Three-dimensional cardiac computational modelling: methods, features and applications

[EN] The combination of computational models and biophysical simulations can help to interpret an array of experimental data and contribute to the understanding, diagnosis and treatment of complex diseases such as cardiac arrhythmias. For this reason, three-dimensional (3D) cardiac computational modelling is currently a rising field of research. The advance of medical imaging technology over the last decades has allowed the evolution from generic to patient-specific 3D cardiac models that faithfully represent the anatomy and different cardiac features of a given alive subject. Here we analyse sixty representative 3D cardiac computational models developed and published during the last fifty years, describing their information sources, features, development methods and online availability. This paper also reviews the necessary components to build a 3D computational model of the heart aimed at biophysical simulation, paying especial attention to cardiac electrophysiology (EP), and the existing approaches to incorporate those components. We assess the challenges associated to the different steps of the building process, from the processing of raw clinical or biological data to the final application, including image segmentation, inclusion of substructures and meshing among others. We briefly outline the personalisation approaches that are currently available in 3D cardiac computational modelling. Finally, we present examples of several specific applications, mainly related to cardiac EP simulation and model-based image analysis, showing the potential usefulness of 3D cardiac computational modelling into clinical environments as a tool to aid in the prevention, diagnosis and treatment of cardiac diseases.This work was partially supported by the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (TIN2012-37546-C03-01 and TIN2011-28067) and the European Commission (European Regional Development Funds - ERDF - FEDER) and by "eTorso project" (GVA/2013-001404) from the Generalitat Valenciana (Spain). ALP is financially supported by the program "Ayudas para contratos predoctorales para la formacion de doctores" from the Ministerio de Economia y Competitividad of Spain (BES-2013-064089).López Pérez, AD.; Sebastián Aguilar, R.; Ferrero De Loma-Osorio, JM. (2015). Three-dimensional cardiac computational modelling: methods, features and applications. BioMedical Engineering OnLine. 14(35):1-31. https://doi.org/10.1186/s12938-015-0033-5S1311435Koushanpour E, Collings W: Validation and dynamic applications of an ellipsoid model of the left ventricle. J Appl Physiol 1966, 21: 1655–61.Ghista D, Sandler H: An analytic elastic-viscoelastic model for the shape and the forces in the left ventricle. J Biomech 1969, 2: 35–47.Janz RF, Grimm AF: Finite-Element Model for the Mechanical Behavior of the Left Ventricle: prediction of deformation in the potassium-arrested rat heart. Circ Res 1972, 30: 244–52.Van den Broek JHJM, Van den Broek MHLM: Application of an ellipsoidal heart model in studying left ventricular contractions. J Biomech 1980, 13: 493–503.Colli Franzone P, Guerri L, Pennacchio M, Taccardi B: Spread of excitation in 3-D models of the anisotropic cardiac tissue. II. Effects of fiber architecture and ventricular geometry. Math Biosci 1998, 147: 131–71.Kerckhoffs RCP, Bovendeerd PHM, Kotte JCS, Prinzen FW, Smits K, Arts T: Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study. Ann Biomed Eng 2003, 31: 536–47.Sermesant M, Moireau P, Camara O, Sainte-Marie J, Andriantsimiavona R, Cimrman R, et al.: Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties. Med Image Anal 2006, 10: 642–56.Okajima M, Fujino T, Kobayashi T, Yamada K: Computer simulation of the propagation process in excitation of the ventricles. Circ Res 1968, 23: 203–11.Horan LG, Hand RC, Johnson JC, Sridharan MR, Rankin TB, Flowers NC: A theoretical examination of ventricular repolarization and the secondary T wave. Circ Res 1978, 42: 750–7.Miller WT, Geselowitz DB: Simulation studies of the electrocardiogram. I. The normal heart. Circ Res 1978, 43: 301–15.Vetter FJ, McCulloch AD: Three-dimensional analysis of regional cardiac function: a model of rabbit ventricular anatomy. Prog Biophys Mol Biol 1998, 69: 157–83.Nielsen PMF, LeGrice IJ, Smaill BH, Hunter PJ: Mathematical model of geometry and fibrous structure of the heart. Am J Physiol Heart Circ Physiol 1991, 260: H1365–78.Stevens C, Remme E, LeGrice I, Hunter P: Ventricular mechanics in diastole: material parameter sensitivity. J Biomech 2003, 36: 737–48.Aoki M, Okamoto Y, Musha T, Harumi KI: Three-dimensional simulation of the ventricular depolarization and repolarization processes and body surface potentials: normal heart and bundle branch block. IEEE Trans Biomed Eng 1987, 34: 454–62.Thakor NV, Eisenman LN: Three-dimensional computer model of the heart: fibrillation induced by extrastimulation. Comput Biomed Res 1989, 22: 532–45.Freudenberg J, Schiemann T, Tiede U, Höhne KH: Simulation of cardiac excitation patterns in a three-dimensional anatomical heart atlas. Comput Biol Med 2000, 30: 191–205.Trunk P, Mocnik J, Trobec R, Gersak B: 3D heart model for computer simulations in cardiac surgery. Comput Biol Med 2007, 37: 1398–403.Siregar P, Sinteff JP, Julen N, Le Beux P: An interactive 3D anisotropic cellular automata model of the heart. Comput Biomed Res 1998, 31: 323–47.Harrild DM, Henriquez CS: A computer model of normal conduction in the human atria. Circ Res 2000, 87: e25–36.Bodin ON, Kuz’min AV: Synthesis of a realistic model of the surface of the heart. Biomed Eng (NY) 2006, 40: 280–3.Ruiz-Villa CA, Tobón C, Rodríguez JF, Ferrero JM, Hornero F, Saíz J: Influence of atrial dilatation in the generation of re-entries caused by ectopic activity in the left atrium. Comput Cardiol 2009, 36: 457–60.Blanc O, Virag N, Vesin JM, Kappenberger L: A computer model of human atria with reasonable computation load and realistic anatomical properties. IEEE Trans Biomed Eng 2001, 48: 1229–37.Zemlin CW, Herzel H, Ho SY, Panfilov AV: A realistic and efficient model of excitation propagation in the human atria. In Comput Simul Exp Assess Card Electrophysiol. Edited by: Virag N, Kappenberger L, Blanc O. Futura Publishing Company, Inc, Arkmonk, New York; 2001:29–34.Seemann G, Höper C, Sachse FB, Dössel O, Holden AV, Zhang H: Heterogeneous three-dimensional anatomical and electrophysiological model of human atria. Philos Trans R Soc A Math Phys Eng Sci 2006, 364: 1465–81.Zhao J, Butters TD, Zhang H, LeGrice IJ, Sands GB, Smaill BH: Image-based model of atrial anatomy and electrical activation: a computational platform for investigating atrial arrhythmia. IEEE Trans Med Imaging 2013, 32: 18–27.Creswell LL, Wyers SG, Pirolo JS, Perman WH, Vannier MW, Pasque MK: Mathematical modeling of the heart using magnetic resonance imaging. IEEE Trans Med Imaging 1992, 11: 581–9.Lorange M, Gulrajani RM: A computer heart model incorporating anisotropic propagation: I. Model construction and simulation of normal activation. J