A project utilizing the supercomputer cluster The University of Texas at Austin’s Texas Advanced Computing Center (TACC) has developed new supercomputer models that come closer than ever before to faithfully simulating behavior of normal human heart valves. The focus of a study by multi-institutional team of scientists from the Institute for Computational Engineering and Sciences (ICES) at The University of Texas at Austin and the Department of Mechanical Engineering at Iowa State University is on how heart valve tissue responds to realistic blood flow, and they’ve harnessed the power of the TACC’s Stampede, Lonestar, and Maverick supercomputers to create new simulation models intended to help doctors achieve more durable heart valve repairs and replacements.
“At the core of what we do is the development of new material models that are much more structurally and biologically informed and can actually integrate mechanisms of failure and remodeling, growth, and adaptation to altered forces that go on,” study co-author Michael Sacks tells TACC Science and Technology writer Jorge Salazar in a TACC news feature. Dr. Sacks is the W.A. Moncrief Endowment Simulation-Based Engineering Science Chair at ICES, and professor of Biomedical Engineering, UT Austin. professor of biomedical engineering and holder of the W. A. “Tex” Moncrief, Jr. Simulation-Based Engineering Science Chair I. He is also director of the ICES Center for Cardiovascular Simulation-based Engineering.
ICES’s relationship with TACC goes all the way back to 2003 when ICES used TACC supercomputers to study turbulent flow. These recent studies that model the leaflet tissue-blood flow interactions through replacement human heart valves have used millions of CPU hours on the Stampede, Lonestar, and Maverick supercomputers at TACC.
Stampede is a Dell PowerEdge cluster equipped with Intel Xeon Phi coprocessors that is one of the most powerful and significant current supercomputers in the U.S. for open science research. Able to perform nearly 10 quadrillion operations per second, Stampede offers a vast range of opportunities for computational science and technology, ranging from highly parallel algorithms, high-throughput computing, scalable visualization, and next generation programming languages, pushing the envelope of computational capabilities.
Lonestar is a Dell Linux cluster funded by The University of Texas at Austin, UT’s Institute of Computational Engineering and Sciences (ICES), UT System, Texas A&M, Texas Tech, and the National Science Foundation, and one of the most productive, multi-use cyberinfrastructure HPC and remote visualization resources in the world. Lonestar contains 23,184 cores within 1,888 Dell PowerEdgeM610 compute blades (nodes), 16 PowerEdge R610 Observer-Nodes, and two PowerEdge M610 (3.3GHz) login nodes, and serves as a unique resource to researchers at all 15 University of Texas System institutions.
Maverick is a dedicated visualization and data analysis resource. It combines capabilities for interactive advanced visualization and large-scale data analytics as well as traditional high performance computing. Recent exponential increases in the size and quantity of digital datasets necessitate systems such as Maverick, capable of fast data movement and advanced statistical analysis and architected with NVIDIA K40 GPUs for remote visualization and data analytics computing to provide specialized support for the national open science community.
“One of the big advantages to being here at ICES is that we have direct access to TACC facilities,” Dr. Sacks continues. “These jobs run multiple processors over a whole wide range to try and get it working over the cardiac cycle. It’s very computationally intensive. The TACC resources are absolutely essential to these models. TACC facilities also allow us to concentrate on the technical and scientific problems at hand, rather than developing and maintaining hardware.”
Mr. Salazar notes that during an average person’s lifetime, their heart will beat about 2.5 billion times, with each pulse putting wear and tear on constituent cells of the mitral valve leaflet, in which the valve tissue will remodel itself continuously in response to the stress and strain of its gatekeeping function.
A study funded by the National Institutes of Health (NIH) and published in the Journal of Theoretical Biology in May 2015, simulated deformations at the cellular level within the anterior leaflet tissue of mitral valve.
