Heart failure, pulmonary hypertension, and congenital heart disease can compromise the capacity of the cardiovascular system to deliver sufficient oxygen (O2) to meet the varying metabolic demands of the organ systems. Mixed venous oxygen saturation measured in the main pulmonary artery is an accurate marker of the systemic delivery of blood and oxygen that provides key diagnostic and prognostic value. However, a true mixed venous saturation requires catheter access to the main pulmonary artery and may be underutilized as a diagnostic measure due to the associated level of invasiveness and risk. A non-invasive means to quickly and accurately measure O2 saturation (O2sat) in the main pulmonary artery, the cardiac chambers, and ideally anywhere in the body, would not only reduce the need for invasive catheterization procedures, but would also provide important physiological information that may be otherwise unavailable or unobtainable. In the blood, the magnetic resonance transverse relaxation time (T2) is related to the oxygen saturation of hemoglobin, and MR relaxometry has been previously proposed for in vivo estimation of blood O2 saturation; however, these estimates have relied on an impractical in vitro calibration on each patient, and results have been corrupted by flow-induced artifacts. A technique previously developed in our lab for rapid, single-shot T2 mapping has been modified to reduce flow artifacts and improve the accuracy of T2 measured in flowing blood. Together with this modified pulse sequence, we propose an entirely new approach to solving the Luz-Meiboom (L-M) equation that describes the relationship between T2 and O2sat in blood. We hypothesize that the use of varied preparation pulse timing along with direct measurement of easily accessible patient specific parameters will support the application of non-linear parameter estimation techniques to provide an accurate quantitative assessment of blood O2sat in the heart and deep vessels, even in locations having limited accessibility with other diagnostic techniques. We propose to optimize and validate this approach to non-invasive blood oximetry by meeting the following specific aims. Aim 1: We will define appropriate limits for acquisition parameters TE and 180 in a flow phantom and optimize acquisition parameters using statistical sensitivity analysis. Aim 2: We will empirically validate O2sat derived from T2 in a porcine model of graded hypoxemia that enables simultaneous acquisition of T2 and invasive O2sat measurement over a broad range of values. Aim 3: We will evaluate feasibility in a small cohort of heart failure patients undergoing clinically indicated pulmonary artery catheterization for mixed venous O2sat measurement. By addressing the flow sensitivity of the T2 preparation pulse and the inaccuracies introduced by oversimplification of the model relating T2 to O2sat, we anticipate that the level of accuracy and reproducibility for this technique will be raised to that required for clinical application in patients with cardiovascular disease. τ

Cardiovascular disease remains the leading cause of death in America. In many types of cardiovascular disease, including heart failure and congenital heart defects, it is important to measure the level of oxygen in the blood in the heart because this is indicative of several important aspects of the patient's health. Today, this can only be measured by invasive cardiac catheterization; we propose to develop a totally non-invasive technique based on cardiac MRI that will make the measurement of blood oxygen safer and more readily available.