title: Fractionated manganese-enhanced MRI.
abstract: We investigated the use of manganese-enhanced MRI (MEMRI) with fractionated doses as a way to retain the unique properties of manganese as a neuronal contrast agent while lessening its toxic effects in animals. First, we followed the signal enhancement on T1-weighted images of the brains of rats receiving 30 mg/kg fractions of MnCl2 . 4H2O every 48 h and found that the signal increased in regions with consecutive fractionated doses and ultimately saturated. Second, we used T1 mapping to test whether the amount of MRI-visible manganese that accumulated depended on the concentration of manganese in the fractions. For a fixed cumulative dose of 180 mg/kg MnCl2 . 4H2O, increasing fraction doses of 6 x 30 mg/kg, 3 x 60 mg/kg, 2 x 90 mg/kg and 1 x 180 mg/kg produced progressively shorter T1 values. The adverse systemic health effects, including complications at the injection site and poor animal well-being, also rose with the fraction dose. Thus, fractionated MEMRI can be used to balance the properties of manganese as a contrast agent in animals against its toxic effects.
authors.affiliation: Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging/National Institute of Neurological Disorders and Stroke/National Institutes of Health, Bethesda, MD 20892-1065, USA. bockn@mail.nih.gov
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bock
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Paiva
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity; D002985:Clinical Protocols; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity; D004334:Drug Administration Schedule; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics* / Q000633:toxicity; D017895:Manganese Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride