From Unlocking Pyruvate Hyperpolarization by Signal Amplification by Reversible Exchange (SABRE) to Clinical Prospects

Abstract

Hyperpolarization in magnetic resonance has emerged as a transformative approach to overcome the intrinsic sensitivity limits of NMR and MRI. Among the accessible hyperpolarization methods, Signal Amplification by Reversible Exchange (SABRE) has attracted considerable attention due to its rapidity, simplicity, and low operational cost. However, extending SABRE to biologically relevant metabolites notably pyruvate, remained challenging because carboxylates do not bind to the iridium-based catalysts. Over the past decade, series of mechanistic insights, catalyst innovations, and field-cycling strategies have been developed to redefin the hyperpolarization landscape, enabling robust SABRE-based polarization of ¹³C-labeled pyruvate. This review provides a comprehensive and coherent synthesis of these developments, beginning with the mechanistic foundations of SABRE, followed by an analysis of the limitations of early approaches, the breakthrough enabled by DMSO-assisted catalyst activation, and the evolution of SABRE-SHEATH, pulsed-field, SLIC-based, and LIGHT-SABRE methodologies. Particular emphasis is placed on catalyst structure–function relationships, substrate exchange kinetics, and the magnetic-field conditions governing polarization transfer. The review examines recent progress toward biocompatible formulations, catalyst recycling, and rapid purification workflows that have allowed the first in vivo metabolic imaging studies using SABRE-polarized pyruvate. The accumulated evidence demonstrates that SABRE is progressing rapidly from a chemical innovation to a practical hyperpolarization approach capable of complementing or even competing with dissolution DNP in preclinical metabolic imaging.

1. Introduction

Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) are indispensable analytical and biomedical tools, but their utility is fundamentally constrained by the low thermal polarization of nuclear spins. This limitation becomes particularly problematic in metabolic imaging, where many biologically relevant substrates are present at low concentrations or undergo rapid transformation. Hyperpolarization techniques address this challenge by generating spin populations far from Boltzmann distribution that enhance NMR signals by several orders of magnitude. Dissolution dynamic nuclear polarization (d-DNP) has dominated the field for more than a decade, enabling groundbreaking studies of real-time metabolism monitoring using hyperpolarized [1-¹³C]­pyruvate. − However, d-DNP requires cryogenic infrastructure, long preparation times, and high operational costs, which limit its widespread adoption. Signal Amplification by Reversible Exchange (SABRE) represents a fundamentally different approach to hyperpolarization. Rather than relying on cryogenic polarization of electronic spins, SABRE uses the spin latent singlet state of parahydrogen (p-H₂) and transfers this state to a substrate via a metal-based catalyst. The process is fast, continuously renewable, and does not chemically modify the substrate. , Early SABRE studies focused on nitrogen containing heterocycles, which have strong affinity to the catalyst. , Extending SABRE to more diverse substrate families including metabolites which are lacking of catalyst affinity has become a major objective. Pyruvate is an essential intermediate in glycolysis and the citric acid cycle. It has been considered as the dominant molecular probe for metabolic MRI due to its central role in cellular energy production and its rapid conversion to lactate, alanine, and bicarbonate. PHIP-SAH (ParaHydrogen Induced Polarization - Side Arm Hydrogenation) a hyperpolarization method based on p-H₂ has been developed to polarize pyruvate and acetate via hydrogenation reaction. However, from the introduction of SABRE in 2009 until 2018, pyruvate hyperpolarization through SABRE remained difficult to achieve because it does not bind strongly to iridium metal center and undergoes competing chemical reactions such as imine formation with amines. ,,, The solution to this challenge emerged only when mechanistic studies revealed that appropriate coligands notably sulfoxides such as dimethyl sulfoxide (DMSO) could stabilize an iridium–pyruvate complex competent for polarization transfer. − Since that breakthrough, SABRE-based pyruvate hyperpolarization has advanced rapidly. Innovations in coligand identity, catalyst architecture, magnetic-field control (microtesla SABRE-SHEATH, pulsed-field schemes), and spin-lock-induced crossing (SLIC) techniques have enabled polarization levels exceeding 10–20% in solution, with even higher values observed for catalyst-bound intermediates. More recently, significant progress has been made toward biocompatible formulations and rapid purification, enabling the first in vivo demonstrations of SABRE-hyperpolarized pyruvate in mices and tumor models. This review integrates these developments into a coherent narrative, emphasizing the mechanistic principles that govern SABRE behavior, the chemical strategies that unlocked pyruvate binding, and the technological advances that transformed SABRE into a viable platform for metabolic imaging.

2. Principles of SABRE Hyperpolarization

SABRE ,− is a p-H₂-based hyperpolarization technique that overcomes many limitations of conventional polarization methods by exploiting the reversible binding of both p-H₂ and a target substrate to a suitable iridium-based catalyst (Figure ). Unlike classical parahydrogen-induced polarization (PHIP), SABRE does not require the chemical incorporation of hydrogen into the substrate. Instead, it relies on transient coordination within a polarization-transfer complex in which J-couplings enable the conversion of p-H₂ singlet order into enhanced nuclear magnetization on the substrate. ,,, The core of SABRE process is the iridium-based precatalyst which is typically derived from [Ir­(IMes)­(COD)­Cl], where IMes (1,3-bis­(2,4,6-trimethylphenyl)­imidazol-2-ylidene) ligand denotes a sterically demanding N-heterocyclic carbene ligand. ,,

1.

SABRE Concept. In the SABRE process, the catalyst mediates polarization transfer from p-H₂ to the target substrate (L) at low field.

