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Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology

  • Computational Biomechanics for Patient-Specific Applications
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Abstract

Computational modelling of the heart is rapidly advancing to the point of clinical utility. However, the difficulty of parameterizing and validating models from clinical data indicates that the routine application of truly predictive models remains a significant challenge. We argue there is significant value in an intermediate step towards prediction. This step is the use of biophysically based models to extract clinically useful information from existing patient data. Specifically in this paper we review methodologies for applying modelling frameworks for this goal in the areas of quantifying cardiac anatomy, estimating myocardial stiffness and optimizing measurements of coronary perfusion. Using these indicative examples of the general overarching approach, we finally discuss the value, ongoing challenges and future potential for applying biophysically based modelling in the clinical context.

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References

  1. Al-Saadi, N., E. Nagel, M. Gross, A. Bornstedt, B. Schnackenburg, C. Klein, W. Klimek, H. Oswald, and E. Fleck. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. Circulation 101:1379–1383, 2000.

    Article  PubMed  CAS  Google Scholar 

  2. Ashikaga, H., H. Arevalo, F. Vadakkumpadan, R. C. Blake, J. D. Bayer, S. Nazarian, M. Muz Zviman, H. Tandri, R. D. Berger, H. Calkins, D. A. Herzka, N. A. Trayanova, and H. R. Halperin. Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia. Hear. Rhythm 10:1109–1116, 2013.

    Article  Google Scholar 

  3. Audoly, S., G. Bellu, L. D’Angiò, M. P. Saccomani, and C. Cobelli. Global identifiability of nonlinear models of biological systems. IEEE Trans. Biomed. Eng. 48:55–65, 2001.

    Article  PubMed  CAS  Google Scholar 

  4. Augenstein, K. F., B. R. Cowan, I. J. LeGrice, P. M. F. Nielsen, and A. A. Young. Method and apparatus for soft tissue material parameter estimation using tissue tagged magnetic resonance imaging. J. Biomech. Eng. 127:148, 2005.

    Article  PubMed  Google Scholar 

  5. Bermejo, J., R. Yotti, C. Pérez del Villar, J. C. del Álamo, D. Rodríguez-Pérez, P. Martínez-Legazpi, Y. Benito, J. C. Antoranz, M. M. Desco, A. González-Mansilla, A. Barrio, J. Elízaga, and F. Fernández-Avilés. Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J. Appl. Physiol. 115:556–568, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Borlaug, B. A., and W. J. Paulus. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur. Hear. J. 32:670–679, 2011.

    Article  Google Scholar 

  7. Butterworth, E., B. E. Jardine, G. M. Raymond, M. L. Neal, and J. B. Bassingthwaighte. JSim, an open-source modeling system for data analysis. F1000 Res 2:288, 2013.

    Google Scholar 

  8. Cebral, J. R., M. A. Castro, J. E. Burgess, R. S. Pergolizzi, M. J. Sheridan, and C. M. Putman. Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. AJNR Am. J. Neuroradiol. 26:2550–2559, 2005.

    PubMed  Google Scholar 

  9. Chapelle, D., J.-F. Gerbeau, J. Sainte-Marie, and I. Vignon-Clementel. A poroelastic model valid in large strains with applications to perfusion in cardiac modeling. Comput. Mech. 46:91–101, 2010.

    Article  Google Scholar 

  10. Clayton, R. H., O. Bernus, E. M. Cherry, H. Dierckx, F. H. Fenton, L. Mirabella, A. V. Panfilov, F. B. Sachse, G. Seemann, and H. Zhang. Models of cardiac tissue electrophysiology: progress, challenges and open questions. Prog. Biophys. Mol. Biol. 104:22–48, 2011.

    Article  PubMed  CAS  Google Scholar 

  11. Cohn, J. N., R. Ferrari, and N. Sharpe. Cardiac remodeling-concepts and clinical implications: a consensus paper from an International Forum on Cardiac Remodeling. J. Am. Coll. Cardiol. 35:569–582, 2000.

    Article  PubMed  CAS  Google Scholar 

  12. Cookson, A. N., J. Lee, C. Michler, R. Chabiniok, E. R. Hyde, D. A. Nordsletten, M. Sinclair, M. Siebes, and N. P. Smith. A novel porous mechanical framework for modelling the interaction between coronary perfusion and myocardial mechanics. J. Biomech. 45:850–855, 2012.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Cookson, A. N., J. Lee, C. Michler, R. Chabiniok, E. Hyde, D. Nordsletten, and N. P. Smith. A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging. Med. Image Anal. 18:1200–1216, 2014.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Cookson, A. N., J. Lee, D. Nordsletten, and N. P. Smith. Contrast agent transport in a multiscale poroelastic model of myocardial perfusion. J. Comput. Phys. Submitted, 2015.

  15. Cootes, T., A. Hill, C. Taylor, and J. Haslam. Use of active shape models for locating structures in medical images. Image Vis. Comput. 12:355–365, 1994.

    Article  Google Scholar 

  16. Cullen, J. H., M. A. Horsfield, C. R. Reek, G. R. Cherryman, D. B. Barnett, and N. J. Samani. A myocardial perfusion reserve index in humans using first-pass contrast-enhanced magnetic resonance imaging. J. Am. Coll. Cardiol. 33:1386–1394, 1999.

    Article  PubMed  CAS  Google Scholar 

  17. DiFrancesco, D., and D. Noble. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos. Trans. R. Soc. L. B Biol. Sci. 307:353–398, 1985.

    Article  CAS  Google Scholar 

  18. Fedak, P. W. M., S. Verma, R. D. Weisel, and R.-K. Li. Cardiac remodeling and failure: from molecules to man (Part I). Cardiovasc. Pathol. 14:1–11, 2005.

    Article  PubMed  Google Scholar 

  19. Finegold, J. A., P. Asaria, and D. P. Francis. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int. J. Cardiol. 168:934–945, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Firstenberg, M. S., P. M. Vandervoort, N. L. Greenberg, N. G. Smedira, P. M. McCarthy, M. J. Garcia, and J. D. Thomas. Noninvasive estimation of transmitral pressure drop across the normal mitral valve in humans: Importance of convective and inertial forces during left ventricular filling. J. Am. Coll. Cardiol. 36:1942–1949, 2000.

    Article  PubMed  CAS  Google Scholar 

  21. Fonseca, C. G., M. Backhaus, D. A. Bluemke, R. D. Britten, J. D. Chung, B. R. Cowan, I. D. Dinov, J. P. Finn, P. J. Hunter, A. H. Kadish, D. C. Lee, J. A. C. Lima, P. Medrano-Gracia, K. Shivkumar, A. Suinesiaputra, W. Tao, and A. A. Young. The cardiac Atlas Project-an imaging database for computational modeling and statistical atlases of the heart. Bioinformatics 27:2288–2295, 2011.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Gaddum, N. R., L. Keehn, A. Guilcher, A. Gomez, S. Brett, P. Beerbaum, T. Schaeffter, and P. Chowienczyk. Altered dependence of aortic pulse wave velocity on transmural pressure in hypertension revealing structural change in the aortic wall. Hypertension 65:362–369, 2015.

    Article  PubMed  CAS  Google Scholar 

  23. Garny, A., D. Noble, and P. Kohl. Dimensionality in cardiac modelling. Prog. Biophys. Mol. Biol. 87:47–66, 2005.

    Article  PubMed  Google Scholar 

  24. Gonzalez, G., D. Nolte, A. Lewandowski, P. Leeson, N. Smith, and P. Lamata. Improving the stratification power of cardiac ventricular shape. J. Cardiovasc. Magn. Reson. 17:O77, 2015.

    Article  PubMed Central  Google Scholar 

  25. Grenander, U., and M. I. Miller. Computational anatomy: an emerging discipline. Q. Appl. Math. 56:617–694, 1998.

    Google Scholar 

  26. Hadjicharalambous, M., R. Chabiniok, L. Asner, E. Sammut, J. Wong, G. Carr-White, J. Lee, R. Razavi, N. Smith, and D. Nordsletten. Analysis of passive cardiac constitutive laws for parameter estimation using 3D tagged MRI. Biomech. Model. Mechanobiol. 2014. doi:10.1007/s10237-014-0638-9.

    PubMed  PubMed Central  Google Scholar 

  27. Hautvast, G. L. T. F., A. Chiribiri, T. Lockie, M. Breeuwer, E. Nagel, and S. Plein. Quantitative analysis of transmural gradients in myocardial perfusion magnetic resonance images. Magn. Reson. Med. 66:1477–1487, 2011.

    Article  PubMed  CAS  Google Scholar 

  28. Heimann, T., and H.-P. Meinzer. Statistical shape models for 3D medical image segmentation: a review. Med. Image Anal. 13:543–563, 2009.

    Article  PubMed  Google Scholar 

  29. Helm, P. A., L. Younes, M. F. Beg, D. B. Ennis, C. Leclercq, O. P. Faris, E. McVeigh, D. Kass, M. I. Miller, and R. L. Winslow. Evidence of structural remodeling in the dyssynchronous failing heart. Circ. Res. 98:125–132, 2006.

    Article  PubMed  CAS  Google Scholar 

  30. Hunter, P. J., and T. K. Borg. Integration from proteins to organs: the Physiome Project. Nat. Rev. Mol. Cell Biol. 4:237–243, 2003.

    Article  PubMed  CAS  Google Scholar 

  31. Hyde, E. R., A. N. Cookson, J. Lee, C. Michler, A. Goyal, T. Sochi, R. Chabiniok, M. Sinclair, D. A. Nordsletten, J. Spaan, J. P. van den Wijngaard, M. Siebes, and N. P. Smith. Multi-scale parameterisation of a myocardial perfusion model using whole-organ arterial networks. Ann. Biomed. Eng. 42:797–811, 2014.

    Article  PubMed  Google Scholar 

  32. Hyde, E. R., C. Michler, J. Lee, A. N. Cookson, R. Chabiniok, D. A. Nordsletten, and N. P. Smith. Parameterisation of multi-scale continuum perfusion models from discrete vascular networks. Med. Biol. Eng. Comput. 51:557–570, 2012.

    Article  Google Scholar 

  33. Ishida, M., G. Morton, A. Schuster, E. Nagel, and A. Chiribiri. Quantitative assessment of myocardial perfusion MRI. Curr. Cardiovasc. Imaging Rep. 3:65–73, 2010.

    Article  Google Scholar 

  34. Jerosch-Herold, M., R. T. Seethamraju, C. M. Swingen, N. M. Wilke, and A. E. Stillman. Analysis of myocardial perfusion MRI. J. Magn. Reson. Imaging 19:758–770, 2004.

    Article  PubMed  Google Scholar 

  35. Jerosch-Herold, M., N. Wilke, and A. E. Stillman. Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med. Phys. 25:73–84, 1998.

    Article  PubMed  CAS  Google Scholar 

  36. Kirk, J. A., M. P. Saccomani, and S. G. Shroff. A priori identifiability analysis of cardiovascular models. Cardiovasc. Eng. Technol. 4:500–512, 2013.

    Article  Google Scholar 

  37. Lamata, P., R. Casero, V. Carapella, S. A. Niederer, M. J. Bishop, J. E. Schneider, P. Kohl, and V. Grau. Images as drivers of progress in cardiac computational modelling. Prog. Biophys. Mol. Biol. 115:198–212, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lamata, P., S. Niederer, D. Nordsletten, D. C. Barber, I. Roy, D. Hose, and N. Smith. An accurate, fast and robust method to generate patient-specific cubic Hermite meshes. Med. Image Anal. 15:801–813, 2011.

    Article  PubMed  Google Scholar 

  39. Lamata, P., A. Pitcher, S. Krittian, D. Nordsletten, M. M. Bissell, T. Cassar, A. J. Barker, M. Markl, S. Neubauer, and N. P. Smith. Aortic relative pressure components derived from four-dimensional flow cardiovascular magnetic resonance. Magn. Reson. Med. 72:1162–1169, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lamata, P., M. Sinclair, E. Kerfoot, A. Lee, A. Crozier, B. Blazevic, S. Land, A. J. Lewandowski, D. Barber, S. Niederer, and N. Smith. An automatic service for the personalization of ventricular cardiac meshes. J. R. Soc. Interface 11(91):20131023, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lee, J., D. Nordsletten, A. Cookson, S. Rivolo, and N. Smith. In silico coronary wave intensity analysis: application of an integrated one-dimensional and poromechanical model of cardiac perfusion. J. Physiol. Under revi, 2014.

  42. Lewandowski, A. J., D. Augustine, P. Lamata, E. F. Davis, M. Lazdam, J. Francis, K. McCormick, A. R. Wilkinson, A. Singhal, and A. Lucas. Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function. Circulation 127:197–206, 2013.

    Article  PubMed  Google Scholar 

  43. Li, L., S. A. Niederer, W. Idigo, Y. H. Zhang, P. Swietach, B. Casadei, and N. P. Smith. A mathematical model of the murine ventricular myocyte: a data-driven biophysically based approach applied to mice overexpressing the canine NCX isoform. Am. J. Physiol. Heart Circ. Physiol. 299:H1045–H1063, 2010.

    Article  PubMed  CAS  Google Scholar 

  44. Maeder, M. T., and D. M. Kaye. Heart failure with normal left ventricular ejection fraction. J. Am. Coll. Cardiol. 53:905–918, 2009.

    Article  PubMed  Google Scholar 

  45. Medrano-Gracia, P., B. Cowan, J. P. Finn, A. Kadish, D. Lee, J. Lima, A. Suinesiaputra, and A. Young. Atlas-based analysis of cardiac shape and function: correction of regional shape bias due to imaging protocol for population studies. J. Cardiovasc. Magn. Reson. 15:80, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Members, A. F., et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur. J. Heart Fail. 14:803–869, 2012.

    Article  Google Scholar 

  47. Michler, C., A. N. Cookson, R. Chabiniok, E. Hyde, J. Lee, M. Sinclair, T. Sochi, A. Goyal, G. Vigueras, D. A. Nordsletten, and N. P. Smith. A computationally efficient framework for the simulation of cardiac perfusion using a multi-compartment Darcy porous-media flow model. Int. J. Numer. Method. Biomed. Eng. 29:217–232, 2013.

    Article  PubMed  CAS  Google Scholar 

  48. Min, J. K., J. Leipsic, M. J. Pencina, D. S. Berman, B.-K. Koo, C. van Mieghem, A. Erglis, F. Y. Lin, A. M. Dunning, P. Apruzzese, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. Jama 308:1237–1245, 2012.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Morris, P. D., D. Ryan, A. C. Morton, R. Lycett, P. V. Lawford, D. R. Hose, and J. P. Gunn. Virtual fractional flow reserve from coronary angiography: modeling the significance of coronary lesions: results from the VIRTU-1 (VIRTUal Fractional Flow Reserve From Coronary Angiography) study. JACC. Cardiovasc. Interv. 6:149–157, 2013.

    Article  Google Scholar 

  50. Motwani, M., A. Kidambi, S. Sourbron, T. A. Fairbairn, A. Uddin, S. Kozerke, J. P. Greenwood, and S. Plein. Quantitative three-dimensional cardiovascular magnetic resonance myocardial perfusion imaging in systole and diastole. J. Cardiovasc. Magn. Reson. 16:19, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Nagel, E., C. Klein, I. Paetsch, S. Hettwer, B. Schnackenburg, K. Wegscheider, and E. Fleck. Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease. Circulation 108:432–437, 2003.

    Article  PubMed  Google Scholar 

  52. Nasopoulou, A., B. Blazevic, A. Crozier, W. Shi, A. Shetty, C. A. Rinaldi, P. Lamata, and S. Niederer. Myocardial stiffness estimation: a novel cost function for unique parameter identification. In: Functional imaging and modeling of the heart SE—41, edited by H. van Assen, P. Bovendeerd, and T. Delhaas. Switzerland: Springer International Publishing, 2015, pp. 355–363.

    Chapter  Google Scholar 

  53. Niederer, S. A., M. Fink, D. Noble, and N. P. Smith. A meta-analysis of cardiac electrophysiology computational models. Exp. Physiol. 94:486–495, 2009.

