Application of Counter-wound Multi-arm Spirals in HTS Resonator Design.

Significant sensitivity improvements have been achieved by utilizing high temperature superconducting (HTS) resonators in nuclear magnetic resonance (NMR) probes. Many nuclei such as 13C benefit from strong excitation fields which cannot be produced by traditional HTS resonator designs. We investigate the use of double-sided, counter-wound multi-arm spiral HTS resonators with the aim of increasing the excitation field at the required nuclear Larmor frequency for 13C. When compared to double-sided, counter-wound spiral resonators with similar geometry, simulations indicate that the multi-arm spiral version develops a more uniform current distribution. Preliminary tests of a two-arm resonator indicate that it may produce a stronger excitation field.

Progress Towards a Higher Sensitivity 13C-Optimized 1.5 mm HTS NMR Probe.

Nuclear magnetic resonance (NMR) probes using thin-film high temperature superconducting (HTS) resonators offer high sensitivity and are particularly suitable for small-sample applications. We are developing an improved 1.5 mm HTS NMR probe designed for operation at 14.1 T and optimized for 13C detection. The total sample volume is about 35 µL and the active sample volume is 20 µL. The probe employs HTS resonators for 13C and 1H transmission and detection and the 2H lock. We examine the interactions of multiple superconducting resonators and normal metal tuning loops on coil resonance frequency and probe sensitivity. We test a recently introduced 13C resonator design, engineered to significantly increase 13C detection sensitivity over previous all-HTS probes. At zero field, we observe a 13C quality factor of 6000 which is several times higher than previous resonators. In this work the coil design considerations and probe build-out procedure are discussed.

Accommodation of Pulsed Field Gradients with Cascade Field Regulation in Powered Magnets.

High magnetic fields significantly improve the resolution and sensitivity of nuclear magnetic resonance (NMR) spectroscopy measurements, which presents exciting research opportunities in areas of chemistry, biology, and material science. Powered magnets can provide much higher magnetic fields than persistent mode superconducting magnets but suffer from temporal magnetic field fluctuations due to power supply ripple and variations in cooling water temperature and flow rate which make powered magnets non-viable for high resolution NMR experiments. Previous work has demonstrated that a multi-rate sampled data cascade control system may be used to improve the resolution of NMR experiments in powered magnets. Despite these advances in reducing temporal magnetic field fluctuations, the field regulation design does not accommodate the use of pulsed field gradients, which are necessary in many NMR experiments. This work presents a control topology which accommodates the use of pulsed field gradient signals with the field regulation system. This control approach is verified using NMR measurements.

Time and Frequency Domain Response of HTS Resonators for Use as NMR Transmit Coils.

Replacing normal metal NMR coils with thin-film high-temperature superconductor (HTS) resonators can significantly improve the sensitivity of analytical NMR. To study the use of these resonators for excitation as well as detection, we investigated the radio frequency properties of the HTS NMR coils in both frequency and time domain at a variety of transmit power levels. Experiments were conducted on a double-sided, counter wound spiral resonator designed to detect NMR signals from 13C nuclei at 14.1 T. Power-dependent nonlinearity was observed in the transmission coefficient and quality factor. The ability of the HTS resonators to accurately generate short pulses was studied in the time domain over the range power levels. The results of this study show that some form of Q switching is needed to get good transmit performance from HTS coils for 13C. For that purpose, the effect of adding a shorted transmission line stub to improve the pulse shapes and reduce phase transients was studied.

Achieving 1 ppm field homogeneity above 24 T: Application of differential mapping for shimming Keck and the Series Connected Hybrid magnets at the NHMFL.

Powered resistive and resistive-superconductive hybrid magnets can reach fields higher than superconducting NMR magnets but lack the field homogeneity and temporal stability needed for high resolution NMR. Due to field fluctuations in powered magnets, commercially available mapping systems fail to produce maps of these magnets with sufficient reproducibility, thus hampering attempts to improve homogeneity of the field they generate. Starting with a commercial mapper, we built a mapping system which uses a two-channel (measurement + reference) mapper probe. We used this system to map and then to shim two magnets of Florida Bitter type at the National High Magnetic Field Laboratory in Tallahassee, FL. With a combination of passive (ferromagnetic) and active shims we achieved 2.3 ppm homogeneity in 1 cm diameter spherical volume (dsv) at 25.0 T in the Keck resistive magnet, and 0.9 ppm homogeneity in 1 cm dsv at 23.5, 28.2, and 35.2 T in the series-connected resistive-superconductive hybrid (SCH) magnet.

Inductively-coupled Frequency Tuning and Impedance Matching in HTS-based NMR Probes.

