Monday, November 30, 2015

Single voxel localization for dynamic hyperpolarized 13C MR spectroscopy


Chen, A.P. and C.H. Cunningham, Single voxel localization for dynamic hyperpolarized 13C MR spectroscopy. J. Magn. Reson., 2015. 258: p. 81-85.


The PRESS technique has been widely used to achieve voxel localization for in vivo 1H MRS acquisitions. However, for dynamic hyperpolarized 13C MRS experiments, the transition bands of the refocusing pulses may saturate the pre-polarized substrate spins flowing into the voxel. This limitation may be overcome by designing refocusing pulses that do not perturb the resonance of the hyperpolarized substrate, but selectively refocuses the spins of the metabolic products. In this study, a PRESS pulse sequence incorporating spectral–spatial refocusing pulses that have a stop band (‘notch’) at the substrate resonance is tested in vivo using hyperpolarized [1-13C]pyruvate. Higher metabolite SNR was observed in experiments using the spectral–spatial refocusing pulses as compared to conventional refocusing pulses.

Sunday, November 29, 2015

[NMR] PhD Position - Uni Leipzig - Solid-state NMR on photoreceptor protein

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PhD Position - Uni Leipzig - Solid-state NMR on photoreceptor protein


The Institute of Analytical Chemistry at the University of Leipzig invites applications for a PhD position in the field of solid-state NMR characterization of photoreceptors. To be appointed from 01.02.16 or later. The position is limited to 3 years.

The NMR research group of Jörg Matysik works on the development of hyperpolarization and optical NMR techniques for studying photo/spin-chemically relevant systems. The successful candidate will work on an interdisciplinary research project combining biochemical work and solid-state NMR spectroscopy. This DFG financed project aims for understanding of the electronic orbital structure of the chromophore in photoreceptors of the phytochrome family.

The candidate should hold a MSc degree and be highly motivated with a strong interest in protein chemistry and biophysics. Previous experience biochemistry of proteins and is desirable. Experience in the field of magnetic resonance spectroscopy is of advantage.

For further information, please contact Jörg Matysik,

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[NMR] Course on "Dissolution Dynamic Nuclear Polarization" December 9-11, 2015 at EPFL, Switzerland

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We would like to announce a three-day course for PhD students and Post-Docs on

"Dissolution Dynamic Nuclear Polarization"

The course will start at 1pm on Wednesday December the 9th and will end at 5pm on Friday the 11th, and will be held at the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, at the Laboratory of Biomolecular Magnetic Resonance (LRMB).

* Registration
please register at the following adress:
subscription fees: 100 CHF

* Information
sami.jannin (at) epfl.ch
geoffrey.bodenhausen (at) epfl.ch

* Objectives
Dissolution Dynamic Nuclear Polarization (D-DNP) provides a way to enhance NMR signals in liquids by more than 4 orders of magnitude. We present the current state-of-the-art and most recent advances of this technique, and we propose experimental demonstrations with hands-on participation. 

* Content
Lectures and seminars: 11 Hours
Hands-on: 7 Hours

Day 1:  Lectures, 1 pm - 5 pm: Theoretical aspects of DNP

- Introduction to DNP-enhanced NMR
- Principles of Dissolution-DNP
- Low temperature DNP mechanisms
- Cross Polarization techniques
- Applications to imaging and chemistry

Day 2:  Lectures, 9 am - 12 am: Experimental aspects of DNP

- Hardware for DNP
- Hardware for Cross Polarization 
- Hardware for Dissolution

Experiments, 1 pm - 5 pm

- Sample Preparation
- Preparation of a dissolution DNP experiment

Day 3: Experiments, 9 am - 12 am: Practical DNP at the Laboratory of Biomolecular Magnetic Resonance (LRMB)

- Low temperature DNP
- Cross Polarization with DNP
- Dissolution DNP


Seminars, 1 pm - 5 pm

 - All participants are invited to give a short presentation, possibly on DNP and/or related to their own research subjects.

