Hyperpolarized 129Xe MRI: Development of hardware, software and its PET-based validation.

无创体内超极化吸入的129Xe磁共振成像被证明是有用的，用于显示通风的肺区，获得有关肺泡大小的区域信息，观察在肺组织中溶解的氙气与红细胞之间的类氧交换，以及脑供血在氙气频率上的成像。然而，即使在发展了20年的超极化129Xe磁共振成像之后，这种成像方式特有的基本限制仍然无法解决。这种限制的一个很好的例子是129Xe图像的低信噪比，这阻碍了许多对SNR高度敏感的新型采集方案的发展，例如各向同性体素静态通风成像、加速多b值扩散加权MRI、加速同时采集肺组织和血液中的129Xe气体和129Xe、129Xe脑灌注成像和129Xe生物传感器成像。造成129Xe图像信噪比低的主要原因有三个：目前存在的图像采集方法效率低下，这是由于图像采集时间有限，结合非优化的图像重建算法；MRI发射/接收线圈的低灵敏度；以及129Xe超极化水平低，结合小批量生产。通过利用核磁共振基本原理，拟议的研究计划将解决数十年来悬而未决的129Xe核磁共振问题。这在加拿大是独一无二的，充分反映了我在129Xe磁共振领域的进步。我在过去20年中积累的在开发收购方法方面的丰富专业知识，以及我在制造先进硬件方面的经验，将使我的研究团队能够克服该领域目前的技术挑战。这项研究计划是开发、测试和验证新的129Xe磁共振成像方法并将其与黄金标准灌注成像模式(PET)进行比较的极佳平台。我的研究小组在2019年的一次实验中证明了这种测量的可行性。该项目的成功将向129Xe研究人员(加拿大6个站点和许多国外站点)、业界(MRI硬件制造商)和临床医生展示129Xe MRI成像的有用性。为什么这一点现在比以往任何时候都更重要？129Xe肺部核磁共振极其强大，是唯一用于肺结构和功能测量的无辐射成像工具，由于新冠肺炎对肺的损害，出现了对它的迫切需求，现在和未来都需要加紧研究和开发。拟议的计划将为准确的肺损伤评估、治疗指导和治疗结果评估提供新的工具。此外，该研究计划还为HQP提供了医学成像、MRI脉冲序列开发和硬件工程、深度学习、量子和热力学建模等领域的培训。

Non-invasive in-vivo inhaled hyperpolarized 129Xe MRI was proven to be useful for visualizing of the ventilated lung regions, obtaining regional information about the lung alveolar sizes, observing the oxygen-like exchange between a xenon "dissolved" in the lung tissue and red blood cells and also imaging of the brain blood supply on the xenon frequency. However, even after 20 years of developing hyperpolarized 129Xe MRI, the fundamental limitations specific to this imaging modality remain unresolvable. A good example of such limitation is the low signal-to-noise ratio (SNR) of 129Xe images, which impedes the development of many novel acquisition schemes that are highly sensitive to the SNR, such as isotropic voxel static ventilation imaging, accelerated multiple b-value diffusion-weighting MRI, accelerated simultaneous collection of 129Xe gas and 129Xe within lung tissue and blood, 129Xe brain perfusion imaging, and 129Xe biosensor imaging. There are three main reasons for low SNR of 129Xe images: the inefficient image acquisition methods that currently exist, due to the limited image acquisition time combined with non-optimal image reconstruction algorithms; low-sensitivity of the MRI transmit/receive coils; and the low level of 129Xe hyperpolarization in combination with the small volume production. By utilizing fundamental MRI principles, the proposed research program will solve decades of unresolved 129Xe MRI problems. This is unique for Canada and fully reflects my progress in the 129Xe MRI field. My extensive expertise, built over the last two decades, in developing acquisition methods along with my experience in building advanced hardware will allow my research team to overcome the current technological challenges in the field. This research plan is an excellent platform to develop, test and validate novel 129Xe MRI imaging methods and compare them to the gold standard perfusion imaging modality (PET). The feasibility of such measurements has been demonstrated by my research group in a single experiment in 2019. The success of this program will demonstrate the usefulness of lung and brain 129Xe MRI imaging to 129Xe researchers (6 sites in Canada and many abroad), industry (MRI hardware makers) and clinicians. Why does this matter now, more than ever? 129Xe lung MRI is extremely powerful and it is the only radiation free imaging tool for lung structure & function measurements, whose urgent need has emerged because of the damage Covid-19 does to the lung, requiring intensive research and development now and in the future. The proposed program will provide new tools for accurate lung damage assessment, therapy guidance, and treatment outcome evaluation. Furthermore, this research plan provides training for HQP in the fields of medical imaging, MRI pulse sequence development and hardware engineering, Deep Learning, quantum and thermodynamic modelling.