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:10040772
- 负责人:
- 金额:$ 19.03万
- 依托单位:
- 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 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAffectAirAlveolarAnestheticsAnimalsAsthmaBronchiolitisCenters for Disease Control and Prevention (U.S.)Cessation of lifeChronic Obstructive Airway DiseaseClinicalClinical TrialsClinical/RadiologicComplexComputer softwareContrast MediaCustomDevicesDiagnosisDiffusionDiseaseDisease OutbreaksDoseEarly DiagnosisEffectivenessElectronic cigaretteEquipmentEthyl EtherFDA approvedFaceFutureGasesGoalsHourHumanHuman ResourcesHydrocarbonsHydrogenationImageImaging TechniquesInfrastructureInhalationInvestmentsIonizing radiationLiquid substanceLungLung diseasesMRI ScansMagnetic Resonance ImagingMammary UltrasonographyMedicineMonitorNoble GasesNoiseNuclearOutcomePartial PressurePathologyPatientsPerfusionPhasePhase I Clinical TrialsPhysiologicalPneumoniaPopulationPositron-Emission TomographyProcessProductionPropanePropertyProtonsPulmonary FibrosisPulmonologyReactionRecording of previous eventsRelaxationReportingResearchResolutionRespiratory physiologyRoentgen RaysSafetyScanningSignal TransductionSpeedStructureTechnologyTemperatureThree-Dimensional ImagingTissuesWorkX-Ray Computed Tomographycancer imagingcatalystclinical imagingclinical translationconstrictioncostdensityhigh throughput technologyimaging modalityimaging studyin vivolung imaginglung injurymagnetic fieldnew technologynon-invasive imagingnovelprocess optimizationprogramsscreeningsuccesstechnology developmenttreatment responsetumorvapingventilationvinyl 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(限制 30 行)
致命疾病,如慢性阻塞性肺病 (COPD)、哮喘、肺损伤、缩窄性肺病
细支气管炎和肺纤维化影响全球超过 3 亿人,每年导致约 300 万人死亡。
然而,目前还没有广泛的临床成像方式来进行高分辨率功能性肺检查
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——但很少或根本不提供有关肺部的信息
通气、灌注、肺泡大小、气体交换效率等。这种情况与癌症形成鲜明对比
成像,包括 MRI、CT、超声波、乳房 X 线摄影、正电子发射断层扫描 (PET) 等,
共同实现早期检测(通过人群筛查)、诊断和监测反应
超极化惰性气体(129Xe 和 3He)的 MRI 报告肺功能:通气、扩散、
尽管该领域取得了显着的研究突破,证明了其有效性和有效性。
超极化惰性气体 MRI 的安全性可检测多种肺部疾病并监测对肺部疾病的反应
治疗(过去 20 多年的研究),该成像技术广泛应用于临床的前景
模式面临重大挑战,包括(i)生产设备的高成本和复杂性
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,该扫描仪能够
129Xe 或 3He 成像 - 请注意,所有 FDA 批准的临床 MRI 扫描仪只能对质子进行成像。
开发仲氢诱导极化(PHIP)新技术,用于生产纯质子
通过成对仲氢加成到不饱和前体(例如乙烯基
此处提出的以太)。这种高通量技术非常简单且成本低廉。
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,我们建议应用该技术来生产二乙醚,二乙醚具有丰富的使用历史
具体来说,我们建议开发和开发第一种吸入式麻醉剂,它彻底改变了医学领域。
优化临床规模生产的过程,人体吸入剂量少于 100 毫升。
低剂量的乙醚会在体内产生浓度,从而不再是可燃的。
我们还将使用低剂量质子超极化乙醚作为安全的 MRI 造影剂。
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
我们设想这种新的安全吸入造影剂可以在人体模型和切除的动物肺部中进行研究。
彻底改变肺部成像和肺部医学。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Eduard Chekmenev其他文献
Eduard Chekmenev的其他文献
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{{ truncateString('Eduard Chekmenev', 18)}}的其他基金
Rapid low-cost production of contrast agents for metabolic imaging
快速低成本生产代谢成像造影剂
- 批准号:
10572052 - 财政年份:2023
- 资助金额:
$ 19.03万 - 项目类别:
Hyperpolarized Diethyl Ether for Sub-second Pulmonary MRI
用于亚秒级肺部 MRI 的超极化乙醚
- 批准号:
10221779 - 财政年份:2020
- 资助金额:
$ 19.03万 - 项目类别:
Magnetic Resonance Spectroscopy and Molecular Imaging of Metabolic Pathways in Cancer
癌症代谢途径的磁共振波谱和分子成像
- 批准号:
9755386 - 财政年份:2017
- 资助金额:
$ 19.03万 - 项目类别:
Magnetic Resonance Spectroscopy and Molecular Imaging of Metabolic Pathways in Cancer
癌症代谢途径的磁共振波谱和分子成像
- 批准号:
9381725 - 财政年份:2017
- 资助金额:
$ 19.03万 - 项目类别:
Pure parahydrogen-enhanced metabolic MRI contrast agents for molecular imaging
用于分子成像的纯仲氢增强代谢 MRI 造影剂
- 批准号:
9130178 - 财政年份:2015
- 资助金额:
$ 19.03万 - 项目类别:
Novel hyperpolarized C-13 and N-15 biomarkers for metabolic MR imaging of cancer
用于癌症代谢 MR 成像的新型超极化 C-13 和 N-15 生物标志物
- 批准号:
7941341 - 财政年份:2009
- 资助金额:
$ 19.03万 - 项目类别:
Novel hyperpolarized C-13 and N-15 biomarkers for metabolic MR imaging of cancer
用于癌症代谢 MR 成像的新型超极化 C-13 和 N-15 生物标志物
- 批准号:
7922512 - 财政年份:2008
- 资助金额:
$ 19.03万 - 项目类别:
Novel hyperpolarized C-13 and N-15 biomarkers for metabolic MR imaging of cancer
用于癌症代谢 MR 成像的新型超极化 C-13 和 N-15 生物标志物
- 批准号:
7914685 - 财政年份:2008
- 资助金额:
$ 19.03万 - 项目类别:
Novel hyperpolarized C-13 and N-15 biomarkers for metabolic MR imaging of cancer
用于癌症代谢 MR 成像的新型超极化 C-13 和 N-15 生物标志物
- 批准号:
7510655 - 财政年份:2008
- 资助金额:
$ 19.03万 - 项目类别:
Novel hyperpolarized C-13 and N-15 biomarkers for metabolic MR imaging of cancer
用于癌症代谢 MR 成像的新型超极化 C-13 和 N-15 生物标志物
- 批准号:
8088064 - 财政年份:2008
- 资助金额:
$ 19.03万 - 项目类别:
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