Nuclear Magnetic Resonance (NMR) probes based on High Temperature Superconducting (HTS) resonators have demonstrated significant gains in detection sensitivity. However, the widespread acceptance of this technology has been limited by some unresolved issues including the mechanical unreliability of the moveable inductive loops used to adjust tuning and matching. In order to improve reliability, we propose to implement frequency tuning and impedance matching of HTS resonators using fixed inductively coupled loops and variable capacitors. By analyzing the loss mechanisms associated with inductive loops, we predict that using a superconducting inductive loop for tuning and matching will not only improve the reliability of HTS probes, but also provide improvements in sensitivity.

NMR spectroscopy up to 35.2T using a series-connected hybrid magnet.

The National High Magnetic Field Laboratory has brought to field a Series-Connected Hybrid magnet for NMR spectroscopy. As a DC powered magnet it can be operated at fields up to 36.1T. The series connection between a superconducting outsert and a resistive insert dramatically minimizes the high frequency fluctuations of the magnetic field typically observed in purely resistive magnets. Current-density-grading among various resistive coils was used for improved field homogeneity. The 48mm magnet bore and 42mm outer diameter of the probes leaves limited space for conventional shims and consequently a combination of resistive and ferromagnetic shims are used. Field maps corrected for field instabilities were obtained and shimming achieved better than 1ppm homogeneity over a cylindrical volume of 1cm diameter and height. The magnetic field is regulated within 0.2ppm using an external 7Li lock sample doped with paramagnetic MnCl2. The improved field homogeneity and field regulation using a modified AVANCE NEO console enables NMR spectroscopy at 1H frequencies of 1.0, 1.2 and 1.5GHz. NMR at 1.5GHz reflects a 50% increase in field strength above the highest superconducting magnets currently available. Three NMR probes have been constructed each equipped with an external lock rf coil for field regulation. Initial NMR results obtained from the SCH magnet using these probes illustrate the very exciting potential of ultra-high magnetic fields.

Effects of Dielectric Substrates and Ground Planes on Resonance Frequency of Archimedean Spirals.

Superconducting self-resonant spiral structures are of current interest for applications both in metamaterials and as probe coils for nuclear magnetic resonance (NMR) spectroscopy for high-sensitivity chemical analysis. Accurate spiral models are available in the literature for behavior of a spiral below and up to self-resonance. However, knowledge of the higher modes is also important. We present the relationships between the spiral parameters and the multiple mode frequencies of single sided spirals on dielectric substrates as modeled by method of moments simulation. In the absence of a ground plane, we find that the mode frequency has a linear though not necessarily harmonic dependence on the mode number. The effect of a thick substrate can be approximated by an effective dielectric constant. But when the thickness is less than 20% of the spiral trace width (router - rinner) this approximation is no longer accurate. We have developed a simple empirical formula to predict the higher modes.

HIV-1 Capsid Function Is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD.

HIV-1 CA capsid protein possesses intrinsic conformational flexibility, which is essential for its assembly into conical capsids and interactions with host factors. CA is dynamic in the assembled capsid, and residues in functionally important regions of the protein undergo motions spanning many decades of time scales. Chemical shift anisotropy (CSA) tensors, recorded in magic-angle-spinning NMR experiments, provide direct residue-specific probes of motions on nano- to microsecond time scales. We combined NMR, MD, and density-functional-theory calculations, to gain quantitative understanding of internal backbone dynamics in CA assemblies, and we found that the dynamically averaged 15N CSA tensors calculated by this joined protocol are in remarkable agreement with experiment. Thus, quantitative atomic-level understanding of the relationships between CSA tensors, local backbone structure, and motions in CA assemblies is achieved, demonstrating the power of integrating NMR experimental data and theory for characterizing atomic-resolution dynamics in biological systems.

(39) K and (23) Na relaxation times and MRI of rat head at 21.1 T.

At ultrahigh magnetic field strengths (B0 ≥ 7.0 T), potassium ((39) K) MRI might evolve into an interesting tool for biomedical research. However, (39) K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of (39) K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared (39) K and sodium ((23) Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. (39) K relaxation times were markedly shorter than those of (23) Na. Compared with the lower field strength, (39) K relaxation times were up to 1.9- (T1 ), 1.4- (T2S ) and 1.9-fold (T2L ) longer at 21.1 T. The increase in the (23) Na relaxation times was less pronounced (up to 1.2-fold). Mono-exponential fits of the (39) K longitudinal relaxation time at 21.1 T revealed T1 = 14.2 ± 0.1 ms for the healthy rat head. The (39) K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T2S ) and long (T2L ) components, respectively. (23) Na relaxation times were markedly longer (T1 = 41.6 ± 0.4 ms; T2S = 4.9 ± 0.2 ms; T2L = 33.2 ± 0.2 ms). (39) K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm(3) within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for (23) Na and (39) K MRI at ultrahigh magnetic field strength. Our results demonstrate that (39) K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.

