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.
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‐phase
- Award ID(s):
- 1904780
- NSF-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
- Page Range / eLocation ID:
- p. 13621-13626
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
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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.
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Purpose To measure dissolved‐phase129Xe T1values at high and low magnetic fields and the field dependence of129Xe depolarization by hollow fiber membranes used to infuse hyperpolarized xenon in solution.
Methods Dissolved‐phase T1measurements were made at 11.7T and 2.1 mT by bubbling xenon in solution and by using a variable delay to allow spins to partially relax back to thermal equilibrium before probing their magnetization. At high field, relaxation values were compared to those obtained by using the small flip angle method. For depolarization studies, we probed the magnetization of the polarized gas diffusing through an exchange membrane module placed at different field strengths.
Results Total loss of polarization was observed for xenon diffusing through hollow fiber membranes at low field, while significant polarization loss (>20%) was observed at magnetic fields up to 2T. Dissolved‐phase129Xe T1values were found consistently shorter at 2.1 mT compared to 11.7T. In addition, both O2and Xe gas concentrations in solution were found to significantly affect dissolved‐phase129Xe T1values.
Conclusion Dissolved‐phase129Xe measurements are feasible at low field, but to assess the feasibility of in vivo dissolved‐phase imaging and spectroscopy the T1of xenon in blood will need to be measured. Both O2and Xe concentrations in solution are found to greatly affect dissolved‐phase129Xe T1values and may explain, along with RF miscalibration, the large discrepancy in previously reported results.
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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 of
Q =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. -
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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 of
Q =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.