Upon activation with p-H₂, the precatalyst yields a dihydride species capable of binding multiple equivalents of the target substrate to form an octahedral complex. In the classical SABRE mechanism, three substrate molecules coordinate to the iridium center, forming complexes of the general formula [Ir­(H)₂(IMes)­(substrate)₃]­Cl. These complexes are in rapid exchange with free substrate in solution. The hyperpolarization process proceeds under low magnetic field conditions, often in the microtesla-to-gauss range, where the spin energy levels of the hydrides and the bound substrate requested nuclei are coupled. This condition promotes coherent evolution of spin order through level anticrossings (LACs). , The two hydride ligands from p-H₂ preserve their singlet character upon binding, and their mutual J-coupling network with the substrate nuclei facilitates polarization transfer through the iridium metal center. Interestingly, the catalyst continuously exchanges substrate molecules which make the polarized magnetization distributed to the bulk solution without any chemical modification. The main factors governing the efficiency of SABRE include: 1- Ligand exchange kinetics, which must be fast enough to deliver polarized substrate to solution but not so fast that the polarization transfer window becomes too short. 2- Hydride lifetime and relaxation, which determine how long the singlet-derived order remains available for transfer. 3- Catalyst geometry and ligand field, which modulate coupling networks and influence the strength of interactions between hydrides and substrate nuclei. 4- Magnetic field strength during polarization, as LACs that optimize polarization transfer for ¹H, ¹³C, or ¹⁵N occur at different field conditions. ,− For ¹³C and ¹⁵N heteronuclear polarizations further enhancements are achieved using SABRE-SHEATH (Shield Enables Alignment Transfer to Heteronuclei). This approach uses high-permeability magnetic shields to achieve ultralow magnetic fields (typically <1 μT) that match the energy differences required for heteronuclear spin order transfer. In this range, hyperpolarization efficiencies can exceed those observed at higher fields, especially when the substrate binds directly to the catalyst. Although SABRE is powerful technique, but it is limited by the need for reversible substrate binding. This requirement has long hindered the hyperpolarization of weakly iridium-bound molecules, particularly carboxylic acids, phosphates, and other oxygen-rich molecules.

3. Early Attempts to Hyperpolarize Pyruvate

The extension of SABRE to biologically relevant molecules, and particularly pyruvate, represented one of the earliest and most persistent challenges in the field. When SABRE was first introduced in 2009, its substrate scope was largely restricted to compounds capable of directly coordinating to iridium via nitrogen lone pairs. Consequently, heteroaromatic amines such as pyridine, nicotinamide, and methyl nicotinate exhibited strong hyperpolarization because they bind strongly to the iridium center. , In contrast, oxygen-based molecules, amines, amides, and phosphates do not efficiently enough bind to the iridium and therefore were assumed to be incompatible for SABRE. Pyruvate, a central metabolite in cellular energetics, was an especially important target because of its transformative impact in dissolution-DNP metabolic imaging. Under classical SABRE conditions, pyruvate fails to bind efficiently enough to iridium due to the weak Lewis basicity of the carboxylate group. As a result, for nearly a decade after SABRE’s introduction, pyruvate hyperpolarization was regarded as chemically inaccessible.

Early attempts to overcome this limitation focused on SABRE- Relay, a variant in which hyperpolarization is first imparted to a donor molecule containing a labile proton typically an amine and subsequently transferred to the target substrate via proton exchange. ,, SABRE-Relay successfully broadened SABRE’s substrate scope to include alcohols, amines, and several heteronuclei (¹³C, ¹⁵N, ³¹P, ²⁹Si). ,, However, pyruvate presented an additional complication. Indeed, in the presence of amines, it undergoes rapid nucleophilic addition to form α-carboxyimine intermediates (Schiff bases), particularly with benzylamine or phenylethylamine. These imine products not only alter the chemical composition of the mixture but also interfere with the formation of silent SABRE polarization-transfer complex. Tickner et al. revealed that the combination of amines, pyruvate, and Ir-based precatalyst forms α-carboxyimine complexes such as [Ir­(H)₂(amine)­(IMes)­(η¹/η²-imine)]­Cl. These complexes exist as two regioisomers depending on the orientation of the amine relative to the hydrides (Scheme ). Although these species demonstrated some catalytic activity, they did not show efficient polarization transfer to pyruvate or its imine derivatives. Their formation effectively prevented the pyruvate binding necessary for SABRE polarization. Nevertheless, the SABRE-Relay approach produced only modest hyperpolarization levels and suffered from the reactivity of pyruvate toward amine molecules. In the case of ¹³C-labeled sodium pyruvate, the ¹³C signal enhancements were observed for only a few minutes before disappearing, because of the instability of the catalytic system and the rapid consumption of reactive intermediates through imine formation.

1. [IrCl­(COD)­(IMes)], 1, Reacts with the Amines and Hydrogen Gas in Dichloromethane-d ₂ To Produce 1b; Further Reaction with an Equilibrium Mixture of Pyruvate and Imine Yield the Iridium α-Carboxyimine Complexes 1c and 1d (Reproduced with Permission from Ref . Copyright 2018, Wiley).

4. Breakthrough Using DMSO Coligands

The long-standing obstacle to pyruvate SABRE hyperpolarization was the absence of a coordination mode that make the pyruvate reversible binding stable to iridium catalyst. Pyruvate, can bind weakly the iridium metal center through its oxygen atoms, and prior attempts produced unstable, nonproductive complexes that usually decomposed upon activation by hydrogen. A conceptual breakthrough occurred when Iali et al, unlocked the pyruvate hyperpolarization by SABRE by the use of DMSO as coligand (Scheme ). Interestingly, DMSO allows the formation of highly reactive polarization transfer catalyst that stabilize pyruvate binding in a bidentate (η²-carboxylate) fashion. In the presence of DMSO, p-H₂, and [Ir­(IMes)­(COD)­Cl], the system no longer collapses into inactive or decomposed species. However, it forms a well-stable iridium complexes, most notably [Ir­(H)₂(η²-pyruvate)­(DMSO)­(IMes)], in which pyruvate binds through both oxygen atoms of the carboxylate group. This bonding mode is significantly stronger and more geometrically favorable than any previously observed for carboxylates in SABRE systems. The NMR characterization revealed two distinct isomers in addition to the activated catalyst [IrCl­(H₂)­(DMSO)₂(IMes)]: an equatorial–equatorial bidentate species (3a), and an axial–equatorial isomer (3b) (Scheme ). ,

2. Pyruvate Hyperpolarization by SABRE Assisted by DMSO Coligand (Reproduced with Permission from Ref . Copyright 2019, Wiley).

3. Activated Pyruvate Catalysts Species (3a and 3b) and the Precursor 2 (Reproduced with Permission from Ref . Copyright 2019, Wiley).

