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 (Mn2+) is a widely used T1 contrast agent in manganese-enhanced MRI studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, Mn2+ is administered at a dose that will maximize the contrast, while minimizing its toxic effects. In rodents, systemic administration of Mn2+ 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 Mn2+ results in faster bioelimination of excess Mn2+ from the plasma due to a steep concentration gradient between plasma and bile. By contrast, following subcutaneous injection (LD50 value = 320 mg kg-1), Mn2+ is released slowly into the bloodstream, thus avoiding immediate hepatic elimination resulting in prolonged accumulation of Mn2+ 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 Mn2+ in rat brain following subcutaneous administration of Mn2+. Dose dependence and temporal dynamics of Mn2+ 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. Copyright © 2012 Wiley Periodicals, Inc.