129Xe MRI radiofrequency coil for in vivo measurements of airways and alveoli to generate novel lung biomechanical models

我们目前对肺的微观结构和生物力学的理解主要来自于对尸体或离体肺的切除组织的体视学和显微CT研究。然而，组织学和显微CT都不能用于正常肺生理学的大规模研究，因为它们依赖于高度侵入性的切除样本，并具有一定的风险。计算机模拟数学肺模型也被构建为具有气道（电阻器）和肺泡（电容器）的系统，其使用在口部处进行的压力和流量测量或在气管处植入的导管。这些全局肺测量忽略了最近的工作，这些工作表明正常健康的肺是区域异质性的，并且这种异质性在肺部疾病中增强。换句话说，存在必须考虑的非随机差异和异常。不幸的是，缺乏区域肺结构和功能信息，使得难以将区域依赖性纳入肺微力学模型，并且使得无法验证它们。 为了直接解决这个几十年的问题，Parraga博士的实验室和她的合作者正在开发新的方法，将体内肺成像测量纳入现有的肺微力学模型，开发新的微力学模型，并对其进行测试和验证。为了实现这一重要目标，我们需要一个国家的最先进的射频（RF）MRI线圈的高空间分辨率129毫米吸入气体通气和扩散加权测量。这一急需的基础设施将推动新型肺部成像生物标志物的开发和验证，该团队将使用这些生物标志物来生成肺部发育和生物力学模型。每天使用类似的（现在灾难性地失败了）射频线圈已经在我们的本地和跨国研究计划中发挥了关键作用。新的射频线圈一旦投入使用，将加速：1）使用新型脉冲序列提高肺部MRI的空间和时间分辨率，2）在不同肺部状态和条件下采集肺泡和气道尺寸，以及3）将区域成像测量纳入计算模型并进行验证。由于我们合作研究的高通量性质，需要定制设计的多通道129 μ m MRI线圈。相反，缺乏这样的设备将大大损害我们的创新基础研究，旨在产生新的肺微机械模型的正常和再生的肺组织在体内。此外，这一基础设施将加速为学术界和私营部门培训医学成像、磁共振物理学、肺组织再生、分子建模和计算机科学方面的高素质人才，包括西方大学、麦克马斯特大学和达尔豪西大学的研究生和博士后研究员。

Our current understanding of lung microstructure and biomechanics derives mainly from stereological and micro-CT investigations of excised tissue from cadavers or explanted lungs. However, neither histology, nor micro-CT may be considered for large-scale studies of normal lung physiology because they rely on excised samples which is highly invasive and carries some risk. In silico mathematical lung models have also been constructed as a system with airways (resistors) and alveoli (capacitors) using pressure and flow measurements made at the mouth or catheters implanted at the trachea. These global lung measurements ignore very recent work that showed that the normal healthy lung is regionally heterogenous and this heterogeneity is enhanced in lung disease. In other words, there are non-stochastic differences and abnormalities that must be considered. Unfortunately, a lack of regional lung structural and functional information has made it difficult to incorporate regional dependencies into lung micromechanical models, and made it impossible to validate them. To directly address this decades-old problem, Dr Parraga’s lab and her collaborators are developing new ways to incorporate in vivo lung imaging measurements into existing models of lung micromechanics, to develop new micromechanical models and to test and validate them. To accomplish this important goal, we require a state-of-the art radiofrequency (RF) MRI coil for high spatial resolution 129Xe inhaled-gas ventilation and diffusion-weighted measurements. This critically-needed infrastructure will drive the development and validation of novel lung imaging biomarkers the team will use to generate models of lung development and biomechanics. Daily access to a similar (and now catastrophically failed) radiofrequency coil has already played a critical role in our local and transnational research program. The new radiofrequency coil, once commissioned, will accelerate: 1) improved spatial and temporal resolution of pulmonary MRI using novel pulse sequences, 2) the acquisition of alveolar and airway dimensions in different lung states and conditions, and, 3) the incorporation and validation of regional imaging measurements into computational models. Due to the high throughput nature of our collaborative research, a custom-designed multichannel 129Xe MRI coil is required. Conversely, the lack of such equipment would significantly compromise our innovative basic research that aims to generate novel lung micromechanical models of normal and regenerated lung tissue in vivo. Moreover, this infrastructure will accelerate the training of highly qualified personnel for academia and the private sector in medical imaging, MR physics, lung tissue regeneration, molecular modelling and computer science including graduate students and postdoctoral fellows at Western, McMaster and Dalhousie Universities.