Optimization of Hyperpolarized Xenon-129 Diffusion MRI for COPD

COPD 超极化 Xenon-129 扩散 MRI 的优化

• 批准号: 8185375
• 负责人: Chengbo Wang
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8185375
• 关键词: Acinus organ component; Affect; Age; Alveolar; Alveolus; American; American Lung Association; Animals; Biological; Carbon Monoxide; Cause of Death; Chest; Chronic Obstructive Airway Disease; Clinical Management; Clinical Trials; Computer Simulation; Detection; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Distal; Elements; Evaluation; Foundations; Future; Gases; Goals; Gold; Helium; Histology; Human; Image; Imaging Techniques; Investigation; Lung; Lung diseases; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical Imaging; Methods; Modality; Modeling; Monitor; Noble Gases; Patients; Performance; Physiological; Price; Public Health; Pulmonary Emphysema; Pulmonary function tests; Quality of life; RF coil; Reporting; Research; Security; Smoker; Solubility; Staging; Techniques; Time; Translating; United States; Work; X-Ray Computed Tomography; Xenon; base; effective therapy; improved; lung imaging; magnetic field; meetings; mortality; research study; tool; trial comparing

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. PUBLIC HEALTH RELEVANCE: Despite the tremendous public-health burden of chronic obstructive pulmonary disease (COPD), which has doubled in mortality in the past 20 years to become the fourth leading cause of death in the United States and the sixth worldwide, there are few effective treatments and there remains much about the disease that is poorly understood including why only 15-25% of smokers develop clinically-apparent COPD. Hyperpolarized xenon- 129 diffusion MRI, an emerging lung-imaging technique, has potential to become a vital tool in COPD research and clinical management by accurately staging and monitoring the progression of COPD. The purpose of this study is to optimize hyperpolarized xenon-129 diffusion MRI for the detection and characterization of the lung structural changes in COPD, and perform a small proof-of-concept trial in patients with COPD comparing this optimized lung-imaging technique with currently-used methods to evaluated COPD including computed tomography, pulmonary-function tests and helium-3 diffusion MRI.

描述（由申请人提供：慢性阻塞性肺病（COPD）是第四大死因，影响超过1100万美国人。目前用于评估COPD的技术具有根本的局限性，因此迫切需要一种用于准确地分期和监测COPD进展的改进方法。基于超极化（HP）惰性气体的扩散MRI显示出无创评估COPD的巨大前景。然而，几乎所有的扩散MRI研究都是使用3 He进行的，由于最近需求的增加，现在医学成像的供应非常有限。由于最近的技术进步，129极化的增加现在使129成为HP气体MR成像的可行替代品。尽管如此，惠普129英寸的研究远远落后于惠普3 He。特别是，对于HP 3 He扩散MRI很好的采集参数不能直接转换用于129 Xe，因为与3 He相比，129 Xe的扩散率低得多，生物溶解度高。因此，在使用HP 129 MRI进行肺部疾病研究之前，需要优化和验证成像参数。本研究的目的是使用计算机模拟作为指导，优化HP 129 MRI弥散成像采集参数，以在两个时间尺度上评估COPD（短时间尺度：~ms;长时间尺度：~s），并进行一项小型概念验证试验，比较优化的HP 129 Ne扩散MRI与优化的HP 3 He扩散MRI，计算机断层扫描（CT）和肺功能检查（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模型（特定目标1）和用于长时间尺度扩散的人类腺泡多分支点模型（特定目标2）进行计算机模拟。对于特定目标1和2，将在10名健康受试者和10名COPD受试者中测量多个扩散时间的扩散值和单次屏气的B值。然后将具体目标1和2的实验结果与现实成像条件相结合，以预测两个时间尺度的最佳成像参数。最后，将使用优化的参数进行一项小型概念验证临床试验，以研究HP 129 MRI弥散MRI用于COPD的性能（特定目标3）。将在两个时间尺度上测量10例健康受试者和30例COPD受试者（10例处于黄金1期，10例处于黄金2期，10例处于黄金3-4期）的局部HP 129 Xe和3 He扩散。将得到的129 Xe扩散图与3 He扩散图和胸部CT图像配准，以评价通过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优化HP 129 MRI弥散成像参数，从而最好地检测和表征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 129弥散MRI作为COPD分期和监测进展的根本性改进方法的潜力。 公共卫生关系：尽管慢性阻塞性肺疾病（COPD）的巨大公共卫生负担，在过去的20年中死亡率翻了一番，成为美国第四大死亡原因和世界第六大死亡原因，但几乎没有有效的治疗方法，并且对该疾病的了解仍然很少，包括为什么只有15-25%的吸烟者发展为临床明显的COPD。超极化氙-129扩散MRI是一种新兴的肺部成像技术，通过准确分期和监测COPD的进展，有可能成为COPD研究和临床管理的重要工具。本研究的目的是优化超极化氙-129扩散MRI用于检测和表征COPD患者的肺结构变化，并在COPD患者中进行一项小型概念验证试验，将这种优化的肺成像技术与目前用于评估COPD的方法（包括计算机断层扫描、肺功能检查和氦-3扩散MRI）进行比较。