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高分辨率、三维无创活体肺部测量的获得，而这是到目前为止还不可能实现的。 我们目前对肺组织结构和形态的了解源于对切除组织的体视学研究，通常来自身体或移植患者的移植肺。这种测量通常集中在患病的肺上，可能会有偏差，因为用于生成这些样本的方法不同。另一种方法涉及体外组织样本的微型CT，这提供了三维采样的优势。不幸的是，切除样本的组织学和显微CT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的样本，这是高度侵入性的，具有一定的风险。另一种方法是将肺组件建模为区域统一的呼吸道(电阻)和空隙(电容)系统。这种肺微机械模型主要是通过测量口腔压力和流量，或使用在切除的肺的气管末端植入逆行导管来获得的。尽管这些方法很重要，而且有大量的工作为它们提供了坚实的基础，但还不可能纳入区域肺功能信息来审问这些模型或帮助它们的发展。这是一个关键的限制，因为众所周知，肺实际上是一个地区性异质器官。 因此，几十年来，对肺局部形态信息的需求一直没有得到满足，这些信息来自与生理相关的活体测量，用于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来的问题，我们建议开发新的方法来生成并将在体肺成像测量的气道和空隙结构纳入现有的肺生长、发育和微观力学模型，并开发新的模型并使用区域成像信息进行测试。 因此，在这项提议中，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的模型。在5年的时间里，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)推导不同肺状态和条件下的肺泡和气道尺寸；4)将区域成像测量纳入计算模型并进行验证。这项研究提供了一种方法来测试和验证成像测量，以生成新的肺部微机械模型，并为学术界和私营部门在医学成像、MR脉冲序列开发、肺组织生成、分子建模和计算机科学方面的高素质人员提供了一种方法。

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.