| "Imaging in Heart Failure" is the central theme of this project aiming at integrating the high accuracy and reproducibility of MRI to assess global LV function, regional myocardial function, and infarcted non-viable myocardium, complemented by echocardiography in some of the studies. Myocardial infarction is determined by imaging late after administration of an interstitial contrast agents (e.g. Gadolinium-DTPA), which makes the necrotic tissue appear bright (delayed contrast enhancement, DCE). The project is focused on the following aspects. 1. Evaluation of myocardial viability in chronic ischemic heart disease. The mechanism of MRI myocardial enhancement in chronic ischemic heart disease relates to the increased extracellular space of ischemic scar in which the interstitial contrast agent accumulates. The primary objectives of the studies are to compare DCE MRI with the current diagnostic gold standard for assessment of viability 18F-FDG PET, and to demonstrate that DCE MRI can predict functional recovery of dysfunctional but viable myocardium after revascularization in patients with chronic ischemic heart disease. These studies also allow to evaluate periprocedural injury from CABG and PCI. 2. Evaluation of acute myocardial infarction and microvascular obstruction ('no reflow'). Controversy exists whether DCE MRI is accurate in detecting non-viable myocardium in acute myocardial infarction. Also in acute myocardial infarction the infarct zone appears bright after gadolinium-DTPA administration, but the mechanism is less clear. Probably there is an increased volume of distribution for the contrast agent due to edema and cell membrane disintegrity coupled to delayed wash-out. After contrast administration the central core of the infarct area may remains dark (non-enhanced) due to a low-flow or no-reflow state. Study objectives include assessing the predictive value of contrast enhancement and microvascular obstruction with respect to infarct healing and LV remodeling. In the Hebe trial modulation of these aspects will be studied by treatment with bone marrow derived progenitor cells. 3. MRI tagging in LV mechanical asynchrony. Resynchronisation by biventricular pacing has emerged as a relatively new treatment for patients with heart failure, when myocardial contraction is asynchronous as in patients with intraventricular conduction delay. However, about 30% of patients do not respond to biventricular pacing. Moreover, the optimal positioning of the leads, and the optimal mode for pacing can only be found by trial and error. To guide pacing and predict response, quantification of the asynchronous contraction of the myocardium is valuable. With MRI myocardial tagging and strain mapping it is possible to measure the regional contractile function of the myocardium as a function of time during the cardiac cycle. The goal is to further develop and apply the tagging and strain mapping techniques to select patients with mechanical dissynchrony who might benefit from biventricular pacing. 4. Tissue Doppler echocardiography in the selection of patients undergoing cardiac resynchronization therapy. Cardiac resynchronization therapy (CRT) is an important therapeutic option in patients with end-stage heart failure, depressed LV function and wide QRS complex. Indeed, the therapy has been demonstrated to improve symptoms, exercise capacity and LV systolic performance. Still, 20-30% of patients do not respond to CRT. It has been hypothetized that substantial LV dyssynchrony is needed to respond to CRT. This LV dyssynchrony can be evaluated by tissue Doppler imaging and has been used in this project. 5. Cardiac MRI and MSCT in non-invasive evaluation of coronary artery disease. A phantom study to evaluate coronary arteries and bypass grafts has been performed. Briefly, a breathhold, echo planar imaging (EPI) sequence was developed and validated in a flow phantom using a fast field echo (FFE) sequence as gold standard. In volunteers aortic flow was measured using both sequences, and in patients flow in the left internal mammary artery (LIMA) and aorta was measured at rest and during adenosine stress, and coronary flow reserve (CFR) was calculated. In addition, vein graft velocities were measured in patients. These results will provide the basis for further non-invasive evaluation of coronary arteries and (arterial and venous) bypass grafts. 6. Software development for quantitative analysis in heart failure. To facilitate the above-mentioned studies, post-processing tools are developed for quantitative analysis of MR images, integrating analysis of LV volumes and myocardial thickening, of contrast-enhanced myocardium for assessment of viability, and of first-pass contrast enhancement for evaluation of perfusion. Specification and development of the software is performed at the LKEB (Leiden). Beta-testing is done in 3 ICIN centers (LUMC, VUMC, Erasmus MC), and a database of normal values is created. Further application and clinical evaluation in heart failure patients is then performed in the three centers. Finally, the software is to be distributed to other ICIN centers for application of MRI in Heart Failure. |
