Monday, April 29, 2013

Detection of Living Anionic Species in Polymerization Reactions Using Hyperpolarized NMR

Lee, Y., et al., Detection of Living Anionic Species in Polymerization Reactions Using Hyperpolarized NMR. J. Am. Chem. Soc., 2013. 135(12): p. 4636-4639.

Intermediates during the anionic polymerization of styrene were observed using hyperpolarized NMR. Dissolution dynamic nuclear polarization (DNP) of monomers provides a sufficient signal-to-noise ratio for detection of 13C NMR signals in real time as the reaction progresses. Because of its large chemical shift dispersion, 13C is well-suited to distinguish and characterize the chemical species that arise during the reaction. At the same time, incorporation of hyperpolarized small-molecule monomers is a unique way to generate polymers that exhibit a transient signal enhancement at the active site. This strategy is applicable despite the decay of the hyperpolarization of the polymer due to rapid spin-lattice relaxation. Real-time measurements on polymerization reactions provide both mechanistic and kinetic information without the need for stable isotope labeling of the molecules of interest. These capabilities are orthogonal to currently established methods that separate synthesis and analysis into two steps, making dissolution DNP an attractive method to study polymerization reactions.


Friday, April 26, 2013

Design of a quadrature surface coil for hyperpolarized 13C MRS cardiac metabolism studies in pigs

Due to ENC I'm a bit behind catching up with the literature ... This article below was just published in Concepts in Magnetic Resonance and shows the diverse applications of DNP.



Giovannetti, G., et al., Design of a quadrature surface coil for hyperpolarized 13C MRS cardiac metabolism studies in pigs. Concepts in Magnetic Resonance Part B: Magnetic Resonance Engineering, 2013. 43(2): p. 69-77.


This work describes the design of a quadrature surface coil constituted by a circular loop and a butterfly coil, employed in transmit/receive (TX/RX) mode for hyperpolarized 13C studies of pig heart with a clinical 3T scanner. The coil characterization is performed by developing an SNR model for coil performance evaluation in terms of coil resistance, sample-induced resistance and magnetic field pattern. Experimental SNR-vs.-depth profiles, extracted from the [1–13C]acetate phantom chemical shift image (CSI), showed good agreement with the theoretical SNR-vs.-depth profiles. Moreover, the performance of the quadrature coil was compared with the single TX/RX circular and TX/RX butterfly coil, in order to verify the advantage of the proposed configuration over the single coils throughout the volume of interest for cardiac imaging in pig. Finally, the quadrature surface coil was tested by acquiring metabolic maps with hyperpolarized [1–13C]pyruvate injected i.v. in a pig.


Wednesday, April 24, 2013

Continuously Tunable 250 GHz Gyrotron with a Double Disk Window for DNP-NMR Spectroscopy

Jawla, S., et al., Continuously Tunable 250 GHz Gyrotron with a Double Disk Window for DNP-NMR Spectroscopy. J Infrared Milli Terahz Waves, 2013. 34(1): p. 42-52.


In this paper, we describe the design and experimental results from the rebuild of a 250 GHz gyrotron used for Dynamic Nuclear Polarization enhanced Nuclear Magnetic Resonance spectroscopy on a 380 MHz spectrometer. Tuning bandwidth of approximately 2 GHz is easily achieved at a fixed magnetic field of 9.24 T and a beam current of 95 mA producing an average output power of >10 W over the entire tuning band. This tube incorporates a double disk output sapphire window in order to maximize the transmission at 250.58 GHz. DNP Signal enhancement of >125 is achieved on a 13C-Urea sample using this gyrotron.

Monday, April 22, 2013

Efficient, balanced, transmission line RF circuits by back propagation of common impedance nodes

Markhasin, E., et al., Efficient, balanced, transmission line RF circuits by back propagation of common impedance nodes. J. Magn. Reson., 2013. 231(0): p. 32-38.


We present a new, efficient strategy for designing fully balanced transmission line RF circuits for solid state NMR probes based on back propagation of common impedance nodes (BPCIN). In this approach, the impedance node phenomenon is the sole means of achieving mutual RF isolation and balance in all RF channels. BPCIN is illustrated using a custom double resonance 3.2 mm MAS probe operating at 500 MHz (1H) and 125 MHz (13C). When fully optimized, the probe is capable of producing high homogeneity (810°/90° ratios of 86% and 89% for 1H and 13C, respectively) and high efficiency (γB1 = 100 kHz for 1H and 13C at 70 W and 180 W of RF input, respectively; up to 360 kHz for 1H). The probe’s performance is illustrated by 2D MAS correlation spectra of microcrystals of the tripeptide N-f-MLF-OH and hydrated amyloid fibrils of the protein PI3-SH3.