*Required prior knowledge
Basic understanding of NMR

Dr. Sami Jannin

EPFL
Av Forel
Batochime BCH 1534
CH-1015 Lausanne 
Switzerland

Phone +41 21 693 97 24
Mobile +41 77 406 61 23
Skype samiboulot
Fax +41 21 693 94 35


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[NMR] Post Doc position in Hyperpolarized Magnetic Resonance

From the Ampere Magnetic Resonance List

Center for Hyperpolarization in Magnetic Resonance at the Technical University of Denmark is looking for a PhD in Magnetic Resonance who wants to work on "HyperPET/MR: a new concept of hybrid molecular imaging in cancer using simultaneous PET and 13C-hyperpolarized MRSI" for a two-year postdoc position. Please share if you know a candidate! "HyperPET/MR" is a collaboration with Copenhagen University, Copenhagen University Hospital, Cambridge University, Stanford University and GE Healthcare. The project is funded by Innovation Fund DK (then Strategic Research Council).


Jan Henrik Ardenkjær-Larsen 
Professor, Center Leader 
Technical University of Denmark 
Department of Electrical Engineering 
Ørsted Plads, bldg 349, office 126 
DK - 2800 Kgs. Lyngby 
Phone +45 40272775 


Monday, November 23, 2015

Direct dynamic measurement of intracellular and extracellular lactate in small-volume cell suspensions with (13)C hyperpolarised NMR


Breukels, V., et al., Direct dynamic measurement of intracellular and extracellular lactate in small-volume cell suspensions with (13)C hyperpolarised NMR. NMR Biomed, 2015. 28(8): p. 1040-8.


Hyperpolarised (HP) (13)C NMR allows enzymatic activity to be probed in real time in live biological systems. The use of in vitro models gives excellent control of the cellular environment, crucial in the understanding of enzyme kinetics. The increased conversion of pyruvate to lactate in cancer cells has been well studied with HP (13)C NMR. Unfortunately, the equally important metabolic step of lactate transport out of the cell remains undetected, because intracellular and extracellular lactate are measured as a single resonance. Furthermore, typical experiments must be performed using tens of millions of cells, a large amount which can lead to a costly and sometimes highly challenging growing procedure. We present a relatively simple set-up that requires as little as two million cells with the spectral resolution to separate the intracellular and extracellular lactate resonances. The set-up is tested with suspensions of prostate cancer carcinoma cells (PC3) in combination with HP [1-(13)C]pyruvate. We obtained reproducible pyruvate to lactate label fluxes of 1.2 and 1.7 nmol/s per million cells at 2.5 and 5.0 mM pyruvate concentrations. The existence of a 3-Hz chemical shift difference between intracellular and extracellular lactate enabled us to determine the lactate transport rates in PC3. We deduced a lactate export rate of 0.3 s(-1) and observed a decrease in lactate transport on addition of the lactate transport inhibitor alpha-cyano-4-hydroxycinnamic acid.

Wednesday, November 18, 2015

Dynamic nuclear polarization in solid samples by electrical-discharge-induced radicals


Katz, I. and A. Blank, Dynamic nuclear polarization in solid samples by electrical-discharge-induced radicals. J Magn Reson, 2015. 261: p. 95-100.


Dynamic nuclear polarization (DNP) is a method for enhancing nuclear magnetic resonance (NMR) signals that has many potential applications in chemistry and medicine. Traditionally, DNP signal enhancement is achieved through the use of exogenous radicals mixed in a solution with the molecules of interest. Here we show that proton DNP signal enhancements can be obtained for solid samples without the use of solvent and exogenous radicals. Radicals are generated primarily on the surface of a solid sample using electrical discharges. These radicals are found suitable for DNP. They are stable under moderate vacuum conditions, yet readily annihilate upon compound dissolution or air exposure. This feature makes them attractive for use in medical applications, where the current variety of radicals used for DNP faces regulatory problems. In addition, this solvent-free method may be found useful for analytical NMR of solid samples which cannot tolerate solvents, such as certain pharmaceutical products.