Electrocardiol 1993, 26: 245–61.Winslow RL, Scollan DF, Holmes A, Yung CK, Zhang J, Jafri MS: Electrophysiological modeling of cardiac ventricular function: from cell to organ. Annu Rev Biomed Eng 2000, 2: 119–55.Virag N, Jacquemet V, Henriquez CS, Zozor S, Blanc O, Vesin JM, et al.: Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria. Chaos 2002, 12: 754–63.Helm PA, Tseng HJ, Younes L, McVeigh ER, Winslow RL: Ex vivo 3D diffusion tensor imaging and quantification of cardiac laminar structure. Magn Reson Med 2005, 54: 850–9.Arevalo HJ, Helm PA, Trayanova NA: Development of a model of the infarcted canine heart that predicts arrhythmia generation from specific cardiac geometry and scar distribution. Comput Cardiol 2008, 35: 497–500.Plotkowiak M, Rodriguez B, Plank G, Schneider JE, Gavaghan D, Kohl P, et al.: High performance computer simulations of cardiac electrical function based on high resolution MRI datasets. In Int Conf Comput Sci 2008, LNCS 5101. Springer–Verlag, Berlin Heidelberg; 2008:571–80.Heidenreich EA, Ferrero JM, Doblaré M, Rodríguez JF: Adaptive macro finite elements for the numerical solution of monodomain equations in cardiac electrophysiology. Ann Biomed Eng 2010, 38: 2331–45.Gurev V, Lee T, Constantino J, Arevalo H, Trayanova NA: Models of cardiac electromechanics based on individual hearts imaging data: Image-based electromechanical models of the heart. Biomech Model Mechanobiol 2011, 10: 295–306.Deng D, Jiao P, Ye X, Xia L: An image-based model of the whole human heart with detailed anatomical structure and fiber orientation. Comput Math Methods Med 2012, 2012: 16.Aslanidi OV, Nikolaidou T, Zhao J, Smaill BH, Gilbert SH, Holden AV, et al.: Application of micro-computed tomography with iodine staining to cardiac imaging, segmentation, and computational model development. IEEE Trans Med Imaging 2013, 32: 8–17.Haddad R, Clarysse P, Orkisz M, Croisille P, Revel D, Magnin IE: A realistic anthropomorphic numerical model of the beating heart. In Funct Imaging Model Heart 2005, LNCS 3504. Springer–Verlag, Berlin Heidelberg; 2005:384–93.Appleton B, Wei Q, Liu N, Xia L, Crozier S, Liu F, et al.: An electrical heart model incorporating real geometry and motion. In 27th Annu Int Conf Eng Med Biol Soc (IEEE-EMBS 2005). IEEE, Shanghai, China; 2006:345–8.Niederer S, Rhode K, Razavi R, Smith N: The importance of model parameters and boundary conditions in whole organ models of cardiac contraction. In Funct Imaging Model Heart 2009, LNCS 5528. Springer–Verlag, Berlin Heidelberg; 2009:348–56.Yang G, Toumoulin C, Coatrieux JL, Shu H, Luo L, Boulmier D: A 3D static heart model from a MSCT data set. In 27th Annu Int Conf IEEE Eng Med Biol Soc (IEEE-EMBS 2005). IEEE, Shangai, China; 2006:5499–502.Romero D, Sebastian R, Bijnens BH, Zimmerman V, Boyle PM, Vigmond EJ, et al.: Effects of the purkinje system and cardiac geometry on biventricular pacing: a model study. Ann Biomed Eng 2010, 38: 1388–98.Lorenzo-Valdés M, Sanchez-Ortiz GI, Mohiaddin R, Rueckert D: Atlas-based segmentation and tracking of 3D cardiac MR images using non-rigid registration. In Med Image Comput Comput Assist Interv 2002, LNCS 2488. Springer–Verlag, Berlin Heidelberg; 2002:642–50.Ordas S, Oubel E, Sebastian R, Frangi AF: Computational anatomy atlas of the heart. In 5th Int Symp Image Signal Process Anal (ISPA 2007). IEEE, Istanbul, Turkey; 2007:338–42.Burton RAB, Plank G, Schneider JE, Grau V, Ahammer H, Keeling SL, et al.: Three-dimensional models of individual cardiac histoanatomy: tools and challenges. Ann N Y Acad Sci 2006, 1080: 301–19.Plank G, Burton RAB, Hales P, Bishop M, Mansoori T, Bernabeu MO, et al.: Generation of histo-anatomically representative models of the individual heart: tools and application. Philos Trans R Soc A Math Phys Eng Sci 2009, 367: 2257–92.Bishop MJ, Plank G, Burton RAB, Schneider JE, Gavaghan DJ, Grau V, et al.: Development of an anatomically detailed MRI-derived rabbit ventricular model and assessment of its impact on simulations of electrophysiological function. Am J Physiol - Heart Circ Physiol 2010, 298: H699–718.Ecabert O, Peters J, Schramm H, Lorenz C, von Berg J, Walker MJ, et al.: Automatic model-based segmentation of the heart in CT images. IEEE Trans Med Imaging 2008, 27: 1189–201.Ecabert O, Peters J, Walker MJ, Ivanc T, Lorenz C, von Berg J, et al.: Segmentation of the heart and great vessels in CT images using a model-based adaptation framework. Med Image Anal 2011, 15: 863–76.Schulte RF, Sands GB, Sachse FB, Dössel O, Pullan AJ: Creation of a human heart model and its customisation using ultrasound images. Biomed Tech Eng 2001, 46: 26–8.Wenk JF, Zhang Z, Cheng G, Malhotra D, Acevedo-Bolton G, Burger M, et al.: First finite element model of the left ventricle with mitral valve: insights into ischemic mitral regurgitation. Ann Thorac Surg 2010, 89: 1546–53.Frangi AF, Rueckert D, Schnabel JA, Niessen WJ: Automatic construction of multiple-object three-dimensional statistical shape models: application to cardiac modeling. IEEE Trans Med Imaging 2002, 21: 1151–66.Hoogendoorn C, Duchateau N, Sánchez-Quintana D, Whitmarsh T, Sukno FM, De Craene M, et al.: A high-resolution atlas and statistical model of the human heart from multislice CT. IEEE Trans Med Imaging 2013, 32: 28–44.Vadakkumpadan F, Rantner LJ, Tice B, Boyle P, Prassl AJ, Vigmond E, et al.: Image-based models of cardiac structure with applications in arrhythmia and defibrillation studies. J Electrocardiol 2009, 42: 157.Perperidis D, Mohiaddin R, Rueckert D: Construction of a 4D statistical atlas of the cardiac anatomy and its use in classification. In Med Image Comput Comput Interv 2005, LNCS 3750. Springer–Verlag, Berlin Heidelberg; 2005:402–10.Lötjönen J, Kivistö S, Koikkalainen J, Smutek D, Lauerma K: Statistical shape model of atria, ventricles and epicardium from short- and long-axis MR images. Med Image Anal 2004, 8: 371–86.Lorenz C, von Berg J: A comprehensive shape model of the heart. Med Image Anal 2006, 10: 657–70.Mansoori T, Plank G, Burton R, Schneider J, Khol P, Gavaghan D, et al.: An iterative method for registration of high-resolution cardiac histoanatomical and MRI images. In 4th IEEE Int Symp Biomed Imaging: From Nano to Macro (ISBI 2007). IEEE, Arlington, VA (USA); 2007:572–5.Gibb M, Burton RAB, Bollensdorff C, Afonso C, Mansoori T, Schotten U, et al.: Resolving the three-dimensional histology of the heart. In Comput Methods Syst Biol - Lect Notes Comput Sci 7605. Springer, Berlin Heidelberg; 2012:2–16.Burton RAB, Lee P, Casero R, Garny A, Siedlecka U, Schneider JE, et al.: Three-dimensional histology: tools and application to quantitative assessment of cell-type distribution in rabbit heart. Europace 2014,16(Suppl 4):iv86–95.Niederer SA, Shetty AK, Plank G, Bostock J, Razavi R, Smith NP, et al.: Biophysical modeling to simulate the response to multisite left ventricular stimulation using a quadripolar pacing lead. Pacing Clin Electrophysiol 2012, 35: 204–14.Weese J, Groth A, Nickisch H, Barschdorf H, Weber FM, Velut J, et al.: Generating anatomical models of the heart and the aorta from medical