Sandra Rugonyi featured in American Society of Mechanical Engineers (ASME)
02/11/13 Portland, Ore.
Fluid Dynamics and Fetal Heart Health
Can computer models created to help the U.S. military deliver better bombs help future mothers deliver healthier babies? Heart researchers and biomedical engineers who study embryonic and fetal heart development think so.
Congenital heart diseases — life-threatening inborn defects in the heart's physical structure — affect about 1% of all live births. They're also a major cause of miscarriage and still birth. Heart murmurs, septal defects, "blue baby" syndrome — all are congenital. Sometimes these diseases run in the family genes, but there is another cause, one that we could learn to control if we understood it better. Computational fluid dynamics (CFD) may be the key to unlocking the complex relationships between embryonic blood flow and the early development of a baby's heart.
The flow of blood through an embryonic heart creates stresses and strains on developing cardiac tissue. Normal blood flow gives cardiac cells proper mechanical cues needed for cardiac tissues to grow normally and adapt to changes imposed by the fast growth of the heart and the embryo as a whole. Abnormal blood flow causes that process to go haywire, and scientists don't yet know why.
Many suspect a link between embryonic development and specific factors in the mother's physical or emotional health during her pregnancy, or even earlier. Biochemical stressors from poor nutrition, obesity, diabetes, emotional stress, or exposure to toxins can cross the placenta and cause myriad changes in the mechanics of normal cell development. When these factors change the flow of blood within the fragile, tubular structure that will one day become a human heart, the consequences can be heartbreaking in every sense of the word.
Until recently, scientists and biomedical engineers have been hard pressed to explain these phenomena.
"It's partly the complexity of the interactions between cardiac tissues, blood flow, and cellular responses to mechanical stimuli," says Dr. Sandra Rugonyi, an associate professor of biomedical engineering and head of the Cardiovascular Computational Mechanics Laboratory at Oregon Health & Science University. "But it's also due to the many technological challenges associated with measuring forces and deformations on small hearts that are beating fast. We're combining engineering and biology tools to unravel the mechanisms by which blood flow affects heart formation."
Dr. Rugonyi's team selected the noncontact imaging technique of optical coherence tomography (OCT) to observe heart dynamics in four dimensions (three physical dimensions plus time) in animal experimental models. OCT is an interferometric technique that measures optical scattering deep within biological tissues, producing images at micrometer-scale resolution. They used OCT to image the embryonic heart outflow tract, a critical segment of the developing heart, from which valves will later form and that is prone to malformations.
"We first characterized the in vivo motion of (heart tissue) over the cardiac cycle, and cardiac wall strains. Using the dynamic geometry of the outflow tract wall, and blood pressure measurements from the developing heart, we estimated myocardial wall stresses and developed dynamic image-based CFD models of the developing heart to quantify in vivo blood flow patterns and wall shear stresses over the cardiac cycle," says Dr. Rugonyi. The team specifically looked at the heart's structural parameters and physical readings such as heart wall motion and pulsatile pressure. The combination of imaging techniques and computational models is allowing scientists to unravel how mechanical cues from blood flow influence a heart's structural development.
For its CFD model, the team used finite element methods in a commercial software package by ADINA R & D, Inc., Watertown, MA. Simulation results were visualized and further post-processed using EnSight software by CEI, Apex, NC. "We used 3-D four-node tetrahedral flow-condition-based interpolation (FCBI) elements to discretize the outflow tract lumen." Dr. Rugonyi's team used the CFD model to quantify the temporal and spatial variation of blood flow velocities in the developing heart outflow tract and of wall shear stresses on the endocardium, which is the innermost tissue layer lining the heart walls known to be very sensitive to wall shear stress.
"Our results show that the biomechanical environment to which cells are subjected varies over the cardiac cycle and over spatial locations within the outflow tract. For example, myocardial wall stresses increased distally, while myocardium and endocardium circumferential strains decreased distally, and wall shear stresses were maximal on the surface of cardiac cushions." The bottom line, she said, is that the biomechanical environment sensed by cardiac cells ultimately determines the fate of the heart. When biomechanical stimuli are non-uniformly distributed through the developing structure, it gives rise to cellular responses that could cause abnormal development of the structures vital to normal heart function.
So how can doctors use these sophisticated models to prevent and correct these dangerous hemodynamic conditions?
"Some percentage of these heart defects could someday be corrected in utero if scientists could better understand the properties of normal blood flow in a developing embryo and create technologies to monitor those dynamics," says Dr. Kent Thornburg, Rugyoni's collaborator and director of translational research at the OHSU Cardiovascular Institute.
Interventions could take the form of drugs or surgery as the field of fetal diagnostics and therapy advances. Biomedical engineers believe that understanding how mechanical cues influence heart development and heart adaptation can tremendously improve surgery planning and outcomes. But at the very least, it would help parents and care providers make smart decisions about prenatal care, delivery, and ongoing treatment of a potentially fragile new baby.
Michael MacRae is an independent writer.