Tuesday, November 17, 2015

Monday, November 16, 2015

Cysteine-Specific Labeling of Proteins with a Nitroxide Biradical for Dynamic Nuclear Polarization NMR


Voinov, M.A., et al., Cysteine-Specific Labeling of Proteins with a Nitroxide Biradical for Dynamic Nuclear Polarization NMR. J Phys Chem B, 2015. 119(32): p. 10180-90.


Dynamic nuclear polarization (DNP) enhances the signal in solid-state NMR of proteins by transferring polarization from electronic spins to the nuclear spins of interest. Typically, both the protein and an exogenous source of electronic spins, such as a biradical, are either codissolved or suspended and then frozen in a glycerol/water glassy matrix to achieve a homogeneous distribution. While the use of such a matrix protects the protein upon freezing, it also reduces the available sample volume (by ca. a factor of 4 in our experiments) and causes proportional NMR signal loss. Here we demonstrate an alternative approach that does not rely on dispersing the DNP agent in a glassy matrix. We synthesize a new biradical, ToSMTSL, which is based on the known DNP agent TOTAPOL, but also contains a thiol-specific methanethiosulfonate group to allow for incorporating this biradical into a protein in a site-directed manner. ToSMTSL was characterized by EPR and tested for DNP of a heptahelical transmembrane protein, Anabaena sensory rhodopsin (ASR), by covalent modification of solvent-exposed cysteine residues in two (15)N-labeled ASR mutants. DNP enhancements were measured at 400 MHz/263 GHz NMR/EPR frequencies for a series of samples prepared in deuterated and protonated buffers and with varied biradical/protein ratios. While the maximum DNP enhancement of 15 obtained in these samples is comparable to that observed for an ASR sample cosuspended with ~17 mM TOTAPOL in a glycerol-d8/D2O/H2O matrix, the achievable sensitivity would be 4-fold greater due to the gain in the filling factor. We anticipate that the DNP enhancements could be further improved by optimizing the biradical structure. The use of covalently attached biradicals would broaden the applicability of DNP NMR to structural studies of proteins.

Friday, November 13, 2015

Implementation and characterization of flow injection in dissolution dynamic nuclear polarization NMR spectroscopy


Chen, H.Y. and C. Hilty, Implementation and characterization of flow injection in dissolution dynamic nuclear polarization NMR spectroscopy. ChemPhysChem, 2015. 16(12): p. 2646-52.


The use of dissolution dynamic nuclear polarization (D-DNP) offers substantially increased signals in liquid-state NMR spectroscopy. A challenge in realizing this potential lies in the transfer of the hyperpolarized sample to the NMR detector without loss of hyperpolarization. Here, the use of a flow injection method using high-pressure liquid leads to improved performance compared to the more common gas-driven injection, by suppressing residual fluid motions during the NMR experiment while still achieving a short injection time. Apparent diffusion coefficients are determined from pulsed field gradient echo measurements, and are shown to fall below 1.5 times the value of a static sample within 0.8 s. Due to the single-scan nature of D-DNP, pulsed field gradients are often the only choice for coherence selection or encoding, but their application requires stationary fluid. Sample delivery driven by a high-pressure liquid will improve the applicability of these types of D-DNP advanced experiments.

Wednesday, November 11, 2015

Open Position at Bridge12: Scientist - Magnetic Resonance Spectroscopy

Bridge12 has currently an opening for a Scientist - Magnetic Resonance Spectroscopy. Details can be found here:

http://www.bridge12.com/content/scientist-instrument-development-magnetic-resonance-spectroscopy


Spin Noise Detection of Nuclear Hyperpolarization at 1.2 K


Poschko, M.T., et al., Spin Noise Detection of Nuclear Hyperpolarization at 1.2 K. ChemPhysChem, 2015: p. n/a-n/a.


We report proton spin noise spectra of a hyperpolarized solid sample of commonly used "DNP juice" containing TEMPOL and irradiated by a microwave field at a temperature of 1.2 K in a magnetic field of 6.7 T. The line shapes of the spin noise power spectra are sensitive to the variation of the microwave irradiation frequency and change from dip to bump, when the electron Larmor frequency is crossed, which is shown to be in good accordance with theory by simulations. Small but significant deviations from these predictions are observed, which can be related to spin noise and radiation damping phenomena that have been reported in thermally polarized systems. The non-linear dependence of the spin noise integral on nuclear polarization provides a means to monitor hyperpolarization semi-quantitatively without any perturbation of the spin system by radio frequency irradiation.

