title: Manganese-enhanced MRI (MEMRI) via topical loading of Mn(2+) significantly impairs mouse visual acuity: a comparison with intravitreal injection.
abstract: Manganese-enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve enhancement comparable to that seen by intravitreal injection. However, the impact of this novel and non-invasive Mn(2+) loading method on visual function requires further assessments. The objective of this study is to determine the optimal topical Mn(2+) loading dosage for MEMRI and to assess visual function after MnCl2 loading. Intravitreal administration was performed to compare the two approaches of MnCl2 loading. Twenty-four hours after topical loading of 0, 0.5, 0.75, and 1 M MnCl2 , T1 -weighted, T2-weighted, diffusion tensor imaging and visual acuity (VA) assessments were performed to determine the best topical loading dosage for MEMRI measurements and to assess the integrity of retinas and optic nerves. Mice were perfusion fixed immediately after in vivo experiments for hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75 M MnCl2 was required to see sufficient enhancement of the optic nerve. At this concentration the visual function was significantly affected, followed by a slow recovery. Intravitreal injection (0.25 μL of 0.2 M MnCl2 ) slightly affected VA, with full recovery a day later. To conclude, intravitreal MnCl2 injection provides more reproducible results with less adverse side-effects than topical loading.
authors.affiliation: Department of Physics, Washington University, St. Louis, MO, USA.
authors.forename: Tsen-Hsuan
authors.initials: TH
authors.lastname: Lin
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chiang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.forename: William M
authors.initials: WM
authors.lastname: Spees
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001921:Brain / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000166:cytology; D012160:Retina / Q000166:cytology; D013194:Staining and Labeling; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D008345:Manganese
keywords: Animal model study; Diffusion tensor imaging (DTI); Diffusion Methods; Exogenous Contrast Methods; Manganese enhanced MRI (MEMRI); topical loading; intravotreal injection; visual acuity