images for personalized physiological simulations. Med Biol Eng Comput 2013, 51: 1209–19.Gibb M, Bishop M, Burton R, Kohl P, Grau V, Plank G, et al.: The role of blood vessels in rabbit propagation dynamics and cardiac arrhythmias. In Funct Imaging Model Heart - FIMH 2009, LNCS 5528. Springer, Berlin Heidelberg; 2009:268–76.Prassl AJ, Kickinger F, Ahammer H, Grau V, Schneider JE, Hofer E, et al.: Automatically generated, anatomically accurate meshes for cardiac electrophysiology problems. IEEE Trans Biomed Eng 2009, 56: 1318–30.Dux-Santoy L, Sebastian R, Felix-Rodriguez J, Ferrero JM, Saiz J: Interaction of specialized cardiac conduction system with antiarrhythmic drugs: a simulation study. IEEE Trans Biomed Eng 2011, 58: 3475–8.Lamata P, Niederer S, Nordsletten D, Barber DC, Roy I, Hose DR, et al.: An accurate, fast and robust method to generate patient-specific cubic Hermite meshes. Med Image Anal 2011, 15: 801–13.Pathmanathan P, Cooper J, Fletcher A, Mirams G, Murray P, Osborne J, et al.: A computational study of discrete mechanical tissue models. Phys Biol 2009, 6: 036001.Niederer SA, Kerfoot E, Benson AP, Bernabeu MO, Bernus O, Bradley C, et al.: Verification of cardiac tissue electrophysiology simulators using an N-version benchmark. Philos Trans R Soc A Math Phys Eng Sci 2011, 369: 4331–51.Ten Tusscher KHWJ, Panfilov AV: Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions. Phys Med Biol 2006, 51: 6141–56.LeGrice I, Smaill B, Chai L, Edgar S, Gavin J, Hunter P: Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog. Am J Physiol Heart Circ Physiol 1995, 269: H571–82.Anderson RH, Smerup M, Sanchez-Quintana D, Loukas M, Lunkenheimer PP: The three-dimensional arrangement of the myocytes in the ventricular walls. Clin Anat 2009, 22: 64–76.Clerc L: Directional differences of impulse spread in trabecular muscle from mammalian heart. J Physiol 1976, 255: 335–46.Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH: Fiber orientation in the canine left ventricle during diastole and systole. Circ Res 1969, 24: 339–47.Scollan D, Holmes A, Winslow R, Forder J: Histological validation of myocardial microstructure obtained from diffusion tensor magnetic resonance imaging. Am J Physiol Heart Circ Physiol 1998, 275: H2308–18.Hsu EW, Muzikant AL, Matulevicius SA, Penland RC, Henriquez CS: Magnetic resonance myocardial fiber-orientation mapping with direct histological correlation. Am J Physiol Heart Circ Physiol 1998, 274: H1627–34.Holmes AA, Scollan DF, Winslow RL: Direct histological validation of diffusion tensor MRI in formaldehyde-fixed myocardium. Magn Reson Med 2000, 44: 157–61.Sermesant M, Forest C, Pennec X, Delingette H, Ayache N: Deformable biomechanical models: application to 4D cardiac image analysis. Med Image Anal 2003, 7: 475–88.Peyrat JM, Sermesant M, Pennec X, Delingette H, Xu C, McVeigh ER, et al.: A computational framework for the statistical analysis of cardiac diffusion tensors: application to a small database of canine hearts. IEEE Trans Med Imaging 2007, 26: 1500–14.Toussaint N, Sermesant M, Stoeck CT, Kozerke S, Batchelor PG: In vivo human 3D cardiac fibre architecture: reconstruction using curvilinear interpolation of diffusion tensor images. Med Image Comput Comput Assist Interv 2010,13(Pt 1):418–25.Toussaint N, Stoeck CT, Schaeffter T, Kozerke S, Sermesant M, Batchelor PG: In vivo human cardiac fibre architecture estimation using shape-based diffusion tensor processing. Med Image Anal 2013, 17: 1243–55.Bishop MJ, Hales P, Plank G, Gavaghan DJ, Scheider J, Grau V: Comparison of rule-based and DTMRI-derived fibre architecture in a whole rat ventricular computational model. In Funct Imaging Model Heart 2009, LNCS 5528. Springer–Verlag, Berlin Heidelberg; 2009:87–96.Bayer JD, Blake RC, Plank G, Trayanova NA: A novel rule-based algorithm for assigning myocardial fiber orientation to computational heart models. Ann Biomed Eng 2012, 40: 2243–54.Dobrzynski H, Anderson RH, Atkinson A, Borbas Z, D’Souza A, Fraser JF, et al.: Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Pharmacol Ther 2013, 139: 260–88.Tranum-Jensen J, Wilde AA, Vermeulen JT, Janse MJ: Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts. Circ Res 1991, 69: 429–37.Boyle PM, Deo M, Plank G, Vigmond EJ: Purkinje-mediated effects in the response of quiescent ventricles to defibrillation shocks. Ann Biomed Eng 2010, 38: 456–68.Behradfar E, Nygren A, Vigmond EJ: The role of Purkinje-myocardial coupling during ventricular arrhythmia: a modeling study. PLoS One 2014., 9: Article ID e88000DiFrancesco D, Noble D: A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc B Biol Sci 1985, 307: 353–98.Stewart P, Aslanidi OV, Noble D, Noble PJ, Boyett MR, Zhang H: Mathematical models of the electrical action potential of Purkinje fibre cells. Philos Trans R Soc A Math Phys Eng Sci 2009, 367: 2225–55.Li P, Rudy Y: A model of canine purkinje cell electrophysiology and Ca(2+) cycling: rate dependence, triggered activity, and comparison to ventricular myocytes. Circ Res 2011, 109: 71–9.Chinchapatnam P, Rhode KS, Ginks M, Mansi T, Peyrat JM, Lambiase P, et al.: Estimation of volumetric myocardial apparent conductivity from endocardial electro-anatomical mapping. In 31st Annu Int Conf IEEE Eng Med Biol Soc (EMBC 2009). IEEE, Minneapolis, MN (USA); 2009:2907–10.Durrer D, Van Dam RT, Freud GE, Janse MJ, Meijler FL, Arzbaecher RC: Total excitation of the isolated human heart. Circulation 1970, 41: 899–912.Pollard AE, Barr RC: Computer simulations of activation in an anatomically based model of the human ventricular conduction system. IEEE Trans Biomed Eng 1991, 38: 982–96.Abboud S, Berenfeld O, Sadeh D: Simulation of high-resolution QRS complex using a ventricular model with a fractal conduction system. Effects of ischemia on high-frequency QRS potentials. Circ Res 1991, 68: 1751–60.Sebastian R, Zimmerman V, Romero D, Sanchez-Quintana D, Frangi AF: Characterization and modeling of the peripheral cardiac conduction system. IEEE Trans Med Imaging 2013, 32: 45–55.Bordas R, Gillow K, Lou Q, Efimov IR, Gavaghan D, Kohl P, et al.: Rabbit-specific ventricular model of cardiac electrophysiological function including specialized conduction system. Prog Biophys Mol Biol 2011, 107: 90–100.Stephenson RS, Boyett MR, Hart G, Nikolaidou T, Cai X, Corno AF, et al.: Contrast enhanced micro-computed tomography resolves the 3-dimensional morphology of the cardiac conduction system in mammalian hearts. PLoS One 2012., 7: Article ID e35299Berenfeld O, Jalife J: Purkinje-Muscle reentry as a mechanism of polymorphic ventricular arrhythmias in a 3-dimensional model of the ventricles. Circ Res 1998, 82: 1063–77.Azzouzi A, Coudière Y, Turpault R, Zemzemi N: A mathematical model of the Purkinje-muscle junctions. Math Biosci Eng MBE 2011, 8: 915–30.Dux-Santoy L, Sebastian R, Rodriguez JF, Ferrero JM: Modeling the different sections of the cardiac conduction system to obtain realistic electrocardiograms. In 35th Annu Int Conf IEEE Eng Med Biol Soc (EMBC 2013). IEEE, Osaka, Japan; 2013:6846–9.Cardenes R, Sebastian R, Berruezo A, Camara O: Inverse