Monday, November 9, 2015

Structure of Colloidal Quantum Dots from Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy


Piveteau, L., et al., Structure of Colloidal Quantum Dots from Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy. J Am Chem Soc, 2015. 137(43): p. 13964-71.


Understanding the chemistry of colloidal quantum dots (QDs) is primarily hampered by the lack of analytical methods to selectively and discriminately probe the QD core, QD surface and capping ligands. Here, we present a general concept for studying a broad range of QDs such as CdSe, CdTe, InP, PbSe, PbTe, CsPbBr3, etc., capped with both organic and inorganic surface capping ligands, through dynamic nuclear polarization (DNP) surface enhanced NMR spectroscopy. DNP can enhance NMR signals by factors of 10-100, thereby reducing the measurement times by 2-4 orders of magnitude. 1D DNP enhanced spectra acquired in this way are shown to clearly distinguish QD surface atoms from those of the QD core, and environmental effects such as oxidation. Furthermore, 2D NMR correlation experiments, which were previously inconceivable for QD surfaces, are demonstrated to be readily performed with DNP and provide the bonding motifs between the QD surfaces and the capping ligands.

Friday, November 6, 2015

Robust hyperpolarized (13)C metabolic imaging with selective non-excitation of pyruvate (SNEP)


Chen, W.C., et al., Robust hyperpolarized (13)C metabolic imaging with selective non-excitation of pyruvate (SNEP). NMR Biomed, 2015. 28(8): p. 1021-30.


In vivo metabolic imaging using hyperpolarized [1-(13)C]pyruvate provides localized biochemical information and is particularly useful in detecting early disease changes, as well as monitoring disease progression and treatment response. However, a major limitation of hyperpolarized magnetization is its unrecoverable decay, due not only to T1 relaxation but also to radio-frequency (RF) excitation. RF excitation schemes used in metabolic imaging must therefore be able to utilize available hyperpolarized magnetization efficiently and robustly for the optimal detection of substrate and metabolite activities. In this work, a novel RF excitation scheme called selective non-excitation of pyruvate (SNEP) is presented. This excitation scheme involves the use of a spectral selective RF pulse to specifically exclude the excitation of [1-(13)C]pyruvate, while uniformly exciting the key metabolites of interest (namely [1-(13)C]lactate and [1-(13)C]alanine) and [1-(13)C]pyruvate-hydrate. By eliminating the loss of hyperpolarized [1-(13)C]pyruvate magnetization due to RF excitation, the signal from downstream metabolite pools is increased together with enhanced dynamic range. Simulation results, together with phantom measurements and in vivo experiments, demonstrated the improvement in signal-to-noise ratio (SNR) and the extension of the lifetime of the [1-(13)C]lactate and [1-(13)C]alanine pools when compared with conventional non-spectral selective (NS) excitation. SNEP has also been shown to perform comparably well with multi-band (MB) excitation, yet SNEP possesses distinct advantages, including ease of implementation, less stringent demands on gradient performance, increased robustness to frequency drifts and B0 inhomogeneity as well as easier quantification involving the use of [1-(13)C]pyruvate-hydrate as a proxy for the actual [1-(13)C] pyruvate signal. SNEP is therefore a promising alternative for robust hyperpolarized [1-(13)C]pyruvate metabolic imaging with high fidelity.

[NMR] job opening in New York

From the Ampere Magenetic Resonance List



Staff scientist / Postdoctoral fellow

The Meriles group at CUNY - City College of New York invites applications for a position at the level of research scientist or postdoctoral associate. The successful candidate will have a strong research background but also the drive and motivation to work in an entrepreneurial setting. Applicants must have a PhD in Physics, Chemistry or a closely related field, be a US citizen or permanent resident, and demonstrate experience in one or more of the following areas:

  • electron or nuclear magnetic resonance, particularly, in connection with schemes of nuclear spin hyperpolarization (e.g., DNP);
  • design and application of microfluidics in liquid state NMR
  • familiarity with nitrogen-vacancy centers in diamond and optically-detected magnetic resonance.

