Category Archives: Instrumentation

XeUS: A second-generation automated open-source batch-mode clinical-scale hyperpolarizer

Birchall, Jonathan R., Robert K. Irwin, Panayiotis Nikolaou, Aaron M. Coffey, Bryce E. Kidd, Megan Murphy, Michael Molway, et al. “XeUS: A Second-Generation Automated Open-Source Batch-Mode Clinical-Scale Hyperpolarizer.” Journal of Magnetic Resonance 319 (October 2020): 106813.

We present a second-generation open-source automated batch-mode 129Xe hyperpolarizer (XeUS GEN2), designed for clinical-scale hyperpolarized (HP) 129Xe production via spin-exchange optical pumping (SEOP) in the regimes of high Xe density (0.66–2.5 atm partial pressure) and resonant photon flux (~170 W, Dk = 0.154 nm FWHM), without the need for cryo-collection typically employed by continuous-flow hyperpolarizers. An Arduino micro-controller was used for hyperpolarizer operation. Processing open-source software was employed to program a custom graphical user interface (GUI), capable of remote automation. The Arduino Integrated Development Environment (IDE) was used to design a variety of customized automation sequences such as temperature ramping, NMR signal acquisition, and SEOP cell refilling for increased reliability. A polycarbonate 3D-printed oven equipped with a thermoelectric cooler/heater provides thermal stability for SEOP for both binary (Xe/N2) and ternary (4He-containing) SEOP cell gas mixtures. Quantitative studies of the 129Xe hyperpolarization process demonstrate that near-unity polarization can be achieved in a 0.5 L SEOP cell. For example, %PXe of 93.2 ± 2.9% is achieved at 0.66 atm Xe pressure with polarization build-up rate constant cSEOP = 0.040 ± 0.005 minÀ1, giving a max dose equivalent % 0.11 L/h 100% hyperpolarized, 100% enriched 129Xe; %PXe of 72.6 ± 1.4% is achieved at 1.75 atm Xe pressure with cSEOP of 0.041 ± 0.001 minÀ1, yielding a corresponding max dose equivalent of 0.27 L/h. Quality assurance studies on this device have demonstrated the potential to refill SEOP cells hundreds of times without significant losses in performance, with average %PXe = 71.7%, (standard deviation rP = 1.52%) and mean polarization lifetime T1 = 90.5 min, (standard deviation rT = 10.3 min) over the first ~200 gas mixture refills, with sufficient performance maintained across a further ~700 refills. These findings highlight numerous technological developments and have significant translational relevance for efficient production of gaseous HP 129Xe contrast agents for use in clinical imaging and bio-sensing techniques.

A temperature-controlled sample shuttle for field-cycling NMR

Today, something that has nothing to do with DNP-NMR spectroscopy, but is a cool piece of equipment.

Hall, Andrew M.R., Topaz A.A. Cartlidge, and Giuseppe Pileio. “A Temperature-Controlled Sample Shuttle for Field-Cycling NMR.” Journal of Magnetic Resonance 317 (August 2020): 106778.

We present a design for a temperature-controlled sample shuttle for use in NMR measurements at variable magnetic field strength. Accurate temperature control was achieved using a mixture of waterethylene glycol as a heat transfer fluid, reducing temperature gradients across the sample to <0.05 °C and minimising convection. Using the sample shuttle, we show how the longitudinal (T1) and singlet order (TS) relaxation time constants were measured for two molecules capable of supporting long-lived states, with new record lifetimes observed at low field and above ambient temperatures.

Organic Reaction Monitoring of a Glycine Derivative Using Signal Amplification by Reversible Exchange-Hyperpolarized Benchtop Nuclear Magnetic Resonance Spectroscopy #DNPNMR #SABRE

Chae, Heelim, Sein Min, Hye Jin Jeong, Sung Keon Namgoong, Sangwon Oh, Kiwoong Kim, and Keunhong Jeong. “Organic Reaction Monitoring of a Glycine Derivative Using Signal Amplification by Reversible Exchange-Hyperpolarized Benchtop Nuclear Magnetic Resonance Spectroscopy.” Analytical Chemistry 92, no. 16 (August 18, 2020): 10902–7.

Currently, signal amplification by reversible exchange (SABRE) using para-hydrogen is an attractive method of hyperpolarization for overcoming the sensitivity problems of nuclear magnetic resonance (NMR) spectroscopy. Additionally, SABRE, using the spin order of para-hydrogen, can be applied in reaction monitoring processes for organic chemistry reactions where a small amount of reactant exists. The organic reaction monitoring system created by integrating SABRE and benchtop NMR is the ideal combination for monitoring a reaction and identifying the small amounts of materials in the middle of the reaction. We used a laboratory-built setup, prepared materials by synthesis, and showed that the products obtained by esterification of glycine were also active in SABRE. The products, which were synthesized esterified glycine with nicotinoyl chloride hydrochloride, were observed with a reaction monitoring system. The maximum SABRE enhancement among them (approximately 147-fold) validated the use of this method. This study is the first example of the monitoring of this organic reaction by SABRE and benchtop NMR. It will open new possibilities for applying this system to many other organic reactions and also provide more fruitful future applications such as drug discovery and mechanism study.