Among these, 3a dominates under typical SABRE conditions and is predicted by DFT calculation to be the thermodynamically preferred isomer. Importantly, 3a provides the optimal orientation of hydrides and substrate nuclei needed for efficient J-coupling polarization transfer. It also exhibits slow ligand exchange relative to the precursor complex, providing enough residence time for parahydrogen-derived spin order to evolve into ¹³C magnetization on pyruvate. ,

The discovery of DMSO’s catalytic role also clarified why previous systems failed. Classical SABRE relies on rapid exchange of substrate molecules on a catalyst surface that remains structurally intact. However, in pyruvate-containing mixtures, the iridium precatalyst tended to undergo rapid decomposition, often forming insoluble black iridium species. DMSO prevents this decomposition by stabilizing hydride-containing complexes, particularly the precursor [IrCl­(H)₂(DMSO)₂(IMes)] (2). This species was essential because it serves as a hydride-exchange reservoir, providing fresh p-H₂ and maintaining a dynamic equilibrium with the catalytically active pyruvate-bound 3a. Thus, pyruvate hyperpolarization is the result of a finely balanced interplay between: a stable, strongly binding complex (3a) that enables polarization transfer, and a rapidly exchanging reservoir (2) that supplies fresh hydrides and facilitates continuous turnover.

This mechanistic scheme explains why pyruvate SABRE operates only under specific ligand conditions, why sulfoxides have unique capabilities as coligands, and why earlier systems were trapped by weak substrate binding and irreversible side reactions.

The initial reports of DMSO-enabled SABRE-SHEATH hyperpolarization of ¹³C-pyruvate demonstrated polarization levels near 1%, enough to acquire the first SABRE-based ¹³C NMR and MRI images of pyruvate and monitor its chemical conversion in vitro. ,, These results have been considered historically significant, as they marked the first time when SABRE could be used to polarize the most important metabolic imaging probe. Furthermore, the approach successfully hyperpolarized multiple isotopologues, including [1-¹³C], [2-¹³C], [1,2-¹³C₂], and fully ¹³C-labeled [1,2,3-¹³C₃] pyruvate. Notably, the [1,2-¹³C₂] isotopologue exhibited long-lived singlet state upon hyperpolarization, opening new avenues for exploiting long-lived spin states in low-field environments.

Interestingly, the introduction of DMSO as a coligand transformed pyruvate from a nonaccessible SABRE substrate into one of the most intensively optimized and deeply studied systems in the SABRE literature. This conceptual shift opened the way for subsequent improvements including coligand screening, catalyst redesign, and field-cycling innovations which dramatically improved polarization levels and robustness, as explored in the following sections.

5. Mechanistic Insights and Catalyst Chemistry Optimization

The emergence of DMSO-enabled SABRE hyperpolarization of pyruvate stimulated a deeper investigation into the mechanistic underpinnings that govern catalyst structure, ligand exchange dynamics, and the efficiency of spin-order transfer. These studies revealed that pyruvate SABRE is governed by a delicate and highly tunable equilibrium between multiple iridium species, each contributing distinctively to polarization build-up, hydride exchange, and relaxation pathways.

5.1. Coordination Geometry and Isomeric Forms

The active polarization-transfer complex consists of pyruvate bound in a bidentate (η²) fashion, forming two principal isomers: 3a: the equatorial–equatorial pyruvate isomer, 3b: the axial–equatorial pyruvate isomer. DFT calculations consistently identify 3a as significantly lower in energy than 3b, and experimental spectra confirm that 3a is the dominant species at room temperature and under typical SABRE conditions. The structural preference for 3a arises from a favorable arrangement of the Ir–H hydrides, the IMes ligand, and the sulfoxide coligand, producing a stable geometry with well-defined J-coupling networks between hydrides and the ¹³C nuclei of the bound pyruvate. The 3b isomer, though observable, exhibits reduced polarization efficiency because its geometric configuration produces less optimal spin connectivity and too short hydride lifetimes for efficient hyperpolarization.

5.2. Role of Precursor Complex 2 in Hydride Exchange

Alongside the active complex 3a, the precatalyst species [IrCl­(H)₂(DMSO)₂(IMes)] (2) serves as a key reservoir for hydride exchange. Unlike 3a, which binds pyruvate strongly and exchanges it slowly, 2 undergoes rapid reversible binding of DMSO and hydrides. This fast exchange enables continuous replenishment of p-H₂-derived hydride ligands, which are essential to maintain the flow of singlet order throughout the SABRE process. Mechanistically, the polarization of pyruvate does not arise directly from the continuous reversible ligand exchange of 3a itself. Instead, it results from a dynamic equilibrium where 2 undergoes rapid hydrogen exchange to supply fresh p-H₂-derived hydrides that subsequently migrate into the pyruvate-bound complex. This interplay ensures that the catalyst simultaneously supports strong substrate binding (in 3a) and rapid hydride turnover (via 2), a dual requirement unique to carboxylate-based SABRE systems.

5.3. Exchange Kinetics and J-Coupling Constraints

Hyperpolarization efficiency is determined by the longitudinal relaxation (T ₁), the substrate dissociation rate and the hydride exchange rate. Experimental studies and numerical simulations indicate that pyruvate dissociates from complex 3a at a rate of approximately 4 s^–1, a value slow enough to allow prolonged spin coherence within the active complex but fast enough to replenish free hyperpolarized pyruvate in solution.

Neatly aligned with these kinetic constraints is the ³J-CH coupling of ∼5 Hz between the hydride and the ¹³C nucleus of [1-¹³C]­pyruvate. This moderate coupling strength supports efficient LAC-driven polarization transfer in the microtesla order. Polarization transfer becomes less efficient outside this field window, underscoring the need for precise magnetic-field control during SABRE-SHEATH or pulsed-field SABRE.

5.4. Influence of Chloride, Coligands, and Electronic Structure

Systematic variation of ligand identity has revealed several important design principles for pyruvate SABRE:

Chloride Concentration

Increasing free chloride shifts the equilibrium away from the pyruvate-bound complex 3a toward the precursor 2, dramatically decreasing polarization. This shift emphasizes the importance of maintaining low halide activity during catalyst activation.

