Cardiovascular Computational Mechanics Lab, Sandra Rugonyi, P.I.

Research Interests


Mechanical forces play a significant role in biological systems and processes. For example, shear forces from blood flow affect attachment and peeling of cells and micro-bubbles (used as contrast agents for ultrasound imaging), hemodynamic forces regulate cardiovascular remodeling and heart development and affect thrombus growth, and surface tension forces determine the spread and transport of pulmonary surfactant inside the lungs.

Research projects in the Cardiovascular Computational Mechanics Lab aim to understand the role of biomechanical forces on heart development, mural thrombogenesis and pulmonary surfactant function. To this end we use a combination of physiological data, imaging, mathematical modeling and computational simulation. Our ultimate goal is to understand the biological mechanisms by which mechanical forces affect biological processes.

Cardiac Growth During Early Developmental Stages

The objective of this project is to better understand the origins of congenital heart disease (CHD), which affects about 1% of newborn babies in the US and is the leading non-infectious cause of death among infants. In particular, we are interested in the role of hemodynamic forces (forces exerted on tissues by the flow of blood) on cardiac development. In animal models, alterations of normal blood flow through the heart during development lead to cardiac defects that resemble those found in humans. While genetic defects are known to underlie some cardiac malformations, abnormal hemodynamic conditions are just as likely to be responsible for many heart defects observed in humans.

Although changes in hemodynamic forces are known to lead to CHD, the mechanisms by which this happens are not fully understood. This is in part due to the complexity of the interactions between cardiac tissue, blood flow and cellular responses to mechanical stimuli, and in part due to the many technological challenges associates with measuring forces and deformations on small hearts that are beating fast. Our goal is to use a combination of engineering and biology tools to unravel the mechanisms by which hemodynamic forces affect heart formation.

Related Links:

Cardiac Development
Biological Shape Spaces

Selected Publications:

  • A. Liu, S. Rugonyi, J.O. Pentecost and K.L. Thornburg. 2007. Finite element modeling of blood flow-induced mechanical forces in the outflow tract of chick embryonic heart, Computers and Structures, 85: 727-738.
  • A. Liu, R. Wang, K.L. Thornburg and S. Rugonyi. 2009. Dynamic Variation of Hemodynamic Shear Stress on the Walls of Developing Chick Hearts: Computational Models of the Heart Outflow Tract, Engineering with Computers; Special issue with papers on Computational Bioengineering, 25: 73-86.
  • S. Rugonyi, C. Shaut, A. Liu, K.L. Thornburg and R.K. Wang. 2008. Changes in wall motion and blood flow in the outflow tract of chick embryonic hearts observed with optical coherence tomography after outflow tract banding and vitelline-vein ligation, Physics in Medicine and Biology, 53: 5077-5091.
  • A. Liu, R. Wang, K.L. Thornburg and S. Rugonyi. 2009, Efficient postacquisition synchronization of 4-D nongated cardiac images obtained from optical coherence tomography: Application to 4-D reconstruction of the chick embryonic heart, Journal of Biomedical Optics 14, 044020.
  • S. Rugonyi, E. Tucker, U. Marzec, A. Gruber and S. Hanson. 2010, Transport-reaction model of mural thrombogenesis: comparisons of mathematical model predictions and results from baboon models. Annals of Biomedical Engineering, 38: 2660-2675.
  • Z. Ma, A. Liu, X. Yin, A. Troyer, R. Wang, S. Rugonyi. 2010, Absolute flow velocity measurement in HH18 chicken embryo outflow tract based on 4D reconstruction using spectral domain optical coherence tomography, Biomedical Optics Express, 1: 798-811. PMCID: PMC2994554.
  • A. Liu, A. Troyer, Z. Ma, R. Cary, X. Yin, A. Nickerson, K. Thornburg, R. Wang, S. Rugonyi. 2011, Quantifying blood flow and wall shear stresses in the outflow tract of chick embryonic hearts, Computers and Structures, 89: 855-867. PMCID: PMC3091009.
  • L. Phan, A.K. Knutsen, P.V. Bayly, S. Rugonyi, C. Grim 2011, Refining shape correspondence for similar objects using strain, Eurographic Workshop on 3D Object Retrieval, April 2011, pp. 17-24.
  • P. Li, X. Yin, L. Shi, A. Liu, S. Rugonyi, R.K. Wang. 2011, Measurement of strain and strain rate in embryonic chick heart in vivo using spectral domain optical coherence tomography, IEEE Transactions on Biomedical Engineering, 58: 2333-2338.
  • P. Li, A. Liu, L. Shi, X. Yin, S. Rugonyi, R.K. Wang. 2011, Assessment of strain and strain rate in embryonic chick heart in vivo using tissue Doppler optical coherence tomography, Physics in Medicine and Biology, 56: 7981-7992.
  • D.E. Scott, S. Rugonyi, D.L. Marks, K.L. Thornburg, M.T. Hinds, Hyperglycemia slows embryonic growth and suppresses cell cycle via Cyclin D1 and P21, submitted to Diabetes, in press.
  • A. Liu, X. Yin, L. Shi, P. Li, K. L. Thornburg, R. Wang, S.Rugonyi. 2012, Biomechanics of the chick embryonic heart outflow tract at HH18 using 4D optical coherence tomography imaging and computational modeling, Plos One, 7: e40869.
  • S. Goenezen*, M. Rennie*, S. Rugonyi. 2012. Biomechanics of Early cardiac Development. Biomechanics and Modeling in Mechanobiology, special issue devoted to the theme “Mechanics of Development”, 11: 1187-1204.

