Category Archives: Technique

Orphan Spin Polarization: A Catalyst for High-Throughput Solid-State NMR Spectroscopy of Proteins

Not an article that directly relates to DNP-NMR spectroscopy, but another interesting technique to enhance sensitivity that can be combined with DNP.

Gopinath, T. and G. Veglia, Orphan Spin Polarization: A Catalyst for High-Throughput Solid-State NMR Spectroscopy of Proteins, in Annual Reports on NMR Spectroscopy, Academic Press.

Magic-angle spinning solid-state NMR (MAS ssNMR) spectroscopy is a powerful method for structure determination of biomacromolecules that are recalcitrant to crystallization (membrane proteins and fibrils). Relatively low sensitivity and poor resolution of protein samples require long acquisition times for multidimensional ssNMR experiments. Conventional multidimensional ssNMR pulse sequences acquire one experiment at a time, which is time consuming and often discards orphan (unused) spin operators. Here, we describe our recent progress in the development of multiple acquisition ssNMR methods for protein structure determination. A family of experiments called polarization optimized experiments (POE) was designed, in which we utilized the orphan spin operators that are discarded in classical NMR experiments to recover them and acquire simultaneously multiple 2D and 3D experiments using conventional probes and spectrometers with one receiver. Three strategies namely, DUMAS, MEIOSIS, and MAeSTOSO were used for the concatenation of various 2D and 3D pulse sequences. These methods open up new avenues for reducing the acquisition time of multidimensional experiments for biomolecular ssNMR spectroscopy.

Constant-variable flip angles for hyperpolarized media MRI #DNPNMR

Deng, H., et al., Constant-variable flip angles for hyperpolarized media MRI. J. Magn. Reson., 2016. 263: p. 92-100.

The longitudinal magnetization of hyperpolarized media, such as hyperpolarized 129Xe, 3He, etc., is nonrenewable. When the MRI data acquisition begins at the k-domain center, a constant flip angle (CFA) results in an image of high signal-to-noise ratio (SNR) but sacrifices the accuracy of spatial information. On the other hand, a variable flip angle (VFA) strategy results in high accuracy but suffers from a low SNR. In this paper, we propose a novel scheme to optimize both the SNR and accuracy, called constant-variable flip angles (CVFA). The proposed scheme suggests that hyperpolarized magnetic resonance signals are firstly acquired through a train of n∗ CFA excitation pulses, followed by a train of N–n∗ VFA excitation pulses. We simulate and optimize the flip angle used in the CFA section, the number of CFA excitation pulses, the number of VFA excitation pulses, and the initial and final variable flip angles adopted in the VFA section. Phantom and in vivo experiments demonstrate the good performance of the CVFA designs and their ability to maintain both high SNR and spatial resolution.

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. 72: p. 79-89.

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.

Dynamic nuclear polarization by frequency modulation of a tunable gyrotron of 260GHz

Yoon, D., et al., Dynamic nuclear polarization by frequency modulation of a tunable gyrotron of 260GHz. J Magn Reson, 2016. 262: p. 62-7.

An increase in Dynamic Nuclear Polarization (DNP) signal intensity is obtained with a tunable gyrotron producing frequency modulation around 260GHz at power levels less than 1W. The sweep rate of frequency modulation can reach 14kHz, and its amplitude is fixed at 50MHz. In water/glycerol glassy ice doped with 40mM TEMPOL, the relative increase in the DNP enhancement was obtained as a function of frequency-sweep rate for several temperatures. A 68 % increase was obtained at 15K, thus giving a DNP enhancement of about 80. By employing lambda/4 and lambda/8 polarizer mirrors, we transformed the polarization of the microwave beam from linear to circular, and achieved an increase in the enhancement by a factor of about 66% for a given power.

Rapid-melt Dynamic Nuclear Polarization

Sharma, M., et al., Rapid-melt Dynamic Nuclear Polarization. J Magn Reson, 2015. 258: p. 40-8.

In recent years, Dynamic Nuclear Polarization (DNP) has re-emerged as a means to ameliorate the inherent problem of low sensitivity in nuclear magnetic resonance (NMR). Here, we present a novel approach to DNP enhanced liquid-state NMR based on rapid melting of a solid hyperpolarized sample followed by ‘in situ’ NMR detection. This method is applicable to small (10nl to 1mul) sized samples in a microfluidic setup. The method combines generic DNP enhancement in the solid state with the high sensitivity of stripline (1)H NMR detection in the liquid state. Fast cycling facilitates options for signal averaging or 2D structural analysis. Preliminary tests show solid-state (1)H enhancement factors of up to 500 for H2O/D2O/d6-glycerol samples doped with TEMPOL radicals. Fast paramagnetic relaxation with nitroxide radicals, In nonpolar solvents such as toluene, we find proton enhancement factors up to 400 with negligible relaxation losses in the liquid state, using commercially available BDPA radicals. A total recycling delay (including sample freezing, DNP polarization and melting) of about 5s can be used. The present setup allows for a fast determination of the hyper-polarization as function of the microwave frequency and power. Even at the relatively low field of 3.4T, the method of rapid melting DNP can facilitate the detection of small quantities of molecules in the picomole regime.

A fast and simple method for calibrating the flip angle in hyperpolarized 13C MRS experiments

Giovannetti, G., et al., A fast and simple method for calibrating the flip angle in hyperpolarized 13C MRS experiments. Concepts in Magnetic Resonance Part B: Magnetic Resonance Engineering, 2015: p. n/a-n/a.

Hyperpolarized 13C Magnetic resonance represents a promising modality for in vivo studies of intermediary metabolism of bio-molecules and new biomarkers. Although it represents a powerful tool for metabolites spatial localization and for the assessment of their kinetics in vivo, a number of technological problems still limits this technology and needs innovative solutions. In particular, the optimization of the signal-to-noise ratio during the acquisitions requires the use of pulse sequences with accurate flip angle calibration, which is performed by adjusting the transmit power in the prescan step. This is even more critical in the case of hyperpolarized studies, because the fast decay of the hyperpolarized signal requires precise determination of the flip angle for the acquisition. This work describes a fast and efficient procedure for transmit power calibration of magnetic resonance acquisitions employing selective pulses, starting from the calibration of acquisitions performed with non-selective (hard) pulses. The proposed procedure employs a simple theoretical analysis of radiofrequency pulses by assuming a linear response and can be performed directly during in vivo studies. Experimental MR data validate the theoretical calculation by providing good agreement. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering), 2015

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