PROJECT SUMMARY/ABSTRACT The goal of this research is to develop cardiac quantitative susceptibility mapping (QSM) for non-invasive meas- urement of blood oxygen saturation, towards the long-term objective of improving early diagnosis, therapeutic decision-making, and clinical outcomes for patients with pulmonary hypertension (PH). PH is a progressive and life shortening disorder affecting ~10% of adults over age 65. Given that PH can be irreversible in its later stages, early diagnosis and physiologic monitoring are critically important. Impaired oxygenation of the lungs and heart chambers (cardiac oxygenation) is a key manifestation of PH that impacts symptoms and clinical outcomes. Increased pulmonary arterial pressure in PH impairs pulmonary oxygen exchange, decreasing delivery of oxy- genated blood to the left heart. Systemic cardiac output is often compromised in PH, resulting a larger differential blood oxygen saturation between the left and right heart. Invasive catheterization (cath) is currently used to measure cardiac oxygenation but entails procedural risks, ionizing radiation exposure, and is impractical for early diagnosis and serial monitoring - a non-invasive method to accurately measure blood oxygenation would be of substantial utility. MRI is well suited for PH assessment as it enables integrated evaluation of pulmonary anat- omy, pressure, as well as cardiac function and remodeling - blood oxygenation is a key gap in MRI evaluation of PH. This gap stems from limitations in current pulse sequence technology rather than fundamental MRI physics. It is well known that deoxygenation changes the magnetic susceptibility of blood. These changes have tradition- ally been probed using a magnitude property of the MR signal: the transverse relaxation time (T2). However, this requires patient-specific calibration that is difficult in clinical practice. In contrast, QSM relies on the phase of the MR signal to directly measure susceptibility and thus cardiac oxygenation. We have obtained highly encouraging preliminary data for QSM measurement of cardiac blood oxygenation, with close agreement between QSM and oxygenation measured invasively. We have identified key challenges for developing cardiac QSM, including motion suppression and prolonged scan times. The current research proposes to develop an accelerated cardiac QSM method, and to test QSM in relation to oxygenation on invasive cath, as well as effort tolerance and clinical prognosis. Study Aims are as follows: (1) Develop accelerated cardiac QSM using free-breathing acquisition and optimized reconstruction. (2) Test accelerated and current cardiac QSM among PH patients in comparison to T2-based cardiac oxygenation and the reference standard of invasive cardiac catheterization. (3) Determine whether cardiac QSM stratifies clinical severity and predicts PH disease progression. The expected outcome of this research is a non-invasive method for measuring cardiac oxygenation – a critically important marker in PH that currently relies on invasive testing. Given the increasing prevalence and therapeutic options for this serious condition, non-invasive oxygenation assessment by cardiac QSM holds broad significance towards the goal of early diagnosis, therapy optimization, and improved clinical outcomes for millions of patients with PH.

PROJECT NARRATIVE The goal of this research is to develop cardiac quantitative susceptibility mapping (QSM), a new magnetic resonance imaging technique, for non-invasive measurement of blood oxygen saturation in the heart – an index that strongly predicts clinical outcomes but currently requires invasive testing. To do so, blood oxygenation on QSM will be validated in relation to invasively measured oxygenation, effort tolerance, and clinical outcomes in patients with pulmonary hypertension (a condition in which low blood oxygen is common). Results will address key technical and clinical knowledge gaps regarding blood oxygen measurement by cardiac QSM - towards the goal of early diagnosis, therapeutic optimization, and improved outcomes for patients with pulmonary hypertension.