About

Thomas Theis is an Associate Professor and the Goodnight Distinguished Scholar in Molecular Characterization at NC State University. His research focuses on developing hyperpolarization chemistry using para-hydrogen to enhance NMR and MRI signals by up to six orders of magnitude. This advancement enables new applications such as portable NMR and cost-efficient molecular imaging. His expertise lies in NMR and MRI, with a particular emphasis on overcoming their low sensitivity through innovative hyperpolarization techniques. Theis has contributed to the field through various publications on hyperpolarized imaging and spectroscopy, including work on SABRE-SHEATH hyperpolarization, zero-field NMR spectroscopy, and MRI of hyperpolarized compounds. He holds a Ph.D. in Chemistry from the University of California at Berkeley and an M.Sc. in Chemistry from the University of Göttingen.

Research topics

• Physics
• Chemistry
• Nuclear magnetic resonance
• Chemical physics
• Materials science
• Stereochemistry
• Physical chemistry
• Condensed matter physics
• Nuclear physics

Selected publications

• Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange

  UNC Libraries · 2026-04-08

  articleOpen access

  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 and transition states are calculated, and harmonic transition state theory is applied to calculate exchange rates that approximate experimental values. The reaction network energy surface can be modulated by chemical potentials that account for the dependence on concentration, temperature, and partial pressure of molecular constituents (hydrogen, methanol, pyridine) supplied to the experiment under equilibrium conditions. We show that, under typical experimental conditions, the Gibbs free energies of the two key states involved in pyridine-hydrogen exchange at the common Ir-IMes catalyst system in methanol are essentially the same, i. e., nearly optimal for SABRE. We also show that a methanol-containing intermediate is plausible as a transient species in the process.

  PublisherDOI

• A Versatile Compact Parahydrogen Membrane Reactor

  UNC Libraries · 2026-04-15

  articleOpen access

  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 with benchtop (1.1 T) and high field (9.4 T) NMR magnets, highlighting the versatility of this system to operate with any NMR or MRI system. The STAR uses semipermeable membranes to efficiently deliver parahydrogen into solutions at nano to milli Tesla fields, which enables ¹ H, ¹³ C, and ¹⁵ N hyperpolarization on a large range of substrates including drugs and metabolites. The unique features of the STAR are leveraged for important applications, including continuous hyperpolarization of metabolites, desirable for examining steady-state metabolism in vivo, as well as for continuous RASER signals suitable for the investigation of new physics.

  PublisherDOI

• Front Cover: Carbon‐13 Hyperpolarization of α‐Ketocarboxylates with Parahydrogen in Reversible Exchange (ChemMedChem 5/2025)

  ChemMedChem · 2025-03-03

  paratextOpen accessSenior authorCorresponding

  Shown on the cover is the hyperpolarization chemistry of α-ketoglutarate using parahydrogen in reversible exchange. Alpha-ketoglutarate is one example of the broad class of α-ketocarboxylates hyperpolarized in this work. These α-ketocarboxylates represent important biomarkers for the study of in vivo metabolic processes. The NMR and MRI sensitivity of these hyperpolarized biomarkers is enhanced by up to 30000-fold. More details can be found in article 10.1002/cmdc.202400378 by Stephen J. McBride, Thomas Theis, and co-workers.

  PublisherOA PDFDOI

• SABRE-SHEATH hyperpolarized ¹⁵ N ₂ -imidazole for Zn ²⁺ sensing

  Chemical Communications · 2025-01-01 · 3 citations

  articleOpen accessSenior authorCorresponding

  SABRE-SHEATH hyperpolarized 15 N 2 -imidazole is introduced as a novel 15 N NMR probe for Zn 2+ sensing. The method achieves 45 700 fold signal enhancement and a detection limit of 1.3 mM, enabling chemical sensing without penetration-depth limitations.

  PublisherOA PDFDOI

• Efficient 15N hyperpolarization of [15N3]metronidazole antibiotic via spin-relayed pulsed SABRE-SHEATH

