Hyperpolarized NMR has emerged as a powerful analytical technique to significantly enhance targeted NMR signals, improving the sensitivity for investigations of unique chemical and biological dynamics. Here, we demonstrate the use of a hyperpolarization strategy based on Signal Amplification By Reversible Exchange (SABRE) to generate highly reproducible doses of a hyperpolarized [1-13C]pyruvate probe for benchtop characterization of yeast metabolism. This method allows rapid, scalable, and benchtop preparation of biocompatible hyperpolarized solutions suitable for live-cell experiments. We show that this production can be dove-tailed into a modular, compact workflow to characterize real-time metabolism in cell cultures, using Saccharomyces cerevisiae (Baker's yeast) as a model organism. With high temporal resolution, we show that this method can resolve the conversion of hyperpolarized [1-13C]pyruvate into oxidative decarboxylation products CO2 and bicarbonate. This conversion exhibits sustained and detectable metabolic activity for over 300 s after introduction of the agent to the cells. We model the metabolite kinetics to show decarboxylation activity and derive estimates of the pH over time from the CO2 and bicarbonate (carbonic acid buffer system) equilibrium to probe changes in the cellular environment during active metabolism. These results highlight the utility of benchtop SABRE-hyperpolarized [1-13C]pyruvate as a scalable, specific probe for metabolic phenotyping of living cells using compact, low-cost instrumentation well-suited for future high-throughput applications across microbial engineering, drug response profiling, and dynamic metabolic screening.

SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) is a parahydrogen-based hyperpolarization technique increasingly used for metabolic sensing. Typically limited to 5-mm NMR tube reactors (0.5-1 mL volumes) and requiring manual sample transfer for quantification, SABRE remains constrained by its throughput. Here, we describe a new low-field magnetic resonance system that enables in-situ polarimetry of hyperpolarized [1-13C]pyruvate. This setup utilizes a mu-metal shielded solenoid magnet, performing hyperpolarization at 0.4 μT (SABRE-SHEATH) and in-situ NMR sensing at 140 μT (1.6 kHz 13C frequency), which eliminates the need for sample transfer. We demonstrate that a surface-coil detection design accommodates diverse sample geometries, including 15-mm ID HPLC columns. By increasing the parahydrogen flow rate 12-fold, we successfully scaled the production of [1-13C]pyruvate to a 10-mL volume, achieving a 7% polarization level-comparable to that of smaller 0.8-mL samples. Furthermore, the integration of automated fluidics and a saddle-shaped RF excitation coil enables both SABRE-SHEATH and Spin-Lock Induced Crossing (SLIC)-SABRE protocols. Notably, we demonstrate the utility of this in-situ detection for optimizing SABRE conditions, including the screening of DMSO concentrations. Finally, the ability to operate with diverse solvent systems and scalable volumes lays the foundation for producing biocompatible hyperpolarized formulations, broadening the potential for metabolic research. These advances establish a scalable, automated framework for producing larger, biocompatible volumes of hyperpolarized molecular probes.

Medicine is evolving beyond therapy largely predicated on anatomical information and towards incorporating patient-specific molecular biomarkers of disease for more accurate diagnosis and effective treatment. The complementary combination of hyperpolarization by spin-lock induced crossing signal amplification by reversible exchange (SLIC SABRE) and low field magnetic resonance imaging (MRI) can enable accessible metabolic imaging to advance personalized medicine. Hyperpolarized 13C-enriched pyruvate has demonstrated promise for imaging metabolism in cancer, heart disease and neurodegenerative disorders; however, broader clinical adoption awaits validated clinical indications, and is further constrained by the cost and limited availability of current hyperpolarization technology. Parahydrogen-based polarization techniques, paired with low-cost high-performance MRI at millitesla fields, offer a means of broadening the reach of metabolic imaging. Here we show results demonstrating in situ hyperpolarization of pyruvate at 6.5 mT by SLIC SABRE, followed by immediate readout without field cycling or sample shuttling. We achieve 13C signal enhancements several million times above thermal equilibrium at 6.5 mT, corresponding to polarization levels of approximately 3%. Leveraging this enhancement, we perform 13C MRI and acquire NMR spectra with resolution sufficient to distinguish chemical shifts between pyruvate isotopomers. These results show a viable pathway towards accessible metabolic imaging with hyperpolarized 13C MRI at ultra-low field.

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 demonstrate the use of a 80/20 acetone/water (A/W) solvent system (Ace-SABRE) to provide hyperpolarized [1-13C]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.

Signal amplification by reversible exchange (SABRE) is a hyperpolarization method that polarizes target nuclei of metabolites quickly and efficiently. Recent SABRE advances, including Ace-SABRE, yield biocompatible, aqueous solutions of hyperpolarized markers for metabolic monitoring. Building on recent advancements, expanding the substrate scope of Ace-SABRE is desirable. However, SABRE polarization is sensitive to many different parameters; therefore, traditional optimization approaches are experimentally time-consuming. In this proof-of-concept application of machine learning (ML), Bayesian optimization (BO) is used for four important input parameters to model the complex SABRE dynamics while saving experimental time. The presented ML model also provides chemical insights that enable predictions of sample compositions for increased polarization levels. In this work, we transition from an original average free polarization of p = ∼0.90% to a maximum observed free polarization of p = ∼6.6% for 1-13C alpha-ketoglutarate (AKG) with 13C at natural abundance, utilizing both direct outputs as well as chemical insights revealed by the ML model.

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.

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.

