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 13 C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dynamic nuclear polarization (DNP) is complex, costly and requires complex infrastructure. In contrast, signal amplification by reversible exchange (SABRE) is a fast, cheap, and scalable hyperpolarization technique. In particular, SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) transfers polarization from parahydrogen to 13 C in pyruvate, however, to date, SABRE-SHEATH of 13 C-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 [1-13 C]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 advantage of the achieved polarization to demonstrate first 13 C pyruvate images with a cryogen-free MRI system operated 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.

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE‐SHEATH) is investigated to achieve rapid hyperpolarization of 13C1 spins of [1‐13C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co‐ligation of DMSO and H2O. Order‐unity 13C (>50 %) polarization of catalyst‐bound [1‐13C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1‐13C]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 13C 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‐[1‐13C]pyruvate sample). Finally, the catalyst‐bound hyperpolarized [1‐13C]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 [1‐13C]pyruvate produced via comparatively fast and simple SABRE‐SHEATH‐based approaches.

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 13 C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dynamic nuclear polarization (DNP) is complex, costly and requires complex infrastructure. In contrast, signal amplification by reversible exchange (SABRE) is a fast, cheap, and scalable hyperpolarization technique. In particular, SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) transfers polarization from parahydrogen to 13 C in pyruvate, however, to date, SABRE-SHEATH of 13 C-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 [1-13 C]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 advantage of the achieved polarization to demonstrate first 13 C pyruvate images with a cryogen-free MRI system operated 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.

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.

This presentation covers the recent advances in spin physics and instrumentation of Signal Amplification By Reversible Exchange (SABRE) in SHield Enables Alignment Transfer to Heteronuclei (SHEATH). Order unity 13C polarization for [1-13C]pyruvate was demonstrated for catalyst-bound species by SABRE-SHEATH, which becomes possible due to favorable 13C relaxation dynamics in a microtesla magnetic field. The magnetic field, temperature and co-solvents heavily modulate the attainable 13C polarization, providing an opportunity for optimization to deliver highly polarized [1-13C]pyruvate quickly and cheaply for biomedical applications. The design of clinical-scale hyperpolarizer is described for production of [1-13C]pyruvate and other metabolically relevant hyperpolarized contrast agents.