Coligand Identity

Many coligands such as triphenylphospine, 4-chlorobenzenemethanethiol, formaldehyde, ethylisothiocyanate, thiophene and others have been tested toward the formation of [Ir­(H)₂(η²-pyruvate)­(L)­(IMes)] but all these coligand failed in favoriting the coordination of pyruvate to the iridium metal center. However, only sulfoxides were capable to support the pyruvate binding to the iridium to form the required complex for polarization transfer. To identify the best sulfoxide, ten coligands sulfoxide based have been selected to study the effect of sulfoxide identities on the pyruvate ¹³C₂ signal enhancement. This study shows that the sulfoxide identity plays a significant role in the determination of active SABRE catalyst 3a concentration in the solution, in the efficiency level of the polarization transfer process and also the stability of 3a. Methylphenyl sulfoxide was identified as the best coligand in terms of ¹³C signal enhancement and catalyst stability. However, DMSO was identified as the best sulfoxide in terms only ¹³C signal enhancement but 23% of the active catalyst was decomposed after 1 h of the preparation. ,

Catalyst and Electronic Properties of NHC Ligands

Since the catalyst played the major role in SABRE hyperpolarization, the study of catalyst identity of pyruvate polarization has been carried out by selection three catalyst families which were NHC-based precatalyst, phosphine precatalyst and asymmetric NHC precatalyst. Symmetric NHC precatalyst favored the formation of 3a and yield to efficient pyruvate polarization whereas others reduced the presence of 3a, leading to weaker pyruvate hyperpolarization. The electronic richness of the NHC ligand dramatically influences the Ir center’s ability to stabilize pyruvate coordination. Symmetric and electron-rich NHC ligands favor the formation of 3a, while electron-poor or sterically asymmetric ligands reduce pyruvate binding and decrease polarization. ,

5.5. Deuteration Effects

No significant effect has been detected when sulfoxide coligand was deuterated. However, the deuteration of NHC ligand of the precatalyst was detrimental to SABRE efficiency for pyruvate due to quadrupolar relaxation effects at low magnetic fields applied during the polarization transfer. This observation was in contrast to commonly observed effect for NHC deuterated ligands in SABRE process.

5.6. Temperature Modulation and Polarization Locking

Temperature plays a profound role in regulating ligand exchange and relaxation processes. At reduced temperatures (−10 °C), pyruvate dissociation from 3a slows dramatically, effectively “locking” polarization into the bound state. Under these conditions, polarization accumulates predominantly on catalyst-bound pyruvate, enabling exceptionally high ¹³C polarization levels (20%) for the bound species after 90 s of p-H₂ bubbling. A subsequent rapid warming step releases the polarized pyruvate into free solution. This reversible “polarization storage and release” mechanism is a distinctive advantage of pyruvate SABRE, allowing temporal separation between polarization buildup and substrate delivery. In summary, pyruvate SABRE is governed by a dynamically balanced network of iridium complexes whose stability, exchange kinetics, relaxation and coupling topologies together define the efficiency of polarization transfer. ,

pH and Temperature Mapping

Adelabu et al. demonstrated that while temperature is a known handle for modulating exchange rates, pH acts as a complementary and significant modulator of pyruvate binding to the iridium-based catalyst. 25% optimal hyperpolarization level of catalyst bound [1-¹³C]­pyruvate was obtained at a pH of 6.5–7.7 and a temperature of +6 °C at 0.4 μT in methanol medium.

5.7. Water as a Beneficial Additive

In contrast to many SABRE systems where water disrupts catalyst performance, pyruvate SABRE unexpectedly benefits from controlled water addition. When water was titrated into methanol solutions of pyruvate, polarization increased nearly 2-fold at an optimum concentration of approximately 0.5 M. Water modifies the system by subtly accelerating ligand exchange, improving the balance between hydride turnover and substrate residence time. Moreover, water decreases the instability associated with DMSO-only catalysts by modulating solvent–ligand competition at the iridium center. This unexpected synergy between sulfoxides and water has important implications for eventual biocompatible formulations.

5.8. Pressure and Hydrogenation Parameters

Hydrogen pressure and mixing dynamics strongly affect SABRE kinetics. Experiments varying p-H₂ pressure (1–5 bar) and shaking/agitation times revealed that 3 bar p-H₂ 5–30 s of vigorous shaking, and rapid re-equilibration inside the shielded environment deliver optimal polarization levels. The early stage of optimization revealed that the lower pressures limit hydride availability, while excessively high pressures catalyst becomes saturated with hydrogen and the signal gain plateaus because the signal exchange reaches the rate limit.

6. Optimization of SABRE-SHEATH for Pyruvate

Following the initial demonstration that DMSO-enabled SABRE complexes could hyperpolarize pyruvate, efforts rapidly shifted toward optimizing the system to achieve higher polarization levels, improved reproducibility, and broader applicability across ¹³C isotopologues. Because hyperpolarization of carboxylate carbons relies on ultralow-field conditions where ¹³C–hydride level anticrossings (LACs) occur, the SABRE-SHEATH method (Shield Enables Alignment Transfer to Heteronuclei) became the central platform for pyruvate optimization. SABRE-SHEATH places the catalyst–substrate mixture inside a high-magnetic-permeability shield, typically lined with mu-metal, producing microtesla magnetic fields where energy levels of the Ir–H hydrides and the bound ¹³C spins align to maximize polarization transfer (Figure ). ,,− Under these conditions, important factors such as ligand exchange rates, coligand identity, catalyst electronics, solvent composition, and even isotope substitution exert strong influence on hyperpolarization efficiency.

2.

SABRE-SHEATH hyperpolarization experiment. Reproduced with permission from ref . Copyright 2015, ACS.

The culmination of all above optimization efforts resulted in dramatic improvements in SABRE-SHEATH performance. In particular, the work of Adelabu et al. marked a new benchmark which was >50% polarization on catalyst-bound [1-¹³C]­pyruvate and up to ∼13% free pyruvate polarization at 0.3 μT, achieved in deuterated methanol, in the presence of 0.5 M water. These polarization levels approach those required for preclinical metabolic imaging and demonstrate that SABRE-SHEATH is not fundamentally limited in efficiency for carboxylate substrates.

6.1. Advanced Polarization Strategies (SLIC, LIGHT-SABRE, Microtesla Pulsing)

The rapid evolution of SABRE-SHEATH for pyruvate stimulated the emergence of several complementary polarization strategies designed to overcome the intrinsic limitations of static-field SABRE at ultralow magnetic fields. These limitations, including most notably sensitivity to residual transverse fields, constraints imposed by fixed level-anticrossing conditions, and the dependence on specialized multinuclear detection hardware motivated a new generation of methods aimed at improving robustness, expanding detection modalities, and enabling practical deployment of SABRE-polarized pyruvate in preclinical environments. The resulting methodologies, including SLIC-SABRE, ,− pulsed microtesla SABRE-SHEATH, and LIGHT-SABRE, , collectively broaden the operational landscape of SABRE and significantly increase its versatility. Nantogma et al. investigated the use of microtesla magnetic field pulses in SABRE-SHEATH to optimize polarization transfer from parahydrogen-derived hydrides to the ¹³C nucleus of pyruvate. Their study specifically explored whether pulsed fields could enhance polarization efficiency compared with conventional static microtesla fields (∼0.4 μT) and provided a mechanistic framework for understanding polarization transfer, dephasing, and relaxation dynamics in this regime. The pulsed SABRE-SHEATH was performed by the use of alternating square microtesla field pluses defined by high and low field segments (Figure ). These pulsed allowed the polarization levels to reach up to 14.8% which exceeded the results obtained with the best static-field previously reported (13%). After careful attention, they found that the microtesla-pulse and static-field approachs yielded overall similar build-up and relaxation decay rates in the microtesla regime. However, the observed high level of polarization with the pulsed field was essentially resulting of the use of high p-H₂ pressure and flow rates. Interestingly, Nantogma et al. showed by the use of numerical simulations the estimated exchange and coupling constants for pyruvate in the active SABRE transfer complex. The pyruvate dissociation rate was determined to be ∼4 s^–1, while the ³J_CH coupling was estimated at +5 Hz. These values help explain why pulsed sequences can attenuate back-transfer (“back-pumping”) effects and could facilitate more efficient net polarization transfer. A central contribution of Nantogma et al. was to extract the true T₁ from the apparent rapid polarization loss observed under near-zero-field SABRE-SHEATH conditions. At static fields close to zero, the measured decay constants shortened drastically (1.9 s at 0 μT, rising to only 20.7 s at – 0.21 μT). This corresponds to an increase of order of magnitude in lifetime for a negligible absolute filed change, suggesting that the main transition in spin-state preservation occurs between 0 and 60 nT. In contrast, much smaller relative increases in lifetime were observed for higher fields (26.4 s at Earth’s field and 79.3 s at 1.4 T). The authors attributed this dramatic reduction not to a new intrinsic T₁ mechanism, but to an ensemble dephasing caused by weak residual transverse fields inside the magnetic shield. Simulations of transverse-field distributions reproduced the observed trends and estimated the residual field at ∼80 nT, sufficient to induce the fast depolarization. It is important to note that pulsed SABRE-SHEATH (Figure ) mitigates these losses by keeping the low-field interval (τ_LOW = 6 ms) much shorter than the residual-field dephasing time (∼2 s) and applying strong high-field pulses (B_HIGH = −28 μT, τ_HIGH = 96 μs) that rephase spins, the sequence interrupts the accumulation of phase errors. This strategy stabilizes polarization build-up and extends apparent lifetimes, providing mechanistic insight into the interplay of dephasing, rephasing, and relaxation in SABRE-SHEATH and highlighting how pulsed sequences can outperform static implementations in robustness and efficiency.

3.

Schematic of SABRE-SHEATH pulse sequence. B _LOW and B _HIGH correspond to low and high-field amplitude. τ_LOW and τ_HIGH correspond to the duration of the low and high-field pulse durations. Reproduced with permission from ref . Copyright 2022, ACS.

Among these developments, SLIC-SABRE (Spin-Lock Induced Crossing) represents a particularly important advance due to its ability to translate ¹³C hyperpolarization into a signal detectable on conventional proton MRI scanners. This capability is grounded in the unique behavior of the [1,2-¹³C₂]­pyruvate isotopologue, which supports long-lived singlet states under SABRE-SHEATH conditions. These states serve as reservoirs of spin order that persist far longer than conventional magnetization. By applying a precisely tuned spin-locking radiofrequency field on the proton channel, the SLIC mechanism induces a crossing between the singlet and triplet manifolds of the ¹³C₂ system, permitting coherent transfer of spin order to the methyl protons of pyruvate. The resulting hyperpolarized proton signal can be detected using standard ¹H MRI hardware, thereby eliminating the need for multinuclear imaging coils and reducing the technological threshold for biomedical implementation. In addition to simplifying detection, SLIC-SABRE maintains the key advantages of SABRE in terms of speed, low cost, and compatibility with continuous polarization, while leveraging the intrinsic sensitivity of proton MRI. Overall, the obtained ¹³C polarization values achieved by high-field SLIC-SABRE have been found to be lower than those previously obtained through SABRE-SHEATH. The reason behind the low P¹³C is that SLIC at tesla fields faces significant challenges: often unfavorable relaxation dynamics because of chemical shift anisotropy (CSA), singlet-to-triplet mixing of p-H₂, and a need for selective excitation of the bound and free SABRE species as a result of larger chemical shift dispersion. In addition, at microtesla fields, ¹³C chemical shift differences are negligible and relaxation times become favorable. Schmidt et al. interestingly performed SABRE with SLIC at microtesla fields, to achieve remarkably high polarization levels up to 22% for ¹³C in methanol-d ₄ solution. The key advance lies in using a continuous rf spin-lock at 50 μT, followed by an adiabatic pulse to align the polarization before transfer to a benchtop NMR system where ¹³C signals were detected. This approach exploits the favorable relaxation regime at microtesla fields: ¹³C chemical shift anisotropy is negligible, and dipolar relaxation is reduced, particularly in deuterated substrates. This high level of ¹³C polarization has been observed notably when the pyruvate was deuterated at the methyl level. The reason behind this observation was reported to the role of deuterium nuclei which had two distinct effects on relaxation.

Alternatively, to SABRE-SHEATH, Pravdivtsev et al. introduced LIGHT-SABRE (Low-Irradiation Generation of High-Tesla SABRE) as a new method enabling continuous hyperpolarization of [1-¹³C]-pyruvate without the need for magnetic field cycling. LIGHT-SABRE relies on the application of a weak continuous-wave (CW) radiofrequency field at the ¹³C Larmor frequency to lock the spins in a state that promotes efficient polarization transfer. Unlike SABRE-SHEATH, which relies on ultralow static magnetic fields to generate level anticrossings, LIGHT-SABRE uses irradiative spin-locking to create an effective Hamiltonian in which the hydride singlet state couples favorably to the ¹³C nuclear spin system. This strategy simplifies the polarization workflow by eliminating the need for magnetic shielding or field modulation. Although the resulting free-pyruvate polarization levels are generally lower than those achieved with SABRE-SHEATH, LIGHT-SABRE offers exceptional operational simplicity, continuous hyperpolarization under steady-state conditions, and compatibility with compact or portable systems, features that may become increasingly important for future point of care or bedside implementations.

Together, these advanced polarization strategies represent a conceptual expansion of SABRE beyond its original formulation as a static low-field technique. They demonstrate that hyperpolarization efficiency can be significantly improved by tailoring the interplay between spin dynamics, magnetic field environment, and radiofrequency control. More broadly, they highlight the adaptability of SABRE to diverse experimental constraints: SLIC-SABRE enables hyperpolarized metabolic imaging on widely available proton MRI scanners; pulsed SABRE-SHEATH enhances robustness under imperfect field conditions; and LIGHT-SABRE reduces hardware requirements to the minimal elements needed to sustain polarization transfer.

