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）是美国第四大死因，影响3000万美国人，但对肺部健康的高分辨率非侵入性图像评估落后于其他重要器官的成像。低成本、高定量的肺功能三维成像模式的可用性将改善疾病的早期诊断和鉴别，加速制药公司对疗法的测试，并最终有助于诊所和医院进行更个性化的疾病管理和干预。超极化气体可以满足这一需求。3他享受了最广泛的研究，主要是由于成熟的偏振技术的可用性。最近，由于UNH集团的创新，129 Ω的高偏振（以升为单位）已经可用，从而可以研究超偏振129 Ω成像的潜在科学优势。肺中超极化原子（3He和129 He）的去极化主要由顺磁性氧气分子的存在所控制。使用超极化3He的T1衰减常数协议已经映射了局部氧分压，并且还显示出对屏气内血流的氧摄取的敏感性。超极化的129对氧气具有相同的敏感性和低得多的扩散，此外还有低成本和供应充足的实用优势。我们建议通过以下测量来证明129He可以成功地与3He竞争：1。我们将使用超极化129氘和氧的混合物在体模中进行信号损失对比成像。2.我们将在人类受试者中使用超极化129氘和氧气进行信号丢失对比成像。3.我们将比较屏气期间的信号损失与其他超极化氙肺健康指标，以量化不确定性。背靠背测量与出版和新的脉冲序列将揭示各自的比较优势。在同一成像会话期间和重新定位之后，在同一受试者中的多次测量将提供系统误差的测量，包括由体素中的部分体积效应引起的系统误差。我们将探索使用质子成像来减少部分体积效应。将屏气后的测量结果与过度换气后的测量结果进行比较，可以将氙损失到血流中和由于O2而损失的信号分离。美国FDA已批准我们的超极化氙用于轻度至中度肺部疾病受试者的2期试验。虽然129He和3He都可用于测量局部肺泡氧浓度并确定肺部的氧摄取，但每一种都对定量解释提出了挑战。我们建议使用各种方法从129mmHg测量值中提取肺功能健康的定量限制，以开发一种诊断协议套件，可以帮助患有慢性阻塞性肺疾病（COPD）的美国人。在超极化气体MRI研究的两种气体中，129 Xe由于其低成本和取之不尽的供应而提供了广泛接受和商业化的最佳可能性。