In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

Abstract

By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 105-fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high-resolution low-field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real-time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low-field (milli-Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen-enhanced NMR and MRI, which are free from the limitations of high-field magnetic resonance (including susceptibility-induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields.

High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7 mT) following murine tail-vein injection

“…However, 13 C (as well as 1 H, 3 He and 129 Xe) MRI imaging can be performed at B 0 > 6 mT (including ~48.7 mT, the field studied here) as has been demonstrated by us [15, 52, 68–70] and others [8, 19, 20, 71–75] previously using conventional MRI approaches. In particular, 13 C frequency encoding can still be accomplished at ~0.5 MHz resonance frequency (f 0 ) as employed here and using a RF coil with suitable quality factor Q and reasonable choice of spectral width (SW) to satisfy the imaging bandwidth condition of f 0 / Q ≫ SW [15].…”

NMR SLIC Sensing of Hydrogenation Reactions Using Parahydrogen in Low Magnetic Fields

“…8 In addition, PHIP naturally employs hydrogenation reactions and therefore can find promising applications beyond biomedicine. For example, it could be a useful modality for in situ detection and imaging of industrial-scale hydrogenation and hydrogen-involving reactions, 23,24 which represent a significant fraction of all industrial chemical processes. 25 …”

“…27,32 Moreover, low-field detection offers other advantages: (i) reduced B 0 susceptibility gradients, and (ii) the possibility of construction of relatively low-cost large homogeneous magnets that, in principle, can encompass large chemical reactors. 24,31−34 …”

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

“…The equipment was tested on the parahydrogen addition product of 2-hydroxyethyl acrylate-1- 13 C- d 3 , whereupon conversion of the initial singlet state of nascent protons to net heteronuclear magnetization, 13 C polarization P was estimated to be 20 % ± 2.5 % corresponding to 13 C signal enhancement of approximately 25-million-fold at this reference low field of 9.1 mT or approximately 77,000-fold at 3 T with respect to thermally induced polarization at room temperature. The central control of the hyperpolarization could also be useful for non-hydrogenative PHIP experiments [43, 64, 78–80] as well as in the context heterogeneous PHIP experiments [81, 82]. For biomedical applications, we anticipate that this design will be especially useful to laboratories already equipped with low field imaging consoles, and additionally, for basic science applications this polarizer design should facilitate translation of PASADENA to multidimensional NMR experiments.…”

“…The setup presented here employs two saddle-shape RF coils operating at 388 kHz and 97.6 kHz using tunable electromagnet vs. 2020 kHz and 508 kHz [63]. We anticipate straightforward translation to lower magnetic fields as well as non-hydrogenative PHIP experiments [64, 65], and note that the electronic infrastructure described could be extended or modified for generic experimental control with a pulse programmer.…”