These innovations collectively reinforce the view that SABRE is not a singular technique but an evolving platform capable of being engineered to meet the diverse demands of contemporary metabolic imaging. The flexibility demonstrated across these methods provides a strong foundation for integrating SABRE into biomedical workflows and for further expanding its capabilities in both research and translational settings.

7. Translation Toward Biomedical Use

The prospect of translating SABRE-hyperpolarized pyruvate from the laboratory to biomedical imaging hinges on overcoming a series of practical and regulatory obstacles that extend well beyond the optimization of polarization efficiency. Chief among these is the need to produce injectable solutions that are biocompatible, catalyst-free, and formulated in physiologically acceptable solvents. As a result, the development of purification strategies, solvent systems compatible with clinical use, and scalable hyperpolarization workflows has become an essential parallel track in the evolution of SABRE technology. ,,−

One of the earliest challenges was the removal of iridium catalyst from the polarized mixture. Although the Ir–IMes system is indispensable for efficient SABRE, the presence of iridium in the final solution is unacceptable for in vivo administration. Initial studies addressed this issue through rapid dilution and silica-based filtration to reduce catalyst. These methods were sufficient for mouse studies to prove the concept but remained insufficient for any transition pathway, because they did not consistently meet strict impurity limits and were associated with partial loss of polarization.

Re-Dissolution SABRE (Re-D SABRE) (Figure ) a new approach was introduced to overcome the major barriers of SABRE toward biomedical application. This method couples SABRE-SHEATH polarization in methanol with a rapid precipitation and reconstitution protocol designed to isolate hyperpolarized pyruvate from the catalyst. Upon completion of polarization, the addition of ethyl acetate selectively precipitates pyruvate while leaving the iridium complex and coligands in the organic phase. The precipitate can then be reconstituted in water or D₂O to yield an aqueous, catalyst-free hyperpolarized solution. This strategy offers several advantages: it dramatically reduces catalyst contamination, typically to the low-ppb range; it produces clean, sterile solutions suitable for metabolic imaging; and it maintains polarization lifetimes comparable to those observed in the methanol solution. Notably, the resulting hyperpolarized pyruvate displays T₁ values on the order of tens of seconds in water, sufficient for in vivo metabolic investigation.

4.

Re-D SABRE procedure for pyruvate polarization in aqueous medium. Reproduced with permission from ref . Copyright 2022, ACS.

An alternative route toward catalyst removal has emerged through the design of perfluorinated, hydrophobic SABRE catalyst to be used in the Redissolution procedure. By incorporating long perfluoroalkyl chains into the N-heterocyclic carbene ligand framework (F-sIMes), the iridium complex becomes strongly hydrophobic while preserving the core structural features required for SABRE-SHEATH hyperpolarization (Figure ). Following polarization in methanol-d ₄, the hydrophobic catalyst remains confined to the organic phase during aqueous extraction, enabling efficient phase separation and catalyst recycling. Importantly, these catalysts maintain polarization performance comparable to that of their nonfluorinated counterparts while offering superior operational stability and dramatically reduced cross-contamination. Such phase-separation strategies represent a promising direction for simplifying SABRE purification workflows and reducing the reliance on multistep chemical manipulations.

5.

Perfluorinated SABRE catalyst. Reproduced with permission from ref . Copyright 2023, ACS.

The solvent environment itself presents another major consideration. Methanol has been the solvent of choice for SABRE due to its ability to solvate both the iridium catalyst and the sulfoxide coligands while supporting fast substrate exchange. However, its toxicity necessitates its removal or substantial dilution prior to biomedical use. Several approaches have been explored to address this issue. Dilution into buffered aqueous media reduces methanol content to tolerable levels and was suitable for early in vivo demonstrations, but more advanced strategies focus on eliminating methanol entirely. One such development, ACE-SABRE, (Figure ) replaces methanol with a mixed acetone/water solvent system during hyperpolarization. This not only avoids the use of methanol but also enables efficient liquid–liquid extraction of pyruvate into an aqueous phase while retaining a substantial fraction of the initial polarization. Under optimized conditions, ACE-SABRE yields polarization levels that are competitive with classical SABRE-SHEATH, while producing solutions immediately suitable for injection.

6.

ACE-SABRE procedure to produce polarized pyruvate in water. Reproduced with permission from ref . Copyright 2025, Wiley.

A final layer of translational readiness concerns sterility, pH, and isotonicity. SLIC-SABRE workflows have demonstrated that sterile, pH-neutral pyruvate solutions can be produced in under 6 min through a combined sequence of hyperpolarization, controlled solvent evaporation, and sterile filtration. These preparations have been successfully used in small-animal studies, providing real-time detection of pyruvate-to-lactate conversion with excellent spectral and spatial fidelity. The rapidity of SABRE preparation stands in marked contrast to dissolution-DNP, offering preparation times an order of magnitude shorter and circumventing the need for cryogenic infrastructure.

Taken together, these advances demonstrate that SABRE is evolving into a practical and flexible hyperpolarization platform capable of producing high-quality, biocompatible pyruvate formulations suitable for metabolic imaging. The ability to remove catalyst, eliminate toxic solvents, and generate sterile injectates in a matter of minutes constitutes a critical step toward the integration of SABRE into preclinical imaging workflows. Continued refinement of catalyst design, purification methodologies, and solvent engineering is likely to strengthen the foundation for eventual clinical translation.

8. In Vivo Applications of SABRE-Hyperpolarized Pyruvate

The successful translation of SABRE-hyperpolarized pyruvate into in vivo imaging represents an essential milestone in the development of SABRE as a viable hyperpolarization platform for metabolic MRI. Although early SABRE studies focused primarily on methodological and mechanistic optimization in vitro, recent advances in catalyst purification, solvent engineering, and proton-detected readout strategies have enabled SABRE-polarized pyruvate to be administered to living models, achieving meaningful metabolic contrast in real time. These demonstrations establish SABRE as a credible alternative to dissolution-DNP for certain preclinical applications. ,,

The first in vivo studies relied on SLIC-SABRE, which enabled proton-detected metabolic imaging by converting ¹³C singlet order into hyperpolarized ¹H magnetization. This innovation allowed hyperpolarized pyruvate to be detected using conventional proton MRI hardware, bypassing the need for multinuclear ¹³C detectors and thereby removing one of the key technical barriers to preclinical deployment. The SLIC workflow also facilitated the preparation of sterile, pH-neutral, isotonic, and catalyst-free pyruvate solutions suitable for intravenous injection, all within a short time frame of approximately 6 min. In mice models, SLIC-SABRE-polarized pyruvate-d ₃ enabled the clear visualization of classical pyruvate metabolic pathways, detecting lactate, alanine, and pyruvate-hydrate with excellent temporal resolution. Importantly, the lactate signals observed following injection displayed the expected kinetic behavior associated with lactate dehydrogenase activity, validating that SABRE-polarized substrates retain their biochemical functionality after injection. The ability to capture these metabolic conversions noninvasively underscores the biological fidelity of SABRE-hyperpolarized pyruvate and establishes that SABRE does not compromise subsequent metabolic processing.

