@article {DHAMALA2020101670,
	title = {Embedding high-dimensional Bayesian optimization via generative modeling: Parameter personalization of cardiac electrophysiological models},
	journal = {Medical Image Analysis},
	volume = {62},
	year = {2020},
	pages = {101670},
	publisher = {Elsevier},
	abstract = {The estimation of patient-specific tissue properties in the form of model parameters is important for personalized physiological models. Because tissue properties are spatially varying across the underlying geometrical model, it presents a significant challenge of high-dimensional (HD) optimization at the presence of limited measurement data. A common solution to reduce the dimension of the parameter space is to explicitly partition the geometrical mesh. In this paper, we present a novel concept that uses a generative variational auto-encoder (VAE) to embed HD Bayesian optimization into a low-dimensional (LD) latent space that represents the generative code of HD parameters. We further utilize VAE-encoded knowledge about the generative code to guide the exploration of the search space. The presented method is applied to estimating tissue excitability in a cardiac electrophysiological model in a range of synthetic and real-data experiments, through which we demonstrate its improved accuracy and substantially reduced computational cost in comparison to existing methods that rely on geometry-based reduction of the HD parameter space.},
	keywords = {High-dimensional Bayesian optimization, personalized modeling, variational autoencoder},
	issn = {1361-8415},
	doi = {https://doi.org/10.1016/j.media.2020.101670},
	url = {http://www.sciencedirect.com/science/article/pii/S1361841520300360},
	author = {Dhamala, Jwala and Bajracharya, Pradeep and Arevalo, Hermenegild and John L. {Sapp} and Hor{\'a}cek, Milan and Katherine C. {Wu} and Natalia A. {Trayanova} and Wang, Linwei}
}
@misc {28271,
	title = {System and method for personalized cardiac arrhythmia risk assessment by simulating arrhythmia inducibility},
	year = {2020},
	note = {US Patent 10,827,983},
	author = {Vadakkumpadan, Fijoy and Arevalo, Hermenegild and Natalia A. {Trayanova} and Wu, Katherine}
}
@article {26369,
	title = {Optimal contrast-enhanced MRI image thresholding for accurate prediction of ventricular tachycardia using ex-vivo high resolution models},
	journal = {Computers in biology and medicine},
	volume = {102},
	year = {2018},
	pages = {426-432},
	publisher = {Pergamon},
	author = {Deng, Dongdong and Plamen P. {Nikolov} and Arevalo, Hermenegild and Natalia A. {Trayanova}}
}
@article {26117,
	title = {Quantifying the uncertainty in model parameters using Gaussian process-based Markov chain Monte Carlo in cardiac electrophysiology},
	journal = {Medical Image Analysis},
	volume = {48},
	year = {2018},
	month = {Jan-08-2018},
	pages = {43 - 57},
	publisher = {Medical Image Analysis},
	issn = {13618415},
	doi = {10.1016/j.media.2018.05.007},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1361841518302925https://api.elsevier.com/content/article/PII:S1361841518302925?httpAccept=text/xmlhttps://api.elsevier.com/content/article/PII:S1361841518302925?httpAccept=text/plain},
	author = {Dhamala, Jwala and Arevalo, Hermenegild and Sapp, John and Hor{\'a}cek, Milan and Katherine C {Wu} and Natalia A. {Trayanova} and Wang, Linwei}
}
@article {24514,
	title = {Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models},
	journal = {Nature Communications},
	volume = {7},
	year = {2016},
	month = {05/2016},
	publisher = {Nature Publishing Group},
	doi = {10.1038/ncomms11437},
