EAGER/Collaborative Research: Experimentally Validated Modeling of the Dynamics of Carbon Dioxide Removal from the Bloodstream via Peritoneal Perfluorocarbon Circulation

EAGER/合作研究：通过腹膜全氟化碳循环从血流中去除二氧化碳的动力学模型经过实验验证

• 批准号: 2031251
• 负责人: Hosam Fathy
• 金额: $ 15万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2031251&HistoricalAwards=false
• 关键词: EAGER; Collaborative; Research; Experimentally; Validated

This EArly-concept Grant for Exploratory Research (EAGER) project brings together a multidisciplinary team of control engineers, biomedical engineers, medical researchers, and clinicians to explore a novel pulmonary-independent method for supplementing gas exchange in an animal. Specifically, the research team will study whether the circulation of oxygenated perfluorocarbon (PFC) through the abdomen (the peritoneal cavity) of a large animal, can serve as a pathway for clearing carbon dioxide (CO2) from the animal’s bloodstream; and what are the governing dynamics of this CO2 clearing process. The peritoneal cavity essentially acts as a “third lung” in this scenario, providing critical life support for patients whose compromised lung function has exceeded the support achievable through mechanical ventilation. There is currently a critical need for this treatment, within the context of the COVID-19 pandemic, but this system also has potential to emerge as a standard modality in the critical care of hundreds of thousands of patients in pulmonary failure. Furthermore, the medical community will benefit from the deep fundamental understanding of the CO2 removal capabilities of peritoneal oxygenated PFC circulation, which will be an essential element in bringing this technology into future clinical trials.This project addresses the challenge of building an experimentally validated model of the dynamics of carbon dioxide transport from the bloodstream of a large animal into oxygenated perfluorocarbon perfused through the animal’s abdominal (peritoneal) cavity. Using the experimental data obtained as part of this project, the team will develop and parameterize a control-oriented, multi-compartment model of the transport dynamics governing CO2 removal. While previous experiments on peritoneal oxygenated PFC circulation have predominantly examined quasi-steady conditions, the research team will ensure the richness of its data by deliberately designing the underlying experiments to maximize the identifiability of the CO2 removal dynamics. The result will be a dataset better suited for the modeling and estimation of underlying system dynamics than the quasi-steady datasets. The system dynamics and control community will benefit from the opportunity to apply its scientific tools and methods to the dynamic modeling of a novel ventilation technology. Particularly important is the degree to which such modeling can help broaden the interdisciplinary impact of the dynamic systems and controls discipline to a new health-related application technology. Addressing this research challenge urgently, but rigorously, has the potential to provide critical assistance to the medical research community, particularly considering the COVID-19 crisis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个早期概念探索性研究资助（EAGER）项目汇集了一个由控制工程师、生物医学工程师、医学研究人员和战士组成的多学科团队，以探索一种新的独立于肺部的方法来补充动物的气体交换。将研究含氧全氟化碳（PFC）通过大型动物腹部（腹膜腔）的循环是否可以作为清除动物血液中二氧化碳（CO2）的途径以及什么；在这种情况下，腹膜腔基本上充当“第三肺”，为肺功能受损的患者提供关键的生命支持，其支持能力已超过机械通气所能实现的水平。在 COVID-19 大流行的背景下，该系统也有可能成为数十万肺衰竭患者重症监护的标准模式。此外，医学界也将从深度治疗中受益。对二氧化碳去除的基本了解腹膜含氧 PFC 循环的能力，这将是将这项技术引入未来临床试验的一个重要因素。该项目解决了建立一个经过实验验证的二氧化碳从大型动物血液输送到含氧全氟化碳动力学模型的挑战通过动物的腹腔（腹膜）进行灌注，该团队将利用作为该项目的一部分获得的实验数据，开发并参数化控制二氧化碳去除的传输动力学模型。关于腹膜含氧 PFC 循环的研究主要检查了准稳态条件，研究团队将通过仔细设计基础实验来确保数据的丰富性，以最大限度地提高 CO2 去除动态的可识别性，结果将是一个更适合建模的数据集。与准稳态数据集相比，系统动力学和控制界将受益于将其科学工具和方法应用于新型通风技术的动态建模的机会。可以帮助扩大动态系统和控制学科对新的健康相关应用技术的跨学科影响，紧急但严格地应对这一研究挑战，有可能为医学研究界提供重要帮助，特别是考虑到 COVID-19。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Experimental Parameterization of a Model of Hypoxia Dynamics in Yorkshire Swine

约克夏猪缺氧动力学模型的实验参数化

• DOI: 10.1016/j.ifacol.2022.11.272
• 发表时间: 2022-01
• 期刊: IFAC-PapersOnLine
• 作者: Wood, Sam;Commins, Annina;Doosthosseini, Mahsa;Naselsky, Warren;Culligan, Melissa;Aroom, Kevin;Aroom, Majid;Kadkhodaeielyaderani, Behzad;Moon, Yejin;Leibowitz, Joshua;et al
• 通讯作者: et al

Estimating the Impact of Peritoneal Perfluorocarbon Perfusion on Carbon Dioxide Transport Dynamics in a Laboratory Animal

评估腹膜全氟化碳灌注对实验动物二氧化碳传输动力学的影响

• DOI: 10.23919/acc53348.2022.9867437
• 发表时间: 2022-01
• 期刊: 2022 American Control Conference
• 作者: Doosthosseini, Mahsa;Moon, Yejin;Commins, Annina;Wood, Sam;Naselsky, Warren;Culligan, Melissa J.;Aroom, Kevin;Aroom, Majid;Shah, Akash;Bittle, Gregory J.;et al
• 通讯作者: et al

Monitoring, Control System Development, and Experimental Validation for a Novel Extrapulmonary Respiratory Support Setup

新型肺外呼吸支持装置的监测、控制系统开发和实验验证

• DOI: 10.1109/tmech.2022.3145832
• 发表时间: 2022-10
• 期刊: IEEE/ASME Transactions on Mechatronics
• 作者: Doosthosseini, Mahsa;Aroom, Kevin;Aroom, Majid;Culligan, Melissa;Naselsky, Warren;Thamire, Chandrasekhar;Haslach, Henry W.;Roller, Stephen;Hughen, James;Friedberg, Joseph;et al
• 通讯作者: et al

Modeling and Experimental Identification of Peritoneal Cavity Pressure Dynamics During Oxygenated Perfluorocarbon Perfusion

含氧全氟化碳灌注过程中腹膜腔压力动力学的建模和实验识别

• DOI: 10.23919/ecc55457.2022.9838204
• 发表时间: 2022-07
• 期刊: European Control Conference
• 作者: Zaleski, Nadia;Moon, Yejin;Doosthosseini, Mahsa;Hopkins, Grace;Aroom, Kevin;Aroom, Majid;Naselsky, Warren;Culligan, Melissa J.;Leibowitz, Joshua;Shah, Aakash;et al
• 通讯作者: et al