A Computational Framework for Patient-Specific Multi-Scale Cardiac Modeling

  • Jazmin Aguado-Sierra
  • Roy C. P. Kerckhoffs
  • Fred Lionetti
  • Darlene Hunt
  • Chris Villongco
  • Matt Gonzales
  • Stuart G. Campbell
  • Andrew D. McCulloch


Systems biology has introduced new paradigms in science by switching from a reductionist point of view to a more integrative approach toward the study of ­systems. As researchers over the past years have produced an extraordinary wealth of knowledge on human physiology, we now aim at integrating this knowledge to decipher the intimate relationships between the different components and scales that form the delicate balance in physiological systems. Our aim is to study the heart.


Sarcomere Length Fiber Angle NURBS Surface Diffusion Tensor Magnetic Resonance Image Fiber Architecture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge the support of NIH grants P41 RR08605, 1R01 HL96544, 1R01 HL086400, 1R01 HL091036, 1R01 HL083359, NSF grant BES-0506252, and UC Discovery grant it106-10159. ADM is a cofounder of Insilicomed, a licensee of UCSD software developed in this research. Insilicomed was not involved and did not support this research.


  1. 1.
    Arts, T, T Delhaas, P Bovendeerd, X Verbeek, and F W Prinzen. “Adaptation to mechanical load determines shape and properties of heart and circulation: the CircAdapt model.” American Journal of Physiology, Heart Circulation Physiology 288 (2005): 1943–1954.CrossRefGoogle Scholar
  2. 2.
    Beeler, G W, and H Reuter. “Reconstruction of the action potential of ventricular myocardial fibres.” The Journal of Physiology 268 (June 1977): 177–210.PubMedGoogle Scholar
  3. 3.
    Beg, Mirza Faisal, Patrick A Helm, Elliot McVeigh, Michael I Miller, and Raimond L Winslow. “Computational cardiac anatomy using MRI.” Magnetic Resonance in Medicine 52, no. 5 (November 2004): 1167–1174.PubMedCrossRefGoogle Scholar
  4. 4.
    Caldwell, Bryan J, Mark L Trew, Gregory B Sands, Darren A Hooks, Ian J LeGrice, and Bruce H Smaill. “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes.” Circulation: Arrhythmia and Electrophysiology 2 (2009): 433–440.CrossRefGoogle Scholar
  5. 5.
    Campbell, Stuart G, et al. “Effect of transmurally heterogenous myocyte excitation–contraction coupling on canine left ventricular electromechanics.” Experimental Physiology 94, no. 5 (May 2009): 541–552.PubMedCrossRefGoogle Scholar
  6. 6.
    Campbell, Stuart G, Sarah N Flaim, Chae H Leem, and Andrew D McCulloch. “Mechanisms of transmurally-varying myocyte electromechanics in an integrated computational model.” Philosophical Transactions of the Royal Society A 366, no. 1879 (September 2008): 3361–3380.CrossRefGoogle Scholar
  7. 7.
    Clancy, C E, Z I Zhu, and Y Rudy. “Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation.” American Journal of Physiology, Heart and Circulatory Physiology 292, no. 1 (January 2007): 66–75.CrossRefGoogle Scholar
  8. 8.
    Costa, K D, P J Hunter, J M Rogers, J M Guccione, L K Waldman, and A C McCulloch. “A three-dimensional finite element method for large elastic deformations of ventricular myocaridum: I – cylindrical and spherical polar coordinates.” Transactions of the ASME, Journal of Biomechanical Engineering (ASME) 118 (November 1996): 452–463.CrossRefGoogle Scholar
  9. 9.
    Costa, K D, P J Hunter, J S Wayne, L K Waldman, J M Guccione, and A D McCulloch. “A three-dimensional finite element method for large elastic deformations of ventricular myocardium: II – prolate spheroidal coordinates.” Transactions of the ASME, Journal of Biomechanical Engineering (ASME) 118 (November 1996): 464–472.CrossRefGoogle Scholar
  10. 10.
    FitzHugh, R. “Impulses and physiological states in theoretical models of nerve membrane.” Biophysical Journal 1, no. 6 (July 1961): 445–466.PubMedCrossRefGoogle Scholar
  11. 11.
    Flaim, Sarah N, Giles R Wayne, and Andrew D McCulloch. “Contributions of sustained INA and IKv43 to transmural heterogeneity of early repolarization and arrhythmogenesis in canine left ventricular myocytes.” American Journal of Physiology Heart Circulatory Physiology 291 (2006): 2617–2629.CrossRefGoogle Scholar
  12. 12.
    Franzone, Colli P, L F Pavarino, and B Taccardi. “Simulating patterns of excitationm, repolarization and action potential duration with cardiac bidomain and monodomain models.” Mathematical Biosciences 197, no. 1 (September 2005): 35–66.CrossRefGoogle Scholar
  13. 13.
    Greenstein, Joseph L, Robert Hinch, and Raimond L Winslow. “Mechanisms of excitation–contraction coupling in an integrative model of the cardiac ventricular myocyte.” Biophysical Journal 90 (January 2006): 77–91.PubMedCrossRefGoogle Scholar
  14. 14.
    Helm, Patrick A, et al. “Evidence of structural remodeling in the dyssynchronous failing heart.” Circulation Research 98 (2006): 125–132.PubMedCrossRefGoogle Scholar
  15. 15.
    Kerckhoffs, Roy CP, Andrew D McCulloch, Jeffrey H Omens, and Lawrence J Mulligan. “Effects of biventricular pacing and scar size in a computational model of the failing heart with left bundle branch block.” Medical Image Analysis 13, no. 2 (April 2009): 362–369.PubMedCrossRefGoogle Scholar