An Empirical Expression to Predict the Resonant Frequencies of Archimedean Spirals.

This work presents an empirical formula to accurately determine the frequencies of the fundamental and higher order resonances of an Archimedean spiral in a uniform dielectric medium in the absence of a ground plane. The formula is based on method-of-moments simulations which have been experimentally validated. This empirical formula is widely applicable to a broad range of spirals from thin-ring to disk-shaped (ratio of inner to outer radii 0 to 1), with 10 or more turns.

In vivo chlorine and sodium MRI of rat brain at 21.1 T.

OBJECT: MR imaging of low-gamma nuclei at the ultrahigh magnetic field of 21.1 T provides a new opportunity for understanding a variety of biological processes. Among these, chlorine and sodium are attracting attention for their involvement in brain function and cancer development. MATERIALS AND METHODS: MRI of (35)Cl and (23)Na were performed and relaxation times were measured in vivo in normal rat (n = 3) and in rat with glioma (n = 3) at 21.1 T. The concentrations of both nuclei were evaluated using the center-out back-projection method. RESULTS: T 1 relaxation curve of chlorine in normal rat head was fitted by bi-exponential function (T 1a = 4.8 ms (0.7) T 1b = 24.4 ± 7 ms (0.3) and compared with sodium (T 1 = 41.4 ms). Free induction decays (FID) of chlorine and sodium in vivo were bi-exponential with similar rapidly decaying components of [Formula: see text] ms and [Formula: see text] ms, respectively. Effects of small acquisition matrix and bi-exponential FIDs were assessed for quantification of chlorine (33.2 mM) and sodium (44.4 mM) in rat brain. CONCLUSION: The study modeled a dramatic effect of the bi-exponential decay on MRI results. The revealed increased chlorine concentration in glioma (~1.5 times) relative to a normal brain correlates with the hypothesis asserting the importance of chlorine for tumor progression.

Development of a ¹³C-optimized 1.5-mm high temperature superconducting NMR probe.

We report a 1.5-mm NMR probe based on high temperature superconductors operating at 14.1T optimized for (13)C detection. The probe has a total sample volume of about 35 microliters (µL) with an active volume of 20 µL and provides exceptional mass sensitivity for (13)C detection. The probe also has excellent (1)H sensitivity and employs a (2)H lock; (15)N irradiation capability can be added in the future. The coils are cooled to about 20K using a standard Agilent cryogenic refrigeration system, and the sample temperature is regulated near room temperature. The coil design considerations are discussed in detail. This probe is ideal for directly detected (13)C NMR experiments for natural products chemistry and metabolomics applications, for which 35 µL is an optimal sample volume. The outstanding (13)C sensitivity of this probe allowed us to directly determine the (13)C connectivity on 1.1mg of natural abundance histidine using an INADEQUATE experiment. We demonstrated the utility of this probe for (13)C-based metabolomics using a synthetic mixture of common natural abundance metabolites whose concentrations ranged from 1 to 5mM (40-200 nmol).

A volume birdcage coil with an adjustable sliding tuner ring for neuroimaging in high field vertical magnets: ex and in vivo applications at 21.1T.

A tunable 900 MHz transmit/receive volume coil was constructed for ¹H MR imaging of biological samples in a 21.1 T vertical bore magnet. To accommodate a diverse range of specimen and RF loads at such a high frequency, a sliding-ring adaptation of a low-pass birdcage was implemented through simultaneous alteration of distributed capacitance. To make efficient use of the constrained space inside the vertical bore, a modular probe design was implemented with a bottom-adjustable tuning and matching apparatus. The sliding ring coil displays good homogeneity and sufficient tuning range for different samples of various dimensions representing large span of RF loads. High resolution in vivo and ex vivo images of large rats (up to 350 g), mice and human postmortem tissues were obtained to demonstrate coil functionality and to provide examples of potential applications at 21.1 T.

Magic angle spinning and oriented sample solid-state NMR structural restraints combine for influenza a M2 protein functional insights.

As a small tetrameric helical membrane protein, the M2 proton channel structure is highly sensitive to its environment. As a result, structural data from a lipid bilayer environment have proven to be essential for describing the conductance mechanism. While oriented sample solid-state NMR has provided a high-resolution backbone structure in lipid bilayers, quaternary packing of the helices and many of the side-chain conformations have been poorly restrained. Furthermore, the quaternary structural stability has remained a mystery. Here, the isotropic chemical shift data and interhelical cross peaks from magic angle spinning solid-state NMR of a liposomal preparation strongly support the quaternary structure of the transmembrane helical bundle as a dimer-of-dimers structure. The data also explain how the tetrameric stability is enhanced once two charges are absorbed by the His37 tetrad prior to activation of this proton channel. The combination of these two solid-state NMR techniques appears to be a powerful approach for characterizing helical membrane protein structure.

Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers.

Oriented solid-state NMR is the most direct methodology to obtain the orientation of membrane proteins with respect to the lipid bilayer. The method consists of measuring (1)H-(15)N dipolar couplings (DC) and (15)N anisotropic chemical shifts (CSA) for membrane proteins that are uniformly aligned with respect to the membrane bilayer. A significant advantage of this approach is that tilt and azimuthal (rotational) angles of the protein domains can be directly derived from analytical expression of DC and CSA values, or, alternatively, obtained by refining protein structures using these values as harmonic restraints in simulated annealing calculations. The Achilles' heel of this approach is the lack of suitable experiments for sequential assignment of the amide resonances. In this Article, we present a new pulse sequence that integrates proton driven spin diffusion (PDSD) with sensitivity-enhanced PISEMA in a 3D experiment ([(1)H,(15)N]-SE-PISEMA-PDSD). The incorporation of 2D (15)N/(15)N spin diffusion experiments into this new 3D experiment leads to the complete and unambiguous assignment of the (15)N resonances. The feasibility of this approach is demonstrated for the membrane protein sarcolipin reconstituted in magnetically aligned lipid bicelles. Taken with low electric field probe technology, this approach will propel the determination of sequential assignment as well as structure and topology of larger integral membrane proteins in aligned lipid bilayers.

Reduction of magnetic field fluctuations in powered magnets for NMR using inductive measurements and sampled-data feedback control.

Resistive and hybrid (resistive/superconducting) magnets provide substantially higher magnetic fields than those available in low-temperature superconducting magnets, but their relatively low spatial homogeneity and temporal field fluctuations are unacceptable for high resolution NMR. While several techniques for reducing temporal fluctuations have demonstrated varying degrees of success, this paper restricts attention to methods that utilize inductive measurements and feedback control to actively cancel the temporal fluctuations. In comparison to earlier studies using analog proportional control, this paper shows that shaping the controller frequency response results in significantly higher reductions in temporal fluctuations. Measurements of temporal fluctuation spectra and the frequency response of the instrumentation that cancels the temporal fluctuations guide the controller design. In particular, we describe a sampled-data phase-lead-lag controller that utilizes the internal model principle to selectively attenuate magnetic field fluctuations caused by the power supply ripple. We present a quantitative comparison of the attenuation in temporal fluctuations afforded by the new design and a proportional control design. Metrics for comparison include measurements of the temporal fluctuations using Faraday induction and observations of the effect that the fluctuations have on nuclear resonance measurements.

Experimental aspects in acquisition of wide bandwidth solid-state MAS NMR spectra of low-γ nuclei with different opportunities on two commercial NMR spectrometers.

The acquisition and different appearances observed for wide bandwidth solid-state MAS NMR spectra of low-γ nuclei, using (14)N as an illustrative nucleus and employing two different commercial spectrometers (Varian, 14.1T and Bruker, 19.6T), have been compared/evaluated and optimized from an experimental NMR and an electronic engineering point of view, to account for the huge differences in these spectra. The large differences in their spectral appearances, employing the recommended/standard experimental set-up for the two different spectrometers, are shown to be associated with quite large differences in the electronic design of the two types of preamplifiers, which are connected to their respective probes through a 50Ω cable, and are here completely accounted for. This has led to different opportunities for optimum performances in the acquisition of nearly ideal wide bandwidth spectra for low-γ nuclei on the two spectrometers by careful evaluation of the length for the 50Ω probe-to-preamp cable for the Varian system and appropriate changes to the bandwidth (Q) of the NMR probe used on the Bruker spectrometer. Earlier, we reported quite distorted spectra obtained with Varian Unity INOVA spectrometers (at 11.4 and 14.1T) in several exploratory wide bandwidth (14)N MAS NMR studies of inorganic nitrates and amino acids. These spectra have now been compared/evaluated with fully analyzed (14)N MAS spectra correspondingly acquired at 19.6T on a Bruker spectrometer. It is shown that our upgraded version of the STARS simulation/iterative-fitting software is capable of providing identical sets for the molecular spectral parameters and corresponding fits to the experimental spectra, which fully agree with the electronic measurements, despite the highly different appearances for the MAS NMR spectra acquired on the Varian and Bruker spectrometers.