Novel Approaches for Hyperpolarized Xenon-129 Magnetic Resonance Imaging

超极化氙-129磁共振成像（MRI）提供了非侵入性和重复测量肺部显微解剖和与肺部疾病相关的功能区域变化的能力。氙-129核磁共振已被证明可用于早期发现和诊断慢性阻塞性肺病、哮喘和肺损伤，这些都是加拿大人的重大保健负担。此外，我们已经在啮齿类动物中证明，与肺内气相相比，利用溶解在肺组织和红细胞中的氙-129产生的不同信号的动力学，可以实现通气、交换和血流（即灌注）的独特功能测量。尽管这些非常令人兴奋的临床前结果，氙-129人类MRI仍然具有挑战性，主要是由于使用单次屏气进行3D成像的信号有限，特别是由于横向松弛，气道几何形状（例如，x射线）的影响而复杂的溶解相。分支)和气相和溶解相之间的交换。提出的研究目标是：(i)开发新的MRI硬件和软件，以提高氙-129图像采集的效率；（ii）开发计算模型，以描述在真实的肺部几何形状中松弛，扩散和交换对氙-129信号的影响；（iii）测量啮齿动物和人类肺部的相关氙-129生物标志物，包括：ADC，通气，灌注和气体交换。拟议的研究将在西部大学罗伯茨研究所的成像研究实验室进行。MRI软件和硬件将首先使用定制的低场动物成像系统进行测试，该系统是由NSERC先前的发现基金开发的，然后在临床MRI平台上转换为动物和人类协议（3t）。本提案中描述的新型超极化氙-129 MRI方法的发展将为培训、知识生成、基础和应用以及转化为医疗保健环境提供重要机会。

Hyperpolarized xenon-129 Magnetic Resonance Imaging (MRI) provides the ability to non-invasively and repeatedly measure regional changes in lung microanatomy and function associated with pulmonary diseases. Xenon-129 MRI has been shown to be useful for early detection and diagnosis of chronic obstructive pulmonary disease, asthma and lung injury, all representing a significant health-care burden to Canadians. Furthermore, we have shown in rodents that unique functional measures of ventilation, exchange and blood flow (i.e. perfusion) are possible using the dynamics of the different signals arising from xenon-129 dissolved in lung tissues and red blood cells compared to the gas phase within the lung. Despite these very exciting pre-clinical results, xenon-129 MRI in humans remains challenging, mainly due to the limited signal available for 3D imaging using a single breath-hold, especially for the dissolved phases which are complicated by the effects of transverse relaxation, airway geometry (eg. branching) and exchange between the gas and dissolved phases.The objectives of the proposed research are: (i) to develop novel MRI hardware and software to improve the efficiency of xenon-129 image acquisition, (ii) to develop computational models to describe the effects of relaxation, diffusion and exchange on the xenon-129 signal in realistic lung geometries and (iii) to measure relevant xenon-129 biomarkers in rodent and human lungs including: ADC, ventilation, perfusion and gas exchange. The proposed research will take place in the Imaging Research Laboratories of the Robarts Research Institute of Western University. MRI software and hardware will initially be tested using a custom-built, low-field, animal imaging system developed with previous NSERC Discovery funding and then be translated to animal and human protocols on a clinical MRI platform (3 T). Development of the novel hyperpolarized xenon-129 MRI methods described in this proposal will provide significant opportunities for training, knowledge generation, both basic and applied as well as translation to the healthcare setting.