	author = {Arevalo, Hermenegild and Vadakkumpadan, Fijoy and Guallar, Eliseo and Jebb, Alexander and Malamas, Peter and Katherine C {Wu} and Natalia A. {Trayanova}}
}
@article {24515,
	title = {Computational rabbit models to investigate the initiation, perpetuation, and termination of ventricular arrhythmia},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {121},
	year = {2016},
	pages = {185-194},
	publisher = {Elsevier},
	author = {Arevalo, Hermenegild and Patrick M {Boyle} and Natalia A. {Trayanova}}
}
@article {24790,
	title = {Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations},
	journal = {The Journal of Clnical Investigation},
	volume = {126},
	year = {2016},
	publisher = {American Society for Clinical Investigation},
	doi = {10.1172/JCI88950},
	author = {Bruegmann, Tobias and Patrick M {Boyle} and Vogt, Christoph and Karathanos, T and Arevalo, Hermenegild and Fleishmann, Bernd and Natalia A. {Trayanova} and Sasse, Philipp}
}
@article {deng2015accuracy,
	title = {Accuracy of prediction of infarct-related arrhythmic circuits from image-based models reconstructed from low and high resolution MRI},
	journal = {Frontiers in Physiology},
	volume = {6},
	year = {2015},
	publisher = {Frontiers Media SA},
	author = {Deng, Dongdong and Arevalo, Hermenegild and Pashakhanloo, Farhad and Prakosa, Adityo and Ashikaga, Hiroshi and McVeigh, Elliot and Halperin, Henry and Natalia A. {Trayanova}}
}
@article {ukwatta2015image,
	title = {Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology},
	journal = {Medical Physics},
	volume = {42},
	year = {2015},
	pages = {4579-90},
	publisher = {American Association of Physicists in Medicine},
	author = {Ukwatta, Eranga and Arevalo, Hermenegild and Rajchl, Martin and White, James and Pashakhanloo, Farhad and Prakosa, Adityo and Daniel A {Herzka} and McVeigh, Elliot and Albert C {Lardo} and Natalia A. {Trayanova}}
}
@article {ukwatta2015myocardial,
	title = {Myocardial Infarct Segmentation from Magnetic Resonance Images for Personalized Modeling of Cardiac Electrophysiology},
	journal = {IEEE Transactions on Medical Imaaging},
	year = {2015},
	publisher = {IEEE},
	issn = {0278-0062},
	doi = {10.1109/TMI.2015.2512711},
	author = {Ukwatta, Eranga and Arevalo, Hermenegild and Li, Kristina and Yuan, Jing and Qiu, Wu and Malamas, Peter and Katherine C {Wu} and Natalia A. {Trayanova} and Vadakkumpadan, Fijoy}
}
@article {Land:2015dq,
	title = {Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour},
	journal = {Proceedings of the Royal Society A},
	volume = {471},
	year = {2015},
	month = {12/2015},
	publisher = {The Royal Society},
	abstract = {Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5\%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.},
	author = {Land, Sander and Arens, Sander and Christoph M {Augustin} and Baron, Lukas and Castro, Sebastian and Crozier, Andrew and Favino, Marco and Thomas E {Fastl} and Fritz, Thomas and Gao, Hao and Gizzi, Alessio and Boyce E {Griffith} and Daniel E {Hurtado} and Krause, Rolf and Luo, Xiaoyu and Martyn P {Nash} and Pezzuto, Simone and Plank, Gernot and Rossi, Simone and Ruprecht, Daniel and Seemann, Gunnar and Nicolas P. {Smith} and Sundnes, Joakim and Rice, Jeremy and Natalia A. {Trayanova} and Wang, Dafang and Zhinuo Jenny {Wang} and Steven A {Niederer}}
}
@article {prakosa2014methodology,
	title = {Methodology for image-based reconstruction of ventricular geometry for patient-specific modeling of cardiac electrophysiology},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {115},
	year = {2014},
	pages = {226-34},
	publisher = {Pergamon},
	author = {Prakosa, A and Malamas, Peter and Zhang, S and Pashakhanloo, F and Arevalo, Hermenegild and Herzka, DA and Lardo, A and Halperin, Henry and McVeigh, E and Natalia A. {Trayanova}}