FROM CONCEPT, TO DESIGN, EVALUATION AND FIRST IN VIVO DEMONSTRATION OF A TELE-OPERATED CATHETER NAVIGATION SYSTEM

Percutaneous transluminal catheter (PTC) intervention is a medical technique used to assess and treat vascular and cardiac diseases, including electrophysiological conditions. A Interventional specialists use the vasculature as a passageway to guide the catheter to the site of interest, using fluoroscopic x-ray imaging for image-guidance. Common PTC procedures include: vascular angiography, inflating balloons and stents, depositing coils, and the treatment of cardiac arrhythmia via catheter ablation. Catheter ablation has gained prevalence over the last two decades, as the treatment success rate for atrial fibrillation reaches 100%. The close proximity between the interventionalist and the radiation source combined with the increased number of procedures performed annually has lead to increased lifetime exposure; escalating the interventionalist probability of developing cancer, cataracts or passing genetic defects to offspring. Furthermore, the lead garments that protect the interventionalist can lead to musculoskeletal injury. Both these factors have lead to increased occupational risk. Catheter navigation systems are commercially available to reduce these risks. Lack of intuitive design is a common failing among these systems. iii This thesis presents the design and validation of a remote catheter navigation system (RCNS) that utilizes dexterous skills of the interventionalist during remote navigation, by keeping the catheter in their hands of the interventionalist during remote navigation. For remote catheter manipulation, the interventionalist pushes, pulls, and twists an input catheter, which is placed inside an electromechanical sensor (CS). Position changes of the input catheter are transferred to a second electromechanical (CM) that replicates the sensed motion with a second, remote catheter. Design of this system begins with understanding the dynamic forces applied to the catheter during intravascular navigation. These dynamics were quantified and then used as operating parameters in the mechanical design of the CM. In a laboratory setting, motion sensed and replicated by the RCNS was found to be 1 mm in the axial direction, 1° in the radial direction, with a latency of 180 ms. In a multi-operator, comparative study using a specially constructed multi-path vessel phantom, comparable navigation efficacy was demonstrated between the RCNS and conventional catheter manipulation, with the RCNS requiring only 9s longer to complete the same tasks. Finally, remote navigation was performed in vivo to fully demonstrate the application of this system towards the diagnosis and treatment of cardiac arrhythmia

