Relationship between blood and myocardium manganese levels during manganese-enhanced MRI (MEMRI) with T1 mapping in rats

Manganese ions (Mn(2+) ) enter viable myocardial cells via voltage-gated calcium channels. Because of its shortening of T(1) and its relatively long half-life in cells, Mn(2+) can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn(2+) is its sensitivity over a limited range of concentrations employing T(1)-weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T(1) mapping method for cardiac manganese-enhanced MRI to enable a quantitative estimate of the influx of Mn(2+) over a wide range of concentrations in male Sprague-Dawley rats. This MRI method was used to compare the relationship between T(1) changes in the heart as a function of myocardium and blood Mn(2+) levels. Results showed a biphasic relationship between ΔR(1) and the total Mn(2+) infusion dose. Nonlinear relationships were observed between the total Mn(2+) infusion dose versus blood levels and left ventricular free wall ΔR(1) . At low blood levels of Mn(2+) , there was proportionally less cardiac enhancement seen than at higher levels of blood Mn(2+) . We hypothesize that Mn(2+) blood levels increase as a result of rate-limiting excretion by the liver and kidneys at these higher Mn(2+) doses.