}
@article {boyle2014sodium,
	title = {Sodium current reduction unmasks a structure-dependent substrate for arrhythmogenesis in the normal ventricles},
	journal = {PLOS ONE},
	year = {2014},
	publisher = {Public Library of Science},
	author = {Patrick M {Boyle} and Carolyn J {Park} and Arevalo, Hermenegild and Edward J {Vigmond} and Natalia A. {Trayanova}}
}
@article {arevalo2013tachycardia,
	title = {Tachycardia in post-infarction hearts: insights from 3D image-based ventricular models},
	journal = {PLOS ONE},
	year = {2013},
	publisher = {PLOS ONE},
	author = {Arevalo, Hermenegild and Plank, Gernot and Helm, Patrick and Halperin, Henry and Natalia A. {Trayanova}}
}
@article {vadakkumpadan2012image,
	title = {Image-based estimation of ventricular fiber orientations for personalized modeling of cardiac electrophysiology},
	journal = {IEEE Transactions on Medical Imaging},
	volume = {31},
	year = {2012},
	pages = {1051-1060},
	publisher = {IEEE},
	author = {Vadakkumpadan, Fijoy and Arevalo, Hermenegild and Ceritoglu, Can and Miller, Michael and Natalia A. {Trayanova}}
}
@article {rantner2012three,
	title = {Three-dimensional mechanisms of increased vulnerability to electric shocks in myocardial infarction: Altered virtual electrode polarizations and conduction delay in the peri-infarct zone},
	journal = {Journal of Physiology},
	volume = {590},
	year = {2012},
	pages = {4537-51},
	publisher = {Blackwell Publishing Ltd},
	author = {Lukas J {Rantner} and Arevalo, Hermenegild and Jason L {Constantino} and Igor R {Efimov} and Plank, Gernot and Natalia A. {Trayanova}}
}
@article {Simula.simula.540,
	title = {Susceptibility to Reentry in the Infarcted Heart Depends on the Active Fibroblast Density},
	journal = {Biophysical Journal},
	volume = {110},
	number = {6},
	year = {2011},
	month = {September},
	pages = {1307-15},
	author = {McDowell, Kathleen and Arevalo, Hermenegild and Maleckar, Molly and Natalia A. {Trayanova}}
}
@article {Simula.camo.4,
	title = {Fibroblast-Myocote Coupling Induces Alterations in Potassium Currents That Trigger Regional Action Potensial During (APD) Prolongation in Infarcted Myocardium},
	journal = {Heart Rhythm},
	volume = {7},
	number = {5},
	year = {2010},
	pages = {163-164},
	author = {McDowell, Kathleen and Arevalo, Hermenegild and Maleckar, Molly and Natalia A. {Trayanova}}
}
@article {vadakkumpadan2010image,
	title = {Image-based models of cardiac structure in health and disease},
	journal = {Wiley Interdisciplinary Reviews: Systems Biology and Medicine},
	year = {2010},
	publisher = {John Wiley \& Sons, Inc.},
	author = {Vadakkumpadan, Fijoy and Arevalo, Hermenegild and Anton J {Prassl} and Chen, Junjie and Kickinger, Ferdinand and Kohl, Peter and Plank, Gernot and Natalia A. {Trayanova}}
}
@misc {Simula.SC.546,
	title = {Effects of Fibroblast-Myocyte Coupling in the Infarcted Rabbit Heart},
	howpublished = {Heart Rhythm},
	volume = {6},
	year = {2009},
	month = {May/2009},
	pages = {S295-296},
	author = {McDowell, Kathleen and Arevalo, Hermenegild and Maleckar, Molly and RC, Blake and G, Plank and Natalia A. {Trayanova}}
}
@article {Simula.SC.448,
	title = {Electrotonic Coupling Between Human Atrial Myocytes and Fibroblasts Alters Excitability and Repolarization},
	journal = {Biophysical Journal},
	volume = {97},
	number = {8},
	year = {2009},
	month = {October},
	pages = {2179-2190},
