Manganese-enhanced MRI of mouse heart during changes in inotropy.

Recently the dual properties of manganese ion (Mn(2+)) 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. T(1)-weighted images were acquired every minute during an experimental time course of 75 min. Varying doses of Mn(2+) (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 MnCl(2) led to a significant increase in signal enhancement in mouse heart that saturated above 3.3 +/- 0.1 nmoles/min/g BW Mn(2+) infusion. At the highest Mn(2+) 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 Mn(2+)-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. Published 2001 Wiley-Liss, Inc.