The study, entitled “Quantification and simulation of layer-specific mitral valve interstitial cells deformation under physiological loading“ (21 May 2015, Vol.373:26–39, doi:10.1016/j.jtbi.2015.03.004), is coauthored by Chung-Hao Lee, Salma Ayoub, and Michael S. Sacks of the Center for Cardiovascular Simulation at The University of Texas at Austin Department of Biomedical Engineering’s Institute for Computational Engineering and Sciences (ICES) at Austin; Christopher A. Carruthers — a Cardiac Rhythm Disease Management (CRDM) Clinical Specialist at Medtronic in Minneapolis, Minnesota; and Robert C. Gorman and Joseph H. Gorman III of the University of Pennsylvania’s Gorman Cardiovascular Research Group in Philadelphia, Pennsylvania.
The research team combined experimental work with computation, stretching heart tissues under a microscope to provide critical data to model the mitral valve leaflet. Heart valve tissues are built like a four-layer cake of fibrous proteins and cells, and one of the scientists’ main findings showed that each layer of the mitral valve tissue causes cells within the layer to stretch differently to the relentless task of pumping blood. Since the cells are the mitral valve’s “maintenance workers” and respond to working demands placed on the valve by its being stretched in various ways, this finding was helpful in modeling changes in the self-maintenance of the heart valve that lead to valve failure.
The coauthors note that within each of the four layers of mitral valve (MV) leaflet tissues resides a heterogeneous population of interstitial cells that maintain the structural integrity of the MV tissue via protein biosynthesis and enzymatic degradation. They observe that there is increasing evidence that tissue stress-induced MV interstitial cell (MVIC) deformations can have deleterious effects on their biosynthetic states that are potentially related to the reduction of tissue-level maintenance and to subsequent organ-level failure.
To better understand the interrelationships between tissue-level loading and cellular responses, the investigators developed an integrated experimental-computational approach. Since in vivo cellular deformations are not directly measurable, they quantified the in-situ layer-specific MVIC deformations for each of the four layers under a controlled biaxial tension loading device coupled to multi-photon microscopy, then explored the interrelationship between MVIC stiffness and deformation to layer-specific tissue mechanical and structural properties using a macro–micro finite element computational model.
In summary, the researchers learned in this study that layer-specific local mitral valve interstitial cells (MVICs) don’t simply follow MVAL bulk tissue deformations, that cellular deformations are a function of the ECM collagen and elastin fiber networks, and that ECM & MVIC properties are critical for accurate modeling the MVIC microenvironment.
“The computational demands result primarily from the large deformations that occur in the native valve, resulting in the need for advanced material models that are computationally very demanding,” Dr. Sacks observes, adding: “There’s also very complex geometries, when valve leaflets ‘contact’ and come together.”
Dr. Sacks and colleagues on another research team including Drs. Chung-Hao Lee and Robert and Joseph Gorman, with Jean-Pierre Rabbah and Ajit P. Yoganathan of the Georgia Institute of Technoloy Department of Biomedical Engineering’s Cardiovascular Fluid Mechanics Laboratory in Atlanta, Georgia, addressed these challenges in another study funded by the NIH and released May 2015 in the journal Biomechanics and Modeling in Mechanobiology.
In that study, entitled “On the effects of leaflet microstructure and constitutive model on the closing behavior of the mitral valve“ (10.1007/s10237-015-0674-0), the. researchers took what they’d learned about the architecture of actual tissue fibers of the mitral heart valve and applied it to a big-picture model that simulated function at the organ level, noting that recent long-term studies had revealed an unsatisfactory recurrence rate of severe mitral regurgitation three-to-five years after surgical repair, suggesting that excessive tissue stresses and the resulting strain-induced tissue failure are potential etiological factors controlling the success of surgical repair for treating mitral valve (MV) diseases.
The coauthors hypothesized that restoring normal MV tissue stresses in MV repair techniques would ultimately lead to improved repair durability through the restoration of MV normal homeostatic state, and therefore they developed a micro- and macro- anatomically accurate MV finite element model by incorporating actual fiber microstructural architecture and a realistic structure-based constitutive model,that they used to investigate MV closing behaviors, with extensive in vitro data used for validating the proposed model.
