A continuous‐flow, high‐throughput, high‐pressure parahydrogen converter for hyperpolarization in a clinical setting

Hövener, Jan‐Bernd; Bär, Sébastien; Leupold, Jochen; Jenne, Klaus; Leibfritz, Dieter; Hennig, Jürgen; Duckett, Simon B.; Elverfeldt, Dominik von

doi:10.1002/nbm.2827

Cited by 91 publications

(142 citation statements)

References 37 publications

(72 reference statements)

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“…Although up to now SABRE feasibility has been shown for a limited number of substrates and complexes it is potentially a very general technique because SABRE, unlike the conventional PHIP method, does not require a hydrogenative chemical reaction. Therefore, firstly, SABRE can potentially be expanded to a broad range of substrates and, secondly, by using SABRE one can continuously generate hyperpolarized signals with strong signal enhancement for protons [17][18][19] as well as for heteronuclei, e.g. 13 C and 15 N [8, 12, 13, 20].…”

Section: Introductionmentioning

confidence: 99%

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

Pravdivtsev

2016

Zeitschrift Für Physikalische Chemie

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A strong limitation of nuclear magnetic resonance is its low inherent sensitivity that can be overcome by using an appropriate hyperpolarization technique. Presently, dynamic nuclear polarization and spin-exchange optical pumping are the only hyperpolarization techniques that are used in applied medicine. However, both are relatively complex in use and expensive. Here we present a modification of the signal amplification by reversible exchange (SABRE) hyperpolarization method -SABRE on stabilized Ir-complexes. A stabilized Ir-complex (here we used bipyridine for stabilization) can be hyperpolarized in a wide range of magnetic fields from a few μT upto 10 T with 15 N polarization of about 1-3%. Moreover, the investigated complex can be incorporated into biomolecules or other bulky molecules; in this situation exchange with para-hydrogen will allow one to continuously generate hyperpolarization.

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Section: Introductionmentioning

confidence: 99%

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

Pravdivtsev

2016

Zeitschrift Für Physikalische Chemie

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“…They found that the conversion profile followed an exponential function with a time constant of around 846 min. Hövener et al 16 observed a similar profile in a borosilicate glass vial monitored over 41 h, again using NMR to determine the pH 2 fraction; they reported a similar time constant of around 820 min.…”

Section: In-situ Monitoring Of the Conversion Of Ph 2 In Nmr Tubesmentioning

confidence: 72%

“…15,16,21,27 The sample was placed in a bench-top NMR spectrometer (Magritek Spinsolve) operating at a 1 H Larmor frequency of 43.5 MHz. A spectrum was recorded using a standard 90…”

Section: Methodsmentioning

confidence: 99%

“…7 For pH 2 based hyperpolarisation methods in NMR, the greater the level of pH 2 enrichment the greater the NMR signal enhancement. 4,11,15 Indeed various methods of generating high purity pH 2 for NMR studies have been reported, 15,16 and major NMR vendors also supply this type of specialised equipment. 17 The research group at the University of Strathclyde has an in-house built pH 2 generator, which is used to provide gaseous pH 2 for signal amplification by reversible exchange (SABRE) hyperpolarisation studies on a bench-top NMR spectrometer.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative In Situ Monitoring of Parahydrogen Fraction Using Raman Spectroscopy

Parrott

Dallin²,

Andrews³

et al. 2018

Appl Spectrosc

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Raman spectroscopy has been used to provide a rapid, non-invasive and non-destructive quantification method for determining the parahydrogen fraction of hydrogen gas. The basis of the method is the measurement of the ratio of the first two rotational bands of hydrogen at 355 cm −1 and 586 cm −1 corresponding to parahydrogen and orthohydrogen, respectively. The method has been used to determine the parahydrogen content during a production process and a reaction. In the first example, the performance of an in-house liquid nitrogen cooled parahydrogen generator was monitored both at-line and on-line. The Raman measurements showed that it took several hours for the generator to reach steady state and hence, for maximum parahydrogen production (50 %) to be reached. The results obtained using Raman spectroscopy were compared to those obtained by at-line low-field NMR spectroscopy. While the results were in good agreement, Raman analysis has several advantages over NMR for this application. The Raman method does not require a reference sample, as both spin isomers (ortho and para) of hydrogen can be directly detected, which simplifies the procedure and eliminates some sources of error. In the second example, the method was used to monitor the fast conversion of parahydrogen to orthohydrogen in-situ. Here the ability to acquire Raman spectra every 30 s enabled a conversion process with a rate constant of 27.4 × 10 −4 s −1 to be monitored. The Raman method described here represents an improvement on previously reported work, in that it can be easily applied on-line and is approximately 500 times faster. This offers the potential of an industrially compatible method for determining parahydrogen content in applications that require the storage and usage of hydrogen.

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“…Importantly, PHIP is a relatively inexpensive technique compared to DNP and SEOP, with the main costs arising from the need to produce para-H 2 by cryo-cooling. 10,11 …”

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confidence: 99%

Demonstration of Heterogeneous Parahydrogen Induced Polarization Using Hyperpolarized Agent Migration from Dissolved Rh(I) Complex to Gas Phase

Kovtunov

Barskiy

Shchepin³

et al. 2014

Anal. Chem.

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Parahydrogen-induced polarization (PHIP) was used to demonstrate the concept that highly polarized, catalyst-free fluids can be obtained in a catalysis-free regime using a chemical reaction with molecular addition of parahydrogen to a water-soluble Rh(I) complex carrying a payload of compound with unsaturated (C=C) bonds. Hydrogenation of norbornadiene leads to formation of norbornene, which is eliminated from the Rh(I) complex and, therefore, leaves the aqueous phase and becomes a gaseous hyperpolarized molecule. The Rh(I) metal complex resides in the original liquid phase, while the product of hydrogen addition is found exclusively in the gaseous phase based on the affinity. Hyperpolarized norbornene 1H NMR signals observed in situ were enhanced by a factor of approximately 10 000 at a static field of 47.5 mT. High-resolution 1H NMR at a field of 9.4 T was used for ex situ detection of hyperpolarized norbornene in the gaseous phase, where a signal enhancement factor of approximately 160 was observed. This concept of stoichiometric as opposed to purely catalytic use of PHIP-available complexes with an unsaturated payload precursor molecule can be extended to other contrast agents for both homogeneous and heterogeneous PHIP. The Rh(I) complex was employed in aqueous medium suitable for production of hyperpolarized contrast agents for biomedical use. Detection of PHIP hyperpolarized gas by low-field NMR is demonstrated here for the first time.

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A continuous‐flow, high‐throughput, high‐pressure parahydrogen converter for hyperpolarization in a clinical setting

Cited by 91 publications

References 37 publications

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

Quantitative In Situ Monitoring of Parahydrogen Fraction Using Raman Spectroscopy

Demonstration of Heterogeneous Parahydrogen Induced Polarization Using Hyperpolarized Agent Migration from Dissolved Rh(I) Complex to Gas Phase

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