Proton Larmor Frequency Research Articles

Probing Noncovalent Interactions by Fast Magic-Angle Spinning NMR at 100 kHz and More.

Noncovalent interactions are the basis for a large number of chemical and biological molecular-recognition processes, such as those occurring in supramolecular chemistry, catalysis, solid-state reactions in mechanochemistry, protein folding, protein-nucleic acid binding, and biomolecular phase separation processes. In this perspective article, some recent developments in probing noncovalent interactions by proton-detected solid-state Nuclear Magnetic Resonance (NMR) spectroscopy at Magic-Angle Spinning (MAS) frequencies of 100 kHz and more are reviewed. The development of MAS rotors with decreasing outer diameters, combined with the development of superconducting magnets operating at high static magnetic-field strengths up to 28.2 T (1200 MHz proton Larmor frequency) improves resolution and sensitivity in proton-detected solid-state NMR, which is the fundamental requirement for shedding light on noncovalent interactions in solids. The examples reported in this article range from protein-nucleic acid binding in large ATP-fueled motor proteins to a hydrogen-π interaction in a calixarene-lanthanide complex.

Detecting soil hydrological connectivity in a badland area by fast field cycling nuclear magnetic resonance relaxometry

AbstractThe ‘hydrological connectivity inside the soil’ refers to both the spatial pattern inside the soil (structural component) and the physical–chemical process at a molecular level (functional component). Fast field cycling (FFC) nuclear magnetic resonance (NMR) relaxometry allows for measuring structural and functional connectivity by two suitable indexes named structural connectivity index (SCI) and functional connectivity index (FCI). In this study, FFC NMR relaxometry was applied to soils sampled in a very degraded environment (i.e., a badland area) to detect the capability of the measurement technique to distinguish the hydrological connectivity of these samples having different conditions (layer explored by roots, sparsely‐vegetated and bare soil). The relaxograms measured by the FFC NMR, using Proton Larmor frequencies in the range 0.01–10 MHz, were integrated and the resulting S‐shaped curves were analysed to obtain the connectivity indexes. Results showed that the ‘Sparsely vegetated’ sample is characterized by more small‐sized pores than the ‘Rooted’ one. The comparison between the ‘Sparsely vegetated’ and ‘Bare’ conditions pointed out that the presence of vegetation reduces the measured relaxation times and, as a consequence, the corresponding pore sizes and modifies the structural connectivity. The analysis also revealed that the three samples are characterized by similar values of SCI, which are independent of the proton Larmor frequency, while the FCI values of the ‘Bare’ soil are the lowest. Conversely, samples from soil with vegetation (‘Rooted’ and ‘Sparsely vegetated’) present comparable functional connectivity. Finally, the analysis of the frequency distribution of the ratio of each connectivity index and its mean value (SCI/m(SCI) and FCI/m(FCI)) allowed to establish its normal distribution. For the investigated samples, this result established that FCI and SCI can be represented by their mean value.

A New Model for Solving Hydrological Connectivity Inside Soils by Fast Field Cycling NMR Relaxometry

In this paper, a new quantitative approach for estimating the structural and functional connectivity inside soil by Fast Field Cycling (FFC) NMR relaxometry is presented, tested by measurements carried out in three samples with different texture characteristics. Measurements by FFC NMR relaxometry have been carried out using water-suspended samples and Proton Larmor frequencies (νL) ranging in the 0.015–35 MHz interval. Two non-degraded soil samples, with different textural characteristics, and a degraded soil collected in a badland area, were analyzed. For a given soil and any applied Proton Larmor frequency, the distribution of the longitudinal relaxation times, T1, (i.e., relaxogram) measured by FFC NMR has been integrated, and the resulting S-shaped curve (i.e., relaxogram integration curve) was represented, for the first time, by Gumbel’s diagram. This new representation of the relaxogram integration curve, transforming the S-shaped curve into a straight line, allowed for distinguishing three linear components, corresponding to three different relaxation time ranges, characterized by three different slopes. Two points, identified by the abrupt slope changes of the relaxogram integration curve plotted in Gumbel’s diagram, are used to identify two characteristic values of relaxation time, T1A and T1B, which define three well-known pore size classes (T1 < T1A micro-pores, T1A < T1 < T1B meso-pores, and T1 > T1B macro-pores). The relaxogram integration curve allowed for calculating the non-exceeding empirical cumulative frequency, F(T1), corresponding to the characteristic T1A and T1B values. The analysis demonstrated that the relaxogram can be used to determine the pore-size ranges of each investigated sample. Finally, using the slope values of the three components of the relaxogram integration curve, a new definition of the Structural Connectivity Index, SCI, and Functional Connectivity Index, FCI, was proposed.

