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129 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（通气）的位置和发生气体交换的位置-肺泡和肺血管膜之间的界面以及毛细血管中红细胞的摄取（灌注）。这种新颖的非侵入性功能性MRI和光谱（MRS）方法是在近30年前基础研究物理发现的基础上开创的。我的研究项目集中于肺129 MRI和MRS采集和分析方法的发展，以详细、机械地理解：1）肺MRI通气及其与气道和实质结构的关系，2）肺气体交换和灌注及其与终末气道和心肺血管的结构和形态学的关系。我们最近发现了两个推动医学物理学研究的发现。首先，我们偶然检测到5倍超增强的129 MRI红细胞信号，这反映了一名无症状青少年先前无症状但严重的先天性心脏病（而不是先前模型中预测的肺动脉重塑或肺动脉高压）。第二，我们首次发现，在长期COVID但肺功能正常的人群中，129 MRI检测到肺气体交换和/或通气异常。这些MRI结果与劳力性呼吸困难和去饱和度高度相关，这巩固了肺气体交换和通气异常作为长期COVID中心的作用。这些意想不到的发现导致了目前对过时基础设施进行升级的提议，并使我们能够提出有关体内129 μ m MRI气体交换测量的生理意义的重要问题。简而言之，我们建议开发一个生物物理模型，以估计毛细血管体积，血流量，血细胞比容，粘度，血管体积，阻抗的基础上129纳米测量。虽然以前的模型忽略了心脏工作负荷对生理变异性的贡献，但我们将模拟不同的工作负荷条件。这项提出的假设驱动的研究和机制建模依赖于高通量129极化（硬件和软件）和一套心肺测试设备，该设备探测心脏和肺部对运动输出的影响。为了升级生命终结设备，我们要求为工具提供资金，这些工具将加速我们的研究，以实现我们解释和验证肺部细微异常的目标，这些异常表现为呼吸困难和运动限制。 有了这些建议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。所要求的基础设施将在我的实验室，目前包括两名研究员，六名博士生，一个硕士和荣誉论文的学生，三个本科生和两名工作人员的研究人员连续的日常运作。