Atrial stretch, caused by pressure and volume overload, contributes to development of atrial fibrosis, in patients with ventricular dysfunction such as mitral regurgitation or congestive heart failure. Atrial structural remodeling-including fibrosis- is a major component in development and progression of atrial fibrillation (AF). Prophylactic treatments which reduce stretch-mediated atrial remodeling exist, and would benefit patients, but the appropriate selection of patients is unclear, because atrial structural remodeling is difficult to assess clinically. This work introduces a new approach, which relies on several innovative ideas in cardiovascular magnetic resonance (CMR). We propose to increase the robustness and reliability of late gadolinium enhancement (LGE) using a sequential acquisition order, with acceptable fat-suppression, and a REPAIR pulse, designed to reduce artifacts in 1RR LGE acquisitions, in the presence of arrhythmias or RR variability. Further, we propose to quantify atrial collagen fraction, by suitably adapting T1 mapping methods to this high resolution application, with dark blood preparation. Extracellular volume fraction (ECV), based on T1 mapping, will be a more precise measure of the presence of collagen. Inflammation will be investigated using a fluid and fat-suppressed T2-mapping method. We will also evaluate 3D atrial strain. This atrial strain measurement would be extraordinarily challenging with conventional tagging methods, because of the thin walls of the atrium. However, we will develop 3D cine atrial imaging which can be processed, based on the expertise of our collaborators, with shape tracking to estimate atrial strain. We will then study these methods in an animal model of mitral regurgitation, and in patients with mitral disease. We will validate our in-vivo LGE and ECV measurements vs. histology in animals, and in the explanted hearts of heart-transplant recipients. Mitral regurgitation is a major risk factor for boh AF and atrial fibrosis development. We will test the major hypothesis that abnormal atrial stretch (low or high) -measured via strain measurements-generates inflammation and, at later time-points, atrial fibrosis. The project carries a health benefit to a broad spectrum of patients, by potentially permitting early treatment with anti-fibrotic medications or interventions in appropriae patients at risk for atrial-fibrosis related AF.

Public Health Relevance

Some arrhythmias are due to scar in the heart chambers, which interacts with the electrical system of the heart. MRI has the possibility of detecting the development of this scar, due to increased stretch and linking it to scar. Development of these capabilities will improve patient care by improving our understanding about why scar-- which causes arrhythmia-develops.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-DTCS-A (81))
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Boineau, Robin
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Yale University
Schools of Medicine
New Haven
United States
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Hu, Chenxi; Huber, Steffen; Latif, Syed R et al. (2018) Reverse double inversion-recovery: Improving motion robustness of cardiac T2 -weighted dark-blood turbo spin-echo sequence. J Magn Reson Imaging 47:1498-1508
Hu, Chenxi; Sinusas, Albert J; Huber, Steffen et al. (2017) T1-refBlochi: high resolution 3D post-contrast T1 myocardial mapping based on a single 3D late gadolinium enhancement volume, Bloch equations, and a reference T1. J Cardiovasc Magn Reson 19:63
Peters, Dana C; Duncan, James S; Grunseich, Karl et al. (2017) CMR-Verified Lower LA Strain in the Presence of Regional Atrial Fibrosis in Atrial Fibrillation. JACC Cardiovasc Imaging 10:207-208