Objective - Ischemic heart disease is a leading cause of morbidity and mortality worldwide. The current gold standard for assessment of infarct size is late Gd-enhanced MRI (LGE-MRI) However, in particular during the early phase, infarct size is often over-estimated, most likely because of edema. In this thesis we will explore alternative proton (1H) MRI and sodium (23Na) MRI methods to discriminate between edema, acute and chronic myocardial infarction (MI). Materials and methods - We have assessed myocardial viability using quantitative T2* mapping, a 1H MRI method, which was compared to cine MRI and LGE MRI in mice with myocardial infarction (MI). Additionally, 23Na Chemical Shift Imaging (CSI) and 1H LGE MRI were used to assess cellular integrity and ion homeostasis in edematous but viable myocardium and during and after myocardial ischemia in isolated rat hearts. Results - Changes of T2* were associated with infarct age, reversibility of the injury, and gave an indication of the structural variation in the myocardium throughout infarct maturation. The local decrease of T2* in the infarct was accompanied by globally and locally reduced ventricular function. In addition, the reduction in T2* with infarct age was associated also with the presence of iron and the formation of significant amounts of collagen. Interestingly, in hearts with small infarcts, T2* in remote tissue normalized, whereas in hearts with big infarcts, T2* in remote tissue also decreased, accompanied by remodeling and heart failure. Cine MRI showed that circulating Toll-like receptor 2 plays an important role in this remodeling. In a model of elevated perfusion pressure, we have further demonstrated that LGE MRI with a Gd contrast agent indeed enhances edematous myocardial tissue, most likely as a result of an increased distribution volume of Gd. Interestingly we found more edema in the subendocardial area than in the subepicardial area. We have also demonstrated in this same edema model that the Na+e signal increases with increasing edema, confirming that Na+e is a useful endogenous marker of extracellular volume. Ischemic myocardium was characterized by highly elevated Na+i levels, caused by Na+/K+ ATPase dysfunction and continued Na+ influx, and a concomitant decrease of Na+e. In contrast, chronic MI was characterized by an almost complete absence of Na+i, indicating the loss of viable myocardium and replacement by scar tissue, corroborated by the observed increased Na+e. The determination of infarct size was very much dependent for both CE MRI and Nae MRI on threshold selection, which is not surprising since both techniques monitor the same compartment. Infarct size determination based on Nai images is also similarly dependent on threshold selection. Furthermore, we have demonstrated that wash-out of contrast agent from edematous tissue occurs much faster than from infarcted tissue, providing further explanation for the threshold dependence of infarct size determination
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