Dose dependence and temporal evolution of the T1 relaxation time and MRI contrast in the rat brain after subcutaneous injection of manganese chloride

Abstract

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.