Wednesday, February 27, 2013

High-Field (13)C Dynamic Nuclear Polarization with a Radical Mixture

Michaelis, V.K., et al., High-Field (13)C Dynamic Nuclear Polarization with a Radical Mixture. J Am Chem Soc, 2013.


We report direct (13)C dynamic nuclear polarization at 5 T under magic-angle spinning (MAS) at 82 K using a mixture of monoradicals with narrow EPR linewidths. We show the importance of optimizing both EPR linewidth and electron relaxation times by studying direct DNP of (13)C using SA-BDPA and trityl radical, and achieve (13)C enhancements above 600. This new approach may be best suited for dissolution DNP and for studies of (1)H depleted biological and other nonprotonated solids.



Monday, February 25, 2013

Solid-State NMR on Bacterial Cells: Selective Cell Wall Signal Enhancement and Resolution Improvement using Dynamic Nuclear Polarization

Takahashi, H., et al., Solid-State NMR on Bacterial Cells: Selective Cell Wall Signal Enhancement and Resolution Improvement using Dynamic Nuclear Polarization. J. Am. Chem. Soc., 2013.

http://dx.doi.org/10.1021/ja312501d

Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.


Wednesday, February 20, 2013

Hyperpolarized (13) C-labelled anhydrides as DNP precursors of metabolic MRI agents

Colombo Serra, S., et al., Hyperpolarized 13C-labelled anhydrides as DNP precursors of metabolic MRI agents. Contrast Media & Molecular Imaging, 2012. 7(5): p. 469-477.


The extraordinary enhancement of the nuclear magnetic resonance (NMR) signal that can be obtained by dynamic nuclear polarization (DNP) techniques is prompting new avenues of research based on the in vivo detection of metabolic abnormalities associated with the onset and progression of human diseases. (13) C-labelled short-chain fatty acids appear to be interesting candidates for this novel class of metabolic-active contrast agents (MCAs), as they have been shown to report on metabolic differences between healthy and ischaemic tissues in mice. In spite of their promising biological efficacy, the formulations of short-chain fatty acids that fulfil the many technical constraints of the DNP procedure, as it is today, may limit their clinical potential. New solutions have been sought to circumvent technology-related challenges and facilitate clinical translation of these molecules. In particular, it has been shown that, by using symmetric anhydrides as chemical precursors for short-chain fatty acids, no glass-forming additives are needed in the DNP formulations. Furthermore, novel esterified trityl radicals and lipophilic gadolinium complexes allow easy removal of the polarization-promoting additives at the end of the DNP process. By applying the three concepts reported, we have succeeded in preparing aqueous formulations of short-chain fatty acids for pharmaceutical use that have favourable properties compared with those obtained from current procedures. The use of organic derivatives as chemical precursors of the MCA of interest appears to be a generally valid concept, not restricted to symmetric anhydrides of fatty acids, which can markedly improve the clinical potential of other (13) C-labelled compounds.



Monday, February 18, 2013

Design of a 13C magnetic resonance probe using a deuterated methoxy group as a long-lived hyperpolarization unit

Doura, T., et al., Design of a 13C Magnetic Resonance Probe Using a Deuterated Methoxy Group as a Long-Lived Hyperpolarization Unit. Angew. Chem. Int. Ed., 2012. 51(40): p. 10114-10117.


How to live longer: A fully deuterated 13C methoxy group (13CD3O) is presented as a new long-lived hyperpolarization unit for designing a sensitive 13C magnetic resonance probe. By utilizing the unit, a hyperpolarized magnetic resonance probe for sensing hypochlorous acid was successfully designed.

Friday, February 15, 2013

Dynamic Nuclear Polarization of Sedimented Solutes

Ravera, E., et al., Dynamic Nuclear Polarization of Sedimented Solutes. J. Am. Chem. Soc., 2013. 135(5): p. 1641-1644.


Using the 480 kDa iron-storage protein complex, apoferritin (ApoF), as an example, we demonstrate that sizable dynamic nuclear polarization (DNP) enhancements can be obtained on sedimented protein samples. In sedimented solute DNP (SedDNP), the biradical polarizing agent is co-sedimented with the protein, but in the absence of a glass-forming agent. We observe DNP enhancement factors ε > 40 at a magnetic field of 5 T and temperatures below 90 K, indicating that the protein sediment state is ?glassy? and suitable to disperse the biradical polarizing agent upon freezing. In contrast, frozen aqueous solutions of ApoF yield ε ≈ 2. Results of SedDNP are compared to those obtained from samples prepared using the traditional glass-forming agent glycerol. Collectively, these and results from previous investigations suggest that the sedimented state can be functionally described as a ?microcrystalline glass? and in addition provide a new approach for preparation of samples for DNP experiments.



Monday, February 11, 2013

Achieving high spatial resolution and high SNR in low-field MRI of hyperpolarised gases with Slow Low Angle SHot

Safiullin, K., C. Talbot, and P.J. Nacher, Achieving high spatial resolution and high SNR in low-field MRI of hyperpolarised gases with Slow Low Angle SHot. J Magn Reson, 2013. 227(0): p. 72-86.


