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Manganese-enhanced MRI of mouse heart during changes in inotropy
T C Hu1, R G Pautler, G A MacGowan
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Abstract:
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.
Insights
Manganese-enhanced MRI (MEMRI) can detect changes in heart calcium influx. This method shows how inotropic therapies affect cardiac calcium levels, offering a new way to evaluate treatment responses.
Area of Science:
- Cardiovascular Imaging
- Biomedical Engineering
- Pharmacology
Background:
- Manganese ion (Mn(2+)) acts as both an MRI contrast agent and a calcium analogue.
- Mn(2+) can enter excitable cells, marking specific cells in the brain and serving as a potential intracellular cardiac contrast agent.
- Manganese-enhanced MRI (MEMRI) has shown promise for visualizing cellular processes.
Purpose of the Study:
- To test the hypothesis that in vivo MEMRI can detect changes in inotropy in the mouse heart.
- To investigate the relationship between Mn(2+) infusion rate and cardiac signal enhancement.
- To evaluate MEMRI's ability to reflect calcium influx in response to inotropic agents.
Main Methods:
- T(1)-weighted MRI images were acquired every minute for 75 minutes.
- Varying doses of Mn(2+) were infused during control conditions and altered inotropy induced by dobutamine and diltiazem.
- Cardiac function was assessed using MRI-determined ejection fractions.
Main Results:
- Mn(2+) infusion significantly increased signal enhancement in the mouse heart, saturating at approximately 3.3 nmoles/min/g BW.
- At the highest Mn(2+) dose, signal intensity increased by 41-47% without altering cardiac function.
- Dobutamine increased both the steady-state level and rate of MRI signal enhancement, while diltiazem decreased them.
Conclusions:
- Cardiac signal enhancement in MEMRI is indicative of the rate of calcium influx into the heart.
- MEMRI can simultaneously measure global cardiac function and calcium influx.
- This technique may offer a valuable method for evaluating in vivo responses to inotropic therapies.