An official website of the United States government
Abstract Hyperpolarized129Xe gas was FDA‐approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP129Xe gas faces two critical challenges: the high cost of the relatively low‐throughput hyperpolarization equipment and the lack of129Xe imaging capability on clinical MRI scanners, which have narrow‐bandwidth electronics designed only for proton (1H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch‐mode production of proton‐hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1‐liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub‐second 2D MRI with up to 2×2 mm2in‐plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner.
more »
« less
Parahydrogen‐Induced Polarization of Diethyl Ether Anesthetic
Abstract The growing interest in magnetic resonance imaging (MRI) for assessing regional lung function relies on the use of nuclear spin hyperpolarized gas as a contrast agent. The long gas‐phase lifetimes of hyperpolarized129Xe make this inhalable contrast agent acceptable for clinical research today despite limitations such as high cost, low throughput of production and challenges of129Xe imaging on clinical MRI scanners, which are normally equipped with proton detection only. We report on low‐cost and high‐throughput preparation of proton‐hyperpolarized diethyl ether, which can be potentially employed for pulmonary imaging with a nontoxic, simple, and sensitive overall strategy using proton detection commonly available on all clinical MRI scanners. Diethyl ether is hyperpolarized by pairwise parahydrogen addition to vinyl ethyl ether and characterized by1H NMR spectroscopy. Proton polarization levels exceeding 8 % are achieved at near complete chemical conversion within seconds, causing the activation of radio amplification by stimulated emission radiation (RASER) throughout detection. Although gas‐phaseT1relaxation of hyperpolarized diethyl ether (at partial pressure of 0.5 bar) is very efficient, withT1of ca. 1.2 second, we demonstrate that, at low magnetic fields, the use of long‐lived singlet states created via pairwise parahydrogen addition extends the relaxation decay by approximately threefold, paving the way to bioimaging applications and beyond.
more »
« less
- Award ID(s):
- 1904780
- PAR ID:
- 10192870
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 26
- Issue:
- 60
- ISSN:
- 0947-6539
- Format(s):
- Medium: X Size: p. 13621-13626
- Size(s):
- p. 13621-13626
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4–8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin‐exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as129Xe. Techniques based on hyperpolarized129Xe are poised to revolutionize clinical lung imaging, offering a non‐ionizing, high‐contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized129Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized129Xe to lung imaging and beyond.more » « less
-
Abstract We report on the utility of Radiofrequency Amplification by Stimulated Emission Radiation (RASER) for background‐free proton detection of hyperpolarized biomolecules. We performed hyperpolarization of ≈0.3 M ethyl acetate via pairwise parahydrogen addition to vinyl acetate. A proton NMR signal with signal‐to‐noise ratio exceeding 100 000 was detected without radio‐frequency excitation at the clinically relevant magnetic field of 1.4 T using a standard (non‐cryogenic) inductive detector with quality factor ofQ=68. No proton background signal was observed from protonated solvent (methanol) or other added co‐solvents such as ethanol, water or bovine serum. Moreover, we demonstrate RASER detection without radio‐frequency excitation of a bolus of hyperpolarized contrast agent in biological fluid. Completely background‐free proton detection of hyperpolarized contrast agents in biological media paves the way to new applications in the areas of high‐resolution NMR spectroscopy and in vivo spectroscopy and imaging.more » « less
-
Abstract Hyperpolarized magnetic resonance imaging (HP‐MRI) has emerged as a powerful tool in molecular imaging, providingin vivo, real‐time insights into metabolic pathways without ionizing radiation. Signal Amplification by Reversible Exchange (SABRE) represents a promising hyperpolarization technique, leveraging parahydrogen to enhance MRI signals. In this concept, we delineate the evolution of SABRE and landmark papers that have enabled us recently to produce biocompatible and low‐cost hyperpolarized pyruvate within minutes forin vivometabolic imaging, showcasing SABRE′s potential for preclinical and near‐future clinical settings. Looking ahead, with ongoing efforts focused on optimizing polarizer technology and expanding applications beyond pyruvate, we envision SABRE as a key player in the research and application of HP‐MRI due to its simplicity and throughput.more » « less
