Summary Coronary artery disease (CAD) is a major healthcare problem that affects over 20 million Americans and costs an estimated $82.8 billion each year. Atrial Fibrillation (AFIB) is a related epidemic that is estimated to affect 12 million Americans by 2030 with costs of ~$26 billion each year. Up to 38% of AFIB patients also have CAD and they have a worse prognosis than patients with CAD alone. In order to prioritize and treat this vulnerable population, clinicians need clear diagnostic tools that point toward specific treatments. Computed Tomography Angiography (CTA) can be used to detect anatomical blockages in the coronaries; however, the hemodynamic significance of the blockage cannot be accurately determined. Myocardial perfusion imaging is a proven tool to detect and characterize CAD by determining the hemodynamic significance of coronary blockages on the myocardium. While Single Photon Emission Computed Tomography (SPECT) perfusion imaging is widely used in the U.S., the specificity of SPECT is low in patients with AFIB and CAD. Positron Emission Tomography (PET) perfusion imaging is less widely available for CAD assessment but offers quantitative myocardial blood flow maps and has superior image resolution compared to SPECT. Magnetic Resonance Imaging (MRI) offers myocardial perfusion imaging with in-plane spatial resolution superior to PET imaging and without the ionizing radiation. However, MR imaging has a few limitations in the context of AFIB patients, (1) MRI relies on good and consistent ECG-gating signals to achieve diagnostic quality images. AFIB patients’ inconsistent R-R intervals result in poor image quality with randomly changing cardiac phases for a given slice and hence are often excluded from MR studies. (2) Quantifying MR perfusion images requires accurate measurement of the arterial input function with a high temporal sampling rate, something challenging in AFIB patients due to changing R-R intervals. (3) MR perfusion has limited slice coverage compared to SPECT and PET and is exacerbated in AFIB patients. Increased slice coverage is desirable for improved confidence and accuracy in perfusion defect assessment. A myocardial perfusion MRI method that (i) does not rely on ECG gating, (ii) has whole-heart coverage and (iii) is quantitative would be extremely valuable in AFIB patients to detect CAD. Specific aims of the project are (I) to develop a flow and motion insensitive steady-state (FAMISS) ungated quantitative simultaneous multi-slice acquisition methods along with novel constrained and deep learning reconstruction techniques for rapid, whole-heart quantitative perfusion MRI, (II) to rigorously compare the quantitative flow values from the FAMISS framework with existing dual-bolus quantitative MRI measures, and (III) to validate the FAMISS framework by comparing it to the gold standard for quantification, PET imaging, and the gold standard for diagnostic accuracy using invasive fractional flow measures. Our team ...