Manganese‐enhanced MRI of mouse heart during changes in inotropy †

Recently the dual properties of manganese ion (Mn2+) as an MRI contrast agent and a calcium analogue to enter excitable cells has been used to mark specific cells in brain and as a potential intracellular cardiac contrast agent. Here the hypothesis that in vivo manganese‐enhanced MRI (MEMRI) can detect changes in inotropy in the mouse heart has been tested. T1‐weighted images were acquired every minute during an experimental time course of 75 min. Varying doses of Mn2+ (3.3–14.0 nmoles/min/g BW) were infused during control and altered inotropy with dobutamine (positive inotropy due to increased calcium influx) and the calcium channel blocker diltiazem (negative inotropy). Infusion of MnCl2 led to a significant increase in signal enhancement in mouse heart that saturated above 3.3 ± 0.1 nmoles/min/g BW Mn2+ infusion. At the highest Mn2+ dose infused there was a 41–47% increase in signal intensity with no alteration in cardiac function as measured by MRI‐determined ejection fractions. Dobutamine increased both the steady‐state level of enhancement and the rate of MRI signal enhancement. Diltiazem decreased both the steady‐state level of enhancement and the rate of MRI signal enhancement. These results are consistent with the model that Mn2+‐induced enhancement of cardiac signal is indicative of the rate of calcium influx into the heart. Thus, the simultaneous measurement of global function and calcium influx using MEMRI may provide a useful method of evaluating in vivo responses to inotropic therapy. Magn Reson Med 46:884–890, 2001. Published 2001 Wiley‐Liss, Inc.