Manganese and Water: in Cardiac Magnetic Resonance Imaging
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The present doctoral thesis contains an introduction and four research papers. Paper I was published in Investigative Radiology (2005) and Paper II and III were published in Magnetic Resonance in Medicine (2007). Paper IV is presented as a manuscript submitted to an international journal (October 2007). The work concerns nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) of water molecules in the myocardium in the presence of paramagnetic manganese ions (Mn2+). The Mn2+ ion has long been known to accelerate the NMR relaxation of protons, mainly present in water molecules, and thus contrast enhancement in MRI of tissues in where it has been accumulated. Manganese ions is effectively taken up in viable cardiac cells through calcium channels, a property that can be utilized in cardiac manganese enhanced MRI (cMEMRI). The active accumulation of Mn2+ in viable and functioning heart muscle, and less accumulation in areas that have been damaged by myocardial infarction, makes cMEMRI a promising technique for assessment of myocardial viability. Whereas one Mn containing contrast agent are clinically accepted for liver and pancreas imaging, cMEMRI is mainly applied in animals, however, recently also in human pilot studies. To explore the mechanisms of intracellular Mn2+ contrast enhancement, a thorough understanding of tissue water exchange and NMR relaxation processes is needed. Therefore in Papers I-III, relaxography with measurements of longitudinal (T1) and transverse (T2) relaxation was performed in excised rat hearts at various degrees of Mn2+ enhancement. Relaxation data were analyzed using advanced postprocessing routines, and water exchange rates across the sarcolemma were determined in a two-site water exchange analysis. In Paper IV, cMEMRI was investigated in an in vivo rat MRI model after intravenous Mn2+ administration. Main findings of the ex vivo studies were that applying relaxography on excised tissue needs close attention to tissue freshness, and that relaxation components were best described by continuous distribution functions. In the in vivo study, Mn2+ enhancement was more properly characterized by T1 mapping than by T1-weighted imaging. Contrast enhancement was superior at 2.35T compared to 7T, but was compensated for by the possibility to improve resolution at the higher field. In conclusion, results from the range of methods, spanning from ex vivo to in vivo animal models, adds to the knowledge of myocardial water compartmentalization and to the optimization of the cMEMRI technique. Future studies should focus on how to further increase the sensitivity of cMEMRI. Developing imaging pulse sequences that combine T1 and T2 relaxography might serve as a place to start, besides the general optimization of signal and static magnetic field strength, for MRI contrast agents containing large paramagnetic complexes.