title: Noninvasive topical loading for manganese-enhanced MRI of the mouse visual system.
abstract: OBJECTIVE
  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 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 20%) in the superior colliculus (P < 0.05) that was equivalent to that of the 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.
authors.affiliation: Department of Radiology, Washington University, St. Louis, Missouri, USA. rsun@llu.edu
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Sun
authors.forename: Bruce
authors.initials: B
authors.lastname: Campbell
authors.forename: Chantal
authors.initials: C
authors.lastname: Lunderville
authors.forename: Eric
authors.initials: E
authors.lastname: Won
authors.forename: Hsiao-Fang
authors.initials: HF
authors.lastname: Liang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005829:Geniculate Bodies / Q000378:metabolism; D007089:Image Enhancement / Q000379:methods; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D017895:Manganese Compounds / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D013477:Superior Colliculi / Q000378:metabolism; D014795:Visual Pathways / Q000378:metabolism*
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride