Liquid-state carbon-13 hyperpolarization generated in an MRI system for fast imaging

Abstract

Hyperpolarized (HP) tracers dramatically increase the sensitivity of magnetic resonance imaging (MRI) to monitor metabolism non-invasively and in vivo. Their production, however, requires an extra polarizing device (polarizer) whose complexity, operation and cost can exceed that of an MRI system itself. Furthermore, the lifetime of HP tracers is short and some of the enhancement is lost during transfer to the application site. Here, we present the production of HP tracers in water without an external polarizer: by Synthesis Amid the Magnet Bore, A Dramatically Enhanced Nuclear Alignment (SAMBADENA) is achieved within seconds, corresponding to a hyperpolarization of ∼20%. As transfer of the tracer is no longer required, SAMBADENA may permit a higher polarization at the time of detection at a fraction of the cost and complexity of external polarizers. This development is particularly promising in light of the recently extended portfolio of biomedically relevant para-hydrogen-tracers and may lead to new diagnostic applications.

Parahydrogen‐Based Hyperpolarization for Biomedicine

“…[61] While not a standalone device, rf transfer at high field in an imaging magnet was demonstrated in 2017. [34] To support these technologies, a diverse range of rf SOT sequences for production of HP CAs have been introduced and validated. [30a, 31–32, 33b, 33c, 58a] …”

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

“…Following chemical addition of parahydrogen to the PHIP precursors, decoupling was turned off and a pulse sequence was applied to transform the singlet-state spin order of parahydrogen into net heteronuclear magnetization on a coupled heteronucleus. The RF pulse sequence developed by Goldman and co-workers [52] was employed (using the following delays: t 1 = 21 ms, t 2 = 37 ms, t 3 = 50 ms), Figure 4, but other pulse sequences can be also used [53–55, 57, 62, 68, 69]. After completion of this step, heteronuclear magnetization was detected with the parent spectrometer by applying a heteronuclear excitation pulse and turning on the receiver.…”

“…While both methods have been shown to yield high polarizations, pulsed methods holding the sample stationary at a fixed magnetic field were pursued here rather than the alternative of either modulating the static field or moving the sample relative to the magnetic fields. Pulsed PHIP device configurations can be further discriminated based on the electronic controller, capability to detect in situ [33, 61], magnetic field strength, magnet type (permanent [61], superconductive [62] or electromagnet [58]), and the overall degree of portability. Specialized portable devices have been described [45], distributed spray types where synthesis and transfer are separate from detection [58, 59], integrated detection with permanent magnets, and more fixed systems using syringe pumps [56].…”

Pulsed Magnetic Resonance to Signal‐Enhance Metabolites within Seconds by utilizing para‐Hydrogen

“…SABRE performs best in organic solvents, which has, so far, excluded in vivo experiments and work is on the way to make polarization accessible in biocompatible solvents . PHIP is an approach in which an unsaturated bond in a precursor molecule is being hydrogenated with para ‐hydrogen . During the hydrogenation process, the symmetry of para ‐hydrogen is broken and observable polarization is obtained .…”