Novel, Non-invasive Multi-spectral, Multi-compartment 129Xe MR Gas-exchange Measurements: MUCXE

新型、非侵入性多光谱、多室 129Xe MR 气体交换测量：MUCXE

• 批准号: RTI-2023-00087
• 负责人: Parraga, Grace
• 金额: $ 10.93万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760733
• 关键词: Novel; Non; invasive; Multi; spectral

Hyperpolarized 129Xe MRI provides a way to simultaneously and rapidly quantify the function of the lung including where inhaled gas travels through the airways (ventilation) AND where gas-exchange occurs - the interface between the alveolar and pulmonary vascular membranes and uptake into red blood cells (perfusion) in the capillaries. This novel, non-invasive functional MRI and spectroscopy (MRS) method was pioneered on the basis of a basic research physics discovery nearly 30 years ago. My research program focuses on the development of pulmonary 129Xe MRI and MRS acquisition and analysis methods towards a detailed, mechanistic understanding of: 1) pulmonary MRI ventilation and its relationship with airway and parenchyma structure, and, 2) pulmonary gas-exchange and perfusion and their relationship with the structure and morphometry of the terminal airways and cardio-pulmonary vasculature. We recently discovered two findings that are driving this medical physics research. First, we serendipitously detected 5-fold super-enhanced 129Xe MRI red blood cell signal, which reflected previously silent but serious congenital heart disease in an asymptomatic teenager (and not pulmonary artery remodelling or pulmonary hypertension predicted in previous models). Second, we showed for the first time that in people with long-haul COVID but normal pulmonary function, 129Xe MRI detected pulmonary gas-exchange and/or ventilation abnormalities. These MRI findings were highly correlated with exertional dyspnea and desaturation which has cemented the role of pulmonary gas-exchange and ventilation abnormalities as central to long-haul COVID. These unexpected findings led to the current proposal to upgrade obsolete infrastructure and would allow us to ask important questions about the physiologic meaning of invivo 129Xe MRI gas-exchange measurements. Briefly, we propose to develop a biophysical model to estimate capillary volume, blood flow, hematocrit, viscosity, vessel volume, impedance based on 129Xe measurements. Whilst previous models have ignored cardiac workload contributions to physiologic variability, we will model diverse workload conditions. This proposed hypothesis-driven research and mechanistic modelling is dependent on high throughput 129Xe polarization (hardware and software) and a suite of cardiopulmonary testing equipment which probes cardiac and pulmonary influences on exercise output. To upgrade end-of-life equipment, we request funding for tools that will accelerate our research towards our goal of explaining and validating subtle abnormalities in the lung that manifest as dyspnea and exercise limitation. With these proposed research tools and my lab's physics R&D expertise, the accomplishment of this goal is possible. The requested infrastructure will be in continuous daily operation in my lab which currently consists of two fellows, six PhD students, a single MSc and honours thesis student, three undergrads and two staff researchers.

超极化的129XE MRI提供了一种同时，快速量化肺功能的方法，包括吸入气体通过气道（通风）以及发生气体交换的位置 - 肺泡和肺血管膜和吸收红细胞的界面（毛细血管中的灌注）。这种新型的非侵入性功能MRI和光谱法（MRS）方法是根据大约30年前的基础研究物理学发现开创的。我的研究计划的重点是开发肺部129XE MRI和MRS的获取和分析方法，以详细的机械理解：1）肺MRI通气及其与气道和实质结构的关系，以及2）肺气 - exexchange and Infusion and Infusion and Infusion and Infusion and Infusion and Infusion and Infusion和它们与末端气道和心肺脉管系统的结构和形态测定法的关系。我们最近发现了两个正在推动这项医学物理研究的发现。首先，我们偶尔检测到5倍超增强的129 XE MRI红细胞信号，这反映了以前无症状的少年（而不是先前模型中预测的肺动脉重塑或肺动脉重塑或肺动脉高压），反映了先前的先天性心脏病）。其次，我们首次表明，在具有长途共同但正常肺功能的患者中，检测到129xE MRI检测到肺气体交换和/或通风异常。这些MRI发现与劳累呼吸困难和去饱和度高度相关，这巩固了肺气交换和通风异常的作用，而异常是长途库维德的中心。这些意外的发现导致了当前升级过时基础架构的建议，并使我们能够询问有关Invivo 129XE MRI MRI MRI GAS交换测量的重要问题。简而言之，我们建议开发一种生物物理模型，以估计毛细血管体积，血流，血细胞比容，粘度，容器体积，基于129 xe测量的阻抗。尽管以前的模型忽略了对生理变异性的心脏工作量贡献，但我们将建模各种工作量条件。这项提出的假设驱动的研究和机械建模取决于高吞吐量129XE极化（硬件和软件）以及一套心肺测试设备，该设备探测心脏和肺部对运动输出的影响。为了升级寿险设备，我们要求为工具提供资金，以加速我们的研究，以解释和验证肺部细微的异常情况，这些异常表现为呼吸困难和运动限制。 借助这些提出的研究工具和我的实验室的物理研发专业知识，这一目标的实现是可能的。要求的基础设施将在我的实验室中进行连续的日常运作，该实验室目前由两个研究员，六个博士学位学生，一名MSC和荣誉论文学生，三名本科生和两名员工研究人员组成。