? ? The clinical consequence of severe, uncorrected mitral regurgitation (MR) is excess mortality and morbidity. The timing of surgical intervention in chronic MR remains one of the most challenging clinical decisions in cardiac surgery. A refinement in our understanding of the pathogenesis of ventricular remodeling in mitral regurgitation is clearly needed to improve clinical outcomes. The canonical model of ventricular remodeling in volume overload hypertrophy does not account for transmural differences in hypertrophic remodeling. We now have exciting preliminary results that demonstrate a transmural gradient in ventricular wall remodeling wherein the epicardium thins by 30% and the endocardium thickens by nearly 10% during chronic MR. The overall hypothesis of the work is that transmural differences in the hypertrophic response to chronic mitral regurgitation may portend a poor clinical outcome. My immediate career goal is to develop the necessary experimental, computational, and theoretical tools to test hypotheses about transmural differences in cardiac ? structure, function, and remodeling in mitral regurgitation. A unique research environment is available to me through an inter-disciplinary collaboration between the Departments of Cardiothoracic Surgery and ? Radiology at Stanford University. This opportunity affords the ability to gain a deep understanding of cardiac pathophysiology research in addition to further developing my expertise in cardiac magnetic resonance imaging. My career plan includes gaining considerable expertise in experimental cardiac physiology research, quantitative histologic methods, diffusion tensor magnetic resonance imaging (DTMRI), and computational techniques for integrating structure and function data. My long-term career goal is to secure a tenure-track faculty position so that I can continue to answer questions about cardiac structure, function, and remodeling in disease. Work during the Independent Phase will develop the first finite element model of integrated cardiac structure and function from a rodent model of mitral regurgitation using data acquired from MRI tissue displacement and DTMRI. The relevance of this research proposal regards improving our understanding of mitral regurgitation, a common cause of heart failure. The results of this research may help elucidate important changes that underlie the progression from chronic mitral regurgitation to over heart failure and may spur the development of innovative therapies to aid in the treatment of this disease. (End of Abstract) ? ? ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Career Transition Award (K99)
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Special Emphasis Panel (ZHL1-CSR-M (F1))
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Scott, Jane
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Stanford University
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Reyhan, Meral; Kim, Hyun J; Brown, Matthew S et al. (2014) Intra- and interscan reproducibility using Fourier Analysis of STimulated Echoes (FAST) for the rapid and robust quantification of left ventricular twist. J Magn Reson Imaging 39:463-8
Reyhan, Meral; Natsuaki, Yutaka; Ennis, Daniel B (2014) Off-resonance insensitive complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) for quantification of left ventricular twist. J Magn Reson Imaging 39:339-45
Middione, Matthew J; Thompson, Richard B; Ennis, Daniel B (2014) Velocity encoding with the slice select refocusing gradient for faster imaging and reduced chemical shift-induced phase errors. Magn Reson Med 71:2014-23
Middione, Matthew J; Ennis, Daniel B (2013) Chemical shift-induced phase errors in phase-contrast MRI. Magn Reson Med 69:391-401
Itoh, Akinobu; Stephens, Elizabeth H; Ennis, Daniel B et al. (2012) Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation. Am J Physiol Heart Circ Physiol 302:H180-7
Reyhan, Meral; Natsuaki, Yutaka; Ennis, Daniel B (2012) Fourier analysis of STimulated echoes (FAST) for the quantitative analysis of left ventricular twist. J Magn Reson Imaging 35:587-93
Kung, Geoffrey L; Nguyen, Tom C; Itoh, Aki et al. (2011) The presence of two local myocardial sheet populations confirmed by diffusion tensor MRI and histological validation. J Magn Reson Imaging 34:1080-91
Ennis, Daniel B; Rudd-Barnard, Gabriel R; Li, Bo et al. (2010) Changes in mitral annular geometry and dynamics with ß-blockade in patients with degenerative mitral valve disease. Circ Cardiovasc Imaging 3:687-93
Ennis, Daniel B; Nguyen, Tom C; Itoh, Akinobu et al. (2009) Reduced systolic torsion in chronic ""pure"" mitral regurgitation. Circ Cardiovasc Imaging 2:85-92
Itoh, Akinobu; Ennis, Daniel B; Bothe, Wolfgang et al. (2009) Mitral annular hinge motion contribution to changes in mitral septal-lateral dimension and annular area. J Thorac Cardiovasc Surg 138:1090-9

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