A compact X-Band ODNP spectrometer towards hyperpolarized 1H spectroscopy #DNPNMR #ODNP

Überrück, Till, Michael Adams, Josef Granwehr, and Bernhard Blümich. “A Compact X-Band ODNP Spectrometer towards Hyperpolarized 1H Spectroscopy.” Journal of Magnetic Resonance, April 2020, 106724.

The demand for compact benchtop NMR systems that can resolve chemical shift differences in the ppm to sub-ppm range is growing. However due to material and size restrictions these magnets are limited in field strength and thus in signal intensity and quality. The implementation of standard hyperpolarization techniques is a next step in an effort to boost the signal. Here we present a compact Overhauser Dynamic Nuclear Polarization (ODNP) setup with a permanent magnet that can resolve 1H chemical shift differences in the ppm range. The assembly of the setup and its components are described in detail, and the functionality of the setup is demonstrated experimentally with ODNP enhanced relaxation measurements yielding a maximal enhancement of -140 for an aqueous 4Hydroxy-TEMPO solution. Additionally, 1H spectroscopic resolution and significant enhancements are demonstrated on acetic acid as a solvent.

Inductance Calculation in Magnetic Resonance Solenoid Coils with Strip and Wire Conductors #Instrumentation #NMR

If you\’ve ever built your own RF circuit for NMR you know that calculating the inductance for a solenoid can be challenging. This article gives some insight where the discrepancies are coming from and how to make the prediction more accurately. However, in the end you still need to get the soldering iron out and adjust capacitors to make it work.

Giovannetti, Giulio, and Francesca Frijia. “Inductance Calculation in Magnetic Resonance Solenoid Coils with Strip and Wire Conductors.” Applied Magnetic Resonance 51, no. 8 (August 2020): 703–10.

Solenoids are employed in Magnetic Resonance (MR) as radiofrequency (RF) coils due to their high sensitivity. In particular, their cylindrical symmetry is optimal for circular cross-sectional samples. Solenoid inductance estimation is a constraint for a correct design and tuning of the resonant circuit constituting the RF coil, suitable to be used for transmitting and receiving the RF signal of the given X-nucleus with the available MR scanner. However, the different literature formulation for solenoid inductance estimation is not optimized for a wide variety of coil geometries and doesn’t take into account conductor geometry. This paper proposes an analytical method for the solenoid inductance calculation in dependence on the conductor cross-sectional geometry (flat strip and circular wire). Simulations accuracy was evaluated with workbench experimental measurement performed on a home-built strip solenoid and by comparisons with literature data referred to wire solenoids.

Automated pneumatic shuttle for magnetic field cycling and parahydrogen hyperpolarized multidimensional NMR

TomHon, Patrick, Evan Akeroyd, Sören Lehmkuhl, Eduard Y. Chekmenev, and Thomas Theis. “Automated Pneumatic Shuttle for Magnetic Field Cycling and Parahydrogen Hyperpolarized Multidimensional NMR.” Journal of Magnetic Resonance 312 (March 2020): 106700.

We present a simple-to-implement pneumatic sample shuttle for automation of magnetic field cycling and multidimensional NMR. The shuttle system is robust allowing automation of hyperpolarized and non-hyperpolarized measurements, including variable field lifetime measurements, SABRE polarization optimization, and SABRE multidimensional experiments. Relaxation-protected singlet states are evaluated by variable-field T1 and TS measurements. Automated shuttling facilitates characterization of hyperpolarization dynamics, field dependence and polarization buildup rates. Furthermore, reproducible hyperpolarization levels at every shuttling event enables automated 2D hyperpolarized NMR, including the first inverse 15N/1H HSQC. We uncover binding mechanisms of the catalytic species through cross peaks that are not accessible in standard one-dimensional hyperpolarized experiments. The simple design of the shuttling setup interfaced with standard TTL signals allows easy adaptation to any standard NMR magnet.

Highly Stable Magic Angle Spinning Spherical Rotors Lacking Turbine Grooves

Osborn Popp, Thomas M., Alexander Däpp, Chukun Gao, Pin-Hui Chen, Lauren E. Price, Nicholas H. Alaniva, and Alexander B. Barnes. “Highly Stable Magic Angle Spinning Spherical Rotors Lacking Turbine Grooves.” Preprint. Solid-state NMR/Instrumentation, April 1, 2020.