They report that comparative and parametric studies were conducted to identify essential model fidelity and information for achieving desirable accuracy, and that more importantly, for the first time, the interrelationship between local fiber ensemble behavior and the organ-level MV closing behavior was investigated using a computational simulation, concluding that the proposed computational model would serve as a logical first step toward achieving the long-term objective of their computer modeling research — simulation-guided design of optimal surgical repair strategies for treating diseased MVs with significantly improved durability of surgically-repaired heart valves, which they note that studies show can fail within as little as three to five years after repair.
“One of the major challenges there result from regurgitation of the valve,” Dr. Sacks explains in the TACC article. “Some blood leaks back across the mitral valve into the left atrium in a medical condition called ischemic mitral regurgitation. What we’re trying to do is develop models that can predict how a particular surgical technique can extend repair durability in a patient-specific manner.”
“Ultimately, this gives surgeons tools to develop and improve surgical procedures,” Dr. sacks continues. “This involves a number of different components, including the use of what’s called an annuloplasty ring. This ring is surgically implanted so that the valve no longer regurgitates, but different shapes induce differing stresses, which are thought to affect repair durability.”
Mr. Salazar notes that beyond repairs, each year more than 280,000 people worldwide replace their diseased heart valves with artificial heart valves, but even the newest artificial heart valves, made from tissue versus the older mechanical versions, only last about 10 to 15 years.
“They’re fabricated from soft tissues that have been chemically processed and therefore represent a challenge in terms of both the material modeling and also the fact they’re in a blood contacting environment,” Dr. Sacks explains, adding that there’s also the significant pressure from blood on the aortic heart valve that present further challenges to scientists’ ability to model them. “If you could make a valve that would last even three to five years longer, on average compared to the current valves, that would corner the market,” he says, “it would have a huge clinical impact,” adding that it’s also “very challenging because of the mathematics handling how a fluid flows and how a solid deforms are fundamentally different. Coupling them is at the cutting edge of computational mechanics.”
Study co-author Ming-Chen Hsu has been working on artificial heart valves since 2012. Formerly a post-doc at ICES, Hsu was a post-doc with Thomas Hughes and Dr. Sacks, and is currently an assistant professor in the Department of Mechanical Engineering at Iowa State University.
“What we found is that it’s extremely challenging to consider the coupling between the blood flow and the heart valve structure using the current simulation frameworks. I think one of the most important contributions in this work is that we developed a computational technology that is able to directly tackle this issue,” Dr. Hsu tells Mr. Salazar, noting that important “quantities of interest” such as mechanical stress emerge from computer models, something that is challenging to get today from even the most sophisticated experiments with live tissue. “What’s new in this work is that we combined everything,” he observes, “we start from the design of the leaflet, use that directly into our analysis framework and perform fluid structure coupling study, and then investigate the mechanical stresses. It involves the idea of isogeometric analysis that has been very popular in the past 10 years. This framework can streamline everything in performing these kind of studies. The impact this will make is, by understanding the interaction between the blood flow and heart valve leaflets, that we may be able to better design the material and the shape of the leaflet so that we can elongate the lifespan of the bioprosthetic heart valve. Hopefully, with the improved design, the patient doesn’t have to go through the painful process of heart valve replacement surgery every 10 to 15 years.”
Dr. Sacks sees this research having impact on pretty much anybody who gets the next generation of heart valve replacements, especially the percutaneous, or non-surgically replaced artificial valve, observing that “Essentially, what you want to do is be able to engineer these devices the same way one engineers your iPhone. At the end of the day the goal is to be able to produce a more effective therapy. That’s it. We’re using these modeling techniques to be able to do that.”
Texas Advanced Computing Center (TACC)
The University of Texas at Austin
Institute for Computational Engineering and Sciences (ICES)
The Journal of Theoretical Biology
The journal Biomechanics and Modeling in Mechanobiology
National Institutes of Health
Texas Advanced Computing Center (TACC)
The University of Texas at Austin
Iowa State University