The Utility of Manganese for Magnetic Resonance Imaging of Transient Myocardial Ischemia

Abstract: In order to improve the diagnosis of coronary artery disease, better methods for detection of myocardial perfusion defects would be useful. One of the methods used for myocardial perfusion evaluation today is magnetic resonance imaging. This method could be improved if a contrast agent that induced long-lasting contrast enhancement in the myocardium could be developed. The paramagnetic manganese(II) ion has promising properties for meeting this need, since it enters cardiomyocytes through voltage-gated calcium channels and remains inside the cells for a long time after an intravenous injection. If these properties can be utilized, manganese-enhanced MRI has potential for detecting transient periods of ischemia in a manner similar to the conventional SPECT stress test.To investigate the contrast-enhancing properties of the manganese(II) ion, a series of experiments was performed in pigs, using a manganese salt (MnCl2) and two manganese-based chelates (MnDPDP and MnHPTA) and measuring the longitudinal relaxation rates before and after contrast agent administration. This was done in normal pig myocardium at rest and during dobutamine-induced stress with several different doses of contrast agent, and in a model for coronary artery stenosis using MnCl2 administered during dobutamine stress to determine whether transient ischemia could be detected with this contrast agent.The results of these experiments showed that of the three contrast agents, MnCl2 induces the greatest increase in ?R1, followed by MnHPTA. Using MnCl2 it was possible to produce images on which transient myocardial ischemia was visible, but only during the first 30 minutes after contrast agent injection.The stenosis model is still far from the clinical situation and several complications, including the potential toxicity of the manganese(II) ion, remain to be overcome. However, the results from this model are promising for the future development of manganese- enhanced magnetic resonance imaging of transient myocardial ischemia.