title: Toward clinical application of manganese-enhanced MRI of retinal function.
abstract: OBJECTIVE
  The application of manganese-enhanced MRI (MEMRI) to measure retinal function in humans is unclear. To begin to address this gap, we tested the hypothesis that an FDA-approved manganese-based MRI contrast agent, Teslascan, is useful for measuring functional intraretinal ionic regulation.
  
  
  METHODS
  Anesthetized dark- or light-adapted male healthy Sprague-Dawley rats were infused for 30 min with 10 micromol/kg of Teslascan (clinically relevant dose; n = 5), 100 micromol/kg Teslascan (n = 5), or saline (n = 5). Four hours post-administration, high resolution MEMRI data were collected. Intraretinal signal intensities and enhancements were measured. Modelling was performed to estimate apparent retinal transfer constant K(i) and to determine optimal data acquisition parameters.
  
  
  RESULTS
  In light-adapted rats, intraretinal enhancements responded in a dose-response manner. In addition, in the outer retina the effect of light-adaptation was to reduce significantly Mn(2+) uptake and K(i) compared to dark-adaptation. A non-significant change was also observed in the inner retina. Modelling shows Mn(2+) plasma concentration reaching a plateau after about 2 h. Apparent K(i) values for the clinically relevant dose are 3-6 x 10(-3) min(-1), decreasing to 0.5-0.6 x 10(-3) min(-1) at the higher dose. Intraretinal signal is almost linear with K(i). Optimal TR for a spin-echo sequence is 0.4-1.4s.
  
  
  CONCLUSIONS
  First time evidence is presented that a clinically relevant dose and route of Teslascan can be used to measure intraretinal function. The potential for future clinical application of MEMRI in a broad range of retinopathies is high.
authors.affiliation: Brighton and Sussex Medical School, Falmer, Sussex BN1 9PX, UK. p.s.tofts@bsms.ac.uk
authors.forename: Paul S
authors.initials: PS
authors.lastname: Tofts
authors.forename: Andre
authors.initials: A
authors.lastname: Porchia
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000378:metabolism; D015233:Models, Statistical; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000033:anatomy & histology* / Q000378:metabolism / Q000502:physiology
chemical_list: D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid