@article{macculloch_browning_tomhon_lehmkuhl_chekmenev_theis_2023, title={Parahydrogen in Reversible Exchange Induces Long-Lived 15N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole}, volume={5}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.2c04817}, DOI={10.1021/acs.analchem.2c04817}, abstractNote={Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance 15N polarization. Distinct substrates require unique optimal parameter sets, including temperature, magnetic field, or a shaped magnetic field profile. The fine tuning of these parameters for individual substrates is demonstrated here to maximize 15N polarization. After optimization, including the usage of pulsed μT fields, the 15N nuclei on common anticancer drugs, letrozole and anastrozole, can be polarized within 1–2 min. The hyperpolarization can exceed 10%, corresponding to 15N signal enhancement of over 280,000-fold at a clinically relevant magnetic field of 1 T. This sensitivity gain enables polarization studies at naturally abundant 15N enrichment level (0.4%). Moreover, the nitrile 15N sites enable long-lasting polarization storage with [15N]T1 over 9 min, enabling signal detection from a single hyperpolarization cycle for over 30 min.}, journal={ANALYTICAL CHEMISTRY}, author={MacCulloch, Keilian and Browning, Austin and TomHon, Patrick and Lehmkuhl, Soeren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2023}, month={May} }
 @article{browning_macculloch_tomhon_mandzhieva_chekmenev_goodson_lehmkuhl_theis_2023, title={Spin dynamics of [1,2-C-13(2)]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields}, volume={25}, ISSN={["1463-9084"]}, url={https://doi.org/10.1039/D3CP00843F}, DOI={10.1039/d3cp00843f}, abstractNote={The spin dynamics during SABRE of [1,2- 13 C 2 ]pyruvate are detailed. An analytical model and numerical simulations are used to understand the selective formation of hyperpolarized magnetization or singlet order on the 13 C 2 -spin pair.}, number={24}, journal={PHYSICAL CHEMISTRY CHEMICAL PHYSICS}, author={Browning, Austin and Macculloch, Keilian and TomHon, Patrick and Mandzhieva, Iuliia and Chekmenev, Eduard Y. and Goodson, Boyd M. and Lehmkuhl, Soeren and Theis, Thomas}, year={2023}, month={Jun}, pages={16446–16458} }
 @article{schmidt_maissin_adelabu_nantogma_ettedgui_tomhon_goodson_theis_chekmenev_2022, title={Catalyst-Free Aqueous Hyperpolarized [1-13C]Pyruvate Obtained by Re-Dissolution Signal Amplification by Reversible Exchange}, volume={11}, ISSN={["2379-3694"]}, url={https://doi.org/10.1021/acssensors.2c01715}, DOI={10.1021/acssensors.2c01715}, abstractNote={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 has enabled unprecedented real-time MRI sensing of metabolism and tissue pH using hyperpolarized [1-13C]pyruvate as a biosensor with great potential for diagnosis and monitoring of cancer patients. However, current d-DNP is expensive and suffers from long hyperpolarization times, posing a substantial translational roadblock. Here, we report the development of Re-Dissolution Signal Amplification By Reversible Exchange (Re-D SABRE), which relies on fast and low-cost hyperpolarization of [1-13C]pyruvate by chemical exchange with parahydrogen at microtesla magnetic fields. [1-13C]pyruvate is precipitated from catalyst-containing methanol using ethyl acetate and rapidly reconstituted in aqueous media. 13C polarization of 9 ± 1% is demonstrated after redissolution in water with residual iridium mass fraction of 8.5 ± 1.5 ppm; further improvement is anticipated via process automation. Re-D SABRE makes hyperpolarized [1-13C]pyruvate biosensor available at a fraction of the cost (<$10,000) and production time (≈1 min) of currently used techniques and makes aqueous hyperpolarized [1-13C]pyruvate "ready" for in vivo applications.}, journal={ACS SENSORS}, author={Schmidt, Andreas B. and Maissin, Henri and Adelabu, Isaiah and Nantogma, Shiraz and Ettedgui, Jessica and TomHon, Patrick and Goodson, Boyd M. and Theis, Thomas and Chekmenev, Eduard Y.}, year={2022}, month={Nov} }
 @article{nantogma_eriksson_adelabu_mandzhieva_browning_tomhon_warren_theis_goodson_chekmenev_2022, title={Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-C-13]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH}, volume={11}, ISSN={["1520-5215"]}, url={https://doi.org/10.1021/acs.jpca.2c07150}, DOI={10.1021/acs.jpca.2c07150}, abstractNote={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 SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-13C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes. Here, we study the application of microtesla pulses to investigate their effect on C-13 polarization efficiency, compared to that of conventional SABRE-SHEATH employing a static field (∼0.4 μT), to provide the matching conditions of polarization transfer from parahydrogen-derived hydrides to the 13C-1 nucleus. Our results demonstrate that using square-microtesla pulses with optimized parameters can produce 13C-1 polarization levels of up to 14.8% (when detected, averaging over all resonances), corresponding to signal enhancement by over 122,000-fold at the clinically relevant field of 1.4 T. We anticipate that our results can be directly translated to other structurally similar biomolecules such as [1-13C]α-ketoglutarate and [1-13C]α-ketoisocaproate. Moreover, other more advanced pulse shapes can potentially further boost heteronuclear polarization attainable via pulsed SABRE-SHEATH.}, journal={JOURNAL OF PHYSICAL CHEMISTRY A}, author={Nantogma, Shiraz and Eriksson, Shannon L. and Adelabu, Isaiah and Mandzhieva, Iuliia and Browning, Austin and TomHon, Patrick and Warren, Warren S. and Theis, Thomas and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2022}, month={Nov} }
 @article{brown_mandzhieva_tomhon_theis_castellano_2022, title={Triplet Photosensitized para-Hydrogen Induced Polarization}, volume={11}, ISSN={["2374-7951"]}, url={https://doi.org/10.1021/acscentsci.2c01003}, DOI={10.1021/acscentsci.2c01003}, abstractNote={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 the associated NMR signals. PHIP often relies on thermal catalysis or, more infrequently, UV-activated catalytic hydrogenation. Light-activated hydrogenation enables direct and timed control over the hyperpolarization of target substrates, critical for identifying short-lived intermediates. Here, we use an established Ir(III) triplet photosensitizer (PS) to visible light sensitize the triplet ligand-field states in the d6-transition metal dihydride Ru(CO)(PPh3)3(H)2 (1). Excitation inside a 9.4 T NMR spectrometer with the PS and a 420 nm blue LED, under 3 atm of p-H2, successfully photosensitized hyperpolarization in 1 and in a range of unsaturated substrates at and below room temperature, up to 1630-fold. In otherwise identical experimental conditions without light activation, no polarization was realized in 1 or the substrates evaluated. We believe triplet-sensitized PHIP (Trip-PHIP) represents a facile experimental means for probing triplet sensitized light activation in transition metal catalysts possessing low-lying triplet ligand-field states, providing mechanistic insight of potentially tremendous value in chemical catalysis.}, journal={ACS CENTRAL SCIENCE}, author={Brown, Emily E. and Mandzhieva, Iuliia and TomHon, Patrick M. and Theis, Thomas and Castellano, Felix N.}, year={2022}, month={Nov} }
 @article{tomhon_han_lehmkuhl_appelt_chekmenev_abolhasani_theis_2021, title={A Versatile Compact Parahydrogen Membrane Reactor}, volume={10}, ISSN={["1439-7641"]}, DOI={10.1002/cphc.202100667}, abstractNote={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.}, journal={CHEMPHYSCHEM}, author={TomHon, Patrick M. and Han, Suyong and Lehmkuhl, Soren and Appelt, Stephan and Chekmenev, Eduard Y. and Abolhasani, Milad and Theis, Thomas}, year={2021}, month={Oct} }
 @article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange}, volume={9}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100204}, DOI={10.1002/cphc.202100204}, abstractNote={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.}, journal={CHEMPHYSCHEM}, publisher={Wiley}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Soren and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Sep} }
 @article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange}, volume={22}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100678}, DOI={10.1002/cphc.202100678}, abstractNote={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.}, number={19}, journal={CHEMPHYSCHEM}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Soren and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Oct}, pages={1937–1938} }
 @article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Front Cover: Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange (ChemPhysChem 19/2021)}, url={https://doi.org/10.1002/cphc.202100677}, DOI={10.1002/cphc.202100677}, journal={ChemPhysChem}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Sören and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Oct} }
 @article{macculloch_tomhon_browning_akeroyd_lehmkuhl_chekmenev_theis_2021, title={Hyperpolarization of common antifungal agents with SABRE}, volume={59}, ISSN={["1097-458X"]}, url={https://doi.org/10.1002/mrc.5187}, DOI={10.1002/mrc.5187}, abstractNote={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 drugs (voriconazole, clotrimazole, and fluconazole) and elicit the detailed HP mechanisms for 1 H and 15 N nuclei. In this exploratory work, 15 N polarization values of ~1% were achieved using 50% pH2 in solution of 3-mM catalyst and 60-mM substrate in perdeuterated methanol. All hyperpolarized 15 N sites exhibited long T1 in excess of 1 min at a clinically relevant field of 1 T. Hyperpolarizing common drugs is of interest due to their potential biomedical applications as MRI contrast agents or to enable studies on protein dynamics at physiological concentrations. We optimize the polarization with respect to temperature and the polarization transfer field (PTF) for 1 H nuclei in the millitesla regime and for 15 N nuclei in the microtesla regime, which provides detailed insights into exchange kinetics and spin evolution. This work broadens the SABRE substrate scope and provides mechanistic and kinetic insights into the HP process.}, number={12}, journal={MAGNETIC RESONANCE IN CHEMISTRY}, publisher={Wiley}, author={MacCulloch, Keilian and Tomhon, Patrick and Browning, Austin and Akeroyd, Evan and Lehmkuhl, Soren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Jun} }
 @article{han_ramezani_tomhon_abdel-latif_epps_theis_abolhasani_2021, title={Intensified continuous extraction of switchable hydrophilicity solvents triggered by carbon dioxide}, volume={23}, ISSN={["1463-9270"]}, url={https://doi.org/10.1039/D1GC00811K}, DOI={10.1039/d1gc00811k}, abstractNote={An intensified continuous flow strategy is developed and utilized for scalable extraction of switchable hydrophilicity solvents triggered by carbon dioxide.}, number={8}, journal={GREEN CHEMISTRY}, publisher={Royal Society of Chemistry (RSC)}, author={Han, Suyong and Ramezani, Mahdi and TomHon, Patrick and Abdel-Latif, Kameel and Epps, Robert W. and Theis, Thomas and Abolhasani, Milad}, year={2021}, month={Apr}, pages={2900–2906} }
 @article{arunkumar_bucher_turner_tomhon_glenn_lehmkuhl_lukin_park_rosen_theis_et al._2021, title={Micron-Scale NV-NMR Spectroscopy with Signal Amplification by Reversible Exchange}, volume={2}, ISSN={2691-3399}, url={http://dx.doi.org/10.1103/prxquantum.2.010305}, DOI={10.1103/PRXQuantum.2.010305}, abstractNote={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 concentration sensitivity of about $10^5$ over thermal polarization by hyperpolarizing sample proton spins through signal amplification by reversible exchange (SABRE), enabling micron-scale NMR of small molecule sample concentrations as low as 1 millimolar in picoliter volumes. The SABRE-enhanced NV-NMR technique may enable detection and chemical analysis of low concentration molecules and their dynamics in complex micron-scale systems such as single-cells.}, number={1}, journal={PRX Quantum}, publisher={American Physical Society (APS)}, author={Arunkumar, Nithya and Bucher, Dominik B. and Turner, Matthew J. and TomHon, Patrick and Glenn, David and Lehmkuhl, Sören and Lukin, Mikhail D. and Park, Hongkun and Rosen, Matthew S. and Theis, Thomas and et al.}, year={2021}, month={Jan}, pages={010305} }
 @article{adelabu_tomhon_kabir_nantogma_abdulmojeed_mandzhieva_ettedgui_swenson_krishna_theis_et al._2021, title={Order-Unity C-13 Nuclear Polarization of [1-C-13]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement}, volume={23}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100839}, DOI={10.1002/cphc.202100839}, abstractNote={Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of 13 C1 spins of [1-13 C]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 between temperature and co-ligation of DMSO and H2 O. Order-unity 13 C (>50 %) polarization of catalyst-bound [1-13 C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1-13 C]pyruvate at lower temperatures. On the catalyst bound pyruvate, 39 % polarization is measured using a 1.4 T NMR spectrometer, and extrapolated to >50 % at the end of build-up in situ. The highest measured polarization of a 30-mM pyruvate sample, including free and bound pyruvate is 13 % when using 20 mM DMSO and 0.5 M water in CD3 OD. Efficient 13 C polarization is also enabled by favorable relaxation dynamics in sub-microtesla magnetic fields, as indicated by fast polarization buildup rates compared to the T1 spin-relaxation rates (e. g., ∼0.2 s-1 versus ∼0.1 s-1 , respectively, for a 6 mM catalyst-[1-13 C]pyruvate sample). Finally, the catalyst-bound hyperpolarized [1-13 C]pyruvate can be released rapidly by cycling the temperature and/or by optimizing the amount of water, paving the way to future biomedical applications of hyperpolarized [1-13 C]pyruvate produced via comparatively fast and simple SABRE-SHEATH-based approaches.}, number={2}, journal={CHEMPHYSCHEM}, publisher={Wiley}, author={Adelabu, Isaiah and TomHon, Patrick and Kabir, Mohammad S. H. and Nantogma, Shiraz and Abdulmojeed, Mustapha and Mandzhieva, Iuliia and Ettedgui, Jessica and Swenson, Rolf E. and Krishna, Murali C. and Theis, Thomas and et al.}, year={2021}, month={Dec} }
 @article{tomhon_abdulmojeed_adelabu_nantogma_kabir_lehmkuhl_chekmenev_theis_2021, title={Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate}, url={https://doi.org/10.26434/chemrxiv-2021-cpz32}, DOI={10.26434/chemrxiv-2021-cpz32}, abstractNote={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, hyperpolarized MRI with dynamic nuclear polarization (DNP) is complex, costly and requires complex in-frastructure. In contrast, signal amplification by reversible exchange (SABRE) is a fast, cheap, and scalable hyperpo-larization technique. In particular, SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) transfers polarization from parahydrogen to 13C in pyruvate, however, to date, SABRE-SHEATH of 13C-pyruvate was limited in polarization levels relative to DNP (1.7% with SABRE-SHEATH vs. ~60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-13C]pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, ~20% polarization is accumulated on SABRE-catalyst bound pyruvate, which is subsequently released into free pyruvate in solution at elevated temperatures. We take ad-vantage of the achieved polarization to demonstrate first 13C pyruvate images with a cryogen-free MRI system operat-ed at 1 T. This illustrates that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.}, author={TomHon, Patrick and Abdulmojeed, Mustapha and Adelabu, Isaiah and Nantogma, Shiraz and Kabir, Mohammad Shah Hafez and Lehmkuhl, Sören and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Aug} }
 @article{tomhon_abdulmojeed_adelabu_nantogma_kabir_lehmkuhl_chekmenev_theis_2021, title={Temperature Cycling Enables Efficient C-13 SABRE-SHEATH Hyperpolarization and Imaging of [1-C-13]-Pyruvate}, volume={12}, ISSN={["1520-5126"]}, url={https://doi.org/10.1021/jacs.1c09581}, DOI={10.1021/jacs.1c09581}, abstractNote={Molecular metabolic imaging in humans is dominated by positron emission tomography (PET). An emerging nonionizing alternative is hyperpolarized MRI of 13C-pyruvate, which is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dissolution dynamic nuclear polarization (d-DNP) is complex costly, and requires significant infrastructure. In contrast, Signal Amplification By Reversible Exchange (SABRE) is a fast, cheap, and scalable hyperpolarization technique. SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) can transfer polarization from parahydrogen to 13C in pyruvate; however, polarization levels remained low relative to d-DNP (1.7% with SABRE-SHEATH versus ≈60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-13C]-pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, ≈20% polarization is accumulated on SABRE catalyst-bound pyruvate, which is released into free pyruvate at elevated temperatures. A kinetic model of differential equations is developed that explains this effect and characterizes critical relaxation and buildup parameters. With the large polarization, we demonstrate the first 13C pyruvate images with a cryogen-free MRI system operated at 1.5 T, illustrating that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, publisher={American Chemical Society (ACS)}, author={TomHon, Patrick and Abdulmojeed, Mustapha and Adelabu, Isaiah and Nantogma, Shiraz and Kabir, Mohammad Shah Hafez and Lehmkuhl, Soren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Dec} }
 @article{tomhon_akeroyd_lehmkuhl_chekmenev_theis_2020, title={Automated pneumatic shuttle for magnetic field cycling and parahydrogen hyperpolarized multidimensional NMR}, volume={312}, ISSN={1090-7807}, url={http://dx.doi.org/10.1016/j.jmr.2020.106700}, DOI={10.1016/j.jmr.2020.106700}, abstractNote={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. Relaxation-protected singlet states are evaluated by variable-field T1 and TS measurements. Automated shuttling facilitates characterization of hyperpolarization dynamics, field dependence and polarization buildup rates. Furthermore, reproducible hyperpolarization levels at every shuttling event enables automated 2D hyperpolarized NMR, including the first inverse 15N/1H HSQC. We uncover binding mechanisms of the catalytic species through cross peaks that are not accessible in standard one-dimensional hyperpolarized experiments. The simple design of the shuttling setup interfaced with standard TTL signals allows easy adaptation to any standard NMR magnet.}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={TomHon, Patrick and Akeroyd, Evan and Lehmkuhl, Sören and Chekmenev, Eduard Y. and Theis, Thomas}, year={2020}, month={Mar}, pages={106700} }