Thrombus Formation

Thrombogenesis is a natural process by which the body acts on an injury to stop bleeding and heal the injured tissues. However, a growing thrombus may block a blood vessel preventing blood from reaching vital organs. Further, parts of a thrombus may detach and travel through the circulatory system causing heart attack and stroke. While the roles of cells and molecules that contribute to thrombus formation have been identified, and the steps that lead to thrombus formation, the so-called coagulation cascade, are fairly well known, the effect of blood flow on thrombus formation and transport of thrombogenic products is less understood.

Thrombus formation on thrombogenic surfaces has been shown to consist of 3 phases: I) initial, slow growth; II) linear growth; III) plateau, during which the thrombus stops growing. Phase three may not be observed if the thrombus occludes the vessel. While phases one and two are somewhat understood, the mechanisms by which the thrombus stops growing are not well understood. Several factors, such as blood and thrombus-surface chemistry as well as blood flow might play a role. Our research focuses on understanding the effect of blood flow on thrombus growth, with the ultimate goal of elucidating the mechanisms by which thrombi break lose or stop growing.

Related Links:

Thrombosis and Hemostasis

Selected Publications:

  • S. Rugonyi. 2008. Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents - A simple formula to estimate boundary layer concentrations, Journal of Biomechanical Engineering, 130: 021010.
  • E.I. Tucker, U.M. Marzec, T.C. White, S. Hurst, S. Rugonyi, O.J.T. McCarty, D. Gailani, A. Gruber, S.R. Hanson. 2009. Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI, Blood, 113:936-944.
  • M.A. Berny, I.A. Patel, T.C. White-Adams, P. Simonson, A. Gruber, S. Rugonyi and O.J.T. McCarty. 2010. Rational design of an ex vivo model of thrombosis, Cellular and Molecular Bioengineering, 3: 187-189.
  • G.W. Tormoen, S. Rugonyi, A. Gruber, O.J.T. McCarty. 2011, Role of carrier number on the procoagulant activity of tissue factor in blood and plasma, Physical Biology, 8:066005.

Pulmonary Surfactant Biophysics

Pulmonary surfactant is essential for normal breathing. The lack of sufficient amount of mature surfactant causes respiratory distress syndrome (RDS) in premature infants, and can worsen the patient condition in adults with acute respiratory distress syndrome (ARDS). In the lungs, pulmonary surfactant forms a thin surface film, generally believed to be a monolayer, at the interface between air and a thin liquid layer that coats the alveoli. This surfactant film reduces surface tension, a force that tends to collapse the alveoli causing lung injury.

In situ experiments demonstrate that surface tension reaches very low values (~1 mN/m) during exhalation. However, these very low values are difficult to reproduce in vitro. Unlike in the lungs, during in vitro compression of pulmonary surfactant monolayers, surface tension decreases until the monolayer starts to thicken forming multi-layer films, process that is usually referred to as monolayer collapse and that occurs at a constant surface tension (the collapse or equilibrium surface tension, ~ 24 mN/m).

Why pulmonary surfactant films responds differently to compression in situ and in vitro is not well understood. My research has focused on the kinetics of surfactant collapse - the formation of multi-layers from a monolayer film - and how collapse rates are affected by I) the rate of film compression; II) the film surface tension; and III) the sub-phase liquid thickness. The ultimate goal is to understand the mechanisms by which proper surfactant function is achieved.

Selected Publications:

  • S. Rugonyi, E. C. Smith and S. B. Hall, "Effect of viscosity and compression rate on the collapse phase transition of pulmonary surfactant at an air-water interface", in Computational Fluid and Solid Mechanics Vol. 2, K.J.Bathe Ed., Elsevier, 2003.
  • S. Rugonyi, E.C. Smith and S.B. Hall. 2004. Transformation diagrams for the collapse of a phospholipid monolayer, Langmuir, 20:10100-10106.
  • S. Rugonyi and S.B. Hall, "The basis of low surface tensions in the lungs", in Lung Surfactant Function and Disorder, K. Nag, Ed., Taylor and Francis Group, 2005, pp. 173-189.
  • S. Rugonyi, E.C. Smith and S.B. Hall. 2005. Kinetics for the collapse of trilayer liquid-crystalline disks from a monolayer at an air-water interface, Langmuir, 21:7303-7307.
  • S.B. Hall and S. Rugonyi, "Alveolar surface mechanics", In Encyclopedia of Respiratory Medicine, Elsevier, 2006, pp. 101-106.
  • S. Rugonyi, S.C. Biswas and S.B. Hall. 2008. The Biophysical Function of Pulmonary Surfactant, Respiratory Physiology and Neurobiology; Special issue on Respiratory Biomechanics, 163: 244-255.
  • T.A. Siebert and S. Rugonyi. 2008. Influence of liquid layer thickness on pulmonary surfactant spreading and collapse, Biophysical Journal, 163:244-255.