Wednesday, April 17, 2013

Analysis of sensitivity enhancement by dynamic nuclear polarization in solid-state NMR: a case study of functionalized mesoporous materials

Kobayashi, T., et al., Analysis of sensitivity enhancement by dynamic nuclear polarization in solid-state NMR: a case study of functionalized mesoporous materials. Phys Chem Chem Phys, 2013. 15(15): p. 5553-62.


We systematically studied the enhancement factor (per scan) and the sensitivity enhancement (per unit time) in (13)C and (29)Si cross-polarization magic angle spinning (CP-MAS) NMR boosted by dynamic nuclear polarization (DNP) of functionalized mesoporous silica nanoparticles (MSNs). Specifically, we separated contributions due to: (i) microwave irradiation, (ii) quenching by paramagnetic effects, (iii) the presence of frozen solvent, (iv) the temperature, as well as changes in (v) relaxation and (vi) cross-polarization behaviour. No line-broadening effects were observed for MSNs when lowering the temperature from 300 to 100 K. Notwithstanding a significant signal reduction due to quenching by TOTAPOL radicals, DNP-CP-MAS at 100 K provided global sensitivity enhancements of 23 and 45 for (13)C and (29)Si, respectively, relative to standard CP-MAS measurements at room temperature. The effects of DNP were also ascertained by comparing with state-of-the-art two-dimensional heteronuclear (1)H{(13)C} and (29)Si{(1)H} correlation spectra, using, respectively, indirect detection or Carr-Purcell-Meiboom-Gill (CPMG) refocusing to boost signal acquisition. This study highlights opportunities for further improvements through the development of high-field DNP, better polarizing agents, and improved capabilities for low-temperature MAS.



Tuesday, April 16, 2013

MR Physicist/Engineer Position for Hyperpolarized DNP NMR/MRI

This was originally posted on the ISMRM webpage at: http://www.ismrm.org/jobs/J04941.pdf


MR Physicist/Engineer Position for Hyperpolarized DNP NMR/MRI

Applications are invited for the position of a MR physicist/engineer in the Department of Radiology and Biomedical Imaging at the University of California San Francisco (UCSF). The successful candidate will be responsible for Dynamic Nuclear Polarization (DNP) instrumentation development and maintenance at the UCSF Hyperpolarized MRI Technology Resource Center. This position will work closely with collaborators to design and test new methods & hardware for dissolution DNP hyperpolarized MR molecular imaging preclinical and clinical research studies.

Monday, April 15, 2013

Temperature Dependence of Electron Spin Relaxation of 2,2-Diphenyl-1-Picrylhydrazyl in Polystyrene

Meyer, V., S. Eaton, and G. Eaton, Temperature Dependence of Electron Spin Relaxation of 2,2-Diphenyl-1-Picrylhydrazyl in Polystyrene. Appl. Magn. Reson., 2013. 44(4): p. 509-517.


The electron spin relaxation rates for the stable radical DPPH (2,2-diphenyl-1-picrylhydrazyl) doped into polystyrene were studied by inversion recovery and electron spin echo at X-band and Q-band between 20 and 295 K. At low concentration (340 muM, 0.01%) spin-lattice relaxation was dominated by the Raman process and a local mode. At high concentration (140 mM, 5%) relaxation is orders of magnitude faster than at the lower concentration, and 1/T1 is approximately linearly dependent on temperature. Spin lattice relaxation rates are similar at X-band and Q-band. The temperature dependence of spin echo dephasing was faster at about 140 K than at higher or lower temperatures, which is attributed to a wagging motion of the phenyl groups.

Friday, April 12, 2013

Strategies for rapid in vivo 1H and hyperpolarized 13C MR spectroscopic imaging

Nelson, S.J., et al., Strategies for rapid in vivo 1H and hyperpolarized 13C MR spectroscopic imaging. J. Magn. Reson., 2013. 229(0): p. 187-197.


In vivo MRSI is an important imaging modality that has been shown in numerous research studies to give biologically relevant information for assessing the underlying mechanisms of disease and for monitoring response to therapy. The increasing availability of high field scanners and multichannel radiofrequency coils has provided the opportunity to acquire in vivo data with significant improvements in sensitivity and signal to noise ratio. These capabilities may be used to shorten acquisition time and provide increased coverage. The ability to acquire rapid, volumetric MRSI data is critical for examining heterogeneity in metabolic profiles and for relating serial changes in metabolism within the same individual during the course of the disease. In this review we discuss the implementation of strategies that use alternative k-space sampling trajectories and parallel imaging methods in order to speed up data acquisition. The impact of such methods is demonstrated using three recent examples of how these methods have been applied. These are to the acquisition of robust 3D 1H MRSI data within 5–10 min at a field strength of 3 T, to obtaining higher sensitivity for 1H MRSI at 7 T and to using ultrafast volumetric and dynamic 13C MRSI for monitoring the changes in signals that occur following the injection of hyperpolarized 13C agents.