  16. 16.
    Kerckhoffs, Roy CP, Sanjiv M Narayan, Jeffrey H Omens, Lawrence J Mulligan, and Andrew D McCulloch. “Computational modeling for bedside application.” Heart Failure Clinics 4 (2008): 371–378.PubMedCrossRefGoogle Scholar
  17. 17.
    Lionetti, F, Andrew D McCulloch, and Scott B Baden. “GPU accelerated solvers for ODEs describing cardiac membrane equations.” nVidia GPU Technology Conference. San Jose, CA: nVidia, 2009. 34.Google Scholar
  18. 18.
    Lionetti, Fred. GPU accelerated cardiac electrophysiology. La Jolla, CA: UCSD, Master’s thesis, 2010.Google Scholar
  19. 19.
    Malm, S, S Frigstad, E Sagberg, H Larsson, and T Skjaerpe. “Accurate and reproducible measurement of left ventricular volume and ejection fraction by contrast echocardiography: a comparison with magnetic resonance imaging.” Journal of the American College of Cardiology 44 (2004): 1030–1035.PubMedCrossRefGoogle Scholar
  20. 20.
    McCulloch, Andrew D. Cardiac biomechanics, vol. I, in The Biomedical Engineering Handbook, by Joseph D Bronzino, 28:1–26. Boca Raton, FL: CRC Press, 2000.Google Scholar
  21. 21.
    Neal, Maxwell Lewis, and Roy CP Kerckhoffs. “Current progress in patient-specific modeling.” Briefings in Bioinformatics 11, no. 1 (January 2010): 111–126.PubMedCrossRefGoogle Scholar
  22. 22.
    Niederer, S A, and N P Smith. “A mathematical model of the slow force response to stretch in rat ventricular myocytes.” Biophysical Journal 92, no. 11 (June 2007): 4030–4044.PubMedCrossRefGoogle Scholar
  23. 23.
    Niederer, Steven A, and Nicolas P Smith. “An improved numerical method for strong coupling of excitation and contraction models in the heart.” Progress in Biophysics and Molecular Biology 96, no. 1–3 (January–April 2008): 90–111.PubMedCrossRefGoogle Scholar
  24. 24.
    Ramanathan, Jia P, R N Ghanem, P Jia, K Ryu, and Y Rudy. “Noninvasive electrocardiographic imaging for cardiac electrophysiology and arrhythmia.” Nature Medicine 10 (2004): 422–428.PubMedCrossRefGoogle Scholar
  25. 25.
    Rice, J J, F Wang, D M Bers, and P P de Tombe. “Approximate model of cooperative activation and crossbridge cycling in cardiac muscle using ordinary differential equations.” Biophysical Journal 95, no. 5 (September 2008): 2368–2390.PubMedCrossRefGoogle Scholar
  26. 26.
    Rogers, J M, and A D McCulloch. “A collocation-Galerkin finite element model of cardiac action potential propagation.” IEEE Transactions on Biomedical Engineering (IEEE EMBS) 41, no. 8 (August 1994): 743–757.CrossRefGoogle Scholar
  27. 27.
    Rudy, Yoram, et al. “Systems approach to understanding electromechanical activity in the human heart.” Circulation (A National Heart, Lung, and Blood Institute Workshop Summary) 118 (2008): 1202–1211.PubMedCrossRefGoogle Scholar
  28. 28.
    Rudy, Yoram, and Jonathan R Silva. “Computational biology in the study of cardiac ion channels and cell electrophysiology.” Quarterly Reviews of Biophysics 39, 1, (2006): 57–116.PubMedCrossRefGoogle Scholar
  29. 29.
    Shaw, James Rochester. “Models for cardiac structure and function in Aristotle.” Journal of the History of Biology 5, no. 2 (September 1972): 355–388.PubMedCrossRefGoogle Scholar
  30. 30.
    Streeter, D D Jr. “Gross morphology and fiber geometry of the heart.” In Handbook of physiology, section 2: the cardiovascular system, chapter 4, by M. B. R., 61–112. Bethesda, MD: American Physiological Society, 1979.Google Scholar
  31. 31.
    Usyk, Taras P, Ian J LeGrice, and Andrew D McCulloch. “Computational model of three-dimensional cardiac electromechanics.” Computing and Visualization in Science 4 (2002): 249–257.CrossRefGoogle Scholar
  32. 32.
    Walker, J C, et al. “MRI-based finite-element analysis of left ventricular aneurysm.” American Journal of Physiology, Heart and Circulation Physiology 289 (2005): 692–700.CrossRefGoogle Scholar
  33. 33.
    Watanabe, H, S Sugiura, H Kafuky, and T Hisada. “Multiphysics simulation of left ventricular filling dynamics using fluid–structure interaction finite element method.” Biophysical Journal 87 (2004): 2074–2085.PubMedCrossRefGoogle Scholar
  34. 34.
    Yue, A M, M R Franz, P R Roberts, and J M Morgan. “Global endocardial electrical restitution in human right and left ventricles determined by noncontact mapping.” Journal of the American College of Cardiology 46 (2005): 1067–1075.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang, Yongjie, Yuri Balzilevs, Samrat Goswami, Chandrajit L Bajaj, and Thomas JR Hughes. “Patient-specific vascular NURBS modeling for isogeometric analysis of blood flow.” Computer Methods in Applied Mechanics and Engineering 196, no. 29–30 (May 2007): 2943–2959.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jazmin Aguado-Sierra
    • 1
  • Roy C. P. Kerckhoffs
  • Fred Lionetti
  • Darlene Hunt
  • Chris Villongco
  • Matt Gonzales
  • Stuart G. Campbell
  • Andrew D. McCulloch
  1. 1.Department of BioengineeringUniversity of CaliforniaSan DiegoUSA

Personalised recommendations