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Assessment of myocardial viability with magnetic resonance imaging techniques

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Title Assessment of myocardial viability with magnetic resonance imaging techniques
Period 06 / 2006 - unknown
Status Completed
Research number OND1318216

Abstract

Distinction between reversible and irreversible myocardial injury in patients suffering from coronary artery disease, (sub)acute myocardial infarction (MI) or chronic MI is essential both for accurate prognosis and for selecting patients that will benefit from coronary revascularization. Delayed contrast-enhancement (DCE) MRI of the myocardium after injection of MR contrast material has been shown to delineate areas of MI. In subacute MI, however, overestimation of the infarct size has been found with DCE-MRI, possibly due to formation of interstitial edema in the peri-infarct zone. An alternative approach is imaging of sodium present in the heart (23Na-MRI). The increased signal intensity in 23Na images of non-viable myocardium is believed to result from intracellular Na-accumulation due to loss of ionic homeostasis, whereas in viable myocardium intracellular Na is kept low by residual Na/K-ATPase activity. Cardiac imaging of intracellular Na is entirely new and essential to interpret total 23Na-MRI. Hypothesis: Intra- and extracellular 23Na-MRI directly assess myocardial membrane function and constitute an attractive alternative for DCE-MRI in assessing myocardial viability in (sub)acute myocardial infarction, where DCE-MRI may overestimate infarct size due to edema formation. Objectives: The aim of this proposal is to evaluate and compare DCE-MRI and intra- and extracellular 23Na-MRI for the assessment of myocardial viability. The influence of interstitial edema in the peri-infarct zone will be investigated and characterized. DCE-MRI and 23Na-MRI findings will be related to global and regional left ventricular myocardial function. Methods: Models with different levels of myocardial edema will be employed in isolated rat hearts. Total, extracellular and intracellular volumes will be monitored with a 31P-MRS method. Next, the effect of interstitial edema on DCE-MR and shift reagent-aided 23Na-MR images will be evaluated and characterized. Rat hearts will be perfused in a dual-perfusion setup, which enables independent perfusion of the left and right coronary beds to produce different levels of edema on either side. Subsequently, DCE-MRI and 23Na-MRI will be evaluated and compared as tools for assessment of myocardial viability in acute, sub-acute and chronic MI models. Acute MI will be induced by ischemia in only one side of the heart in a dual-perfusion setup. The other side will serve as a control. Ischemia will be followed by reperfusion. Sub-acute or chronic MI will be induced in rats by LAD occlusion for 2-3 days (sub-acute) or 4 weeks (chronic). After this, hearts will be excised and perfused. TTC-staining will be used to independently assess infarct size at the end of the experiments. Finally, myocardial viability will be evaluated in live rats at various time points after LAD occlusion with DCE-MRI and 23Na-MRI. Expected results: We expect that DCE-MRI will overestimate infarct size in acute and sub-acute MI due to edema formation in the peri-infarct zone and thus cannot fully distinguish irreversibly damaged from viable tissue. Intra- and extracellular 23Na-MRI is expected to accurately distinguish between normal, edematous and infarcted myocardium in acute, sub-acute as well as chronic MI. The results of this study may contribute to the development of new clinical diagnostic imaging modalities for early detection of ischemia and viability. Objectives The aim of this proposal is to evaluate and compare DCE-MRI and intra- and extracellular 23Na-MRI for the assessment of myocardial viability. The influence of interstitial edema in the peri-infarct zone will be investigated. The results of these studies may contribute to new clinical diagnostic imaging modalities for early and accurate detection of ischemia and viability. Study 1. To develop isolated heart models with different levels of myocardial edema, which will be monitored by a 31P-MRS method. Study 2. To evaluate and characterize the effect of interstitial edema on DCE-MR and intra- and extracellular 23Na-MR images in a dual-perfusion setup of isolated rat hearts. Study 3. To evaluate and compare DCE-MRI and 23Na-MRI as tools for assessment of myocardial viability in an acute model of myocardial infarction (MI) employing the dual-perfusion setup of study 2. DCE-MRI and 23Na-MRI findings will be related to global and regional left ventricular myocardial function. Study 4. To evaluate and compare DCE-MRI and 23Na-MRI as tools for assessment of myocardial viability in isolated hearts with sub-acute or chronic MI. DCE-MRI and 23Na-MRI findings will be related to global and regional left ventricular myocardial function. Study 5. To evaluate and compare myocardial viability in live rats at various time points after LAD occlusion with DCE-MRI and 23Na-MRI. DCE-MRI and 23Na-MRI findings will be related to global and regional left ventricular myocardial function. Relevance for cardiovascular diseases Distinction between reversible and irreversible myocardial injury in patients suffering from coronary artery disease, (sub)acute myocardial infarction (MI) or chronic MI is essential both for accurate prognosis and for selecting patients that will benefit from coronary revascularization. Several clinical image modalities exist for assessment of viable myocardium, e.g. SPECT, PET, stress-echocardiography, and delayed contrast-enhanced (DCE) MRI, which have proven to be useful in the chronic situation. In the (sub)acute situation, however, a reliable technique for the assessment of myocardial viability does not exist. Although the results with DCE-MRI are very promising, it remains unclear how exactly the difference in contrast is established. Furthermore, signal enhancement due to edema in the peri-infarct zone may lead to overestimation of the affected area. 23Na MRI is a noninvasive methodology for measuring Na, but so far, studies using this technique are scarce and mostly concerned with imaging of total Na. We have previously shown in isolated rat hearts that intracellular Na-MRI can be used for assessment of myocardial viability. We expect that intra- and extracellular 23Na-MRI can accurately distinguish between normal, edematous and infarcted myocardium in acute, sub-acute as well as chronic MI. The results of this study may contribute to the development of new clinical diagnostic imaging modalities for early and accurate detection of ischemia and viability.

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Classification

A73200 Second-line health care
D23220 Internal medicine
D23330 Radiology, radiotherapy

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