Computational modelling of the human heart and multiscale simulation of its electrophysiological activity aimed at the treatment of cardiac arrhythmias related to ischaemia and Infarction

[ES] Las enfermedades cardiovasculares constituyen la principal causa de morbilidad y mortalidad a nivel mundial, causando en torno a 18 millones de muertes cada año. De entre ellas, la más común es la enfermedad isquémica cardíaca, habitualmente denominada como infarto de miocardio (IM). Tras superar un IM, un considerable número de pacientes desarrollan taquicardias ventriculares (TV) potencialmente mortales durante la fase crónica del IM, es decir, semanas, meses o incluso años después la fase aguda inicial. Este tipo concreto de TV normalmente se origina por una reentrada a través de canales de conducción (CC), filamentos de miocardio superviviente que atraviesan la cicatriz del infarto fibrosa y no conductora. Cuando los fármacos anti-arrítmicos resultan incapaces de evitar episodios recurrentes de TV, la ablación por radiofrecuencia (ARF), un procedimiento mínimamente invasivo realizado mediante cateterismo en el laboratorio de electrofisiología (EF), se usa habitualmente para interrumpir de manera permanente la propagación eléctrica a través de los CCs responsables de la TV. Sin embargo, además de ser invasivo, arriesgado y requerir mucho tiempo, en casos de TVs relacionadas con IM crónico, hasta un 50% de los pacientes continúa padeciendo episodios recurrentes de TV tras el procedimiento de ARF. Por tanto, existe la necesidad de desarrollar nuevas estrategias pre-procedimiento para mejorar la planificación de la ARF y, de ese modo, aumentar esta tasa de éxito relativamente baja. En primer lugar, realizamos una revisión exhaustiva de la literatura referente a los modelos cardiacos 3D existentes, con el fin de obtener un profundo conocimiento de sus principales características y los métodos usados en su construcción, con especial atención sobre los modelos orientados a simulación de EF cardíaca. Luego, usando datos clínicos de un paciente con historial de TV relacionada con infarto, diseñamos e implementamos una serie de estrategias y metodologías para (1) generar modelos computacionales 3D específicos de paciente de ventrículos infartados que puedan usarse para realizar simulaciones de EF cardíaca a nivel de órgano, incluyendo la cicatriz del infarto y la región circundante conocida como zona de borde (ZB); (2) construir modelos 3D de torso que permitan la obtención del ECG simulado; y (3) llevar a cabo estudios in-silico de EF personalizados y pre-procedimiento, tratando de replicar los verdaderos estudios de EF realizados en el laboratorio de EF antes de la ablación. La finalidad de estas metodologías es la de localizar los CCs en el modelo ventricular 3D para ayudar a definir los objetivos de ablación óptimos para el procedimiento de ARF. Por último, realizamos el estudio retrospectivo por simulación de un caso, en el que logramos inducir la TV reentrante relacionada con el infarto usando diferentes configuraciones de modelado para la ZB. Validamos nuestros resultados mediante la reproducción, con una precisión razonable, del ECG del paciente en TV, así como en ritmo sinusal a partir de los mapas de activación endocárdica obtenidos invasivamente mediante sistemas de mapeado electroanatómico en este último caso. Esto permitió encontrar la ubicación y analizar las características del CC responsable de la TV clínica. Cabe destacar que dicho estudio in-silico de EF podría haberse efectuado antes del procedimiento de ARF, puesto que nuestro planteamiento está completamente basado en datos clínicos no invasivos adquiridos antes de la intervención real. Estos resultados confirman la viabilidad de la realización de estudios in-silico de EF personalizados y pre-procedimiento de utilidad, así como el potencial del abordaje propuesto para llegar a ser en un futuro una herramienta de apoyo para la planificación de la ARF en casos de TVs reentrantes relacionadas con infarto. No obstante, la metodología propuesta requiere de notables mejoras y validación por medio de es[CA] Les malalties cardiovasculars constitueixen la principal causa de morbiditat i mortalitat a nivell mundial, causant entorn a 18 milions de morts cada any. De elles, la més comuna és la malaltia isquèmica cardíaca, habitualment denominada infart de miocardi (IM). Després de superar un IM, un considerable nombre de pacients desenvolupen taquicàrdies ventriculars (TV) potencialment mortals durant la fase crònica de l'IM, és a dir, setmanes, mesos i fins i tot anys després de la fase aguda inicial. Aquest tipus concret de TV normalment s'origina per una reentrada a través dels canals de conducció (CC), filaments de miocardi supervivent que travessen la cicatriu de l'infart fibrosa i no conductora. Quan els fàrmacs anti-arítmics resulten incapaços d'evitar episodis recurrents de TV, l'ablació per radiofreqüència (ARF), un procediment mínimament invasiu realitzat mitjançant cateterisme en el laboratori de electrofisiologia (EF), s'usa habitualment per a interrompre de manera permanent la propagació elèctrica a través dels CCs responsables de la TV. No obstant això, a més de ser invasiu, arriscat i requerir molt de temps, en casos de TVs relacionades amb IM crònic fins a un 50% dels pacients continua patint episodis recurrents de TV després del procediment d'ARF. Per tant, existeix la necessitat de desenvolupar noves estratègies pre-procediment per a millorar la planificació de l'ARF i, d'aquesta manera, augmentar la taxa d'èxit, que es relativament baixa. En primer lloc, realitzem una revisió exhaustiva de la literatura referent als models cardíacs 3D existents, amb la finalitat d'obtindre un profund coneixement de les seues principals característiques i els mètodes usats en la seua construcció, amb especial atenció sobre els models orientats a simulació de EF cardíaca. Posteriorment, usant dades clíniques d'un pacient amb historial de TV relacionada amb infart, dissenyem i implementem una sèrie d'estratègies i metodologies per a (1) generar models computacionals 3D específics de pacient de ventricles infartats capaços de realitzar simulacions de EF cardíaca a nivell d'òrgan, incloent la cicatriu de l'infart i la regió circumdant coneguda com a zona de vora (ZV); (2) construir models 3D de tors que permeten l'obtenció del ECG simulat; i (3) dur a terme estudis in-silico de EF personalitzats i pre-procediment, tractant de replicar els vertaders estudis de EF realitzats en el laboratori de EF abans de l'ablació. La finalitat d'aquestes metodologies és la de localitzar els CCs en el model ventricular 3D per a ajudar a definir els objectius d'ablació òptims per al procediment d'ARF. Finalment, a manera de prova de concepte, realitzem l'estudi retrospectiu per simulació d'un cas, en el qual aconseguim induir la TV reentrant relacionada amb l'infart usant diferents configuracions de modelatge per a la ZV. Validem els nostres resultats mitjançant la reproducció, amb una precisió raonable, del ECG del pacient en TV, així com en ritme sinusal a partir dels mapes d'activació endocardíac obtinguts invasivament mitjançant sistemes de mapatge electro-anatòmic en aquest últim cas. Això va permetre trobar la ubicació i analitzar les característiques del CC responsable de la TV clínica. Cal destacar que aquest estudi in-silico de EF podria haver-se efectuat abans del procediment d'ARF, ja que el nostre plantejament està completament basat en dades clíniques no invasius adquirits abans de la intervenció real. Aquests resultats confirmen la viabilitat de la realització d'estudis in-silico de EF personalitzats i pre-procediment d'utilitat, així com el potencial de l'abordatge proposat per a arribar a ser en un futur una eina de suport per a la planificació de l'ARF en casos de TVs reentrants relacionades amb infart. No obstant això, la metodologia proposada requereix de notables millores i validació per mitjà d'estudis de simulació amb grans cohorts de pacients.