Hyperpolarized [1-13C]pyruvate has emerged as a next-generation molecular probe for in vivo metabolic flux imaging in deep tissue. This molecular contrast agent is now under evaluation in over 50 clinical trials, according to clinicaltrials.gov. Hyperpolarized [1-13C]pyruvate is produced through dissolution dynamic nuclear polarization (d-DNP) for clinical research use. This remarkable hyperpolarization technique is regarded as expensive (>$2 M equipment cost) and slow (1 h production). One alternative hyperpolarization technique called Signal Amplification By Reversible Exchange (SABRE) in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) has recently garnered substantial attention for production of hyperpolarized [1-13C]pyruvate quickly (in 1 min) and inexpensively (<$20K equipment). It has been successfully demonstrated in vivo for metabolic imaging of cancer. This technique relies on the simultaneous chemical exchange of parahydrogen, acting as a source of nuclear spin order, and [1-13C]pyruvate on a Ir-IMes polarization transfer catalyst at ∼0.4 μm magnetic field. The SABRE catalyst forms two kinds of complexes with parahydrogen-derived hydrides, pyruvate, and dimethyl sulfoxide, acting as a critically important coligand; however, only the complex that binds pyruvate in an equatorial position can release hyperpolarized [1-13C]pyruvate into the solution to enable bulk HP [1-13C]pyruvate production for use in molecular imaging and other applications. Here, we investigate the interplay of pH and temperature with the SABRE-SHEATH hyperpolarization of [1-13C]pyruvate. Temperature and pH modulate this process in remarkable and complementary ways, greatly affecting pyruvate exchange and 13C relaxation dynamics. The overall process is optimal at pH (methanol) of 6.5-7.7 and a temperature of 6 °C: indeed, the catalyst-bound pyruvate exhibits high 13C polarization levels in excess of 25%. The 13C polarization results are additionally supported by 13C relaxation dynamics at a polarization field of 0.4 microtesla. These results provide deeper understanding of the SABRE-SHEATH process and pave the way to further improve the efficiency of the hyperpolarization technique.

Hyperpolarized (HP) 13C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-13C2]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD. Here, we pioneered the hyperpolarization of [1,5-13C2]Z-OMPD via SABRE-SHEATH (signal amplification by reversible exchange in shield enabling alignment transfer to heteronuclei), which is relatively simple and fast and promises to be highly scalable. With SABRE-SHEATH, we achieve enhancement values of ∼3950 and ∼2400 at 1.1 T (P13C = 0.4 and 0.25%) on the labeled C-1 and C-5 positions of Z-OMPD. Density functional theory calculations at the B3LYP level of theory were used to investigate possible binding modes of Z-OMPD on the iridium-based polarization transfer catalyst. The experimental and theoretical results suggest that the equatorial binding mode to the catalyst, where Z-OMPD binds to the catalyst at both C-1 and C-5 carboxylate positions, is the most stable complex. The HP signals were used to measure the Z-OMPD chemical shift as a function of pH showing an ∼3 ppm shift across pH 4-11. This work lays a foundation for the development of a simple, low-cost hyperpolarization technique to image pH.

Signal Amplification by Reversible Exchange (SABRE) is a relatively simple and fast hyperpolarization technique that has been used to hyperpolarize the alpha-ketocarboxylate pyruvate, a central metabolite and the leading hyperpolarized MRI contrast agent. In this work, we show that SABRE can readily be extended to hyperpolarize 13C nuclei at natural abundance on many other alpha-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P13C=17 %) and 2-oxobutyrate (P13C=25 %) with alkyl chains in the R-group, oxaloacetate (P13C=11 %) and alpha-ketoglutarate (P13C=13 %) with carboxylate moieties in the R group, and phenylpyruvate (P13C=2 %) and phenylglyoxylate (P13C=2 %) with phenyl rings in the R-group. New catalytically active SABRE binding motifs of the substrates to the hyperpolarization transfer catalyst - particularly for oxaloacetate - are observed. We experimentally explore the connection between temperature and exchange rates for all of these SABRE systems and develop a theoretical kinetic model, which is used to fit the hyperpolarization build-up and decay during SABRE activity.

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.

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. Biocompatible formulations of hyperpolarized [1-13C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging.

Hyperpolarization of 13C-pyruvate via Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for in vitro or in vivo studies. Here, we analyze the [1,2-13C2]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride-13C2 Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride-13C2-CH3 system. The analytical and the numerical results are compared to matching systematic experiments. With these methods we unravel the observed spin state mixing of singlet states and triplet states at microTesla fields and we also analyze the dynamics during transfer from micro-Tesla field to high field for detection to understand the resulting spectra from the [1,2-13C2]pyruvate-SABRE system.

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe the first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. A biocompatible formulation of hyperpolarized [1-13C]pyruvate was injected into healthy Sprague Dawley and Wistar rats, and metabolic conversion of pyruvate to lactate, alanine, pyruvate-hydrate, and bicarbonate was detected. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop scalable, next-generation molecular imaging.

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 (TripPHIP) 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.

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.

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of C-13(1) spins of [1-C-13]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 H2O. Order-unity C-13 (>50 %) polarization of catalyst-bound [1-C-13]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1-C-13]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 CD3OD. Efficient C-13 polarization is also enabled by favorable relaxation dynamics in sub-microtesla magnetic fields, as indicated by fast polarization buildup rates compared to the T-1 spin-relaxation rates (e. g., similar to 0.2 s(-1) versus similar to 0.1 s(-1), respectively, for a 6 mM catalyst-[1-C-13]pyruvate sample). Finally, the catalyst-bound hyperpolarized [1-C-13]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-C-13]pyruvate produced via comparatively fast and simple SABRE-SHEATH-based approaches.

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.

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.