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

1151232 Frakes，David心血管流体动力学与许多重大疾病的发病、进展和治疗密切相关。心脏病和中风是两个例子，两者都是美国三大死亡原因之一。颅内动脉瘤（ICA）是大脑中血管膨胀的另一个例子。据估计，它们占世界的6%。仅在美国，每年就有大约20，000人死亡。预防和/或治疗心血管疾病（CVD）可能是极其困难的，因为它们的复杂的、多因素的病因学并且因为人体固有的限制。然而，如果医疗设备可以用来控制心血管流体动力学，则治疗问题变得更加容易处理。例如，在过去十年中，使用血管内器械治疗ICA（通过阻断血流）导致的死亡率比不使用器械的最佳治疗方案低50%。不幸的是，ICA的血管内治疗仍然高达50%的时间不成功。这种令人不安的程度的故障率在许多基于设备的CVD治疗中是一致的，这是当前基础知识和资源差距的直接结果，限制了流体动力学工程的能力。具体而言，流体动力学工程的最新技术缺乏生物医学流动的基本知识和医疗设备建模的资源。这些代价高昂的缺点阻碍了在改进的生物医学系统中实现最佳健康流动的治疗设计（例如，用装置处理的ICA）。该CAREER计划将开发新的和显着改进的方法，用于设计有效的基于设备的CVD治疗。成像驱动的工程工具，包括在体内和体外成像，物理和计算建模，流体动力学测量和模拟的协同组合将提供开发的方法学基础。具体而言，该计划将建立新的实验知识和计算设备模型的基础，以告知和执行可靠和现实的ICA模拟。所提出的研究有直接的潜力，从松散的，不确定的公约，充分知情的，最佳的工程ICA治疗。更广泛地说，该计划代表了一种新的研究范式的实例，其中多学科技术被重新用于解决由修改后的生物医学系统提出的未解决的流体动力学问题的新兴类别。该计划将在人类健康的背景下支持流体动力工程的长期发展，从而推动基础知识的进步，更有效的研究技术，增强的临床能力以及超越生物医学领域的跨领域影响。本职业生涯提案的具体计划目标（PO）是：1。构建ICA的物理模型用于流体动力学实验2.用医疗设备治疗物理模型并实验性地测量流体动力学3.开发用于流体动力学模拟的医疗器械的改进计算模型4。使用实验结果和改进的设备模型来通知和执行流体动力学模拟研究计划的智能优点是：1）包括流体动力学数据和治疗病例的ICA的前所未有的物理和计算库，2）用于在改进的生物医学系统中实验性地测量流体动力学的先进方法，3）用于在改进的生物医学系统中模拟流体动力学的新颖的医疗设备模型和方法，以及4）增强了对处理过的ICA的流体动力学结果的认识。研究计划的更广泛影响包括：1）以伊卡图书馆的形式加强研究和教育基础设施，2）广泛传播有价值的物理和计算模型以及新的流体动力学数据，3）在学术界和工业界新产生的伙伴关系，以及4）对社会的影响，包括降低医疗保健成本和提高人类生活质量和寿命。该职业计划的主要教育目标是增加对关键但高度不可用的工程技术的接触，并扩大对工程的参与。为了实现这些目标，由内而外的教育计划将通过基于多感官体验的创新课程和推动研究计划的核心技术（医学成像和快速原型）吸引广泛的学生群体（高中，本科和研究生）。通过关注这些技术及其在研究计划中的协同作用，教育计划直接将拟议的研究与教育相结合。该研究计划对西班牙裔和妇女特别重要，因为这些群体受到ICA的影响不成比例。这一重要性将被用来从科学和工程领域代表性不足的群体中招募参与者，参与研究和教育项目。这些计划将使当地和全球的多个群体（研究人员，患者，学生，代表性不足的群体）和机构（学术界，工业界，医疗保健，教育）受益。

1151232Frakes, DavidCardiovascular 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). Intracranial aneurysms (ICAs), which are ballooning blood vessels in the brain, are another example. They are present in an estimated 6% of the world?s population and account for approximately 20,000 deaths each year in the US alone. Preventing and/or treating 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 devices to treat ICAs (by occluding blood flow) has led to 50% fewer deaths over the last decade than the best option for treatment without the devices. Unfortunately, endovascular treatments for ICAs are still unsuccessful up to 50% of the time. Failure rates of this disturbing magnitude, which are consistent across many device-based CVD treatments, are a direct result of current gaps in fundamental knowledge and resources that limit the capabilities of fluid dynamic engineering. Specifically, the state-of-the-art in fluid dynamic engineering is lacking in fundamental knowledge of biomedical flows and in resources for medical device modeling. These costly shortcomings prohibit the design of treatments that achieve optimally healthy flows in modified biomedical systems (e.g. ICAs treated with devices). This CAREER program will develop novel and markedly improved methods for the design of effective device-based CVD treatments. Synergetic combinations of imaging-driven engineering tools including in vivo and in vitro imaging, physical and computational modeling, and fluid dynamic measurement and simulation will provide the methodological basis for development. Specifically, the program will build a foundation of new experimental knowledge and computational device models to inform and execute simulations of treated ICAs that are both dependable and realistic. The proposed research has direct potential to transform ICA treatment from loosely-founded, uncertain convention to well-informed, optimal engineering. More broadly, this program represents an instantiation of a novel research paradigm wherein multi-disciplinary techniques are repurposed to address the emergent class of unsolved fluid dynamic problems presented by modified biomedical systems. The program will underpin long-term advancement of fluid dynamic engineering in the context of human health, leading 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 ICAs for use in fluid dynamic experiments2. Treat physical models with medical devices and measure fluid dynamics experimentally3. Develop improved computational models of medical devices for use in fluid dynamic simulations4. Use experimental results and improved device models to inform and execute fluid dynamic simulationsIntellectual merits of the research program are: 1) an unprecedented physical and computational library of ICAs including fluid dynamic data and treated cases, 2) advanced methods for measuring fluid dynamics experimentally in modified biomedical systems, 3) novel medical device models and methods for simulating fluid dynamics in modified biomedical systems, and 4) enhanced knowledge of fluid dynamic outcomes in treated ICAs.Broader impacts of the research program include: 1) enhanced infrastructure for research and education in the form of an ICA library, 2) broad dissemination of valuable physical and computational models and novel fluid dynamic data, 3) newly generated partnerships in both academia and industry, and 4) impacts on society including reduced healthcare costs and improved quality and duration of human life. The primary educational goals of this CAREER program are to increase exposure to crucial but highly unavailable engineering technologies and to broaden participation in engineering. Toward those ends, the Inside Out education program will engage broad student populations (high school, undergraduate, and graduate) through innovative curricula based on multi-sensory experience and the core technologies that drive the research program (medical imaging and rapid prototyping). By focusing on those technologies and their synergy in the research program, the education program directly integrates the proposed research with education. The research program is particularly significant to Hispanics and women because those groups are disproportionately affected by ICAs. That significance will be leveraged to recruit participants from groups that are underrepresented in science and engineering to both the research and education programs. The programs will benefit multiple groups (researchers, patients, students, underrepresented groups) and institutions (academia, industry, healthcare, education) both locally and globally.