title: Fractionated manganese injections: effects on MRI contrast enhancement and physiological measures in C57BL/6 mice.
abstract: Manganese-enhanced MRI (MEMRI) is an increasingly used imaging method in animal research, which enables improved T(1)-weighted tissue contrast. Furthermore accumulation of manganese in activated neurons allows visualization of neuronal activity. However, at higher concentrations manganese (Mn2+) exhibits toxic side effects that interfere with the animals' behaviour and well-being. Therefore, when optimizing MEMRI protocols, a compromise has to be found between minimizing side effects and intensifying image contrast. Recently, a low concentrated fractionated Mn2+ application scheme has been proposed as a promising alternative. In this study, we investigated effects of different fractionated Mn2+ dosing schemes on vegetative, behavioural and endocrine markers, and MEMRI signal contrast in C57BL/6N mice. Measurements of the animals' well-being included telemetric monitoring of body temperature and locomotion, control of weight and observation of behavioural parameters during the time course of the injection protocols. Corticosterone levels after Mn2+ application served as endocrine marker of the stress response. We compared three MnCl2  x 4H2O application protocols: 3 times 60 mg/kg with an inter-injection interval of 48 h, six times 30 mg/kg with an inter-injection interval of 48 h, and 8 times 30 mg/kg with an inter-injection interval of 24 h (referred to as 3 x 60/48, 6 x 30/48 and 8 x 30/24, respectively). Both the 6 x 30/48 and the 8 x 30/24 protocols showed attenuated effects on animals' well-being as compared to the 3 x 60/48 scheme. Best MEMRI signal contrast was observed for the 8 x 30/24 protocol. Together, these results argue for a fractionated application scheme such as 30 mg/kg every 24 h for 8 days to provide sufficient MEMRI signal contrast while minimizing toxic side effects and distress.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Grünecker
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Kaltwasser
authors.forename: Yorick
authors.initials: Y
authors.lastname: Peterse
authors.forename: Philipp G
authors.initials: PG
authors.lastname: Sämann
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Wotjak
authors.forename: Michael
authors.initials: M
authors.lastname: Czisch
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013312:Stress, Physiological; D013686:Telemetry
chemical_list: D003287:Contrast Media; D008345:Manganese