  Journal of Magnetic Resonance Open · 2025-07-24 · 3 citations

  articleOpen access

  • 15N-labeled metronidazole antibiotic was hyperpolarized via pulsed SABRE-SHEATH method; • 15N polarization of up to 18% was achieved for 20 mM drug in 80 seconds; • Feasibility of spin-relayed polarization transfer between three 15N sites was demonstrated in pulsed SABRE-SHEATH; • 15N relaxation dynamics is reported in a wide range of magnetic fields. Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) is an NMR hyperpolarization technique that relies of the simultaneous exchange of parahydrogen and a to-be-hyperpolarized molecule on the metal center of a polarization-transfer catalyst in a microtesla magnetic field. Until recently, this method has been understood to perform hyperpolarization by establishing level anti-crossings between the nuclear spins of the parahydrogen derived hydrides (acting as a source of hyperpolarization) and those of the substrate. Recently, the application of highly non-intuitive pulse sequences (comprising pulses of microtesla DC fields) was predicted to hyperpolarize nuclear spins more efficiently than the canonical (static-field) SABRE-SHEATH approach. Here we show that by employing a basic “on-off” pulse sequence of rectangular microtesla pulses, it is possible to improve the hyperpolarization efficiency for SABRE-SHEATH of [ 15 N 3 ]metronidazole, an FDA-approved antibiotic (in non-enriched and non-hyperpolarized form) and potential hypoxia sensing molecule. Specifically, we demonstrate that 15 N polarization of 18.5% can be obtained in 80 s of parahydrogen bubbling parahydrogen through a solution containing 20 mM [ 15 N 3 ]metronidazole. In practice, (1.32±0.14)-fold improvements in P 15N was obtained with the pulsed method described here compared to static field technique variant. These results show that pulsed SABRE-SHEATH was successfully applied to 15 N-labeled biologically relevant molecule. Moreover, we also demonstrate that although the pulsed SABRE-SHEATH sequence was designed for polarization transfer from parahydrogen derived hydrides to the metronidazole’s 15 N catalyst-binding site, all three 15 N sites of [ 15 N 3 ]metronidazole attained the hyperpolarized state. This spin-relayed polarization transfer becomes possible due to the 15 N relay network established by their spin-spin J -couplings. The feasibility of the spin-relayed polarization transfer is demonstrated here for the first time for pulsed SABRE-SHEATH (as opposed to the static-field SABRE-SHEATH reported previously) and it paves the way to broad applicability of the technique.

  PublisherDOI

• Scalable Hyperpolarized MRI Enabled by Ace-SABRE of [1-13C]Pyruvate

  ChemRxiv · 2025-01-29 · 1 citations

  preprintOpen access

  Hyperpolarized (HP) MRI using [1-13C]pyruvate is emerging as a promising molecular imaging approach. Among hyperpolarization methods, Signal Amplification By Reversible Exchange (SABRE) is attractive because SABRE polarizes the substrates directly in room-temperature solutions avoiding complex hardware. Most SABRE experiments have historically been performed in methanol, a relatively toxic and difficult to remove solvent. Here we first demonstrate the use of a acetone-water-solvent system (Ace-SABRE) to provide hyperpolarized [1-13C]pyruvate with up to 40% polarization, then implement a solvent processing protocol to achieve injectable solutions, and lastly demonstrate HP in vivo spectroscopy and imaging using the Ace-SABRE platform to showcase metabolic tracking in a hepatocellular carcinoma (HCC) tumor as well as HP-MRI, both in direct comparison to dissolution dynamic nuclear polarization (d-DNP) experiments. The Ace-SABRE technique promises faster adoption of SABRE hyperpolarization in biological experiments, overall lowering the barriers to entry for HP-NMR and HP-MRI.

  PublisherOA PDFDOI

• Biocompatible SABRE Hyperpolarization of [1‐ ¹³ C]Ketoleucine for Cellular Metabolic Flux Sensing

  Chemistry - A European Journal · 2025-11-30 · 1 citations

  articleOpen access

  ABSTRACT Ketoleucine (α‐ketoisocaproate) is a novel hyperpolarized substrate for noninvasive metabolic imaging, enabling rapid, high‐sensitivity detection of branched‐chain amino acid flux, a pathway that is aberrant in many diseases including cancer and Alzheimer's disease. Utilizing NMR Signal Amplification by Reversible Exchange (SABRE) with an 80:20 acetone:water solvent system, we achieved >11% polarization of [1‐ 13 C]ketoleucine (corresponding to signal enhancement over 230,000‐fold at 0.55 T) at 70 mM within 2 min, using parahydrogen as a cheap and fast source of hyperpolarization. A two‐stage liquid–liquid extraction and gas stripping protocol removes excess excipients, yielding a biocompatible aqueous solution of [1‐ 13 C]ketoleucine (79 ± 10 mM). When mixed with Saccharomyces cerevisiae (Baker's yeast), hyperpolarized [1‐ 13 C]ketoleucine produced strong, long‐lasting signals, where downstream metabolites are observed for >200 s, allowing first‐order kinetic modeling of CO 2 and bicarbonate. These cell experiments demonstrate both the biocompatibility and signal strength of SABRE–hyperpolarized KL, establishing KL as a versatile hyperpolarized agent and opening avenues for real‐time investigation of metabolic dysregulation in cancer, neurodegenerative disorders, and beyond.

