title: Continuous infusion of manganese improves contrast and reduces side effects in manganese-enhanced magnetic resonance imaging studies.
abstract: The ability to administer systemically high doses of manganese as contrast agent while circumventing its toxicity is of particular interest for exploratory MRI studies of the brain. Administering low doses either repeatedly or continuously over time has been shown to enable the acquisition of satisfactory MRI images of the mouse brain without apparent side effects. Here we have systematically compared the obtained MRI contrast and recorded potential systemic side effects such as stress response and muscle strength impairment in relation to the achieved contrast. We show in mice that administering MnCl2via osmotic infusion pumps allows for a side-effect free delivery of a high cumulative dose of manganese chloride (480mg/kg bodyweight in 8 days). High contrast in MRI was achieved while we did not observe the weight loss or distress seen in other studies where mice received manganese via fractionated intraperitoneal injections of lower doses of manganese. As the normal daily conduct of the mice was not affected, this new manganese delivery method might be of particular use to study brain activity over several days. This may facilitate the phenotyping of new transgenic mouse models, the study of chronic disease models and the monitoring of changes in brain activity in long-term behavioral studies.
authors: Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands. Electronic address: D.Poole@lumc.nl.
authors: Dana S
authors: DS
authors: Poole
authors: Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands; Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands.
authors: Nathalie
authors: N
authors: Doorenweerd
authors: Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands.
authors: Jaap J
authors: JJ
authors: Plomp
authors: Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands; Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands.
authors: Ahmed
authors: A
authors: Mahfouz
authors: Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands.
authors: Marcel J T
authors: MJT
authors: Reinders
authors: Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands.
authors: Louise
authors: L
authors: van der Weerd
mesh_terms: D000818:Animals; D002712:Chlorides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D007089:Image Enhancement; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects; D013315:Stress, Psychological / Q000139:chemically induced / Q000523:psychology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride; D003345:Corticosterone
keywords: Longitudinal monitoring; MEMRI; Manganese MRI; Manganese toxicity; Side effects