    Article  PubMed  CAS  Google Scholar 

  54. Niederer, S. A., G. Plank, P. Chinchapatnam, M. Ginks, P. Lamata, K. S. Rhode, C. A. Rinaldi, R. Razavi, and N. P. Smith. Length-dependent tension in the failing heart and the efficacy of cardiac resynchronization therapy. Cardiovasc. Res. 89:336–343, 2010.

    Article  PubMed  Google Scholar 

  55. Nolte, F., E. R. Hyde, C. Rolandi, J. Lee, P. van Horssen, K. Asrress, J. P. H. M. van den Wijngaard, A. N. Cookson, T. van de Hoef, R. Chabiniok, R. Razavi, C. Michler, G. L. T. F. Hautvast, J. J. Piek, M. Breeuwer, M. Siebes, E. Nagel, N. P. Smith, and J. A. E. Spaan. Myocardial perfusion distribution and coronary arterial pressure and flow signals: clinical relevance in relation to multiscale modeling, a review. Med. Biol. Eng. Comput. 51:1271–1286, 2013.

    Article  PubMed  Google Scholar 

  56. Opie, L. H., P. J. Commerford, B. J. Gersh, and M. A. Pfeffer. Controversies in ventricular remodelling. Lancet 367:356–367, 2006.

    Article  PubMed  Google Scholar 

  57. Pathmanathan, P., and R. A. Gray. Ensuring reliability of safety-critical clinical applications of computational cardiac models. Front. Physiol. 4:358, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Rappaport, D., E. Konyukhov, L. Shulman, Z. Friedman, P. Lysyansky, A. Landesberg, and D. Adam. Detection of the cardiac activation sequence by novel echocardiographic tissue tracking method. Ultrasound Med. Biol. 33:880–893, 2007.

    Article  PubMed  Google Scholar 

  59. Relan, J., P. Chinchapatnam, M. Sermesant, K. Rhode, M. Ginks, H. Delingette, C. A. Rinaldi, R. Razavi, and N. Ayache. Coupled personalization of cardiac electrophysiology models for prediction of ischaemic ventricular tachycardia. Interface Focus 1:396–407, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Schileo, E., F. Taddei, L. Cristofolini, and M. Viceconti. Subject-specific finite element models implementing a maximum principal strain criterion are able to estimate failure risk and fracture location on human femurs tested in vitro. J. Biomech. 41:356–367, 2008.

    Article  PubMed  Google Scholar 

  61. Sermesant, M., R. Chabiniok, P. Chinchapatnam, T. Mansi, F. Billet, P. Moireau, J. M. Peyrat, K. Wong, J. Relan, K. Rhode, M. Ginks, P. Lambiase, H. Delingette, M. Sorine, C. A. Rinaldi, D. Chapelle, R. Razavi, and N. Ayache. Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation. Med. Image Anal. 16:201–215, 2012.

    Article  PubMed  CAS  Google Scholar 

  62. Sermesant, M., P. Moireau, O. Camara, J. Sainte-Marie, R. Andriantsimiavona, R. Cimrman, D. L. G. Hill, D. Chapelle, and R. Razavi. Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties. Med Image Anal 10:642–656, 2006.

    Article  PubMed  CAS  Google Scholar 

  63. Shi, W., X. Zhuang, H. Wang, S. Duckett, D. Luong, C. Tobon-Gomez, K. Tung, P. Edwards, K. S. Rhode, R. S. Razavi, S. Ourselin, and D. Rueckert. A comprehensive cardiac motion estimation framework using both untagged and 3D tagged MR images based on nonrigid registration. IEEE Trans. Med. Imaging 31:1263–1275, 2012.

    Article  PubMed  Google Scholar 

  64. Smith, N. P. A computational study of the interaction between coronary blood flow and myocardial mechanics. Physiol. Meas. 25:863–877, 2004.

