Dose dependence and temporal evolution of the T 1 relaxation time and MRI contrast in the rat brain after subcutaneous injection of manganese chloride

Divalent manganese ion (Mn 2+ ) is a widely used T 1 contrast agent in manganese‐enhanced MRI studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, Mn 2+ is administered at a dose that will maximize the contrast, while minimizing its toxic effects. In rodents, systemic administration of Mn 2+ via intravenous injection has been shown to create unique MRI contrast in the brain at a maximum dose of 175 mg kg −1 . However, intravenous administration of Mn 2+ results in faster bioelimination of excess Mn 2+ from the plasma due to a steep concentration gradient between plasma and bile. By contrast, following subcutaneous injection (LD 50 value = 320 mg kg −1 ), Mn 2+ is released slowly into the bloodstream, thus avoiding immediate hepatic elimination resulting in prolonged accumulation of Mn 2+ in the brain via the choroid plexus than that obtained via intravenous administration. The goal of this study was to investigate MRI dose response of Mn 2+ in rat brain following subcutaneous administration of Mn 2+ . Dose dependence and temporal dynamics of Mn 2+ after subcutaneous injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.