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

摘要

Manganese ions (Mn2+) enter viable myocardial cells via voltage-gated calcium channels. Because of its shortening of T1 and its relatively long half-life in cells, Mn2+ can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn2+ is its sensitivity over a limited range of concentrations employing T1-weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T1 mapping method for cardiac manganese-enhanced MRI to enable a quantitative estimate of the influx of Mn2+ over a wide range of concentrations in male Sprague-Dawley rats. This MRI method was used to compare the relationship between T1 changes in the heart as a function of myocardium and blood Mn2+ levels. Results showed a biphasic relationship between ΔR1 and the total Mn2+ infusion dose. Nonlinear relationships were observed between the total Mn2+ infusion dose versus blood levels and left ventricular free wall ΔR1. At low blood levels of Mn2+, there was proportionally less cardiac enhancement seen than at higher levels of blood Mn2+. We hypothesize that Mn2+ blood levels increase as a result of rate-limiting excretion by the liver and kidneys at these higher Mn2+ doses. Examples of short-axis rodent heart images with T1 mapping at the particular manganese infusion rate, 4.0 nmoles/min/gm BW. (a) T1-weighted pre-Mn2+ infusion image; (b) T1-weighted post-Mn2+ infusion image; (c) pre-Mn2+ R1 map; (d) post-Mn2+ R1 map. Effect of altering the doses of infused Mn2+ on relaxation of left ventricular wall. The x-axis shows the total dose of Mn2+ normalized to rat BW. The y-axis shows the difference of relaxation pre- and post-infusion (error bars=1SD).