
- Toxicology
Background:
- Optic nerve degeneration, as seen in glaucoma and multiple sclerosis, progresses over months to years.
- Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) offers potential for studying visual system disease progression.
- Previous studies established topical administration for Mn(2+) delivery to the visual system.
Purpose of the Study:
- To assess the impact of repeated topical Mn(2+) administration (biweekly vs. monthly) on mouse visual pathways using MEMRI.
- To evaluate the influence of Mn(2+) solution pH on MEMRI outcomes.
- To determine the safety and efficacy of repeated MEMRI protocols.
Main Methods:
- Mice underwent MEMRI using either acidic or pH-neutral 1 M MnCl(2) solutions.
- Repeated MEMRI was performed biweekly (seven times) or monthly (three times) to assess feasibility.
- Visual system enhancement was quantified; corneas, retinal ganglion cells (RGCs), and optic nerves were examined post-MEMRI.
Main Results:
- Consistent MEMRI enhancement was observed in the visual system after repeated administrations.
- Acidic Mn(2+) solutions yielded greater MEMRI enhancement compared to neutral solutions.
- Biweekly Mn(2+) treatments resulted in significant RGC loss (20%), unlike monthly treatments. Corneal thickness increased after seven biweekly MEMRIs.
Conclusions:
- Acidic Mn(2+) solutions improve Mn(2+) uptake for MEMRI.
- Increasing the interval between repeated topical Mn(2+) administrations mitigates adverse effects, such as RGC loss and corneal changes.