    Article  PubMed  Google Scholar 

  65. Smith, N. P., E. J. Crampin, S. A. Niederer, J. B. Bassingthwaighte, and D. A. Beard. Computational biology of cardiac myocytes: proposed standards for the physiome. J. Exp. Biol. 210(9):1576–1583, 2007.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Smith, N., A. de Vecchi, M. McCormick, D. Nordsletten, O. Camara, A. F. Frangi, H. Delingette, M. Sermesant, J. Relan, N. Ayache, M. W. Krueger, W. H. W. Schulze, R. Hose, I. Valverde, P. Beerbaum, C. Staicu, M. Siebes, J. Spaan, P. Hunter, J. Weese, H. Lehmann, D. Chapelle, and R. Rezavi. euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling. Interface Focus 1:349–364, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Sourbron, S. A tracer-kinetic field theory for medical imaging. IEEE Trans. Med. Imaging 33:935–946, 2014.

    Article  PubMed  Google Scholar 

  68. Spaan, J. A., N. P. Breuls, and J. D. Laird. Diastolic-systolic coronary flow differences are caused by intramyocardial pump action in the anesthetized dog. Circ. Res. 49:584–593, 1981.

    Article  PubMed  CAS  Google Scholar 

  69. Tofts, P. S., G. Brix, D. L. Buckley, J. L. Evelhoch, E. Henderson, M. V. Knopp, H. B. Larsson, T.-Y. Lee, N. A. Mayr, G. J. Parker, R. E. Port, J. Taylor, and R. M. Weisskoff. Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusable tracer: standardized quantities and symbols. J. Magn. Reson. Imaging 10:223–232, 1999.

    Article  PubMed  CAS  Google Scholar 

  70. Wang, V. Y., H. I. Lam, D. B. Ennis, B. R. Cowan, A. A. Young, and M. P. Nash. Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function. Med. Image Anal. 13:773–784, 2009.

    Article  PubMed  Google Scholar 

  71. Winslow, R., L. N. Trayanova, D. Geman, and M. I. Miller. Computational medicine: translating models to clinical care. Sci. Transl. Med. 4:158rv11, 2012.

    PubMed  PubMed Central  Google Scholar 

  72. Wong, K. C. L., M. Sermesant, K. Rhode, M. Ginks, C. A. Rinaldi, R. Razavi, H. Delingette, and N. Ayache. Velocity-based cardiac contractility personalization from images using derivative-free optimization. J. Mech. Behav. Biomed. Mater. 43:35–52, 2015.

    Article  PubMed  Google Scholar 

  73. Xi, J., P. Lamata, J. Lee, P. Moireau, D. Chapelle, and N. Smith. Myocardial transversely isotropic material parameter estimation from in silico measurements based on a reduced-order unscented Kalman filter. J. Mech. Behav. Biomed. Mater. 4:1090–1102, 2011.

    Article  PubMed  Google Scholar 

  74. Xi, J., P. Lamata, S. Niederer, S. Land, W. Shi, X. Zhuang, S. Ourselin, S. G. Duckett, A. K. Shetty, C. A. Rinaldi, D. Rueckert, R. Razavi, and N. P. Smith. The estimation of patient-specific cardiac diastolic functions from clinical measurements. Med. Image Anal. 17:133–146, 2013.

    Article  PubMed  Google Scholar 

  75. Xi, J., W. Shi, D. Rueckert, R. Razavi, N. Smith, and P. Lamata. Understanding the need of ventricular pressure for the estimation of diastolic biomarkers. Biomech. Model. Mechanobiol. 13:747–757, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Zierler, K. L. Theoretical basis of indicator-dilution methods for measuring flow and volume. Circ. Res. 10:393–407, 1962.

    Article  Google Scholar 

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Acknowledgments

The authors would like to acknowledge funding from the Engineering and Physical Sciences Research Council (EP/G0075727/2), the Wellcome Trust Medical Engineering Centre at King’s College London (WT 088641/Z/09/Z). PL holds a Sir Henry Dale Fellowship funded jointly by the Wellcome Trust and the Royal Society (Grant No. 099973/Z/12/Z). This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Associate Editor Karol Miller oversaw the review of this article.

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Lamata, P., Cookson, A. & Smith, N. Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology. Ann Biomed Eng 44, 46–57 (2016). https://doi.org/10.1007/s10439-015-1439-8

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