[EN] Cardiovascular diseases represent the main cause of morbidity and mortality worldwide, causing around 18 million deaths every year. Among these diseases, the most common one is the ischaemic heart disease, usually referred to as myocardial infarction (MI). After surviving to a MI, a considerable number of patients develop life-threatening ventricular tachycardias (VT) during the chronic stage of the MI, that is, weeks, months or even years after the initial acute phase. This particular type of VT is typically sustained by reentry through slow conducting channels (CC), which are filaments of surviving myocardium that cross the non-conducting fibrotic infarct scar. When anti-arrhythmic drugs are unable to prevent recurrent VT episodes, radiofrequency ablation (RFA), a minimally invasive procedure performed by catheterization in the electrophysiology (EP) laboratory, is commonly used to interrupt the electrical conduction through the CCs responsible for the VT permanently. However, besides being invasive, risky and time-consuming, in the cases of VTs related to chronic MI, up to 50% of patients continue suffering from recurrent VT episodes after the RFA procedure. Therefore, there exists a need to develop novel pre-procedural strategies to improve RFA planning and, thereby, increase this relatively low success rate. First, we conducted an exhaustive review of the literature associated with the existing 3D cardiac models in order to gain a deep knowledge about their main features and the methods used for their construction, with special focus on those models oriented to simulation of cardiac EP. Later, using a clinical dataset of a chronically infarcted patient with a history of infarct-related VT, we designed and implemented a number of strategies and methodologies to (1) build patient-specific 3D computational models of infarcted ventricles that can be used to perform simulations of cardiac EP at the organ level, including the infarct scar and the surrounding region known as border zone (BZ); (2) construct 3D torso models that enable to compute the simulated ECG; and (3) carry out pre-procedural personalized in-silico EP studies, trying to replicate the actual EP studies conducted in the EP laboratory prior to the ablation. The goal of these methodologies is to allow locating the CCs into the 3D ventricular model in order to help in defining the optimal ablation targets for the RFA procedure. Lastly, as a proof-of-concept, we performed a retrospective simulation case study, in which we were able to induce an infarct-related reentrant VT using different modelling configurations for the BZ. We validated our results by reproducing with a reasonable accuracy the patient's ECG during VT, as well as in sinus rhythm from the endocardial activation maps invasively recorded via electroanatomical mapping systems in this latter case. This allowed us to find the location and analyse the features of the CC responsible for the clinical VT. Importantly, such in-silico EP study might have been conducted prior to the RFA procedure, since our approach is completely based on non-invasive clinical data acquired before the real intervention. These results confirm the feasibility of performing useful pre-procedural personalized in-silico EP studies, as well as the potential of the proposed approach to become a helpful tool for RFA planning in cases of infarct-related reentrant VTs in the future. Nevertheless, the developed methodology requires further improvements and validation by means of simulation studies including large cohorts of patients.During the carrying out of this doctoral thesis, the author Alejandro Daniel López Pérez was financially supported by the Ministerio de Economía, Industria y Competitividad of Spain through the program Ayudas para contratos predoctorales para la formación de doctores, with the grant number BES-2013-064089.López Pérez, AD. (2019). Computational modelling of the human heart and multiscale simulation of its electrophysiological activity aimed at the treatment of cardiac arrhythmias related to ischaemia and Infarction [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124973TESI

Prog Biophys Mol Biol

Patient-specific modeling of ventricular electrophysiology requires an interpolated reconstruction of the 3-dimensional (3D) geometry of the patient ventricles from the low-resolution (Lo-res) clinical images. The goal of this study was to implement a processing pipeline for obtaining the interpolated reconstruction, and thoroughly evaluate the efficacy of this pipeline in comparison with alternative methods. The pipeline implemented here involves contouring the epi- and endocardial boundaries in Lo-res images, interpolating the contours using the variational implicit functions method, and merging the interpolation results to obtain the ventricular reconstruction. Five alternative interpolation methods, namely linear, cubic spline, spherical harmonics, cylindrical harmonics, and shape-based interpolation were implemented for comparison. In the thorough evaluation of the processing pipeline, Hi-res magnetic resonance (MR), computed tomography (CT), and diffusion tensor (DT) MR images from numerous hearts were used. Reconstructions obtained from the Hi-res images were compared with the reconstructions computed by each of the interpolation methods from a sparse sample of the Hi-res contours, which mimicked Lo-res clinical images. Qualitative and quantitative comparison of these ventricular geometry reconstructions showed that the variational implicit functions approach performed better than others. Additionally, the outcomes of electrophysiological simulations (sinus rhythm activation maps and pseudo-ECGs) conducted using models based on the various reconstructions were compared. These electrophysiological simulations demonstrated that our implementation of the variational implicit functions-based method had the best accuracy.DP1 HL123271/HL/NHLBI NIH HHS/United StatesDP1HL123271/DP/NCCDPHP CDC HHS/United StatesR01 HL103428/HL/NHLBI NIH HHS/United StatesR01-HL103428/HL/NHLBI NIH HHS/United States2015-08-19T00:00:00Z25148771PMC425386

