Abstract: Congenital heart defects (CHDs) are among the most severe congenital abnormalities, accounting for over 29 percent of deaths from developmental abnormalities. Of these, approximately 25 percent require palliative surgery in the first year of life.  While the precise origins of CHDs remain unknown, they arise from disturbances in cardiac morphogenesis, a complex interconnected process involving changing hemodynamic forces concomitant with cellular and molecular signaling. Despite advances in surgical and medical management, their potential to restore cardiac function remains compromised, largely due to continued complications from implanted devices. To that end, I explore innovative ways to advance treatment options for patients suffering from CHD, through the identification of new mechanistic insights into the origin of such defects and the optimization of current treatment options. To understand causation, I rely on the chick embryo as a mechanical model of development. Through the use of two- photon microscopy and femtosecond laser ablations, I minimally invasively occlude flow inside the primitive great vessels and detail resulting structural and hemodynamic changes. I subsequently use numerical simulations to distinguish between the immediate effects of flow redistribution and longer-term compensation mechanisms. Ultimately, by uncovering in-utero targets of cardiac malformations, restorative in-utero procedures may become possible. Towards optimization, I lay the groundwork for fluid-structure growth simulations of tissue engineered vascular grafts in single ventricle physiology patients. I perform subject-specific fluid-structure simulations to understand and predict the body’s response to changing hemodynamics loads. I further explore the constrained mixture growth framework, in which changes in cellular and extracellular matrix components initiate growth and remodeling in response to mechanical perturbations.

Bio: Stephanie Lindsey is currently a postdoctoral researcher in the Cardiovascular Biomechanics Computation Lab at Stanford University, where she investigates growth and remodeling of tissue engineered vascular grafts. Globally, she works to combine targeted experimental manipulations and subject-specific computational models to delineate the role of hemodynamics in the creation of cardiac malformations of the outflow tract. Dr. Lindsey is an alumna of Washington University in St. Louis and Cornell University. She has been awarded individual research fellowships from the National Institute of Health, National Science Foundation, Alfred P. Sloan Foundation and Whitaker International Foundation. Dr. Lindsey has held international research positions at Inria-Paris, the University of Montpellier and INSERM.

BME Faculty Host: Ed Bartlett

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