Inhaled gas and Ultra-short/zero-echo time MRI of pulmonary airways and airspaces for modelling the morphometry and biomechanical properties of pulmonary parenchyma and airways

使用常规和吸入气体磁共振成像（MRI）的肺部成像的最新进展加速了迄今为止从未可能的高分辨率、三维非侵入性体内肺部测量的获取。 我们目前对肺组织结构和形态的理解来自于对切除组织的体视学研究，通常来自于尸体或接受移植的患者的切除肺。 这种测量通常集中在患病的肺上，并且由于用于生成这些样本的方法而可能有偏差。 另一种方法涉及离体组织样品的微CT，这提供了三维采样的优点。 不幸的是，无论是组织学，还是显微CT的切除样本都不能用于正常生理和发育中的肺的大型研究，因为它们依赖于切除样本，这是高度侵入性的，并带有一定的风险。 另一种方法是将肺组件建模为气道（电阻器）和气隙（电容器）的区域均匀系统。 这种肺微机械模型主要是通过在口部测量压力和流量，或通过在离体肺的气管末端植入逆行导管而得到的。 尽管这些方法的重要性和提供其坚实基础的大量工作，但还不可能将区域功能性肺信息纳入这些模型或协助其开发。这是一个关键的限制，因为众所周知，肺实际上是一个区域异质性器官。 因此，几十年来，对于从生理相关的体内测量导出的肺区域形态信息存在显著未满足的需求，以包含在肺微观力学的数学模型中。 为了直接解决这个几十年的老问题，我们建议开发新的方法来生成和纳入现有的模型肺生长，发育和微观力学的气道和空域结构的体内肺成像测量，并开发新的模型和测试这些使用区域成像信息。 因此，在本提案中，我们将开发新的方法来使用肺成像测量来生成肺发育和生物力学模型。 五年后，我们将：1）使用新的脉冲序列提高肺部MRI的空间和时间分辨率，2）导出不同肺部状态和状况下的肺泡和3）气道尺寸，以及4）将区域成像测量结合并验证到计算模型中。这项研究提供了一种方法来测试和验证成像测量的新的肺的微机械模型的生成和高素质的人员为学术界和私营部门在医学成像，磁共振脉冲序列开发，肺组织生成，分子建模和计算机科学。

Recent advances in lung imaging using conventional and inhaled gas magnetic resonance imaging (MRI) have accelerated the acquisition of high-resolution, three-dimensional non-invasive in vivo lung measurements that until now have never been possible. Our current understanding of lung tissue architecture and morphology derive from stereiological investigations of excised tissue, typically from cadavers or explanted lungs from patients undergoing transplant. Such measurements are typically focused on diseased lung and may be biased because of the methods used to generate these samples. Another approach involves micro-CT of ex vivo tissue samples and this provides the advantage of 3-dimensional sampling. Unfortunately, neither histology, nor micro-CT of excised samples can be used for large studies of normal physiology and the developing lung because they rely on the excised samples which is highly invasive and carries some risk. Another approach is to model the lung components as a regionally uniform system of airways (resistors) and airspaces (capacitors). Such lung micromechanical models have been derived mainly using pressure and flow measurements at the mouth or using retrograde catheters implanted at the end of the trachea of excised lungs. Despite the importance of these approaches and the huge body of work that provide their strong foundation, it has not been possible to incorporate regional functional lung information to interrogate these models or to assist in their development. This is a critical limitation because it is well understood that the lung is in fact, a regionally heterogeneous organ. Therefore there has been, for decades, a significant unmet need for lung regional morphological information derived from physiologically-relevant in vivo measurements for inclusion in mathematical models of lung micromechanics. To directly address this decades-old problem, we propose to develop new ways to generate and incorporate in vivo lung imaging measurements of airway and airspace structure into existing models of lung growth, development and micromechanics and to develop new models and test these using regional imaging information. Therefore, in this proposal we will develop new ways to use lung imaging measurements to generate models of lung development and biomechanics. Over 5 years, we will: 1) improve spatial and temporal resolution of pulmonary MRI using novel pulse sequences, 2) derive alveolar and 3) airway dimensions in different lung states and conditions, and, 4) incorporate and validate regional imaging measurements into computational models. This research provides a way to test and validate imaging measurements for the generation of novel micromechanical models of the lung and highly qualified personnel for academia and the private sector in medical imaging, MR pulse sequence development, lung tissue generation, molecular modelling and computer science.