Sodium handling by the myocyte plays a key role in cardiac function. Active pumping of sodium by membrane- based channels normally maintains a large electrochemical gradient across the cell membrane, which enables depolarization and repolarization during the cardiac cycle. Coupling of sodium transport to the transport of other ionic species, including calcium, also has important effects on the cardiac cycle. Myocardial ischemia decreases the ability to actively transport sodium out of the myocyte, contributing to the associated loss of cardiac contractility and increased arrhythmogenicity. Molecular abnormalities of sodium transport (e.g., in Brugada and long-QT syndromes) also predispose to arrhythmias, as do many drugs that affect sodium transport. The ability to quantify intracellular and extracellular sodium concentrations in the heart would thus likely contribute useful information on both normal and abnormal cardiac function. There are very limited means available for the noninvasive assessment of cardiac sodium. Magnetic resonance imaging (MRI) can create images of sodium content in cardiac tissue. However, technical difficulties associated with sodium cardiac MRI, including poor signal-to-noise ratio (SNR), and difficulty in separating intracellular and extracellular sodium concentrations, have limited its current clinical utility. The proposed research will address some of these difficulties, with the goal of significantly improving the ability to quantify cardiac sodium with MRI.
The aims of the research include: (1) Implementation of 3D linogram sodium imaging, which offers potentially fast and accurate image reconstruction, and implementation of XD-GRASP sodium imaging and reconstruction methods, which offer improved SNR and motion compensation; (2) Combining sodium MRI and contrast-enhanced hydrogen MRI to enable calculation of intracellular sodium concentration and extracellular volume fraction in myocardial tissue; and (3) Testing these methods for feasibility on both normal subjects and patients with abnormal sodium handling, such as Brugada syndrome and arrhythmogenic cardiomyopathy. In addition to providing a useful set of tools to investigate sodium handling in the heart, which is a fundamental aspect of normal and abnormal cardiac physiology or function, these new methods should also be useful for other applications of sodium MRI.
Although sodium handling by the heart plays an essential role in normal and abnormal cardiac function, it is still poorly understood. Magnetic resonance imaging (MRI) of sodium can provide vital information on cardiac sodium handling, but its use has been hampered by technical difficulties. The proposed research will develop some promising new methods for cardiac sodium MRI, with the goal of developing useful means for quantitative assessment of cardiac intracellular sodium concentration in health and disease.