MRI of hyperpolarised gases is usually performed with fast data acquisition to achieve high spatial resolutions despite rapid diffusion-induced signal attenuation. We describe a double-cross k-space sampling scheme suitable for Slow Low Angle SHot (SLASH) acquisition and yielding an increased SNR. It consists of a series of anisotropic partial acquisitions with a reduced resolution in the read direction, which alleviates signal attenuation and still provides a high isotropic resolution. The advantages of SLASH imaging over conventional FLASH imaging are evaluated analytically, using numerical lattice calculations, and experimentally in phantom cells filled with hyperpolarised (3)He-N(2) gas mixtures. Low-field MRI is performed (here 2.7mT), a necessary condition to obtain long T(2)( *) values in lungs for slow acquisition. Two additional benefits of the SLASH scheme over FLASH imaging have been demonstrated: it is less sensitive to the artefacts due to concomitant gradients and it allows measuring apparent diffusion coefficients for an extended range of times.

Friday, February 8, 2013

Achieving high spatial resolution and high SNR in low-field MRI of hyperpolarised gases with Slow Low Angle SHot

Safiullin, K., C. Talbot, and P.J. Nacher, Achieving high spatial resolution and high SNR in low-field MRI of hyperpolarised gases with Slow Low Angle SHot. J Magn Reson, 2013. 227(0): p. 72-86


MRI of hyperpolarised gases is usually performed with fast data acquisition to achieve high spatial resolutions despite rapid diffusion-induced signal attenuation. We describe a double-cross k-space sampling scheme suitable for Slow Low Angle SHot (SLASH) acquisition and yielding an increased SNR. It consists of a series of anisotropic partial acquisitions with a reduced resolution in the read direction, which alleviates signal attenuation and still provides a high isotropic resolution. The advantages of SLASH imaging over conventional FLASH imaging are evaluated analytically, using numerical lattice calculations, and experimentally in phantom cells filled with hyperpolarised (3)He-N(2) gas mixtures. Low-field MRI is performed (here 2.7mT), a necessary condition to obtain long T(2)( *) values in lungs for slow acquisition. Two additional benefits of the SLASH scheme over FLASH imaging have been demonstrated: it is less sensitive to the artefacts due to concomitant gradients and it allows measuring apparent diffusion coefficients for an extended range of times.



Wednesday, February 6, 2013

Dissolution DNP-NMR spectroscopy using galvinoxyl as a polarizing agent

Lumata, L.L., et al., Dissolution DNP-NMR spectroscopy using galvinoxyl as a polarizing agent. J Magn Reson, 2013. 227(0): p. 14-9.


The goal of this work was to test feasibility of using galvinoxyl (2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p- tolyloxy) as a polarizing agent for dissolution dynamic nuclear polarization (DNP) NMR spectroscopy. We have found that galvinoxyl is reasonably soluble in ethyl acetate, chloroform, or acetone and the solutions formed good glasses when mixed together or with other solvents such as dimethyl sulfoxide. W-band electron spin resonance (ESR) measurements revealed that galvinoxyl has an ESR linewidth D intermediate between that of carbon-centered free radical trityl OX063 and the nitroxide-based 4-oxo-TEMPO, thus the DNP with galvinoxyl for nuclei with low gyromagnetic ratio gamma such as (13)C and (15)N is expected to proceed predominantly via the thermal mixing process. The optimum radical concentration that would afford the highest (13)C nuclear polarization (approximately 6% for [1-(13)C]ethyl acetate) at 3.35T and 1.4K was found to be around 40mM. After dissolution, large liquid-state NMR enhancements were achieved for a number of (13)C and (15)N compounds with long spin-lattice relaxation time T(1). In addition, the hydrophobic galvinoxyl free radical can be easily filtered out from the dissolution liquid when water is used as the solvent. These results indicate that galvinoxyl can be considered as an easily available free radical polarizing agent for routine dissolution DNP-NMR spectroscopy.



Monday, February 4, 2013

Dynamic nuclear polarization and optimal control spatial-selective 13C MRI and MRS

Vinding, M.S., et al., Dynamic nuclear polarization and optimal control spatial-selective (13)C MRI and MRS. J Magn Reson, 2013. 227(0): p. 57-61.


Aimed at (13)C metabolic magnetic resonance imaging (MRI) and spectroscopy (MRS) applications, we demonstrate that dynamic nuclear polarization (DNP) may be combined with optimal control 2D spatial selection to simultaneously obtain high sensitivity and well-defined spatial restriction. This is achieved through the development of spatial-selective single-shot spiral-readout MRI and MRS experiments combined with dynamic nuclear polarization hyperpolarized [1-(13)C]pyruvate on a 4.7T pre-clinical MR scanner. The method stands out from related techniques by facilitating anatomic shaped region-of-interest (ROI) single metabolite signals available for higher image resolution or single-peak spectra. The 2D spatial-selective rf pulses were designed using a novel Krotov-based optimal control approach capable of iteratively fast providing successful pulse sequences in the absence of qualified initial guesses. The technique may be important for early detection of abnormal metabolism, monitoring disease progression, and drug research.

Friday, February 1, 2013

Localized in vivo hyperpolarization transfer sequences

Mishkovsky, M., et al., Localized in vivo hyperpolarization transfer sequences. Magnetic Resonance in Medicine, 2012. 68(2): p. 349-352.


In vivo localized and fully adiabatic homonuclear and heteronuclear polarization transfer experiments were designed and performed in the rat brain at 9.4 T after infusion of hyperpolarized sodium [1,2-(13)C(2)] and sodium [1-(13)C] acetate. The method presented herein leads to highly enhanced in vivo detection of short-T(1) (13)C as well as attached protons. This indirect detection scheme allows for probing additional molecular sites in hyperpolarized substrates and their metabolites and can thus lead to improved spectral resolution such as in the case of (13)C-acetate metabolism.