Thomas Theis

Thomas Theis
North Carolina State University | NCSU · Department of Chemistry

PhD

About

107
Publications
9,501
Reads
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3,336
Citations
Citations since 2017
70 Research Items
2801 Citations
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20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
Introduction
We focus on spin physics and hyperpolarization technology to create magnetic resonance spectroscopy and imaging tools for next-generation biomolecular sensing.
Additional affiliations
January 2014 - May 2014
Duke University
Position
  • Lecturer
Description
  • Quantum mechanics
June 2013 - August 2013
RWTH Aachen University
Position
  • Researcher
June 2013 - August 2013
RWTH Aachen University
Position
  • Professor
Description
  • Graduate student seminar series on low and zero-field NMR
Education
August 2007 - May 2012
University of California, Berkeley
Field of study
  • physical Chemistry
June 2005 - November 2006
August 2004 - June 2005

Publications

Publications (107)
Article
Signal Amplification By Reversible Exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as hyperpolarization source. However, current SABRE faces a number of stumbling blocks for translation to biochemical and clinical settings. Difficulties include inefficient polarization in in water, r...
Article
Full-text available
Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed me...
Article
Parahydrogen is demonstrated to efficiently transfer its nuclear spin hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B3) by conducting “Signal Amplification By Reversible Exchange” (SABRE) at microtesla fields within a magnetic shield. Following transfer of the sample from the magnetic shield chamber to a conventional high-r...
Article
Full-text available
Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in Shield Enables Alignment Transfer...
Article
We have recently demonstrated that sensitive and chemically specific NMR spectra can be recorded in the absence of a magnetic field using hydrogenative parahydrogen induced polarization (PHIP) (1-3) and detection with an optical atomic magnetometer. Here, we show that non-hydrogenative parahydrogen-induced polarization (4-6) (NH-PHIP) can also dram...
Article
Carbon‐13 radiofrequency amplification by stimulated emission of radiation (C‐13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1‐13C]acetate, as reported by Thomas Theis, Eduard Y. Chekmenev et al. in their Communication (DOI: 10.1002/anie.202215678). Spontaneous RASER signal emissions were detected using a 1.4 T NMR spectromete...
Article
Carbon‐13 radiofrequency amplification by stimulated emission of radiation (C‐13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1‐13C]acetate, as reported by Thomas Theis, Eduard Y. Chekmenev et al. in their Communication (DOI: 10.1002/anie.202215678). Spontaneous RASER signal emissions were detected using a 1.4 T NMR spectromete...
Article
Hyperpolarized [1-13C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging S...
Article
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‐d...
Article
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‐d...
Article
Hyperpolarized MRI is emerging as a next-generation molecular imaging modality that can detect metabolic transformations in real time deep inside tissue and organs. 13C-hyperpolarized pyruvate is the leading hyperpolarized contrast agent that can probe cellular energetics in real time. Currently, hyperpolarized MRI requires specialized "multinuclea...
Article
Despite great successes in oncology, patient outcomes are often still discouraging, and hence the diagnostic imaging paradigm is increasingly shifting toward functional imaging of the pathology to better understand individual disease biology and to personalize therapies. The dissolution Dynamic Nuclear Polarization (d-DNP) hyperpolarization method...
Article
Full-text available
Despite its enormous utility in structural characterization, nuclear magnetic resonance (NMR) spectroscopy is inherently limited by low spin polarization. One method to address the low polarization is para-hydrogen (p-H2) induced polarization (PHIP) which uses the singlet spin isomer of H2 to generate disparate nuclear spin populations to amplify t...
Article
α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metaboli...
Article
Full-text available
The spatial resolution of magnetic resonance imaging (MRI) is limited by the width of Lorentzian point spread functions associated with the transverse relaxation rate 1/ T 2 * . Here, we show a different contrast mechanism in MRI by establishing RASER (radio-frequency amplification by stimulated emission of radiation) in imaged media. RASER imaging...
Preprint
Full-text available
The spatial resolution of magnetic resonance imaging (MRI) is fundamentally limited by the width of Lorentzian point spread functions (PSF) associated with the exponential decay rate of transverse magnetization (1/T2*). Here we show a different contrast mechanism in MRI by establishing RASER (Radio-frequency Amplification by Stimulated Emission of...
Article
he unique properties of the entangled, antisymmetric nuclear spin state of dihydrogen, parahydrogen (pH2), has intrigued physicists, chemists, and other scientists for almost a century. pH2 was used as a model system in the early days of quantum mechanics1 and is used for fueling rockets as well as combustion-free cars today. In the 1980s, pH2 was...
