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Optimization and Validation of Ferumoxytol-Enhanced Myocardial T1 Reactivity and Myocardial Blood Volume Mapping for Detection of Myocardial Ischemia

Abstract

Cardiovascular disease remains the global leading cause of death. Noninvasive imaging techniques to detect and quantify myocardial ischemia continue to have wide-ranging impact in clinical cardiovascular care. This body of research aims to develop several novel noninvasive quantitative cardiac magnetic resonance imaging (MRI) techniques for the detection of ischemic heart disease. We designed, manufactured, and percutaneously deployed 3D printed implants in the left anterior descending (LAD) artery of 13 swine to investigate the feasibility and efficacy of the implants to cause hypoperfusion and ischemia on MRI. This novel animal model offers a success rate comparable to that of highly invasive methods, allowing for more rapid and cost-effective translational imaging studies. In a cohort of these swine models, we found that ferumoxytol improves the diagnostic performance of T1 reactivity as a measure of myocardial ischemia. Next, we aimed to use FE-MRI to capture a hemodynamic response to myocardial hypoperfusion at rest. We derived and tested a two-compartment water exchange model for quantification of fractional myocardial blood volume (fMBV) before developing an integrated image registration and compartmental modelling platform. We demonstrated the feasibility of a two-compartment model for estimation of fMBV using steady-state MOLLI T1 mapping over multiple ferumoxytol doses. Our technical developments to our image processing pipeline advance the current state of pixelwise fMBV mapping toward a more integrated in-line approach. We ultimately found that this fMBV mapping approach can be used to distinguish between ischemic and remote myocardium in a broader study in 19 ischemic swine models. Finally, our investigation of the in-vitro and in-vivo MRI properties of three comparable iron-based contrast agents contributes may help to expand the adoption of this unique class of contrast agents. In addition to our contributions to the development of two novel imaging biomarkers of heart disease, this body of research enables a broad range of new research in quantitative cardiovascular MRI.

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