@ARTICLE{10.3389/fphys.2018.00539, AUTHOR={Sack, Kevin L. and Aliotta, Eric and Ennis, Daniel B. and Choy, Jenny S. and Kassab, Ghassan S. and Guccione, Julius M. and Franz, Thomas}, TITLE={Construction and Validation of Subject-Specific Biventricular Finite-Element Models of Healthy and Failing Swine Hearts From High-Resolution DT-MRI}, JOURNAL={Frontiers in Physiology}, VOLUME={9}, YEAR={2018}, URL={https://www.frontiersin.org/articles/10.3389/fphys.2018.00539}, DOI={10.3389/fphys.2018.00539}, ISSN={1664-042X}, ABSTRACT={Predictive computational modeling has revolutionized classical engineering disciplines and is in the process of transforming cardiovascular research. This is particularly relevant for investigating emergent therapies for heart failure, which remains a leading cause of death globally. The creation of subject-specific biventricular computational cardiac models has been a long-term endeavor within the biomedical engineering community. Using high resolution (0.3 × 0.3 × 0.8 mm) ex vivo data, we constructed a precise fully subject-specific biventricular finite-element model of healthy and failing swine hearts. Each model includes fully subject-specific geometries, myofiber architecture and, in the case of the failing heart, fibrotic tissue distribution. Passive and active material properties are prescribed using hyperelastic strain energy functions that define a nearly incompressible, orthotropic material capable of contractile function. These materials were calibrated using a sophisticated multistep approach to match orthotropic tri-axial shear data as well as subject-specific hemodynamic ventricular targets for pressure and volume to ensure realistic cardiac function. Each mechanically beating heart is coupled with a lumped-parameter representation of the circulatory system, allowing for a closed-loop definition of cardiovascular flow. The circulatory model incorporates unidirectional fluid exchanges driven by pressure gradients of the model, which in turn are driven by the mechanically beating heart. This creates a computationally meaningful representation of the dynamic beating of the heart coupled with the circulatory system. Each model was calibrated using subject-specific experimental data and compared with independent in vivo strain data obtained from echocardiography. Our methods produced highly detailed representations of swine hearts that function mechanically in a remarkably similar manner to the in vivo subject-specific strains on a global and regional comparison. The degree of subject-specificity included in the models represents a milestone for modeling efforts that captures realism of the whole heart. This study establishes a foundation for future computational studies that can apply these validated methods to advance cardiac mechanics research.} }