Article
The Cover Feature illustrates a Spin Transfer Automated Reactor (STAR), which produces a continuous stream of nuclear spin hyperpolarization. In the STAR, parahydrogen diffuses through a semi‐permeable membrane to hyperpolarize small molecules in solution, including the antibiotic drug metronidazole and the metabolite pyruvate. The STAR also produc...
Article
Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE‐SHEATH) is investigated to achieve rapid hyperpolarization of 13C1 spins of [1‐13C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay betwee...
Article
Radiofrequency amplification by stimulated emission radiation (RASER) is the version of lasers and masers operating in radiofrequency spectral range. In their Communication (DOI: 10.1002/anie.202108939), Eduard Y. Chekmenev et al. employ 61-MHz proton RASER to demonstrate robust background-free detection of biomolecular NMR resonances even in the e...
Article
RASER (radiofrequency amplification by stimulated emission radiation) ist die Variante von Laser und Maser, die im Hochfrequenzspektralbereich arbeiten. Eduard Y. Chekmenev et al. setzen in ihrer Zuschrift 61‐MHz‐Protonen‐RASER ein, um eine robuste, untergrundfreie Detektion biomolekularer NMR‐Resonanzen zu demonstrieren, selbst in den extremen Fäl...
Article
The front cover artwork is provided by the groups of Prof. Thomas Theis (North Carolina State University) Prof. Volker Blum (Duke University). The image shows the reaction network of Signal Amplification by Reversible Exchange (SABRE), elucidated by density functional theory (DFT). Read the full text of the Review at 10.1002/cphc.202100204. “We pro...
Article
The Front Cover shows the reaction network of Signal Amplification by Reversible Exchange (SABRE), elucidated by density functional theory (DFT). More information can be found in the Article by T. Theis, V. Blum, and co‐workers.
Article
An in‐depth theoretical analysis of key chemical equilibria in Signal Amplification by Reversible Exchange (SABRE) is provided, employing density functional theory calculations to characterize the likely reaction network. For all reactions in the network, the potential energy surface is probed to identify minimum energy pathways. Energy barriers an...
Article
We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction...
Article
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. Proton NMR signal with signal‐to‐noise ratio exceeding 100,000 was detected...
Article
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. Proton NMR signal with signal‐to‐noise ratio exceeding 100,000 was detected...
Preprint
Current metabolic imaging in humans is dominated by positron emission tomography (PET) methods. An emerging non-ionizing alternative for molecular imaging is hyperpolarized MRI. In particular, imaging of hyperpolarized 13C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, simi-lar to PET, h...
Preprint
Full-text available
Current metabolic imaging in humans is dominated by positron emission tomography (PET) methods. An emerging non-ionizing alternative for molecular imaging is hyperpolarized MRI. In particular, imaging of hyperpolarized 13C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, simi-lar to PET, h...
Article
Signal amplification by reversible exchange (SABRE) is a robust and inexpensive hyperpolarization (HP) technique to enhance nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) signals using parahydrogen (pH2). The substrate scope of SABRE is continually expanding. Here, we present the polarization of three antifungal...
Article
Green solvent utilization and recovery enabled by switchable hydrophilicity solvents (SHSs), using carbon dioxide as the switching trigger, offer intriguing advantages in sustainable chemistry. To further elevate SHSs, an intensified...
Article
Full-text available
Optically probed nitrogen-vacancy (NV)) quantum defects in diamond can detect nuclear magnetic resonance (NMR) signals with high-spectral resolution from micron-scale sample volumes of about 10 pl. However, a key challenge for NV-NMR spectroscopy is detecting samples at millimolar concentrations. Here we demonstrate an increase in NV-NMR proton con...
Article
In a RASER (Radio-frequency Amplification by Stimulated Emission of Radiation), the fast relaxing electromagnetic modes of an LC resonator are enslaved by the slow nuclear spin motion, whose coherence decays with the transverse relaxation rate γm=1/T2∗. Such a system obeys the slaving principle, mathematically identical with the adiabatic eliminati...
Preprint
Optically-probed nitrogen-vacancy (NV) quantum defects in diamond can detect nuclear magnetic resonance (NMR) signals with high-spectral resolution from micron-scale sample volumes of about 10 picoliters. However, a key challenge for NV-NMR is detecting samples at millimolar concentrations. Here, we demonstrate an improvement in NV-NMR proton conce...
Article
High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR in...