Wednesday, April 10, 2013

PhD positions available in solid-state DNP at BMRZ Frankfurt

Dear Colleagues, 

Please take notice of the below attached job posting. I'd appreciate if you could forward it to anyone who might be interested. Additional information is available on http://www.solidstateDNP.com/jobs.html

Applications are invited for PhD positions in solid-state DNP Spectroscopy in an Emmy Noether research group by Björn Corzilius at the Goethe University Frankfurt/Main, Germany. Salary will be according to E13 TV-G-U on 67% part-time basis. The PhD students will be placed at the seam between the BMRZ and the Institute of Physical and Theoretical Chemistry. 

The research group focuses on method development and basic research of DNP towards biomolecular applications. Possible topics are: 

i) Development and investigation of site-specific DNP using molecular model systems 
ii) Investigation of endogenous paramagnetic centers of biomolecules as polarizing agents for DNP. 

Qualification requirements 

To qualify, the applicant must hold a diploma or masters degree or a qualification deemed equivalent in chemistry, physics, biochemistry, or biophysics. The applicant must be ambitious and demonstrate a strong motivation and an appropriate background to help develop the proposed research area. Experience in magnetic resonance methods is beneficial but not required. Good language skills in English are a crucial requirement. 

We offer a comprehensive training in magnetic resonance methods, including solid-state NMR, EPR, and DNP. The applicant will work in a cutting-edge field situated at the seam between EPR and NMR and will therefore gain an invaluable integral knowledge and expertise in the field of magnetic resonance. Experiments will be performed using state-of-the-art instrumentation at the BMRZ or external collaboration sites. 

The successful candidate must have very good collaborative skills, have integrity and be flexible and capable of working in a structured and efficient way. The successful candidates should also be able to contribute to the innovative climate within the group. 

Please send your relevant and comprehensive application material to Björn Corzilius: corzilius@em.uni-frankfurt.de


Dr. Björn Corzilius 
Emmy Noether Research Group Leader 
Institute for Physical and Theoretical Chemistry,
Institute for Biophysical Chemistry,
and Center for Biomolecular Magnetic Resonance (BMRZ) 

Goethe University Frankfurt 
Building N140, Room 1 

Max-von-Laue-Str. 7
60438 Frankfurt am Main 

phone: +49-(0)69-798-29467
fax: +49-(0)69-798-29404 


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Perspectives of hyperpolarized noble gas MRI beyond 3He

Lilburn, D.M.L., G.E. Pavlovskaya, and T. Meersmann, Perspectives of hyperpolarized noble gas MRI beyond 3He. J. Magn. Reson., 2013. 229(0): p. 173-186.


Nuclear Magnetic Resonance (NMR) studies with hyperpolarized (hp) noble gases are at an exciting interface between physics, chemistry, materials science and biomedical sciences. This paper intends to provide a brief overview and outlook of magnetic resonance imaging (MRI) with hp noble gases other than hp 3He. A particular focus are the many intriguing experiments with 129Xe, some of which have already matured to useful MRI protocols, while others display high potential for future MRI applications. Quite naturally for MRI applications the major usage so far has been for biomedical research but perspectives for engineering and materials science studies are also provided. In addition, the prospects for surface sensitive contrast with hp 83Kr MRI is discussed.



Monday, April 8, 2013

Meet Bridge12 at ENC

Again, the Bridge12 team is looking forward to attending this year’s 54th Experimental Nuclear Magnetic Resonance Conference (ENC) held at the Asilomar Conference Grounds in Pacific Grove from April 14th to 29th, 2013.

Let me know in advance if you would like to meet up with me (email to tmaly@bridge12.com), or simply pull me aside at the conference. I'm looking forward to this exciting event to discuss how Bridge12 can help you push the boundaries of DNP-NMR research.

Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized 13C magnetic resonance spectroscopic imaging


Park, J.M., et al., Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized 13C magnetic resonance spectroscopic imaging. Neuro-Oncology, 2013. 15(4): p. 433-41.