	abstract = {Atrial fibrosis has been implicated in the development and maintenance of atrial arrhythmias, and is characterized by expansion of the extracellular matrix and an increased number of fibroblasts (Fbs). Electrotonic coupling between atrial myocytes and Fbs may contribute to the formation of an arrhythmogenic substrate. However, the role of these cell-cell interactions in the function of both normal and diseased atria remains poorly understood. The goal of this study was to gain mechanistic insight into the role of electrotonic Fb-myocyte coupling on myocyte excitability and repolarization. To represent the system, a human atrial myocyte (hAM) coupled to a variable number of Fbs, we employed a new ionic model of the hAM, and a variety of membrane representations for atrial Fbs. Simulations elucidated the effects of altering the intercellular coupling conductance, electrophysiological Fb properties, and stimulation rate on the myocyte action potential. The results demonstrate that the myocyte resting potential and action potential waveform are modulated strongly by the properties and number of coupled Fbs, the degree of coupling, and the pacing frequency. Our model provides mechanistic insight into the consequences of heterologous cell coupling on hAM electrophysiology, and can be extended to evaluate these implications at both tissue and organ levels.},
	author = {Maleckar, Molly and Joseph L. {Greenstein} and Wayne R. {Giles} and Natalia A. {Trayanova}}
}
@article {Simula.SC.450,
	title = {K+ Current Changes Account for the Rate Dependence of the Action Potential in the Human Atrial Myocyte},
	journal = {American Journal of Physiology - Heart and Circulatory Physiology},
	volume = {297},
	number = {4},
	year = {2009},
	note = {Should be listed in 2010 Annual Report},
	month = {October},
	pages = {1398-1410},
	abstract = {Ongoing investigation of the electrophysiology and pathophysiology of the human atria requires an accurate representation of the membrane dynamics of the human atrial myocyte. However, existing models of the human atrial myocyte action potential do not accurately reproduce experimental observations with respect to the kinetics of key repolarizing currents or rate dependence of the action potential and fail to properly enforce charge conservation, an essential characteristic in any model of the cardiac membrane. In addition, recent advances in experimental methods have resulted in new data regarding the kinetics of repolarizing currents in the human atria. The goal of this study was to develop a new model of the human atrial action potential, based on the Nygren et al. model of the human atrial myocyte and newly available experimental data, that ensures an accurate representation of repolarization processes and reproduction of action potential rate dependence and enforces charge conservation. Specifically, the transient outward K(+) current (I(t)) and ultrarapid rectifier K(+) current (I(Kur)) were newly formulated. The inwardly recitifying K(+) current (I(K1)) was also reanalyzed and implemented appropriately. Simulations of the human atrial myocyte action potential with this new model demonstrated that early repolarization is dependent on the relative conductances of I(t) and I(Kur), whereas densities of both I(Kur) and I(K1) underlie later repolarization. In addition, this model reproduces experimental measurements of rate dependence of I(t), I(Kur), and action potential duration. This new model constitutes an improved representation of excitability and repolarization reserve in the human atrial myocyte and, therefore, provides a useful computational tool for future studies involving the human atrium in both health and disease.},
	author = {Maleckar, Molly and Joseph L. {Greenstein} and Wayne R. {Giles} and Natalia A. {Trayanova}}
}
