Computer simulation as a predictive tool to test surgical methods for babies with heart defects

For babies with congenital heart defects mortality rates are high, surgeries are risky, and families are fraught with stress and anxiety throughout each grueling stage. Dr. Alison Marsden and her team at Stanford University are collaborating with clinicians to create new tools for these babies through virtual surgery that will allow surgeons and clinicians to test surgical methods before trying them on patients, thus reducing patient risk and fostering innovation. Her research is uniquely interdisciplinary, combining traditional tools from engineering with cutting edge problems in cardiovascular medicine. Dr. Marsden and her team are actively seeking to translate tools from fields of engineering and mathematics, including optimization, uncertainty quantification and high performance computing, to the clinical world. They are coming up with new treatment strategies for children with life threatening heart defects. Due to ethical and technical considerations, testing new surgical methods in patients or animals is challenging and computer simulations can provide a risk-free approach to testing "out of the box" new ideas. Dr. Marsden's initiatives are being well-received by private and public funding agencies. The NSF, NIH, Leducq Foundation, and Burroughs Wellcome Fund are funding her research in cardiovascular simulations and Google has provided funding for the research related to the uses of non-invasive data for the prediction of heart failure.

Dr. Marsden's lab develops computer simulation codes for cardiovascular disease and devices. Starting from medical image data such as CT scans, they construct 3D patient specific models of the vasculature. They then simulate blood flow in these models using computational fluid dynamics, using the same types of computer codes that are used to design and test airplanes. Their simulations also include multi scale models that account for the physiology of the patient. Dr. Marsden's lab uses simulations for several things:  1) they can perform virtual surgery to test new surgical concepts, 2) develop new metrics to predict patient risk, 3) and augment clinical imaging methods that typically provide anatomy but not blood flow.

Dr. Marsden is working on a number of applications in acquired and congenital heart disease:

  •  They are designing novel surgical methods for babies born with complex single ventricle heart defects. Patients born with single ventricle congenital defects have only one functional pumping chamber in their heart and typically undergo three surgeries starting as neonates. They have already designed a new Y-graft procedure for the Fontan procedure (the third surgery in the single ventricle pathway). The Y-graft, which was designed and optimized using computer simulations, has been implanted in two major clinical centers in the US in pilot studies. They are now working on a new surgical concept for the stage 1 surgery (called the Norwood or BT shunt). This idea is based on the concept of an ejector pump from fluid mechanics and would combine the first and second stage surgeries into one, thus potentially reducing the high risk of the stage I surgery, which currently has about 30% mortality.
  • They are working to uncover mechanisms of vein graft failure in adult patients following coronary artery bypass graft surgery. Vein grafts are used in roughly 70% of bypass surgeries. However, they fail at alarmingly high rates of about 50% within 5-10 years. The mechanisms of this failure are poorly understood. Methods are being developed to simulate flow and mechanical forces in bypass grafts and to predict the resulting changes in vessel material properties and composition resulting from changing hemodynamic conditions.
  • They are performing the first ever computational simulations of blood flow in patients with coronary artery aneurysms caused by Kawasaki disease (KD). KD is the leading cause of acquired heart disease in children. Some children with KD develop life-threatening aneurysms in their coronary arteries. The major questions with this work are 1) which patients are at highest risk of developing blood clots in their coronary arteries, 2) which patients should be treated with anti-coagulation drugs? By correlating hemodynamics with patient outcomes data Dr. Marsden hopes to develop a new risk stratification index that can be used clinically.
  • They have created the SimVascular Project. This is the first open source software that provides a complete pipeline for patient specific modeling from image data to simulation results. This powerful tool is now available to the research community free of charge through support from the NSF, which currently has more than 1,000 users from around the world.

By maintaining close communications and collaborative relationships with clinicians, Dr. Marsden and her team are developing methods that are driven by clinical needs. She feels her successes are based on her deep understanding of pediatric cardiology and the challenges clinicians face when treating real patients. "I have embedded myself in the clinical environment," she says further emphasizing her desire to work collaboratively with clinicians and the medical world. In addition to her research at Stanford, Dr. Marsden is collaborating with multiple international institutions including Great Ormand Street Hospital in London. Dr. Marsden also collaborates with Jay Humphrey (Yale University) on vascular growth and remodeling.

Dr. Marsden was introduced to the academic life early on, her father was a math professor and she saw early the positive impact a life in academics could make on the world. She found herself gravitate towards math and science and majored in engineering in college. Her Ph.D continued down the traditional role of mechanical engineering, looking at optimization of airfoil shapes for noise reduction in turbulent flow.

She found she was able to use those same tools to human applications and began working in the area of cardiovascular blood flow simulation. Through collaborations with the medical school Dr. Marsden developed a particular focus on pediatric cardiology. Her lab now uses computer simulation tools to design and optimize surgeries and devices for children with severe congenital heart defects.

Dr. Marsden's work explores the interface between medicine and the quantitative, physical, and theoretical disciplines. Her postdoctoral research focused on simulation and optimization of the Fontan, a surgery used to treat single-ventricle congenital heart defects. This work led to the development of a new modification of the Fontan surgery. A goal of her ongoing work is that rigorous modeling and optimization of treatments for cardiovascular disease according to engineering principles will complement doctors' clinical judgment and experience to improve outcomes for patients suffering from both congenital and acquired heart disease. In previous work, her thesis research applied novel shape optimization techniques to airfoil design for trailing-edge noise reduction in turbulent flow. 

This work established a viable framework for optimization in many challenging fluid mechanics problems including turbulence, complex geometries and unsteady flows. Her research interests include the development of derivative-free optimization methods, identification of vascular design principles, treatment planning for pediatric cardiology, and the development of numerical methods for fluid mechanics.

Alison Marsden joined the Jacobs School faculty in 2007. Pursuing studies in Mechanical Engineering, she received her B.S.E. from Princeton University in 1998 and an M.S.E from Stanford University in 2000. She received her Ph.D. from Stanford in 2005 working with Professor Parviz Moin. Marsden then had a postdoctoral fellowship from the American Heart Association and worked with Professor Charles Taylor and Jeffrey Feinstein in Stanford's Department of Pediatrics where she applied her computational skills and optimization techniques to study flow in the heart and arterial systems of patients born with heart defects. She was a 2007 winner of a Career Award at the Scientific Interface from the Burroughs Welcome Fund. Dr. Marsden joined the Stanford faculty in 2015.

Career Award at the Scientific Interface from the Burroughs Wellcome Fund, 2007

2012 NSF CAREER award winner, 2012

UCSD Panhellenic Society Outstanding Professor Award, 2013

UCSD Graduate Student Association Faculty Mentor Award, 2014