The use of spherical rotors for magic angle spinning offers a number of advantages including improved sample exchange, efficient microwave coupling for dynamic nuclear polarization nuclear magnetic resonance (NMR) experiments and, most significantly, high frequency and stable spinning with minimal risk of rotor crash. Here we demonstrate the simple retrofitting of a commercial NMR probe with MAS spheres for solid-state NMR. We analyze a series of turbine groove 5 geometries to investigate the importance of the rotor surface on spinning performance. Of note, rotors lacking any surface modification spin rapidly and stably even without feedback control. The high stability of a spherical rotor about the magic angle is shown to be dependent on its inertia tensor rather than the presence of turbine grooves.

Cryogenic Platforms and Optimized DNP Sensitivity #DNPNMR

Matsuki, Yoh, and Toshimichi Fujiwara. “Cryogenic Platforms and Optimized DNP Sensitivity,” 7:16, 2018.

Modern high-field DNP NMR spectrometers are typically based on a cryogenic magic-angle sample spinning (MAS) capability. Conventionally, sample temperatures of T ∼100 K have been widely used, enabling substantial NMR signal enhancement with DNP at high external field conditions such as B0 =9.4 T. Today, however, the need for performing MAS DNP at much lower temperatures (T ≪100 K) is receiving growing attention for its ability to recover the rapidly degrading efficiency of the cross-effect (CE)-based DNP at even higher magnetic fields, B0 >10 T. In this article, we describe three contemporary cryogenic DNP MAS NMR probe systems: one is N2 based for T ∼100 K, and the other two are helium based for T ≪100 K. Principal requirements important in designing the cryogenic MAS NMR systems include long-term stability, cost efficiency, and readiness of operation. All the described setups incorporated various modifications and novel features to meet these challenges. In particular, the novel closed-cycle helium MAS system realizes all the requirements to a high standard, establishing an efficient and practical platform for ultralow sample temperature (T ∼30 K) MAS DNP. The resulting dramatic increase in sensitivity gain suggests the regained promise for the CE-based DNP at very high-field conditions (B0 >10 T). The experimental DNP data and effective sensitivity gain obtained with the described systems operating at 14.1 and 16.4 T are also discussed.

Versatile Dynamic Nuclear Polarization Hardware with Integrated Electron Paramagnetic Resonance Capabilities #DNPNMR

Leavesley, Alisa, Ilia Kaminker, and Songi Han. “Versatile Dynamic Nuclear Polarization Hardware with Integrated Electron Paramagnetic Resonance Capabilities,” 7:22, 2018.

Successful application of dynamic nuclear polarization (DNP) often relies on procedures and sample formulations that are empirically optimized. In order to expand the scope of DNP to a wider range of sample systems and applications, a better understanding of the underlying DNP mechanism and spin dynamics is required. An aspect of DNP spin dynamics that is understudied is the electron spins, which can be attributed to high-field EPR capabilities not being commonly available under DNP conditions. Here, we present a combined and versatile DNP/EPR instrument that allows us to simultaneously follow the electron and nuclear spin dynamics during the course of the DNP experiment. A modular design ensures the versatility of such an instrument, where a solid-state microwave (μw) source permits high agility for electron spin manipulation. This article presents a detailed description of the DNP/EPR instrument, including the discussion of the components required for a dual DNP/EPR instrument, the integration of arbitrary waveform generation for shape μw pulses, and a two-source quasi-optical configuration that enables artifact-free electron–electron double resonance experiments at 200 GHz. We conclude by providing select examples in which the evaluation of electron spin dynamics was necessary to elucidate the underlying DNP mechanism.

Creating a clinical platform for carbon‐13 studies using the sodium‐23 and proton resonances #DNPNMR

Grist, James T., Esben S.S. Hansen, Juan D. Sánchez‐Heredia, Mary A. McLean, Rasmus Tougaard, Frank Riemer, Rolf F. Schulte, et al. “Creating a Clinical Platform for Carbon‐13 Studies Using the Sodium‐23 and Proton Resonances.” Magnetic Resonance in Medicine, March 13, 2020, mrm.28238.

Purpose: Calibration of hyperpolarized 13C-MRI is limited by the low signal from endogenous carbon-containing molecules and consequently requires 13C-enriched external phantoms. This study investigated the feasibility of using either 23Na-MRI or 1H-MRI to calibrate the 13C excitation.

Methods: Commercial 13C-coils were used to estimate the transmit gain and center frequency for 13C and 23Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1H resonance to predict [1-13C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13C-pyruvate.

Results: The difference in center frequencies and transmit gain between tissue 23Na and [1-13C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1H water peak, it was possible to retrospectively predict the 13C-pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral–spatial excitation-based studies.

Conclusion: We demonstrate the feasibility of using the 23Na and 1H resonances to calibrate the 13C transmit B1 using commercially available 13C-coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

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