Hyperpolarized xenon MRI of oxygen in human lungs

人肺中氧气的超极化氙 MRI

• 批准号: 7405591
• 负责人: Iulian Constantin Ruset
• 金额: $ 9.94万
• 依托单位: XEMED, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7405591
• 关键词: Academia; Address; Affect; Alveolar; American; Animals; Back; Biomedical Engineering; Blood Circulation; Businesses; Calibration; Cause of Death; Chronic; Chronic Obstructive Airway Disease; Classification; Clinical; Clinics and Hospitals; Collaborations; Data; Data Analyses; Dependence; Detection; Development; Diagnostic; Diffusion; Discrimination; Disease; Disease Management; Early Diagnosis; Equipment and Supplies; Functional Magnetic Resonance Imaging; Funding; Gases; Goals; Health; Helium; Heterogeneity; Hospitals; Human; Human Resources; Image; Imaging Phantoms; Intervention; Invasive; Lung; Lung diseases; MRI Scans; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Metric; Modality; Monitor; New Hampshire; Numbers; Organ; Oxygen; Partial Pressure; Pathology; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Phenotype; Physicians; Physiologic pulse; Physiological; Physiology; Procedures; Property; Protocols documentation; Protons; Publishing; Pulse taking; Radiation; Rate; Recruitment Activity; Research; Research Methodology; Resolution; Respiratory physiology; Science; Signal Transduction; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Techniques; Technology; Technology Transfer; Testing; Three-Dimensional Imaging; Time; Uncertainty; United States Food and Drug Administration; Universities; Urination; Variant; Woman; Work; Xenon; base; commercialization; comparative; cost; experience; human subject; improved; innovation; instrumentation; lung imaging; novel; programs; regional difference; response; uptake

DESCRIPTION (provided by applicant): While Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the US and affects 30 million Americans, high-resolution non-invasive image-based assessment of lung health is lagging behind imaging of the other vital organs. The availability of a low-cost, highly quantitative modality for 3-D imaging of lung function would improve early diagnosis and discrimination of diseases, accelerate testing of therapies by pharmaceutical companies, and ultimately assist in more personalized disease management and intervention in clinics and hospitals. Hyperpolarized gases can address this need. 3He has enjoyed the most widespread study largely due to the availability of mature polarization technologies. Recently high polarization of 129Xe in liter quantities has become available due to innovations by the UNH group, allowing the potential scientific advantages of hyperpolarized 129Xe imaging to be investigated. Depolarization of hyperpolarized atoms, both 3He and 129Xe, in lungs is dominated by the presence of paramagnetic oxygen gas molecules. T1 decay constant protocols using hyperpolarized 3He have mapped local oxygen partial pressures and furthermore show sensitivity to oxygen uptake by the bloodstream within a breath hold. Hyperpolarized 129Xe has the same sensitivity to oxygen and much lower diffusion, in addition to practical advantages of low cost and abundant supply. We propose to demonstrate that 129Xe can compete successfully with 3He by performing the following measurements:1. We will perform signal loss contrast imaging with mixtures of hyperpolarized 129Xe and oxygen in phantoms. 2. We will perform signal loss contrast imaging using hyperpolarized 129Xe and oxygen in human subjects. 3. We will compare signal loss during a breath hold with other hyperpolarized xenon metrics of lung health to quantify uncertainties. Back to back measurements with published and new pulse sequences will reveal comparative merits of each. Multiple measurements in the same subject, both during the same imaging session and after repositioning will provide a measure of the systematic errors, including those resulting from partial volume effects in voxels. We will explore reducing partial volume effects using proton imaging. Comparing measurements after breath holding with others after hyperventilating will allow separation of xenon lost to the bloodstream and signal lost due to O2. The US FDA has approved our hyperpolarized xenon for Phase 2 trials in subjects with mild to moderate lung disease.While both 129Xe and 3He can be used to measure local alveolar oxygen concentration and determine the uptake of oxygen by the lungs, each poses challenges to quantitative interpretation. We propose to push the quantitative limits to extracting lung functional health from 129Xe measurements using a variety of methods, in order to develop a diagnostic protocol suite that could help Americans suffering from Chronic Obstructive Pulmonary Disease (COPD). Of the two gases being investigated for hyperpolarized gas MRI, 129Xe offers the best possibility of widespread acceptance and commercialization due to its low cost and inexhaustible supply.

描述（由申请人提供）：虽然慢性阻塞性肺疾病（COPD）是美国的第四大死亡原因，影响了3000万美国人，但高分辨率的非基于基于图像的肺部健康评估落后于其他重要器官的成像。低成本，高度定量的方式用于肺功能的3D成像将改善疾病的早期诊断和歧视，加速制药公司对疗法的测试，并最终协助对临床和医院进行更个性化的疾病管理和干预。超极化气体可以解决这种需求。 3He享受了最广泛的研究，这主要是由于成熟的极化技术的可用性。最近，由于UNH群体的创新，已经获得了129倍升数量的高极化，从而可以研究超极化的129xE成像的潜在科学优势。肺中的超极化原子（3HE和129xE）的去极化由顺磁性氧气分子的存在主导。 T1使用超极化3HE的T1衰减恒定方案绘制了局部氧气部分压力，并在呼吸内表现出对血液摄取的氧气吸收的敏感性。除了低成本和供应丰富的实际优势外，超极化的129xE对氧气具有相同的敏感性和较低的扩散。我们建议证明129xE可以通过执行以下测量值成功与3HE竞争：1。我们将使用超极化的129xE和氧气中的混合物进行信号损失对比成像。 2。我们将使用人类受试者中使用超极化的129xE和氧进行信号损失对比成像。 3。我们将在呼吸期间与其他超极化氙气指标进行比较，以量化不确定性。背靠背测量以已发表的新脉冲序列揭示每个脉冲的比较优点。在同一成像过程中和重新定位后，在同一受试者中进行了多次测量，将提供系统误差的量度，包括由体素效应造成的误差。我们将使用质子成像探索减少部分体积效应。在过度换气后与其他人进行呼吸后的测量，将允许将XENON分离到血液中，并因O2而丢失的信号。美国FDA已批准了在轻度到中度肺部疾病的受试者中的超极化氙气进行2期试验。虽然129xE和3HE均可用于测量局部肺泡氧浓度并确定肺对氧气的吸收，但每种肺都构成了挑战以定量解释。我们建议使用各种方法将定量限制从129XE测量中提取肺功能健康，以开发一个可以帮助患有慢性阻塞性肺疾病（COPD）的美国人的诊断方案套件。在研究超极化气体MRI的两种气体中，129xE由于其低成本和不取证的供应而提供了广泛接受和商业化的最佳可能性。