Work will be carried out in close connection with researchers at UC Berkeley and an industrial partner. Records of creative research demonstrated by publications in peer-reviewed journals, excellent oral and written communication skills, and the ability to work collaboratively in a team environment are necessary. Prior entrepreneurial experience or employment within industry is viewed positively. Salary will be commensurate with the applicant’s experience. Interested candidates should submit a CV with a publication list, a brief biosketch, and the contact information of three references to Prof. Carlos Meriles (cmeriles@sci.ccny.cuny.edu).

All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, or disability.


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Wednesday, November 4, 2015

Design and characterization of a W-band system for modulated DNP experiments


Guy, M.L., L. Zhu, and C. Ramanathan, Design and characterization of a W-band system for modulated DNP experiments. J. Magn. Reson., 2015. 261: p. 11-18.


Magnetic-field and microwave-frequency modulated DNP experiments have been shown to yield improved enhancements over conventional DNP techniques, and even to shorten polarization build-up times. The resulting increase in signal-to-noise ratios can lead to significantly shorter acquisition times in signal-limited multi-dimensional NMR experiments and pave the way to the study of even smaller sample volumes. In this paper we describe the design and performance of a broadband system for microwave frequency- and amplitude-modulated DNP that has been engineered to minimize both microwave and thermal losses during operation at liquid helium temperatures. The system incorporates a flexible source that can generate arbitrary waveforms at 94 GHz with a bandwidth greater than 1 GHz, as well as a probe that efficiently transmits the millimeter waves from room temperature outside the magnet to a cryogenic environment inside the magnet. Using a thin-walled brass tube as an overmoded waveguide to transmit a hybrid HE11 mode, it is possible to limit the losses to 1 dB across a 2 GHz bandwidth. The loss is dominated by the presence of a quartz window used to isolate the waveguide pipe. This performance is comparable to systems with corrugated waveguide or quasi-optical components. The overall excitation bandwidth of the probe is seen to be primarily determined by the final antenna or resonator used to excite the sample and its coupling to the NMR RF coil. Understanding the instrumental limitations imposed on any modulation scheme is key to understanding the observed DNP results and potentially identifying the underlying mechanisms. We demonstrate the utility of our design with a set of triangular frequency-modulated DNP experiments.

Monday, November 2, 2015

Frequency swept microwaves for hyperfine decoupling and time domain dynamic nuclear polarization


Hoff, D.E., et al., Frequency swept microwaves for hyperfine decoupling and time domain dynamic nuclear polarization. Solid State Nucl Magn Reson, 2015.


Hyperfine decoupling and pulsed dynamic nuclear polarization (DNP) are promising techniques to improve high field DNP NMR. We explore experimental and theoretical considerations to implement them with magic angle spinning (MAS). Microwave field simulations using the high frequency structural simulator (HFSS) software suite are performed to characterize the inhomogeneous phase independent microwave field throughout a 198GHz MAS DNP probe. Our calculations show that a microwave power input of 17W is required to generate an average EPR nutation frequency of 0.84MHz. We also present a detailed calculation of microwave heating from the HFSS parameters and find that 7.1% of the incident microwave power contributes to dielectric sample heating. Voltage tunable gyrotron oscillators are proposed as a class of frequency agile microwave sources to generate microwave frequency sweeps required for the frequency modulated cross effect, electron spin inversions, and hyperfine decoupling. Electron spin inversions of stable organic radicals are simulated with SPINEVOLUTION using the inhomogeneous microwave fields calculated by HFSS. We calculate an electron spin inversion efficiency of 56% at a spinning frequency of 5kHz. Finally, we demonstrate gyrotron acceleration potentials required to generate swept microwave frequency profiles for the frequency modulated cross effect and electron spin inversions.