Background The metabolic phenotype that derives disproportionate energy via glycolysis in solid tumors, including glioma, leads to elevated lactate labeling in metabolic imaging using hyperpolarized [1-13C]pyruvate. Although the pyruvate dehydrogenase (PDH)–mediated flux from pyruvate to acetyl coenzyme A can be indirectly measured through the detection of carbon-13 (13C)-labeled bicarbonate, it has proven difficult to visualize 13C-bicarbonate at high enough levels from injected [1-13C]pyruvate for quantitative analysis in brain. The aim of this study is to improve the detection of 13C-labeled metabolites, in particular bicarbonate, in glioma and normal brain in vivo and to measure the metabolic response to dichloroacetate, which upregulates PDH activity.Methods An optimized protocol for chemical shift imaging and high concentration of hyperpolarized [1-13C]pyruvate were used to improve measurements of lactate and bicarbonate in C6 glioma-transplanted rat brains. Hyperpolarized [1-13C]pyruvate was injected before and 45 min after dichloroacetate infusion. Metabolite ratios of lactate to bicarbonate were calculated to provide improved metrics for characterizing tumor metabolism.Results Glioma and normal brain were well differentiated by lactate-to-bicarbonate ratio (P = .002, n = 5) as well as bicarbonate (P = .0002) and lactate (P = .001), and a stronger response to dichloroacetate was observed in glioma than in normal brain.Conclusion Our results clearly demonstrate for the first time the feasibility of quantitatively detecting 13C-bicarbonate in tumor-bearing rat brain in vivo, permitting the measurement of dichloroacetate-modulated changes in PDH flux. The simultaneous detection of lactate and bicarbonate provides a tool for a more comprehensive analysis of glioma metabolism and the assessment of metabolic agents as anti-brain cancer drugs.

Friday, April 5, 2013

NMR at Low and Ultralow Temperatures

Tycko, R., NMR at Low and Ultralow Temperatures. Acc. Chem. Res., 2013.

Solid state nuclear magnetic resonance (NMR) measurements at low temperatures have been common in physical sciences for many years and are becoming increasingly important in studies of biomolecular systems. This Account reviews a diverse set of projects from my laboratory, dating back to the early 1990s, that illustrate the motivations for low-temperature solid state NMR, the types of information that are available from the measurements, and likely directions for future research. These projects include NMR studies of both physical and biological systems, performed at low (cooled with nitrogen, down to 77 K) and ultralow (cooled with helium, below 77 K) temperatures, and performed with and without magic-angle spinning (MAS). NMR studies of physical systems often focus on phenomena that occur only at low temperatures. Two examples from my laboratory are studies of molecular rotation and orientational ordering in solid C60 at low temperatures and studies of unusual electronic states, called skyrmions, in two-dimensionally confined electron systems within semiconductor quantum wells. To study quantum wells, we used optical pumping of nuclear spin polarizations to enhance their NMR signals. The optical pumping phenomenon exists only at ultralow temperatures. In studies of biomolecular systems, low-temperature NMR has several motivations. In some cases, low temperatures suppress molecular tumbling, thereby permitting solid state NMR measurements on soluble proteins. Studies of AIDS-related peptide/antibody complexes illustrate this effect. In other cases, low temperatures suppress conformational exchange, thereby permitting quantitation of conformational distributions. Studies of chemically denatured states of the model protein HP35 illustrate this effect. Low temperatures and rapid freeze-quenching can also be used to trap transient intermediate states in a non-equilibrium kinetic process, as shown in studies of a transient intermediate in the rapid folding pathway of HP35. NMR sensitivity generally increases with decreasing sample temperature. Therefore, it can be useful to carry out experiments at the lowest possible temperatures, particularly in studies of biomolecular systems in frozen solutions. However, solid state NMR studies of biomolecular systems generally require rapid MAS. A novel MAS NMR probe design that uses nitrogen gas for sample spinning and cold helium only for sample cooling allows a wide variety of solid state NMR measurements to be performed on biomolecular systems at 20?25 K, where signals are enhanced by factors of 12?15 relative to measurements at room temperature. MAS NMR at ultralow temperatures also facilitates dynamic nuclear polarization (DNP), allowing sizeable additional signal enhancements and large absolute NMR signal amplitudes with relatively low microwave powers. Current research in my laboratory seeks to develop and exploit DNP-enhanced MAS NMR at ultralow temperatures, for example, in studies of transient intermediates in protein folding and aggregation processes and studies of peptide/protein complexes that can be prepared only at low concentrations.



Monday, April 1, 2013

DNP at ENC

With ENC just around the corner the full conference program is now available at:

http://www.enc-conference.org/Conference/Program/tabid/63/Default.aspx

This year DNP-NMR spectroscopy has its own parallel session (Monday, 4:00 - 5:50pm, Chapel), with talks by Shahin Pourrahimir, David Doty, Robert Meier, Emilio Nanni, Melanie Rosay and Songi Han and a plenary session (Wednesday, 8:30 - 10:10 am, Merill Hall) with contributions by Maja Cassidy, Sami Jannin, Gunnar Jeschke, Kent Thurber and Joshua Wand.

Besides that there are several more DNP related talks by Loren Andreas in the Biomolecular Structure and Function session (Wednesday 10:45 - 12:20pm, Merril Hall) and by Hartmut Oschkinat in the Frontiers session (Thursday, 4:00 - 5:50pm, Merril Hall).

So far in total 23 posters are dedicated to the topic of DNP-NMR (section PE). You can find all poser abstracts at:

http://bit.ly/ZwzLgu