&amp;lt;i&amp;gt;Geminal&amp;lt;/i&amp;gt; parahydrogen-induced polarization: accumulating long-lived singlet order on methylene proton pairs

Dagys, Laurynas; Ripka, Barbara; Leutzsch, Markus; Moustafa, Gamal A. I.; Eills, James; Colell, Johannes F. P.; Levitt, Malcolm H.

doi:10.5194/mr-1-175-2020

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…The relatively short proton singlet lifetime in water (8 s) will likely limit this specific molecular system to studying samples with high metabolic flux. We expect this imaging method to be extended to alternative PHIP systems, [67] or other nuclear spin species, for example, 15 N or 13 C singlet pairs, [68–73] which are known to be long‐lived in aqueous solution.…”

Section: Resultsmentioning

confidence: 99%

Singlet‐Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism**

et al. 2021

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Hyperpolarization‐enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13C, 15N, or 129Xe due to their long spin‐polarization lifetimes and the absence of a proton‐background signal from water and fat in the images. Here we present a novel type of 1H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long‐lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para‐enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization‐enhanced 1H‐imaging modality presented here can allow for hyperpolarized imaging without the need for low‐abundance, low‐sensitivity heteronuclei.

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Section: Resultsmentioning

confidence: 99%

Singlet‐Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism**

et al. 2021

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“…The bubbling set up used in this work is described in detail by Dagys et al . [28] Concentration profile for species involved in the reaction was obtained by integrating the corresponding region in a

NMR spectrum. Propargyl acetate: 2.85 to 2.95 ppm; allyl acetate 5.00 to 5.50 ppm; propyl acetate 3.97 to 4.06 ppm; catalyst 2.49 to 2.64 ppm.…”

Section: Methodsmentioning

confidence: 99%

Spatially Resolved Kinetic Model of Parahydrogen Induced Polarisation (PHIP) in a Microfluidic Chip

2021

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We report a spatially resolved kinetic finite element model of parahydrogen-induced polarisation (PHIP) in a microfluidic chip that was calibrated using on-chip and off-chip NMR data. NMR spectroscopy has great potential as a read-out technique for lab-on-a-chip (LoC) devices, but is often limited by sensitivity. By integrating PHIP with a LoC device, a continuous stream of hyperpolarised material can be produced, and mass sensitivities of pmol ffi ffi s p have been achieved. However, the yield and polarisation levels have so far been quite low, and can still be optimised. To facilitate this, a kinetic model of the reaction has been developed, and its rate constants have been calibrated using macroscopic kinetic measurements. The kinetic model was then coupled with a finite element model of the microfluidic chip. The model predicts the concentration of species involved in the reaction as a function of flow rate and position in the device. The results are in quantitative agreement with published experimental data.

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“…S2). An interesting side product from this reaction is one in which the protons end up in geminal positions, which can lead to geminal-PHIP, and this is discussed in a paper by L. Dagys et al [75]. The other curves show less significant…”

Section: Influence Of the Sodium Sulphite Concentration On The Reactionmentioning

confidence: 97%

Optimizing the Reaction Conditions for the Formation of Fumarate via Trans-Hydrogenation

et al. 2021

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Parahydrogen-induced polarization is a hyperpolarization method for enhancing nuclear magnetic resonance signals by chemical reactions/interactions involving the para spin isomer of hydrogen gas. This method has allowed for biomolecules to be hyperpolarized to such a level that they can be used for real time in vivo metabolic imaging. One particularly promising example is fumarate, which can be rapidly and efficiently hyperpolarized at low cost by hydrogenating an acetylene dicarboxylate precursor molecule using parahydrogen. The reaction is relatively slow compared to the timescale on which the hyperpolarization relaxes back to thermal equilibrium, and an undesirable 2nd hydrogenation step can convert the fumarate into succinate. To date, the hydrogenation chemistry has not been thoroughly investigated, so previous work has been inconsistent in the chosen reaction conditions in the search for ever-higher reaction rate and yield. In this work we investigate the solution preparation protocols and the reaction conditions on the rate and yield of fumarate formation. We report conditions to reproducibly yield over 100 mM fumarate on a short timescale, and discuss aspects of the protocol that hinder the formation of fumarate or lead to irreproducible results. We also provide experimental procedures and recommendations for performing reproducible kinetics experiments in which hydrogen gas is repeatedly bubbled into an aqueous solution, overcoming challenges related to the viscosity and surface tension of the water.

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<i>Geminal</i> parahydrogen-induced polarization: accumulating long-lived singlet order on methylene proton pairs

Cited by 18 publications

References 38 publications

Singlet‐Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism**

Singlet‐Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism**

Spatially Resolved Kinetic Model of Parahydrogen Induced Polarisation (PHIP) in a Microfluidic Chip

Optimizing the Reaction Conditions for the Formation of Fumarate via Trans-Hydrogenation

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