Article
Signal Amplification By Reversible Exchange (SABRE) is a particularly simple hyperpolarisation approach. However, compared to other hyperpolarisation methods, SABRE is more limited in substrate scope. Therefore, it is critical to understand and overcome the factors limiting generalization. Past developments in SABRE catalyst optimization have empha...
Article
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 n...
Article
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 n...
Article
N2-Diazirines represent an attractive class of imaging tags for hyperpolarized magnetic resonance imaging (HP-MRI), offering desirable biocompatibility, ease of incorporation into a variety of molecules, and ability to deliver long-lasting polarization. We have recently established hyperpolarization of ¹⁵N2-diazirines in organic solvents using SABR...
Article
We present a simple-to-implement pneumatic sample shuttle for automation of magnetic field cycling and multidimensional NMR. The shuttle system is robust allowing automation of hyperpolarized and non-hyperpolarized measurements, including variable field lifetime measurements, SABRE polarization optimization, and SABRE multidimensional experiments....
Article
PHIP und SABRE: Dieser Kurzaufsatz gibt einen Überblick über zwei Hyperpolarisationstechniken, Parawasserstoff‐induzierte Polarisation (PHIP) und Signalverstärkung durch reversiblen Austausch (SABRE), in Bezug auf die Erzeugung hyperpolarisierter Gase für mögliche biomedizinische Anwendungen in der Bildgebung und darüber hinaus. Abstract Die Bildg...
Article
Imaging of gases is a major challenge for any modality including MRI. NMR and MRI signals are directly proportional to the nuclear spin density and the degree of alignment of nuclear spins with applied static magnetic field, which is called nuclear spin polarization. The level of nuclear spin polarization is typically very low, i.e ., one hundred t...
Article
A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA mediated transformation occurs via three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of ami...
Article
Signal Amplification By Reversible Exchange (SABRE) and its heteronuclear variant SABRE in SHield Enables Alignment Transfer to Heteronuclei create large nuclear magnetization in target ligands, exploiting level crossings in an iridium catalyst that transiently binds both the ligands and parahydrogen. This requires a specific, small magnetic field...
Article
We report on an extension of the QUASi-Resonance (QUASR) pulse sequence used for Signal Amplification by Reversible Exchange (SABRE), showing that we may target distantly J-coupled 19F-spins. Polarization transfer from the parahydrogen-derived hydrides to the 19F nucleus is accomplished via weak five-bond J-couplings using a shaped QUASi-Resonance...
Article
Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, whi...
Article
Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, whi...
Article
NMR hyperpolarization of uniformly 15N‐labeled metronidazole‐15N3 is demonstrated using SABRE‐SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In this antibiotic, a 15NO2 group is hyperpolarized via spin relays created by 15N spins in metronidazole‐15N3, and the polarization is transferred f...
Article
Full-text available
Signal amplification by reversible exchange (SABRE) is an efficient method to hyperpolarize spin-1/2 nuclei and affords signals that are orders of magnitude larger than those obtained by thermal spin polarization. Direct polarization transfer to heteronuclei such as 13C or 15N has been optimized at static microTesla fields or using coherence transf...
Article
Here we present the feasibility of NMR Signal Amplification by Reversible Exchange (SABRE) using radio-frequency irradiation at low magnetic field (0.05 T) in the regime, where the chemical shifts of free and catalyst bound species are similar. In SABRE, the 15N-containing substrate and parahydrogen perform simultaneous chemical exchange on an Irid...
Preprint
We describe an accurate and scalable implementation for the computation of molecular nuclear magnetic resonance shieldings, J-couplings, and magnetizabilities within nonrelativistic semilocal density functional theory, based on numeric atom-centered orbital (NAO) basis sets. We compare the convergence to the basis set limit for two established type...
Article
Full-text available
Hyperpolarized magnetic resonance (HP-MR) is a powerful, sensitive, and noninvasive approach to visualize molecular structure, function, and dynamics in vitro and in vivo. Current applications of HP-MR mostly rely on hyperpolarization of target compounds in dedicated hyperpolarizers because biomolecules can typically not be hyperpolarized directly...
Article
NMR is one of the most versatile and useful physical effects used for human imaging, chemical analysis and the elucidation of molecular structures. Yet, the full potential of NMR is hardly ever used, because only a small fraction of the nuclear spin ensemble is polarized - i.e. aligned with the applied static magnetic field. This fraction is termed...
