Category Archives: dDNP

Dynamic Nuclear Polarization and Other Magnetic Ideas at EPFL #DNPNMR

Bornet, A., et al., Dynamic Nuclear Polarization and Other Magnetic Ideas at EPFL. CHIMIA International Journal for Chemistry, 2012. 66(10): p. 734-740.

https://doi.org/10.2533/chimia.2012.734

Although nuclear magnetic resonance (NMR) can provide a wealth of information, it often suffers from a lack of sensitivity. Dynamic Nuclear Polarization (DNP) provides a way to increase the polarization and hence the signal intensities in NMR spectra by transferring the favourable electron spin polarization of paramagnetic centres to the surrounding nuclear spins through appropriate microwave irradiation. In our group at EPFL, two complementary DNP techniques are under investigation: the combination of DNP with magic angle spinning at temperatures near 100 K (\’MAS-DNP\’), and the combination of DNP at 1.2 K with rapid heating followed by the transfer of the sample to a high-resolution magnet (\’dissolution DNP\’). Recent applications of MAS-DNP to surfaces, as well as new developments of magnetization transfer of 1H to 13C at 1.2 K prior to dissolution will illustrate the work performed in our group. A second part of the paper will give an overview of some \’non-enhanced\’ activities of our laboratory in liquid- and solid-state NMR.

Microwave-gated dynamic nuclear polarization #DNPNMR

Bornet, A., et al., Microwave-gated dynamic nuclear polarization. Phys. Chem. Chem. Phys., 2016. 18(44): p. 30530-30535.

http://dx.doi.org/10.1039/C6CP05587G

Dissolution dynamic nuclear polarization (D-DNP) has become a method of choice to enhance signals in nuclear magnetic resonance (NMR). Recently, we have proposed to combine cross-polarization (CP) with D-DNP to provide high polarization P(13C) in short build-up times. In this paper, we show that switching microwave irradiation off for a few hundreds of milliseconds prior to CP can significantly boost the efficiency. By implementing microwave gating, 13C polarizations on sodium [1-13C]acetate as high as 64% could be achieved with a polarization build-up time constant as short as 160 s. A polarization of P(13C) = 78% could even be reached for [13C]urea.

Dissolution Dynamic Nuclear Polarization capability study with fluid path

Malinowski, R.M., et al., Dissolution Dynamic Nuclear Polarization capability study with fluid path. J Magn Reson, 2016. 272: p. 141-146.

https://www.ncbi.nlm.nih.gov/pubmed/27693965

Signal enhancement by hyperpolarization is a way of overcoming the low sensitivity in magnetic resonance; MRI in particular. One of the most well-known methods, dissolution Dynamic Nuclear Polarization, has been used clinically in cancer patients. One way of ensuring a low bioburden of the hyperpolarized product is by use of a closed fluid path that constitutes a barrier to contamination. The fluid path can be filled with the pharmaceuticals, i.e. imaging agent and solvents, in a clean room, and then stored or immediately used at the polarizer. In this study, we present a method of filling the fluid path that allows it to be reused. The filling method has been investigated in terms of reproducibility at two extrema, high dose for patient use and low dose for rodent studies, using [1-13C]pyruvate as example. We demonstrate that the filling method allows high reproducibility of six quality control parameters with standard deviations 3-10 times smaller than the acceptance criteria intervals in clinical studies.

Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking

Zhang, G., et al., Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking. J Magn Reson, 2016. 272: p. 123-128.

https://www.ncbi.nlm.nih.gov/pubmed/27689531

Off-resonance decoupling using the method of Scaling of Heteronuclear Couplings by Optimal Tracking (SHOT) enables determination of heteronuclear correlations of chemical shifts in single scan NMR spectra. Through modulation of J-coupling evolution by shaped radio frequency pulses, off resonance decoupling using SHOT pulses causes a user-defined dependence of the observed J-splitting, such as the splitting of 13C peaks, on the chemical shift offset of coupled nuclei, such as 1H. Because a decoupling experiment requires only a single scan, this method is suitable for characterizing on-going chemical reactions using hyperpolarization by dissolution dynamic nuclear polarization (D-DNP). We demonstrate the calculation of [13C, 1H] chemical shift correlations of the carbanionic active sites from hyperpolarized styrene polymerized using sodium naphthalene as an initiator. While off resonance decoupling by SHOT pulses does not enhance the resolution in the same way as a 2D NMR spectrum would, the ability to obtain the correlations in single scans makes this method ideal for determination of chemical shifts in on-going reactions on the second time scale. In addition, we present a novel SHOT pulse that allows to scale J-splittings 50% larger than the respective J-coupling constant. This feature can be used to enhance the resolution of the indirectly detected chemical shift and reduce peak overlap, as demonstrated in a model reaction between p-anisaldehyde and isobutylamine. For both pulses, the accuracy is evaluated under changing signal-to-noise ratios (SNR) of the peaks from reactants and reaction products, with an overall standard deviation of chemical shift differences compared to reference spectra of 0.02ppm when measured on a 400MHz NMR spectrometer. Notably, the appearance of decoupling side-bands, which scale with peak intensity, appears to be of secondary importance.