A 3-Dimensional In Silico Test Bed for Radiofrequency Ablation Catheter Design Evaluation and Optimization

Atrial fibrillation (AF) is the disordered activation of the atrial myocardium, which is a major cause of stroke. Currently, the most effective, minimally traumatic treatment for AF is percutaneous catheter ablation to isolate arrhythmogenic areas from the rest of the atrium. The standard in vitro evaluation of ablation catheters through lesion studies is a resource intensive effort due to tissue variability and visual measurement methods, necessitating large sample sizes and multiple prototype builds. A computational test bed for ablation catheter evaluation was built in SolidWorks® using the morphology and dimensions of the left atrium adjacent structures. From this geometry, the physical model was built in COMSOL Multiphysics®, where a combination of the laminar fluid flow, electrical currents, and bioheat transfer was used to simulate radiofrequency (RF) tissue ablation. Simulations in simplified 3D geometries led to lesions sizes within the reported ranges from an in-vivo ablation study. However, though the ellipsoid lesion morphologies in the full atrial model were consistent with past lesion studies, perpendicularly oriented catheter tips were associated with decreases of -91.3% and -70.0% in lesion depth and maximum diameter. On the other hand, tangentially oriented catheter tips produced lesions that were only off by -28.4% and +7.9% for max depth and max diameter. Preliminary investigation into the causes of the discrepancy were performed for fluid velocities, contact area, and other factors. Finally, suggestions for further investigation are provided to aid in determining the root cause of the discrepancy, such that the test bed may be used for other ablation catheter evaluations

Multiscale computational analysis of the bioelectric consequences of myocardial ischaemia and infarction

[EN] Ischaemic heart disease is considered as the single most frequent cause of death, provoking more than 7 000 000 deaths every year worldwide. A high percentage of patients experience sudden cardiac death, caused in most cases by tachyarrhythmic mechanisms associated to myocardial ischaemia and infarction. These diseases are difficult to study using solely experimental means due to their complex dynamics and unstable nature. In the past decades, integrative computational simulation techniques have become a powerful tool to complement experimental and clinical research when trying to elucidate the intimate mechanisms of ischaemic electrophysiological processes and to aid the clinician in the improvement and optimization of therapeutic procedures. The purpose of this paper is to briefly review some of the multiscale computational models of myocardial ischaemia and infarction developed in the past 20 years, ranging from the cellular level to whole-heart simulations.This work was partially supported by the 'VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica' from the Ministerio de Economia y Competitividad of Spain (grant number TIN2012-37546-C03-01) and the European Commission (European Regional Development Funds-ERDF-FEDER), and by the Direccion General de Politica Cientifica de la Generalitat Valenciana (grant number GV/2013/119).Ferrero De Loma-Osorio, JM.; Trénor Gomis, BA.; Romero Pérez, L. (2014). Multiscale computational analysis of the bioelectric consequences of myocardial ischaemia and infarction. EP-Europace. 16(3):405-415. https://doi.org/10.1093/europace/eut405S40541516

FROM CONCEPT, TO DESIGN, EVALUATION AND FIRST IN VIVO DEMONSTRATION OF A TELE-OPERATED CATHETER NAVIGATION SYSTEM

Percutaneous transluminal catheter (PTC) intervention is a medical technique used to assess and treat vascular and cardiac diseases, including electrophysiological conditions. Interventional specialists use the vasculature as a passageway to guide the catheter to the site of interest, using fluoroscopic x-ray imaging for image-guidance. Common PTC procedures include: vascular angiography, inflating balloons and stents, depositing coils, and the treatment of cardiac arrhythmia via catheter ablation. Catheter ablation has gained prevalence over the last two decades, as the treatment success rate for atrial fibrillation reaches 100%. The close proximity between the interventionalist and the radiation source combined with the increased number of procedures performed annually has lead to increased lifetime exposure; escalating the interventionalist probability of developing cancer, cataracts or passing genetic defects to offspring. Furthermore, the lead garments that protect the interventionalist can lead to musculoskeletal injury. Both these factors have lead to increased occupational risk. Catheter navigation systems are commercially available to reduce these risks. Lack of intuitive design is a common failing among these systems. iii This thesis presents the design and validation of a remote catheter navigation system (RCNS) that utilizes dexterous skills of the interventionalist during remote navigation, by keeping the catheter in their hands of the interventionalist during remote navigation. For remote catheter manipulation, the interventionalist pushes, pulls, and twists an input catheter, which is placed inside an electromechanical sensor (CS). Position changes of the input catheter are transferred to a second electromechanical (CM) that replicates the sensed motion with a second, remote catheter. Design of this system begins with understanding the dynamic forces applied to the catheter during intravascular navigation. These dynamics were quantified and then used as operating parameters in the mechanical design of the CM. In a laboratory setting, motion sensed and replicated by the RCNS was found to be 1 mm in the axial direction, 1° in the radial direction, with a latency of 180 ms. In a multi-operator, comparative study using a specially constructed multi-path vessel phantom, comparable navigation efficacy was demonstrated between the RCNS and conventional catheter manipulation, with the RCNS requiring only 9s longer to complete the same tasks. Finally, remote navigation was performed in vivo to fully demonstrate the application of this system towards the diagnosis and treatment of cardiac arrhythmia

Multimodal ventricular tachycardia analysis : towards the accurate parametrization of predictive HPC electrophysiological computational models

