Tailoring Stress Cardiac MRI for Women with Ischemic Heart Disease

Ischemia with non-obstructive chronic coronary artery disease (CAD) is more prevalent than obstructive CAD in women. Veterans in particular, are at higher risk of ischemic heart disease (IHD) due to prevalent non- traditional (mental illness, Agent Orange exposure, and lifestyle choices) and traditional risk factors, regardless of sex. Half of patients referred for invasive coronary angiograms have no obstructive CAD, whereas 3 in 4 have coronary microvascular disease (CMD), most of whom are women. Often, CMD passes undiagnosed but contributes to excess morbidity, health resource utilization, impaired quality of life, and major adverse cardiovascular events. This is partly because current non-invasive imaging approaches are not specifically tailored for CMD but were optimized for detection of obstructive epicardial CAD, and invasive coronary testing is necessary to confirm the diagnosis of CMD. In the past 4 years, our group has focused on a gadolinium-free stress cardiac MRI approach that overcomes several drawbacks of first-pass perfusion stress cardiac MRI for women with IHD. We showed that MRI-derived myocardial vasoreactivity and fractional myocardial blood volume mapping have high specificity as markers of hypoperfusion. Our preliminary results illustrate that MRI- derived fractional myocardial blood volume mapping has potential to depict the full spectrum of IHD. In this MERIT renewal, we aim to further target our gadolinium-free MRI approach for CMD by enabling whole-heart coverage and depiction of coronary morphologic indices. We further propose to develop computational hemodynamic models that enable patient-specific mechanistic relationships between CMD and IHD to be studied. Cardiac MRI is attractive for depiction of myocardial IHD in women because it has high spatial resolution, lacks ionizing radiation, and when coupled with iron-based blood pool agents, imaging in the steady-state offers higher spatial resolution than is possible with first-pass gadolinium perfusion approaches. MRI better captures the spatial heterogeneity inherent in the spectrum of IHD. Successful completion of the proposed work would result in clinical deployment of a comprehensive gadolinium-free cardiac MRI approach for detection of CMD and a set of methods for in silico estimation of patient-specific coronary hemodynamic parameters based on imaging targets.