Cardiovascular engineering research involves the application of engineering principles and technologies in the conduct of basic cardiovascular research and in the pursuit of new methodologies and devices for the diagnosis, prevention, treatment, and remediation of cardiovascular problems. Cardiovascular research at OHSU is done both within the Department of Biomedical Engineering (BME) and in other OHSU units. This research is an integral part of the many strong basic and clinical cardiovascular programs within the university. Graduate students in BME with an interest in cardiovascular engineering do research in the laboratories of advisors both within BME and in other departments and institutes.
Understanding the mechanisms leading to thrombosis and to develop more effective new drug therapies
In particular, we are interested in understanding the interplay between the extracellular matrix, cell biology, and fluid mechanics in the cardiovascular system. The research into the balance between hydrodynamic shear forces and chemical adhesive interactions has great relevance to underlying processes of cancer, cardiovascular disease, and inflammation.
We investigate key hemostatic mechanisms, blood component interactions with natural and synthetic surfaces and the effects of blood-flow phenomena. For example, we are studying the role of contact activation in acute intraluminal thrombus propagation using ex vivo and animal disease models. If the functionality of the contact system enzyme complex is relevant to the pathogenesis of thrombosis but has limited role in hemostasis, a contact system inhibitor could become a safe antithrombotic agent. We also study the potential role of protein C in hemostasis. We are characterizing the effects of endogenous protein C activation on acute arterial thrombogenesis and hemostasis using rationally engineered recombinant enzymes. A pharmacologically viable protein C activator could help utilize the body's own antithrombotic and anti-inflammatory system similar to the way streptokinase and tPA became useful fibrinolysis activators. Moreover, we aim to identify thrombogenic and inflammatory triggers, including those that are associated with metastatic cancer, infections, and injuries, so that we can identify novel molecular targets for therapeutic interventions.
Understanding the origins of congenital heart disease, particularly related to hemodynamic forces
Cardiac growth and 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 U.S. and is the leading non-infectious cause of death among infants. The Rugonyi Lab is 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 embryonic 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. To this end, we alter blood flow conditions during early embryonic cardiac development. We use chicken embryos because they are easy to access and manipulate, while genetic processes are highly conserved among vertebrate species. We use state-of-the-art imaging techniques to visualize the response of tissues to altered blood flow conditions.
Our experiments are complemented by computational investigations of blood flow and wall stresses in the developing heart, both under normal and abnormal hemodynamic conditions. The combination of both experimental and computational approaches enables us to shed more light towards understanding development of the heart and CHD.
We have obtained valuable data on blood flow velocities, pressures and histological composition of the developing heart. Together, our data suggests that blood flow is a strong determinant of cardiac tissue growth and remodeling.
Understanding hemodynamics in vascular cell functions in disease and designing new devices to treat cardiovascular disease
Research in vascular biology and vascular tissue engineering is represented by a multidisciplinary group of materials scientists, biomedical and tissue engineers, chemists, physiologists, dentists, and physicians. Faculty projects include the following research: vascular stents and grafts, non-invasive and non-destructive evaluation of engineered tissues, natural, protein-based biomaterials, the role of cytoskeletal structures on vascular cell functions, and tissue engineered vascular construct.
To understand the mechanisms of vascular healing responses, we utilize in vitro cell culture systems and animal models to identify key hemostatic mechanisms, blood component interactions with natural and synthetic surfaces, and the effects of blood-flow on vascular cell functions. The relationships between strains, extracellular matrix scaffolds, and vascular cell functions are a focus of our research. In understanding of the effects of biomechanics on vascular cell function, we will improve cell engraftment and retention on vascular grafts. Our ultimate goal is to develop more effective anti-thrombotic and anti-arteriosclerotic therapies, and to improve the performance of prosthetic cardiovascular devices.
Finding relationships between shape and function of biological systems
The goal of the Biological Shape Spaces project is to enable scientists to efficiently find relationships between the shape and function of biological systems, and to better understand how alterations in shape can alter function and vice-versa (see http://bioshapes.org).
For biological systems, shape (i.e., the morphology of an organ or organism) is frequently retrieved in the form of images, which then need to be processed and interpreted. Advances in imaging technologies are allowing an ever-increasing amount of image information with increasing resolution. Despite these advances, the analysis of images in Medicine and Biology remains largely manual, and thus time consuming and subject to operator interpretation. Quantitative, functional interpretation of shape variations remains a fundamental challenge. Computational algorithms to analyze images and shape, while available, are often ad hoc, not easily generalizable and thus usually difficult to optimize for specific applications, and frequently out of the reach of non-experts.
Advances in high-throughput imaging have led to the rapid accumulation of shape information, but the tools to analyze these data have not kept pace. The lack of a coherent framework for quantifying and analyzing biological shape has prevented the objective testing of many hypotheses that rely on morphological data. Our inability to systematically link shape to genetics, development, function, environment, and evolution has frustrated advances in biological research across multiple spatial and temporal scales, from understanding how environmental influences alter developmental morphology to interpreting adaptive responses and radiations in the paleontological record.
To breach this important gap, investigators from eight institutions, including OHSU, are collaborating in a project funded by NSF to develop the next-generation computational tools that will allow biologists and physicians to analyze and retrieve shape information automatically, and enable discovering of relationships between shape and function. The goal is to not only develop better tools for mathematically describing shape, but also methods for extracting biologically meaningful information on morphological variation. The group consists of experts in biology, engineering, computer science and mathematics determined to develop and bring tools to the scientific community that will enable optimal and fast analysis of shape and large imaging files. The collaborating PIs in this project are: Dr. Washington Mio (lead PI) from Florida State University; Dr. Surangi Punyasena, from University of Illinois at Urbana-Champaign; Dr. Ge Yang, from Carnegie Mellon University; Dr. Rolf Mueller, from Virginia Tech; Dr. Cindy Grimm, from Oregon State University; Dr. Charless Fowlkes, from University of California at Irvine; and Dr. Sandra Rugonyi, from the OHSU Department of Biomedical Engineering.
The collaborative project was launched in November 2010, with the First Workshop on Quantification of Biological Shape, organized by Dr. Rugonyi, and hosted at OHSU. The group has developed a website (see bioshapes.org) that will facilitate search and retrieval of images and image shape data, as well as sharing developed computational tools to find meaningful relationships between biological shape and function.