Article
NMR is one of the most versatile and useful physical effects used for human imaging, chemical analysis and the elucidation of molecular structures. Yet, the full potential of NMR is hardly ever used, because only a small fraction of the nuclear spin ensemble is polarized - i.e. aligned with the applied static magnetic field. This fraction is termed...
Article
A systematic experimental study is reported on the polarization transfer to distant spins, which do not directly bind to the polarization transfer complexes employed in Signal Amplification By Reversible Exchange (SABRE) experiments. Both, long-range transfer to protons and long-range transfer to heteronuclei i.e. 13C and 15N are examined. Selectiv...
Article
We review experimental techniques in our laboratory for nuclear magnetic resonance (NMR) in zero and ultralow magnetic field (below 0.1 μT) where detection is based on a low-cost, non-cryogenic, spin-exchange relaxation free ⁸⁷Rb atomic magnetometer. The typical sensitivity is 20-30 fT/Hz1/2 for signal frequencies below 1 kHz and NMR linewidths ran...
Article
Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. In their Communication (DOI: 10.1002/anie.201704970) W. S. Warren, S. J. Malcolmson, Q. Wang, and co-workers show with a ¹⁵N2-diazirine-containing choline derivati...
Article
Diazirine sind dank ihrer Biokompatibilität und ihres leichten Einbaus in verschiedenartige Verbindungen aussichtsreiche molekulare Marker für Kernspintomographie und NMR-Spektroskopie. In ihrer Zuschrift (DOI: 10.1002/ange.201704970) zeigen W. S. Warren, S. J. Malcolmson, Q. Wang und Mitarbeiter anhand eines entsprechenden Cholinderivats, dass ¹⁵N...
Article
The Inside Cover picture visualizes the chemistry and spin physics endowing spontaneous polarization transfer from parahydrogen gas to ¹⁹F nuclear spins using reversible exchange of parahydrogen and to-be-hyperpolarized ¹⁹F-containing substrates on Iridium hexacoordinate complex.More information can be found in the Communication by E. Y. Chekmenev...
Article
Diazirines represent an attractive class of potential molecular tags for magnetic resonance imaging due to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15N2-diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path t...
Article
Diazirines represent an attractive class of potential molecular tags for magnetic resonance imaging due to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15N2-diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path t...
Article
Fluorine-19 has high NMR detection sensitivity-similar to that of protons, owing to its large gyromagnetic ratio and high natural abundance (100%). Unlike protons, however, fluorine-19 (19F) has a negligible occurrence in biological objects, as well as a more sensitive chemical shift. As a result, in vivo 19F NMR spectroscopy and MR imaging offer a...
Article
Nuclear spin hyperpolarization techniques are revolutionizing the field of 13C molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring ≈1 h) and costly (≈$USD10^6). As a consequence of carbon's central place in biochemistry, tremendous progress using 13C d-DNP bioimag...
Article
Full-text available
We review instrumentation for nuclear magnetic resonance (NMR) in zero and ultra-low magnetic field (ZULF, below 0.1 $\mu$T) where detection is based on a low-cost, non-cryogenic, spin-exchange relaxation free (SERF) $^{87}$Rb atomic magnetometer. The typical sensitivity is 20-30 fT/Hz$^{1/2}$ for signal frequencies below 1 kHz and NMR linewidths r...
Article
Full-text available
Direct NMR hyperpolarization of naturally abundant 15N sites in metronidazole is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In only a few tens of seconds, nuclear spin polarization P15N of up to ~24% is achieved using parahydrogen with 80% para- fraction corres...
Article
Nuclear magnetic resonance (NMR) with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios such, as 15N. To overcome this traditional NMR sensitivitylimitation, we use a recently introduced hyperpolarization method called "Signal Amplification By Reversible Exchange in...
Article
Full-text available
(15)N nuclear spins of imidazole-(15)N2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A (15)N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole-(15)N2 in methanol:aqueous buffer (∼1:1). Pr...
Article
In this paper we demonstrate long-lived states involving a pair of chemically equivalent protons, with lifetimes ∼30 times T1 up to a total lifetime of ∼117 s at high field (8.45 T). This is demonstrated on trans-ethylene-d2 in solution, where magnetic inequivalence gives access to the long-lived states. It is shown that the remaining J-coupling be...
Article
We report NMR Signal Amplification by Reversible Exchange (SABRE) hyperpolarization of the rare isotopes in "neat" liquids, each composed only of an otherwise pure target compound with isotopic natural abundance (n.a.) and millimolar concentrations of dissolved catalyst. Pyridine (Py) or Py derivatives are studied at 0.4% isotopic natural abundance...