@article {vigmond2009towards,
	title = {Towards predictive modelling of the electrophysiology of the heart},
	journal = {Experimental Physiology},
	year = {2009},
	publisher = {Blackwell Publishing Ltd},
	author = {Vigmond, Edward and Vadakkumpadan, Fijoy and Arevalo, Hermenegild and Deo, Makarand and Plank, Gernot and Natalia A. {Trayanova}}
}
@misc {Simula.SC.540,
	title = {Coupling of Human Atrial Myocytes and Myofibroblasts Can Lead to Conduction Disturbances},
	howpublished = {HRS Scientific Sessions 2008},
	year = {2008},
	month = {May},
	author = {Maleckar, Molly and Joseph L. {Greenstein} and Wayne R. {Giles} and Natalia A. {Trayanova}}
}
@article {Simula.SC.452,
	title = {Mathematical Simulations of Ligand-Gated and Specific Cell-Type Effects in the Human Atrium},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {98},
	number = {2-3},
	year = {2008},
	pages = {161-70},
	author = {Maleckar, Molly and Joseph L. {Greenstein} and Natalia A. {Trayanova} and Wayne R. {Giles}}
}
@article {Simula.SC.454,
	title = {Polarity Reversal Lowers Activation Time During Diastolic Field Stimulation of the Rabbit Ventricles: Insight Into Mechanisms},
	journal = {American Journal of Physiology - Heart and Circulatory Physiology},
	volume = {295},
	number = {4},
	year = {2008},
	pages = {H1626-H1633},
	author = {Maleckar, Molly and Marcella C. {Woods} and Veniamin Y. {Sidorov} and Mark R. {Holcomb} and David N. {Mashburn} and John P. {Wikswo} and Natalia A. {Trayanova}}
}
@article {Simula.SC.458,
	title = {Cardiac Defibrillation and the Role of Mechano-Electric Feedback in Postshock Arrhythmogenesis},
	journal = {Annals of the New York Academy of Sciences},
	volume = {1080},
	year = {2006},
	pages = {320-33},
	author = {Gurev, Viatcheslav and Maleckar, Molly and Natalia A. {Trayanova}}
}
@article {Simula.SC.456,
	title = {Mechanistic Enquiry Into the Effect of Increased Pacing Rate on the Upper Limit of Vulnerability},
	journal = {Philosophical Transactions of the Royal Society A},
	volume = {346},
	year = {2006},
	pages = {1333-48},
	author = {David W. {Bourn} and Maleckar, Molly and Rodriguez, Blanca and Natalia A. {Trayanova}}
}
@misc {Simula.SC.544,
	title = {Polarity Reversal Lowers Activation Time During Diastolic Field Stimulation of the Rabbit Heart},
	howpublished = {HRS Scientific Sessions 2006},
	year = {2006},
	month = {May},
	author = {Marcella C. {Woods} and Maleckar, Molly and Veniamin Y. {Sidorov} and Mark R. {Holcomb} and David N. {Mashburn} and Natalia A. {Trayanova} and John P. {Wikswo}}
}
@misc {Simula.SC.552,
	title = {Mechanistic Insight Into the Increase in the Upper Limit of Vulnerability for Rapid Pacing},
	howpublished = {HRS Scientific Sessions 2005},
	year = {2005},
	month = {May},
	author = {Maleckar, Molly and David W. {Bourn} and Rodriguez, Blanca and Natalia A. {Trayanova}}
}
@misc {Simula.SC.554,
	title = {Mechanistic Insight Into the Increase in the Upper Limit of Vulnerability for Rapid Pacing},
	howpublished = {GRC Conference 2005 - Cardiac Arrhythmia Mechanisms},
	year = {2005},
	month = {February},
	author = {Maleckar, Molly and David W. {Bourn} and Rodriguez, Blanca and Natalia A. {Trayanova}}
}
@misc {Simula.SC.556,
	title = {Negative VEP Affects Activation During Diastolic Stimulation in the Rabbit Ventricles},
	howpublished = {NASPE Scientific Sessions 2004},
	year = {2004},
	month = {May},
	author = {Maleckar, Molly and Natalia A. {Trayanova}}
}
@misc {Simula.SC.558,
	title = {Paradoxical Activation Time During Diastolic Stimulation in the Rabbit Ventricles},
	year = {2003},
	month = {October},
	author = {Maleckar, Molly and Natalia A. {Trayanova}}
}