Subsequent studies extended these observations to disease models. In mouse models of breast cancer (MMTV-PyMT), SABRE-hyperpolarized pyruvate enabled the visualization of spatially heterogeneous lactate production, corresponding to variations in tumor metabolic phenotype. This capacity to differentiate metabolic regions within tumors highlights SABRE’s potential for applications in oncologic imaging, including metabolic phenotyping, response assessment, and potentially early stage lesion detection. The signal-to-noise ratio achieved in these studies was obviously not yet equivalent to the latest DNP techniques but was sufficient to resolve multiple metabolic pathways simultaneously.

Further in vivo progress was made through the introduction of fluorinated iridium catalysts, which facilitated the phase separation and removal of catalyst during sample preparation. Using phase-transfer purification or Re-Dissolution workflows, investigators achieved aqueous formulations with minimal catalyst contamination while maintaining polarization values compatible with metabolic MRI. These preparations were successfully applied in murine pancreatic cancer xenografts, enabling the detection of pyruvate-to-lactate conversion and providing metabolic contrasts characteristic of malignant tissues. Such studies demonstrate that catalyst removal is sufficiently effective to prevent toxicity and that SABRE-derived hyperpolarized substrates can be used safely in living organisms when appropriate purification pipelines are applied.

A complementary advance was provided by ACE-SABRE, a methanol-free workflow that generates aqueous, catalyst-free hyperpolarized pyruvate suitable for direct administration. This method reduces the complexity of postpolarization handling and minimizes unwanted dilution effects, thereby preserving higher effective polarization levels in vivo (Figure ). By integrating hyperpolarization and purification steps into a streamlined process, ACE-SABRE brings SABRE closer to operational compatibility with common preclinical MRI facilities.

7.

Comparison of Ace-SABRE and d-DNP hyperpolarized [1–¹³C]­pyruvate. The figure illustrates (a) metabolic conversion kinetic in a xenograft tumor model and (b–e) spatial distribution and signal evolution in healthy mice. Results indicate that Ace-SABRE-polarized pyruvate yields metabolic data and image quality equivalent to traditional d-DNP methods for in vivo applications. Reproduced with permission from ref . Copyright 2025, Wiley.

Although SABRE-based in vivo studies remain in their early stages, the results to date provide compelling evidence that SABRE is capable of producing hyperpolarized metabolic tracers of sufficient quality, purity, and polarization for preclinical use. The principal remaining challenges reside in enhancing more the free pyruvate polarization, scaling up the quantity, refining catalyst removal, and improving long-term stability. These challenges are considered as technical rather than conceptual, and ongoing efforts in catalyst design, solvent engineering, and low-field optimization continue to close these gaps.

Taken together, these achievements demonstrate that SABRE has crossed a critical threshold: it is no longer confined to in vitro spectroscopy but is now capable of probing real biochemical processes in living organisms. As purification workflows, field control methods, and hardware integration continue to advance, the scope of SABRE’s in vivo applications is expected to expand significantly, potentially rivaling or complementing dissolution-DNP for a range of metabolic imaging tasks.

9. Current Challenges and Future Directions

Despite the remarkable progress made in the development of SABRE pyruvate hyperpolarization, several scientific, technical, and translational challenges remain before SABRE can be considered a fully mature platform for routine metabolic imaging. These challenges relate not only to the fundamental chemistry of SABRE and the physical limits of polarization transfer but also to practical constraints associated with the catalyst removal, solvent systems, hardware integration, and compliance with biomedical standards. Understanding these limitations is essential for guiding future research and ensuring that SABRE continues to develop toward both robust preclinical use and, eventually, clinical translation.

A persistent limitation concerns the disparity between the high polarization levels achieved on catalyst-bound pyruvate and the lower levels observed for free pyruvate in solution. Although bound-state polarization in excess of 50% has been achieved under optimized SABRE-SHEATH conditions, the polarization that survives the release step where hyperpolarization is transferred from the active complex to free pyruvate remains significantly lower. This discrepancy arises from a delicate balance between substrate residence time in the active complex, hydride exchange kinetics, and relaxation losses that occur during dissociation. Improving free-substrate polarization will likely require refined strategies for manipulating exchange rates, possibly through rational coligand design, tailored solvent environments, or temperature-jump protocols that optimize the release of polarization while minimizing relaxation during the transition.

Another major challenge concerns catalyst removal. Although recent innovations such as Re-D SABRE and fluorinated catalyst systems have dramatically lowered residual iridium concentrations, the purification workflows remain operationally demanding. Achieving consistent removal of catalyst to subppb levels, while preserving polarization and maintaining sterility, represents an ongoing technical challenge. Future developments may require the creation of fully water-soluble or biocompatible SABRE catalysts, enabling hyperpolarization to occur directly in aqueous media followed by simple filtration or capture by affinity. Alternatively, ligand designs that enable reversible, enzyme-like immobilization of the catalyst on solid supports could eliminate the need for postpolarization purification entirely.

Solvent compatibility poses a related challenge. Although methanol has been central to SABRE chemistry due to its favorable solvation properties and ability to sustain rapid exchange at the metal center, its toxicity necessitates removal or substitution before in vivo use. Methods such as ACE-SABRE demonstrate the feasibility of methanol-free hyperpolarization, yet these workflows remain comparatively new and require further optimization to achieve the reliability and reproducibility needed for widespread adoption. Discovering solvent systems that balance biocompatibility with efficient catalyst performance possibly including mixed aqueous–organic environments or engineered protic solvents remains an essential priority.

