MRI MONITORED UPTAKE OF MANGANESE IN THE MOUSE DURING CONTINUOUS ADMINISTRATION USING OSMOTIC INFUSION PUMPS

Introduction Cellular uptake of manganese (Mn) through Ca channels [1] combined with the paramagnetic properties of Mn, is exploited in Mn-enhanced magnetic resonance imaging (MEMRI) studies to provide information on brain anatomy and function of neuronal circuits. However, exposure to Mn is known to cause cellular toxicity. In humans Mn exposure may cause manganism, a Parkinson-like disease [2]. In rats and mice MEMRI studies currently require repeated bolus injections to optimize contrast in T1-weighted images. Fractionated injections were shown to decrease toxicity [3]. In this study, we designed a new in vivo model of Mn neurotoxicity with a constant release of the agent by implantation of miniosmotic pumps. This would allow detailed elucidation of anatomical information and neuronal, activity-dependent, uptake while toxicity remains minimal. A study of the ion-pumps involved in uptake and clearance of Mn in the brain and hormone-regulating glands, such as the pituitary and thyroid glands, could furthermore help in limiting the toxicity and understanding the activity-dependent neuronal uptake.