MRI of Left Atrial Hemodynamic Disorders in Atrial Fibrillation

Project Summary/Abstract: The three therapeutic goals of AF management are rhythm control, rate control, and stroke prevention. The attributable risk of stroke from AF increases progressively with age. Anticoagulation therapies are effective, but regrettably associated with non-negligible complications of major bleeding (~3% per year). This is because currently used risk profiles such as the CHA2DS2-VASc score are based on upstream clinical factors (age, sex, diabetes, etc.) rather than individual physiologic mechanisms implicated in left atrium (LA) or LA appendage (LAA) thrombus formation. As a first step towards personalizing anticoagulation therapy, this application seeks to develop and validate a new imaging test for establishing a risk stratification system based on individual physiologic factors implicated in thrombus formation. The scientific premise of this study is based on a growing interest in non-invasive imaging of known parameters of atrial pathology in AF: LA/LAA volume, contractile function, geometry, and blood stasis - one component of Virchow’s triad - as a contributor to atrial thrombogenesis. This is supported by transesophageal echocardiography (TEE) studies which reported that decreased peak emptying LAA flow velocities and the presence of atrial flow stasis are risk factors for stroke in AF. However, TEE is invasive and can only assess isolated components (e.g. peak emptying LAA blood velocities) of the 3D LA/LAA blood flow dynamics inside a complex cardiac chamber (geometry, in-flow through 4 pulmonary veins, rapid mitral-valve outflow). Cardiovascular MRI is an excellent modality for imaging atrial hemodynamics. By leveraging an unprecedented imaging speed from compressed sensing (CS), this application seeks to further advance cardiovascular MRI and develop a 15-min MRI protocol for a comprehensive assessment of persistent and beat-to-beat variation in hemodynamics (LA and LAA flow, function, and volume) in AF. The specific objectives of this application are: (1) To develop a rapid MRI protocol along with image processing tools for atrial hemodynamics by combining highly-accelerated dual-venc 4D flow and real-time cine and flow MRI methods with CS, (2) to validate a new atrial MRI protocol in patient-specific models with a pulsatile flow pump in simulated regular and irregular rhythm conditions and to establish in-vivo test-retest reproducibility, and (3) to establish the relationship between MRI metrics, AF burden, age, and stroke in a patient pilot study. Unlike conventional cardiovascular MRI protocols, this rapid comprehensive atrial MRI protocol (15 min) is a major step forward in MRI technology, because it eliminates demands on patients for breath holding, improves scan efficiency, simplifies scan operation, and does not require gadolinium-based contrast agent administration. These features are important pre-requisites for a screening tool. Our proposal has high impact potential because, if successful, it will deliver a rapid, non-contrast MRI protocol for a comprehensive assessment of atrial hemodynamics in the setting of AF.