After a myocardial infarction, the affected areas of the cardiac tissue suffer changes in their electrical and mechanical properties. This post-infarction scar tissue has been related with a particular type of arrhythmia: ventricular tachycardia (VT). A thorough study on the experimental data acquired with clinical tools is presented in this thesis with the objective of defining the limitations of the clinical data towards predictive computational models. Computational models have a large potential as predictive tools for VT, but the verification, validation and uncertain quantification of the numerical results is required before they can be employed as a clinical tool. Swine experimental data from an invasive electrophysiological study and Cardiac Magnetic Resonance imaging is processed to obtain accurate characterizations of the post-infarction scar. Based on the results, the limitation of each technique is described. Furthermore, the volume of the scar is evaluated as marker for post-infarction VT induction mechanisms. A control case from the animal experimental protocol is employed to build a simulation scenario in which biventricular simulations are done using a detailed cell model adapted to the ionic currents present in the swine myocytes. The uncertainty of the model derived from diffusion and fibre orientation is quantified. Finally, the recovery of the model to an extrastimulus is compared to experimental data by computationally reproducing an S1-S2 protocol. Results from the cardiac computational model show that the propagation wave patterns from numerical results match the one described by the experimental activation maps if the DTI fibre orientations are used. The electrophysiological activation is sensitive to fibre orientation. Therefore simulations including the fibre orientations from DTI are able to reproduce a physiological wave propagation pattern. The diffusion coefficients highly determine the conduction velocity. The S1-S2 protocol produced restitution curves that have similar slopes to the experimental curves. This work is a first step forward towards validation of cardiac electrophysiology simulations. Future work will address the limitations about optimal parametrization of the O'Hara-Rudy cell model to fully validate the cardiac computational model for prediction of VT inducibility.Tras un infarto de miocardio, las zonas de tejido cardiaco afectadas sufren cambios en sus propiedades eléctricas y mecánicas. Este substrato miocárdico se ha relacionado con la taquicardia ventricular (TV), un tipo de arritmia. En esta tesis se presenta un estudio exhaustivo de los datos experimentales adquiridos con protocolos clínicos con el objetivo de definir las limitaciones de los datos clínicos antes de avanzar hacia modelos computacionales. Los modelos computacionales tienen un gran potencial como herramientas para la predicción de TV, pero es necesaria su verificación, validación y la cuantificación de la incertidumbre en los resultados numéricos antes de poderlos emplear como herramientas clínicas. La caracterización precisa del sustrato miocárdico, cicatriz, se realiza mediante el procesado de los datos experimentales porcinos obtenidos del estudio electrofisiológico invasivo y la resonancia magnética cardiaca. Como consecuencia, se describen las limitaciones de cada técnica. Ademas, se estudia si el volumen da la cicatriz puede actuar como indicador de la aparición de VT. El escenario de simulación para los modelos computacionales biventriulares se construye a partir de los datos experimentales de un caso control incluido en el protocolo experimental. En el, se realizan simulaciones electrofisiológicas empleando un modelo celular detallado adaptado a las propiedades de las corrientes iónicas en los miocitos de los cerdos. Se cuantifica la incertidumbre del modelo generada por la difusión y la orientación de las fibras. Por ultimo, se compara la recuperación del modelo a un extraestímulo con datas experimentales mediante la simulación de un protocolo S1-S2. Los resultado numéricos obtenidos muestran que los patrones de propagación de la onda de las simulación cardiaca coinciden con los descritos por los mapas de activación experimentales si la fibras incluidas en el modelo corresponden a los datos de DTI. El modelo de activación es sensible a la orientación de fibras impuesta. Las simulaciones incluyendo la orientación de fibras de DTI es capaz de reproducir los patrones fisiológicos de la onda de propagación eléctrica en ambos ventrículos. El velocidad de conducción obtenida es muy dependiente del coeficiente de difusión impuesto. El protocolo S1-S2 protocolo genera curvas de restitución con pendientes simulares a las curvas experimentales. Esta tesis es un primer paso hacia la validación de las simulaciones electrofisiológicas cardiacas. En el futuro, se mejoraran las limitaciones relacionadas con una optima parametrización del modelo celular de O?Hara-Rudy para validar por completo el modelo computacional cardiaco para avanzar hacia la predicción de la predicción de VT.Postprint (published version

Computer-Assisted Electroanatomical Guidance for Cardiac Electrophysiology Procedures

Cardiac arrhythmias are serious life-threatening episodes affecting both the aging population and younger patients with pre-existing heart conditions. One of the most effective therapeutic procedures is the minimally-invasive catheter-driven endovascular electrophysiology study, whereby electrical potentials and activation patterns in the affected cardiac chambers are measured and subsequent ablation of arrhythmogenic tissue is performed. Despite emerging technologies such as electroanatomical mapping and remote intraoperative navigation systems for improved catheter manipulation and stability, successful ablation of arrhythmias is still highly-dependent on the operator’s skills and experience. This thesis proposes a framework towards standardisation in the electroanatomical mapping and ablation planning by merging knowledge transfer from previous cases and patient-specific data. In particular, contributions towards four different procedural aspects were made: optimal electroanatomical mapping, arrhythmia path computation, catheter tip stability analysis, and ablation simulation and optimisation. In order to improve the intraoperative electroanatomical map, anatomical areas of high mapping interest were proposed, as learned from previous electrophysiology studies. Subsequently, the arrhythmic wave propagation on the endocardial surface and potential ablation points were computed. The ablation planning is further enhanced, firstly by the analysis of the catheter tip stability and the probability of slippage at sparse locations on the endocardium and, secondly, by the simulation of the ablation result from the computation of convolutional matrices which model mathematically the ablation process. The methods proposed by this thesis were validated on data from patients with complex congenital heart disease, who present unusual cardiac anatomy and consequently atypical arrhythmias. The proposed methods also build a generic framework for computer guidance of electrophysiology, with results showing complementary information that can be easily integrated into the clinical workflow.Open Acces

Personalized Multi-Scale Modeling of the Atria: Heterogeneities, Fiber Architecture, Hemodialysis and Ablation Therapy

This book targets three fields of computational multi-scale cardiac modeling. First, advanced models of the cellular atrial electrophysiology and fiber orientation are introduced. Second, novel methods to create patient-specific models of the atria are described. Third, applications of personalized models in basic research and clinical practice are presented. The results mark an important step towards the patient-specific model-based atrial fibrillation diagnosis, understanding and treatment