Following Metabolism in Living Microorganisms by Hyperpolarized (1)H NMR

Dzien, P., et al., Following Metabolism in Living Microorganisms by Hyperpolarized (1)H NMR. J Am Chem Soc, 2016. 138(37): p. 12278-86.

https://www.ncbi.nlm.nih.gov/pubmed/27556338

Dissolution dynamic nuclear polarization (dDNP) is used to enhance the sensitivity of nuclear magnetic resonance (NMR), enabling monitoring of metabolism and specific enzymatic reactions in vivo. dDNP involves rapid sample dissolution and transfer to a spectrometer/scanner for subsequent signal detection. So far, most biologically oriented dDNP studies have relied on hyperpolarizing long-lived nuclear spin species such as (13)C in small molecules. While advantages could also arise from observing hyperpolarized (1)H, short relaxation times limit the utility of prepolarizing this sensitive but fast relaxing nucleus. Recently, it has been reported that (1)H NMR peaks in solution-phase experiments could be hyperpolarized by spontaneous magnetization transfers from bound (13)C nuclei following dDNP. This work demonstrates the potential of this sensitivity-enhancing approach to probe the enzymatic process that could not be suitably resolved by (13)C dDNP MR. Here we measured, in microorganisms, the action of pyruvate decarboxylase (PDC) and pyruvate formate lyase (PFL)-enzymes that catalyze the decarboxylation of pyruvate to form acetaldehyde and formate, respectively. While (13)C NMR did not possess the resolution to distinguish the starting pyruvate precursor from the carbonyl resonances in the resulting products, these processes could be monitored by (1)H NMR at 500 MHz. These observations were possible in both yeast and bacteria in minute-long kinetic measurements where the hyperpolarized (13)C enhanced, via (13)C –> (1)H cross-relaxation, the signals of protons binding to the (13)C over the course of enzymatic reactions. In addition to these spontaneous heteronuclear enhancement experiments, single-shot acquisitions based on J-driven (13)C –> (1)H polarization transfers were also carried out. These resulted in higher signal enhancements of the (1)H resonances but were not suitable for multishot kinetic studies. The potential of these (1)H-based approaches for measurements in vivo is briefly discussed.

Dissolution Dynamic Nuclear Polarization capability study with fluid path

Malinowski, R.M., et al., Dissolution Dynamic Nuclear Polarization capability study with fluid path. J Magn Reson, 2016. 272: p. 141-146.

https://www.ncbi.nlm.nih.gov/pubmed/27693965

Signal enhancement by hyperpolarization is a way of overcoming the low sensitivity in magnetic resonance; MRI in particular. One of the most well-known methods, dissolution Dynamic Nuclear Polarization, has been used clinically in cancer patients. One way of ensuring a low bioburden of the hyperpolarized product is by use of a closed fluid path that constitutes a barrier to contamination. The fluid path can be filled with the pharmaceuticals, i.e. imaging agent and solvents, in a clean room, and then stored or immediately used at the polarizer. In this study, we present a method of filling the fluid path that allows it to be reused. The filling method has been investigated in terms of reproducibility at two extrema, high dose for patient use and low dose for rodent studies, using [1-13C]pyruvate as example. We demonstrate that the filling method allows high reproducibility of six quality control parameters with standard deviations 3-10 times smaller than the acceptance criteria intervals in clinical studies.

Renal MR angiography and perfusion in the pig using hyperpolarized water

Wigh Lipso, K., et al., Renal MR angiography and perfusion in the pig using hyperpolarized water. Magn Reson Med, 2016: p. n/a-n/a.

https://www.ncbi.nlm.nih.gov/pubmed/27690362

PURPOSE: To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. METHODS: Protons dissolved in deuterium oxide (D2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. RESULTS: A liquid state polarization of 5.3 +/- 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T1 of 24 +/- 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 +/- 123 mL/100 mL/min. CONCLUSION: Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine.

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