Optimization of Hyperpolarized Xenon-129 Diffusion MRI for COPD

描述(申请人提供：慢性阻塞性肺病(COPD)是第四大致死原因，影响1100多万美国人。目前评估COPD的技术有根本的局限性，因此迫切需要一种改进的方法来准确地分期和监测COPD的进展。基于超极化(HP)稀有气体的扩散磁共振成像在非侵入性评估COPD方面显示出巨大的前景。然而，几乎所有的弥散磁共振研究都是使用3He进行的，由于最近需求的上升，现在医学成像的供应非常有限。由于最近的技术进步，129Xe的偏振增加，现在使129Xe成为HP气体磁共振成像的可行替代品。尽管如此，惠普129Xe的研究远远落后于惠普3He。特别是，用于HP 3He扩散磁共振成像的采集参数不能直接转换为用于129Xe，因为与3He相比，129Xe的扩散系数低得多，生物溶解度高得多。因此，在将HP 129Xe扩散磁共振用于肺部疾病的研究之前，需要对成像参数进行优化和验证。这项拟议工作的目的是利用计算机模拟作为优化HP 129Xe扩散磁共振成像采集参数的指南，以在两个时间尺度(短时间尺度：~ms；长时间尺度：~S)评估已被证明对HP 3He有用的COPD，并进行小型概念验证试验，比较优化的HP 129Xe扩散MRI与优化的HP 3He扩散MRI、计算机断层扫描(CT)和肺功能(PFT)。为了确定用于优化的适当参数空间，将基于用于短时间尺度扩散的肺泡-袖子模型(特定目标1)和基于用于长时间尺度扩散的人腺泡多分支点模型(特定目标2)进行计算机模拟。对于特定的目标1和2，随后将测量10名健康受试者和10名COPD受试者在多次扩散时的扩散值和单次屏气中的b值。然后，将特定目标1和2的实验结果与实际成像条件相结合，以预测两个时间尺度的最佳成像参数。最后，将进行一项小型概念验证临床试验，使用优化的参数来研究HP 129Xe扩散磁共振成像在COPD(特定目标3)中的性能。对10例健康人和30例COPD患者(其中10例为Gold 1期，10例为Gold 2期，10例为Gold 3-4期)在两个时间尺度上测量Hp~(129Xe)和~3He扩散。得到的129Xe扩散图将与3He扩散图和胸部CT图像配准，以评估MRI和CT检测到的COPD结构变化的一致性。该项目的成功完成将导致HP 129Xe扩散磁共振成像参数的优化，该成像参数将最好地检测和表征COPD患者的肺微结构变化。这将为未来的临床试验奠定基础，以评估HP 129Xe扩散磁共振成像作为COPD分期和监测进展的根本改进方法的潜力。

DESCRIPTION (provided by applicant: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and affects more than 11 million Americans. Current techniques for assessing COPD have fundamental limitations, and therefore an urgent need exists for an improved method for accurately staging and monitoring progression of COPD. Diffusion MRI based on hyperpolarized (HP) noble gases has shown great promise for non-invasively evaluating COPD. However, nearly all diffusion MRI research has been performed using 3He, which, due to recent escalation in demand, is now in very limited supply for medical imaging. Increases in 129Xe polarization from recent technical advances now make 129Xe a viable alternative for HP-gas MR imaging. Nonetheless, research with HP 129Xe lags significantly behind that for HP 3He. In particular, acquisition parameters that have served well for HP 3He diffusion MRI cannot be directly translated for use with 129Xe because of its much lower diffusivity and higher biological solubility compared to 3He. As a result, before HP 129Xe diffusion MRI can be used to investigate lung diseases, the imaging parameters need to be optimized and validated. The purpose of the proposed work is to use computer simulations as a guide for optimizing HP 129Xe diffusion MRI acquisition parameters for the evaluation of COPD at the two time scales (short-time scale: ~ms; long-time scale: ~s) that have proven useful with HP 3He, and to perform a small proof-of-concept trial comparing optimized HP 129Xe diffusion MRI with optimized HP 3He diffusion MRI, computed tomography (CT) and pulmonary function tests (PFTs). To determine appropriate parameter spaces for optimization, computer simulations will be performed based on the alveolar-sleeve model for short-time scale diffusion (Specific Aim 1) and on a multi-branch-point model of the human acini for long-time scale diffusion (Specific Aim 2). For both Specific Aims 1 and 2, diffusion values will then be measured at multiple diffusion times and b values in a single breath hold in 10 healthy subjects and 10 subjects with COPD. The experimental results of Specific Aims 1 and 2 will then be combined with realistic imaging conditions to predict optimum imaging parameters for both time scales. Finally, a small proof-of-concept clinical trial will be performed using the optimized parameters to investigate the performance of HP 129Xe diffusion MRI for COPD (Specific Aim 3). Regional HP 129Xe and 3He diffusion will be measured at both time scales in 10 healthy subjects and 30 subjects with COPD (10 at Gold Stage 1, 10 at Gold Stage 2, 10 at Gold Stage 3-4). The resulting 129Xe diffusion maps will be registered with 3He diffusion maps and chest CT images to permit evaluation of the concordance of the structural changes in COPD as detected by MRI and CT. Successful completion of this project will result in optimized imaging parameters for HP 129Xe diffusion MRI that will best detect and characterize lung microstructural changes in COPD. This will lay the foundation for future clinical trials to evaluate the potential of HP 129Xe diffusion MRI as a fundamentally improved approach for staging and monitoring progression of COPD.