  PublisherOA PDFDOI

• Scalable Hyperpolarized MRI Enabled by Ace‐SABRE of [1‐ ¹³ C]Pyruvate

  Angewandte Chemie International Edition · 2025-04-23 · 12 citations

  articleOpen access

  Abstract Hyperpolarized (HP) MRI using [1– 13 C]pyruvate is emerging as a promising molecular imaging approach. Among hyperpolarization methods, Signal Amplification By Reversible Exchange (SABRE) is attractive because SABRE polarizes the substrates directly in room‐temperature solutions avoiding complex hardware. Most SABRE experiments have historically been performed in methanol, a relatively toxic and difficult‐to‐remove solvent. Here we demonstrate the use of a 80/20 acetone/water (A/W) solvent system (Ace‐SABRE) to provide hyperpolarized [1– 13 C]pyruvate with up to 17% polarization, then implement a solvent processing protocol to achieve injectable solutions retaining 74% of the initial polarization, and lastly we demonstrate HP in vivo spectroscopy and imaging using the Ace‐SABRE platform to showcase metabolic tracking in a hepatocellular carcinoma (HCC) tumor as well as HP‐MRI, both in direct comparison to dissolution dynamic nuclear polarization (d‐DNP) experiments. The Ace‐SABRE technique promises faster adoption of SABRE hyperpolarization in biological experiments, overall lowering the barriers to entry for HP‐NMR and HP‐MRI.

  PublisherOA PDFDOI

• >106 x enhancement of 13C-enriched pyruvate via in situ hyperpolarization in an ultra-low field MRI scanner

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: Altered cell metabolism is one of the hallmarks of cancer. 13C metabolic MRI has shown promise in delineating, grading and monitoring treatment response in cancer but 13C MRI has been dominated by dynamic nuclear polarization technology that is expensive and slow. Goal(s): A flexible and accessible alternative is necessary to enable the adoption of 13C MRI in standard of care cancer diagnosis and treatment. Approach: Spin-lock induced crossing signal amplification by reversible exchange (SLIC SABRE), a quick and versatile hyperpolarization technique, was used to polarize [1-13C] pyruvate in situ at 6.5mT. Results: Here we show hyperpolarized [1-13C] pyruvate enhanced by factors >106 times. Impact: These results are the first demonstration of 13C hyperpolarization generated and measured in situ at 6.5mT and showcase the flexibility and utility of SLIC SABRE as a hyperpolarization method to drive widespread adoption of 13C metabolic MRI in the clinic.

  PublisherDOI

• Photo-ejected ligands hyperpolarized by parahydrogen in reversible exchange

  Chemical Communications · 2025-01-01 · 4 citations

  articleOpen accessSenior authorCorresponding

  Hyperpolarization derived from signal amplification by reversible exchange (SABRE) is valued for its relative simplicity among hyperpolarization approaches. Here, we demonstrate that photoejection of the ligands pyridazine and pyrazine from prodrug Ru(II) polypyridyl complexes offers a new modality for activating SABRE hyperpolarization, achieving enhancements of over 3200-fold.

  PublisherOA PDFDOI

Recent grants

• Molecular imaging with a hyperpolarized Vitamin Shot

  NIH · $661k · 2018–2020

• Molecular MRI of Brain Metabolism Enabled by Long-Lived Spin States

  NIH · $807k · 2020–2023

Frequent coauthors

• Eduard Y. Chekmenev

  The Barbara Ann Karmanos Cancer Institute

  212 shared

• Warren S. Warren

  69 shared

• Andreas B. Schmidt

  German Cancer Research Center

  67 shared

• Gábor V. Horváth

  University of Szeged

  64 shared

• Aijun Deng

  Anhui University of Technology

  64 shared

• Chanaka Keerthisinghe

  New York Proton Center

  64 shared

• Ana Rita Silva

  University of Sydney

  64 shared

• Paulino Tardáguila

  University of Lisbon

  64 shared

Labs

• Thomas Theis LabPI

Education

• PhD, Chemistry

  University of California Berkeley

  2012

• Diplom, Chemistry

  Georg-August-Universitat Gottingen

  2006