An official website of the United States government
Abstract Radio amplification by stimulated emission of radiation (RASER) was recently discovered in a low‐field NMR spectrometer incorporating a highly specialized radio‐frequency resonator, where a high degree of proton‐spin polarization was achieved by reversible parahydrogen exchange. RASER activity, which results from the coherent coupling between the nuclear spins and the inductive detector, can overcome the limits of frequency resolution in NMR. Here we show that this phenomenon is not limited to low magnetic fields or the use of resonators with high‐quality factors. We use a commercial bench‐top 1.4 T NMR spectrometer in conjunction with pairwise parahydrogen addition producing proton‐hyperpolarized molecules in the Earth's magnetic field (ALTADENA condition) or in a high magnetic field (PASADENA condition) to induce RASER without any radio‐frequency excitation pulses. The results demonstrate that RASER activity can be observed on virtually any NMR spectrometer and measures most of the important NMR parameters with high precision.
more »
« less
Background‐Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation
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
- Award ID(s):
- 1904780
- PAR ID:
- 10302565
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 50
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 26298-26302
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract The feasibility of Carbon‐13 Radiofrequency (RF) Amplification by Stimulated Emission of Radiation (C‐13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1‐13C]acetate. Hyperpolarized ethyl [1‐13C]acetate was prepared via pairwise addition of parahydrogen to vinyl [1‐13C]acetate and polarization transfer from nascent parahydrogen‐derived protons to the carbon‐13 nucleus via magnetic field cycling yielding C‐13 nuclear spin polarization of approximately 6 %. RASER signals were detected from samples with concentration ranging from 0.12 to 1 M concentration using a non‐cryogenic 1.4T NMR spectrometer equipped with a radio‐frequency detection coil with a quality factor (Q) of 32 without any modifications. C‐13 RASER signals were observed for several minutes on a single bolus of hyperpolarized substrate to achieve 21 mHz NMR linewidths. The feasibility of creating long‐lasting C‐13 RASER on biomolecular carriers opens a wide range of new opportunities for the rapidly expanding field of C‐13 magnetic resonance hyperpolarization.more » « less
-
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
-
Abstract Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced. Here, we show that pairwise addition of parahydrogen to various propargylic compounds induces RASER activity of other protons beyond those chemically introduced in the reaction. In high-field PHIP, negative polarization initiating RASER is transferred via intramolecular cross-relaxation. When parahydrogen is added in Earth’s field followed by adiabatic transfer to a high field, RASER activity of other protons is induced via bothJ-couplings and cross-relaxation. This through-bond and through-space induction of RASER holds potential for the ongoing development and expansion of RASER applications and can potentially enhance spectral resolution in two-dimensional NMR spectroscopy techniques.more » « less
-
Abstract It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1‐13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio‐frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22‐fold (to 1,670) via parametric pumping. This active‐feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated.more » « less
