Methods for myocardial measurements of blood oxygen saturation using magnetic resonance imaging

Oxygenation is a fundamental physiological parameter of the myocardium which is modulated by variations in both coronary blood flow and oxygen metabolic rate. These factors are intrinsic to the viability of heart muscle cells or myocytes since oxygen phosphorylation is the fuel for their fundamental metabolic processes. Myocardial ischemia, characterized by metabolic abnormalities and a ceasing of the heart's contractile function, results when the oxygen demand outstrips the oxygen supply. The pathophysiological processes of the coronary vasculature which induce ischemia and the effects of ischemia on myocytes are the leading cause of mortality in Western society, a set of conditions collectively termed ischemic heart disease. The overall research motivation is the development of non-invasive oximetry methods to augment or supplant measurements of blood flow and metabolism for vascular and myocardial evaluation. Oximetry in clinical practice is based on the optical properties of hemoglobin, which can only be evaluated invasively in deep tissue structures. Magnetic resonance imaging, or MRI, is the only technology which can generate oxygen-sensitive images non-invasively within arbitrarily-positioned 2D-imaging planes. The source of oxygen-sensitivity is water's thermal motion through spatially-varying magnetic fields in the vicinity of red blood cells containing deoxygenated hemoglobin. The extent of deoxygenation is quantified in the relaxation time of the MRI signal, termed T2. The precision of the oxygen measurement is thus strongly correlated with the precision of the T2 measurement, thus motivating the development of very good T2 measurements. This thesis addresses the development of oxygen-level measurements using T2 relaxation which can applied to ischemic heart disease. The first contribution is the design and testing of a MRI method for coronary venous oximetry, optimized for performance equivalent to the invasive gold standard. The technique is the only non-invasive approach for oxygen level measurement in the coronary veins. The second contribution is the design of a method for performing myocardial measurements. It includes the first in-depth evaluation of factors affecting both measurement accuracy and precision for myocardial applications. The method is suitable for pre-clinical studies, since it has been optimized to maximize robustness and oxygen sensitivity within total scan times which are relatively long by clinical standards. The third contribution is the characterization of biophysical mechanisms underlying elevations in myocardial T2 relaxation during vasodilation. This study was the first to document using an animal model that T2 relaxation changes during intracoronary adenosine infusion, a common vasodilator, was caused by elevations in microcirculation oxygen levels, with tissue blood volumes and oxygen metabolic rate remaining constant. Together, these contributions lay a foundation for experimental and clinical studies into diseases of the coronay vasculature and myocardium which affect the supply and utilization of oxygen, while motivating design improvements which facilitate each technique's integration into standard clinical practice.