title: Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn(2+).
abstract: OBJECTIVE
  To provide dose-response data for the safe and effective use of MnCl(2) for manganese (Mn(2+)) -enhanced MRI (MEMRI) of the visual pathway.
  
  
  METHODS
  Retinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density resolution for MEMRI, mode of axonal transport and clearance of Mn(2+) from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl(2), neural toxicity was measured by counting surviving RGC back-filled with FluroGold (FG), CNR of the vitreous body and visual pathway by three-dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with axon density, and axonal transport of Mn(2+) by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl(2).
  
  
  RESULTS
  There were no changes in RGC density after ivit MnCl(2) <or= 150 nmol, and reductions of 12%, 57%, and 94% occurred after 300, 1500, and 3000 nmol MnCl(2). CNR increased in the visual pathway with MnCl(2) <or= 300 nmol, and decreased when the dose was raised further. Minimum detectable ON axon densities were 125,000/mm(2). After 200 nmol ion MnCl(2), CNR>0 were recorded distally from the ion site, but there was no signal in the retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired.
  
  
  CONCLUSIONS
  The optimal dose for MEMRI of the rat visual pathway was found to be 150-300 nmol ivit MnCl(2). Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn(2+) enhancement throughout the visual pathway. Mn(2+) traffic within RGC axons is mediated mainly by anterograde transport.
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Trondheim, Norway. marte.thuen@ntnu.no
authors.forename: Marte
authors.initials: M
authors.lastname: Thuen
authors.forename: Martin
authors.initials: M
authors.lastname: Berry
authors.forename: Tina Bugge
authors.initials: TB
authors.lastname: Pedersen
authors.forename: Pål Erik
authors.initials: PE
authors.lastname: Goa
authors.forename: Mike
authors.initials: M
authors.lastname: Summerfield
authors.forename: Olav
authors.initials: O
authors.lastname: Haraldseth
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.forename: Christian
authors.initials: C
authors.lastname: Brekken
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride