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Hyperpolarized Diethyl Ether for Sub-second Pulmonary MRI

用于亚秒级肺部 MRI 的超极化乙醚

基本信息

批准号：
10221779
负责人：
Eduard Chekmenev
金额：
$ 22.86万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-22 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10221779
关键词：
3-Dimensional Affect Air Alveolar Anesthetics Animals Asthma Bronchiolitis Centers for Disease Control and Prevention (U.S.)Cessation of life Chronic Obstructive Airway Disease Clinical Clinical Trials Clinical/Radiologic Complex Computer software Contrast Media Custom Devices Diagnosis Diffusion Disease Disease Outbreaks Dose Early Diagnosis Effectiveness Electronic cigarette Equipment Ethyl Ether FDA approved Face Future Gases Goals Hour Human Human Resources Hydrocarbons Hydrogenation Image Imaging Techniques Infrastructure Inhalation Investments Ionizing radiation Liquid substance Lung Lung diseases MRI Scans Magnetic Resonance Imaging Mammary Ultrasonography Medicine Monitor Noble Gases Noise Nuclear Outcome Partial Pressure Pathology Patients Perfusion Phase Phase I Clinical Trials Physiological Pneumonia Population Positron-Emission Tomography Process Production Propane Property Protons Pulmonary Fibrosis Pulmonology Reaction Recording of previous events Relaxation Reporting Research Resolution Roentgen Rays Safety Scanning Signal Transduction Speed Structure Technology Temperature Three-Dimensional Imaging Tissues Work X-Ray Computed Tomography cancer imaging catalyst clinical imaging clinical translation constriction cost density high throughput technology imaging modality imaging study in vivo lung imaging lung injury magnetic field new technology non-invasive imaging novel process optimization programs pulmonary function screening success technology development treatment response tumor vaping ventilation vinyl ether

项目摘要

PROJECT SUMMARY (30-line limit) Deadly diseases such as chronic obstructive pulmonary disease (COPD), asthma, lung injury, constrictive bronchiolitis, and pulmonary fibrosis affect >300 million people worldwide and cause ~3 million annual deaths. However, there is currently no widespread clinical imaging modality to perform high-resolution functional lung imaging: Computed Tomography (CT), conventional MRI, and X-ray can only provide structural images of dense tissues—informing about pathologies like tumors and pneumonia—but yielding little or no information about lung ventilation, perfusion, alveoli size, gas-exchange efficiency, etc. This state of affairs contrasts with cancer imaging, which includes MRI, CT, ultrasound, mammography, Positron Emission Tomography (PET) and others, which collectively enable early detection (via population screening), diagnoses, and monitoring response to treatment. MRI of hyperpolarized noble gases (129Xe and 3He) reports on lung function: ventilation, diffusion, and gas exchange. Despite remarkable research breakthroughs in this field demonstrating the effectiveness and safety of hyperpolarized noble gas MRI to detect a wide range of lung diseases and monitor response to treatment (over the past 20+ years of studies), the prospects for widespread clinical adaptation of this imaging modality face major challenges, including (i) the high cost and complexity of the equipment for production of hyperpolarized noble gases, and (ii) the requirement for a highly specialized custom MRI scanner capable of 129Xe or 3He imaging – note, all FDA-approved clinical MRI scanners can image only protons. We have been developing a new technology of Parahydrogen Induced Polarization (PHIP) for production of pure proton- hyperpolarized hydrocarbon gases via pairwise parahydrogen addition to an unsaturated precursor (e.g., vinyl ether proposed here). This high-throughput technology is remarkably simple and low-cost. Most importantly, it can be deployed on FDA-approved MRI scanners without any additional of hardware and software upgrades. Here we propose applying this technology for production of diethyl ether, which has a rich history of use as the first inhalable anesthetic, which has revolutionized the field of medicine. Specifically, we propose to develop and optimize the process of clinical-scale production of a human dose of less than 100 mL of gas. Once inhaled, this low dose diethyl ether will render in vivo concentration, which is no longer is flammable. Therefore, we envision the use of low-dose proton-hyperpolarized diethyl ether as a safe MRI contrast agent. We will also perform detailed mapping of relaxation properties of this novel HP contrast agents, and will perform feasibility imaging studies in phantoms and excised animal lungs. We envision that this new safe inhalable contrast agent can revolutionize pulmonary imaging and pulmonary medicine in general.

项目摘要（30行限制）慢性阻塞性肺疾病（COPD）、哮喘、肺损伤、收缩性肺炎等致命疾病细支气管炎和肺纤维化影响全世界> 3亿人，并且每年造成约300万人死亡。然而，目前还没有广泛的临床成像模式来执行高分辨率功能肺成像：计算机断层扫描（CT）、常规MRI和X射线只能提供致密的结构图像。组织-提供肿瘤和肺炎等病理信息，但很少或根本没有关于肺的信息通气、灌注、肺泡大小、气体交换效率等。这种状态与癌症形成对比成像，包括MRI、CT、超声、乳房X线摄影、正电子发射断层扫描（PET）等，这些措施共同实现了早期检测（通过人群筛查）、诊断和监测对治疗超极化惰性气体（129 He和3 He）的MRI报告肺功能：通气，弥散，气体交换。尽管在这一领域取得了显着的研究突破，超极化惰性气体MRI检测各种肺部疾病并监测对治疗（在过去20多年的研究），这种成像的广泛临床适应的前景（i）生产的设备成本高，复杂性高，超极化惰性气体，以及（ii）对高度专业化的定制MRI扫描仪的要求， 129氚或3 He成像-注意，所有FDA批准的临床MRI扫描仪只能成像质子。我们一直开发了一种新的氢诱导极化（PHIP）技术，用于生产纯质子- 通过成对仲氢加成到不饱和前体的超极化烃气体（例如，乙烯基在此提出）。这种高通量技术非常简单且成本低。最重要的是它可以部署在FDA批准的MRI扫描仪上，无需任何额外的硬件和软件升级。在这里，我们建议将这种技术应用于生产乙醚，乙醚作为第一种吸入式麻醉剂，它彻底改变了医学领域。具体而言，我们建议发展和优化临床规模生产人体剂量小于100 mL气体的工艺。一旦吸入，低剂量乙醚将使体内浓度，这是不再易燃。因此，我们设想使用低剂量质子超极化乙醚作为安全的MRI造影剂。我们还将表演详细绘制这种新型HP造影剂的弛豫特性，并将进行可行性成像在幻影和切除的动物肺中的研究。我们设想这种新的安全的可吸入造影剂可以彻底改变了肺部成像和肺部医学。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bridging the Gap: From Homogeneous to Heterogeneous Parahydrogen-induced Hyperpolarization and Beyond.

DOI：
10.1002/cphc.202001031
发表时间：
2021-04-19
期刊：
Chemphyschem : a European journal of chemical physics and physical chemistry
影响因子：
0
作者：
Chekmenev EY;Goodson BM;Bukhtiyarov VI;Koptyug IV
通讯作者：
Koptyug IV

Background-Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation.

DOI：
10.1002/anie.202108939
发表时间：
2021-12-06
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
0
作者：
Joalland B;Theis T;Appelt S;Chekmenev EY
通讯作者：
Chekmenev EY

Clinical-Scale Production of Nearly Pure (>98.5%) Parahydrogen and Quantification by Benchtop NMR Spectroscopy.

DOI：
10.1021/acs.analchem.0c05129
发表时间：
2021-02-23
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Nantogma S;Joalland B;Wilkens K;Chekmenev EY
通讯作者：
Chekmenev EY

Low-Cost High-Pressure Clinical-Scale 50% Parahydrogen Generator Using Liquid Nitrogen at 77 K.

DOI：
10.1021/acs.analchem.1c00716
发表时间：
2021-06-22
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Chapman B;Joalland B;Meersman C;Ettedgui J;Swenson RE;Krishna MC;Nikolaou P;Kovtunov KV;Salnikov OG;Koptyug IV;Gemeinhardt ME;Goodson BM;Shchepin RV;Chekmenev EY
通讯作者：
Chekmenev EY

Heterogeneous Parahydrogen-Induced Polarization of Diethyl Ether for Magnetic Resonance Imaging Applications.

用于磁共振成像应用的非均相仲氢诱导乙醚极化。

DOI：
10.1002/chem.202003638
发表时间：
2021-01-18
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
0
作者：
Salnikov OG;Svyatova A;Kovtunova LM;Chukanov NV;Bukhtiyarov VI;Kovtunov KV;Chekmenev EY;Koptyug IV
通讯作者：
Koptyug IV