Technical constraints associated with magnetic-field control also persist. Conventional SABRE-SHEATH requires precise microtesla environments that are susceptible to perturbations from weak external fields or variations in magnetic shielding. Although pulsed SABRE strategies have begun to address these limitations by explicitly compensating for dephasing and modulating LAC dynamics. In addition, further engineering advances for SABRE have led to develop a compact device, robust field-control modules called MATRESHCA which can be integrated into standard NMR and MRI laboratories. Overcoming these hardware limitations was important not only for improving reproducibility but also for enabling automated or user-friendly SABRE systems suitable for biomedical workflows.

Another frontier lies in the design of next-generation catalysts and coligands. The current reliance on symmetric NHC ligands and sulfoxide coligands reflects the unique synergy required for bidentate pyruvate binding. However, this chemical space remains only partially explored. Catalyst systems capable of activating parahydrogen while simultaneously stabilizing carboxylate substrates in water, avoiding quadrupolar relaxation pathways, or supporting reversible immobilization could profoundly expand the utility of SABRE. Likewise, tailoring ligands to control hydride lifetime, modulate exchange dynamics, or suppress unwanted decomposition pathways will be essential for further improvements in polarization efficiency and chemical robustness.

A final challenge concerns scalability and workflow integration. For SABRE to become a translationally relevant technology, it must be embedded within reproducible, automated systems capable of generating consistent hyperpolarized doses with minimal operator intervention. Early steps in this direction include flow-based SABRE reactors such as MATRESHCA, temperature-controlled polarization modules, and microfluidic implementations capable of integrating hyperpolarization, purification, and injection in a single workflow. Such developments not only promise greater reproducibility but also align SABRE with the stringent process-control requirements of biomedical imaging facilities.

Looking ahead, several opportunities offer exciting potential for SABRE’s expansion. The discovery of long-lived spin states in pyruvate isotopologues suggests that SABRE may enable novel contrast mechanisms not accessible by conventional DNP. The speed and low cost of SABRE also open possibilities for dynamic, repeated-dose metabolic imaging, allowing real-time monitoring of biochemical fluxes on time scales inaccessible to DNP. More broadly, innovations in parahydrogen delivery, portable field-control devices, and catalyst engineering may ultimately position SABRE as a practical, scalable, and widely accessible hyperpolarization method.

In sum, while significant challenges remain, none represent fundamental barriers to SABRE’s continued advancement. The trajectory of recent work strongly indicates that SABRE is moving steadily toward more reliable, biocompatible, and technologically integrated forms. Continued collaboration across chemistry, engineering, and biomedical imaging will be essential for transforming SABRE from a promising laboratory technique into a mainstream platform for metabolic MRI.

10. Conclusion

Over the past decade, SABRE has progressed from a promising parahydrogen-based spin-physics concept into a sophisticated hyperpolarization platform capable of addressing one of the central challenges in metabolic MRI: the rapid and efficient hyperpolarization of biologically relevant substrates. The case of pyruvate is particularly striking. Initially viewed as inaccessible due to its weak binding affinity to iridium catalysts and its propensity to form off-pathway chemical adducts, pyruvate has become one of the most thoroughly studied and successfully optimized SABRE substrates. This transformation has been enabled by a series of conceptual and methodological breakthroughs that have been collectively redefined the boundaries of SABRE chemistry.

The introduction of sulfoxide coligands notably DMSO was the essential advance that unlocked bidentate pyruvate coordination and made polarization transfer feasible. Subsequent mechanistic investigations clarified the roles of active and precursor complexes, elucidated the delicate interplay between kinetic exchange rates and hydride lifetimes, and revealed how subtle changes in catalyst electronics and geometry profoundly influence overall polarization performance. These insights enabled the rational optimization of SABRE-SHEATH, elevating pyruvate polarization levels from subpercent values to tens of percent on the catalyst-bound species and, under optimized conditions, to clinically relevant levels for free pyruvate in solution.

Concurrently, the development of advanced polarization strategies including SLIC-SABRE, microtesla-pulsed SABRE-SHEATH, and LIGHT-SABRE expanded the operational flexibility of SABRE and demonstrated that the method could be adapted to diverse magnetic field environments and detection modalities. These techniques not only improve polarization efficiency but also facilitate proton-detected readout, enhance robustness to field imperfections, and simplify the hardware requirements needed for practical deployment.

A parallel line of progress has focused on translating SABRE hyperpolarization from chemical optimization toward biologically compatible systems. Innovations such as Re-Dissolution SABRE, fluorinated phase-separable catalysts, and methanol-free workflows have significantly lowered catalyst contamination and improved the feasibility of generating sterile, isotonic, pH-neutral injections suitable for in vivo studies. These efforts culminated in the first demonstrations of SABRE-hyperpolarized pyruvate in living organisms, providing real-time visualization of metabolic fluxes in both healthy tissues and tumor models.

Despite these advances, several challenges remain before SABRE can be considered a fully established tool for metabolic imaging. Key challenges include the need to further improve the free-pyruvate polarization, streamline catalyst-removal workflows, and develop scalable, automated systems that produce reproducible hyperpolarized doses with minimal operator intervention. However, none of these challenges appear insurmountable, and the pace of recent progress suggests that continued integration of chemistry, engineering, and imaging expertise will rapidly close these gaps.

In summary, SABRE has demonstrated exceptional potential as a rapid, low-cost, and versatile hyperpolarization method for metabolic MRI. Its ability to generate high polarization levels within seconds, without cryogenic infrastructure, positions it as a compelling alternative to dissolution-DNP, especially for preclinical applications requiring high temporal throughput or repeated dosing. As the method continues to mature, its impact is likely to extend well beyond pyruvate to a broader family of biologically significant molecules, thereby opening new avenues for the noninvasive interrogation of metabolism in health and disease. SABRE’s evolution over the past decade strongly suggests that it will play an increasingly central role in the future landscape of hyperpolarized MRI.

Biography

Dr. Wissam Iali is an Assistant Professor in the Department of Chemistry at the American University of Beirut (AUB). He obtained his PhD in Chemistry from the University of Strasbourg in 2012. Following his doctoral studies, he held a postdoctoral position at the French Alternative Energies and Atomic Energy Commission (CEA) in Grenoble (2013–2015), followed by a second postdoctoral fellowship with Prof. Simon Duckett at the University of York (2015–2019). He served as Assistant professor in the Chemistry Department (2019-2023) at King Fahd University of Petroleum and Minerals (KFUPM) and before joining AUB in 2025 he served as a Senior Scientist NMR expert at SABIC (Saudi Basic Industries Corporation). His current research program focuses on the chemical development of SABRE methodologies.

The author declares no competing financial interest.