CAREER: Imaging-Driven Fluid Dynamic Engineering of Modified Biomedical Systems

Cardiovascular fluid dynamics are deeply involved in the onset, progression, and treatment of many major diseases. Heart disease and stroke are two examples, both of which are among the three leading causes of death in the United States (US). Cerebral aneurysms are another example. They are present in an estimated 2% of the worlds population and account for approximately 20,000 deaths each year in the US alone. Treating and/or preventing cardiovascular diseases (CVDs) can be extremely difficult because of their complex, multifactorial etiologies and because of constraints inherent to the human body. However, the treatment problem becomes more tractable if medical devices can be used to control cardiovascular fluid dynamics. For example, the use of endovascular coils to treat cerebral aneurysms (by occluding blood flow) has led to 50% fewer deaths over the last decade than the best treatment alternative. Unfortunately, endovascular coiling is still unsuccessful up to 50% of the time, which is consistent with the failure rates of many other device-based treatments for CVDs. These disturbing failure rates are manifestations of a fundamental gap in knowledge and capabilities that impedes the effective use of medical devices to control cardiovascular fluid dynamics. The research proposed in this CAREER program is designed to fill that gap, and more specifically to enable the engineering of markedly improved treatments for CVDs. One primary reason that current device-based treatments are not more successful is that the cardiovascular system becomes far more difficult to model when it is modified with devices. The result is that treatment outcomes can not be planned well because flow in the modified cardiovascular system can not be modeled well. The same is true for other essential systems in the human body, the digestive and lymphatic systems for example. Accordingly, the engineering of fluid dynamics in modified biomedical systems represents both a formidable and critically important challenge. The proposed program will address that challenge by building a foundation of new knowledge and uniquely effective methods to underpin long-term advancement of fluid dynamic engineering in the context of human health. The program will couple complementary imaging-driven tools ( in vivo and in vitro imaging, physical and computational modeling, and fluid dynamic measurement and simulation) and apply them to investigate, understand, and control fluid dynamics in a challenging class of modified biomedical systems: treated cerebral aneurysms. This framework represents a novel fluid dynamic engineering paradigm wherein powerful engineering tools are purposed in a new way to address an emergent set of unsolved problems. The proposed approach has direct potential to transform the treatment of cerebral aneurysms from loosely founded, uncertain convention to well informed, optimal engineering. More broadly, the program will lead to advances in fundamental knowledge, more effective research techniques, enhanced clinical capabilities, and cross-cutting impacts that transcend the biomedical field. The specific program objectives (POs) of this CAREER proposal are: 1. Construct physical models of cerebral aneurysms for use in fluid dynamic experiments 2. Treat physical models with medical devices and measure fluid dynamics experimentally 3. Develop improved computational models of medical devices for use in fluid dynamic simulations 4. Use experimental results and improved device models to inform and execute fluid dynamic simulations