Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain

Manganese-enhanced magnetic resonance imaging is a technique that employs the divalent ion of the paramagnetic metal manganese (Mn²⁺) as an effective contrast agent to visualize, in vivo, the mammalian brain. As total achievable contrast is directly proportional to the net amount of Mn²⁺ accumulated in the brain, there is a great interest in optimizing administration protocols to increase the effective delivery of Mn²⁺ to the brain while avoiding the toxic effects of Mn²⁺ overexposure. In this study, we investigated outcomes following continuous slow systemic infusion of manganese chloride (MnCl₂) into the mouse via mini-osmotic pump administration. The effects of increasing fractionated rates of Mn²⁺ infusion on signal enhancement in regions of the brain were analyzed in a three-treatment study. We acquired whole-brain 3-D T1-weighted images and performed region of interest quantitative analysis to compare mean normalized signal in Mn²⁺ treatments spanning 3, 7, or 14 days of infusion (rates of 1, 0.5, and 0.25 μL/h, respectively). Evidence of Mn²⁺ transport at the conclusion of each infusion treatment was observed throughout the brains of normally behaving mice. Regions of particular Mn²⁺ accumulation include the olfactory bulbs, cortex, infralimbic cortex, habenula, thalamus, hippocampal formation, amygdala, hypothalamus, inferior colliculus, and cerebellum. Signals measured at the completion of each infusion treatment indicate comparable means for all examined fractionated rates of Mn²⁺ infusion. In this current study, we achieved a significantly higher dose of Mn²⁺ (180 mg/kg) than that employed in previous studies without any observable toxic effects on animal physiology or behavior.