Computational studies, both biomechanical and electrophysiological, based on structural models of the myocardium have provided valuable insight into the functions of both normal and diseased hearts beyond empirical experimentation. However, to date, few computational models of the heart are available, and most existing models are methodologically hampered by the labor-intensive and destructive nature of conventional histological techniques. More importantly, since previous models were constructed from limited numbers of specimens, the degree to which they represent the """"""""typical"""""""" heart, even of the same species, gender, age and contractile state, is unclear. These challenges are exacerbated for structural models of the mouse heart because of its small physical size, despite that the species is often preferred for investigating the pathophysiology and treatment of human diseases. The current proposal seeks to address these critical needs by developing and combining advanced high-resolution MRI acquisition methods and imaged-based population """"""""atlas"""""""" analysis techniques. The overall hypothesis is that structural models representative of the normal mouse myocardium across gender, strain, age, and cardiac cycle can be constructed from a finite number of diffusion MRI datasets.
Specific aims i nclude (1a) develop multi-dimensional constrained reconstruction of reduced k- space sampling data and optimize diffusion-encoding schemes to accelerate diffusion imaging scan time, (1b) enhance the utility of diffusion MRI for characterizing myocardial structures, (2a) construct and validate static structural atlases of the normal mouse myocardium, (2b) apply diffeomorphic mapping to investigate the gender and genotype-dependence of mouse heart structural atlases, (2c) combine group regression analysis and diffeomorphic mapping to investigate the maturational adaptive modulation of the normal mouse heart, and (3) generate validated dynamic structural models of the beating normal mouse myocardium by applying Hyperelastic Warping analysis to static structural models.

Public Health Relevance

The overall aim of this proposal is to construct structural atlases of the normal mouse heart that are representative of the species regardless of gender, strain, age, and cardiac contractile state. Results of this research will provide essential foundations for computational studies of the anatomy, electrophysiology and biomechanics of both normal and diseased hearts.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Applebaum-Bowden, Deborah
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University of Utah
Biomedical Engineering
Schools of Engineering
Salt Lake City
United States
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Gomez, Arnold D; Zou, Huashan; Bowen, Megan E et al. (2017) Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure Overload: A Computational Study. J Biomech Eng 139:
Abdullah, Osama M; Gomez, Arnold David; Merchant, Samer et al. (2016) Orientation dependence of microcirculation-induced diffusion signal in anisotropic tissues. Magn Reson Med 76:1252-62
Merchant, Samer S; Gomez, Arnold David; Morgan, James L et al. (2016) Parametric Modeling of the Mouse Left Ventricular Myocardial Fiber Structure. Ann Biomed Eng 44:2661-73
Abdullah, Osama M; Seidel, Thomas; Dahl, MarJanna et al. (2016) Diffusion tensor imaging and histology of developing hearts. NMR Biomed 29:1338-49
Merchant, Samer S; Kosaka, Yasuhiro; Yost, H Joseph et al. (2016) Micro-Computed Tomography for the Quantitative 3-Dimensional Assessment of the Compact Myocardium in the Mouse Embryo. Circ J 80:1795-803
Welsh, Christopher L; DiBella, Edward V R; Hsu, Edward W (2015) Higher-Order Motion-Compensation for In Vivo Cardiac Diffusion Tensor Imaging in Rats. IEEE Trans Med Imaging 34:1843-53
David Gomez, Arnold; Bull, David A; Hsu, Edward W (2015) Finite-Element Extrapolation of Myocardial Structure Alterations Across the Cardiac Cycle in Rats. J Biomech Eng 137:101010
McKellar, Stephen H; Javan, Hadi; Bowen, Megan E et al. (2015) Animal model of reversible, right ventricular failure. J Surg Res 194:327-33
Abdullah, Osama M; Drakos, Stavros G; Diakos, Nikolaos A et al. (2014) Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation. NMR Biomed 27:1378-86
Gomez, Arnold David; Zou, Huashan; Shiu, Yan-Ting et al. (2014) Characterization of regional deformation and material properties of the intact explanted vein by microCT and computational analysis. Cardiovasc Eng Technol 5:359-370

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