High and fast: NMR protein-proton side-chain assignments at 160 kHz and 1.2 GHz.

The NMR spectra of side-chain protons in proteins provide important information, not only about their structure and dynamics, but also about the mechanisms that regulate interactions between macromolecules. However, in the solid-state, these resonances are particularly difficult to resolve, even in relatively small proteins. We show that magic-angle-spinning (MAS) frequencies of 160 kHz, combined with a high magnetic field of 1200 MHz proton Larmor frequency, significantly improve their spectral resolution. We investigate in detail the gain for MAS frequencies between 110 and 160 kHz MAS for a model sample as well as for the hepatitis B viral capsid assembled from 120 core-protein (Cp) dimers. For both systems, we found a significantly improved spectral resolution of the side-chain region in the 1H-13C 2D spectra. The combination of 160 kHz MAS frequency with a magnetic field of 1200 MHz, allowed us to assign 61% of the aliphatic protons of Cp. The side-chain proton assignment opens up new possibilities for structural studies and further characterization of protein-protein or protein-nucleic acid interactions.

Band-selective universal 90° and 180° rotation pulses covering the aliphatic carbon chemical shift range for triple resonance experiments on 1.2 GHz spectrometers

Biomolecular NMR spectroscopy requires large magnetic field strengths for high spectral resolution. Today’s highest fields comprise proton Larmor frequencies of 1.2 GHz and even larger field strengths are to be expected in the future. In protein triple resonance experiments, various carbon bandwidths need to be excited by selective pulses including the large aliphatic chemical shift range. When the spectrometer field strength is increased, the length of these pulses has to be decreased by the same factor, resulting in higher rf-amplitudes being necessary in order to cover the required frequency region. Currently available band-selective pulses like Q3/Q5 excite a narrow bandwidth compared to the necessary rf-amplitude. Because the maximum rf-power allowed in probeheads is limited, none of the selective universal rotation pulses reported so far is able to cover the full ^{13}C aliphatic region on 1.2 GHz spectrometers. In this work, we present band-selective 90° and 180° universal rotation pulses (SURBOP90 and SURBOP180) that have a higher ratio of selective bandwidth to maximum rf-amplitude than standard pulses. Simulations show that these pulses perform better than standard pulses, e. g. Q3/Q5, especially when rf-inhomogeneity is taken into account. The theoretical and experimental performance is demonstrated in offset profiles and by implementing the SURBOP pulses in an HNCACB experiment at 1.2 GHz.

High-resolution ultra-low field magnetic resonance imaging with a high-sensitivity sensing coil.

We present high-resolution magnetic resonance imaging (MRI) at ultra-low field (ULF) with a proton Larmor frequency of around 120 kHz. The key element is a specially designed high-sensitivity sensing coil in the shape of a solenoid with a few millimeter gap between windings to decrease the proximity effect and, hence, increase the coil's quality ( ) factor and sensitivity. External noise is strongly suppressed by enclosing the sensing coil in a copper cylindrical shield, large enough not to negatively affect the coil's factor and sensitivity, measured to be 217 and 0.47 fT/Hz , respectively. To enhance small polarization of proton spins at ULF, a strong pulsed 0.1 T prepolarization field is applied, making the signal-to-noise ratio (SNR) of ULF MRI sufficient for high-quality imaging in a short time. We demonstrate ULF MRI of a copper sulfate solution phantom with a resolution of and SNR of 10. The acquisition time is 6.3 min without averaging. The sensing coil size in the current realization can accommodate imaging objects of 9 cm in size, sufficient for hand, and it can be further increased for human head imaging in the future. Since the in-plane resolution of is typical in anatomical medical imaging, this ULF MRI method can be an alternative low-cost, rapid, portable method for anatomical medical imaging of the human body or animals. This ULF MRI method can supplement other MRI methods, especially when such methods are restricted due to high cost, portability requirement, imaging artifacts, and other factors.

An Antenna Based on Three Coupled Dipoles With Minimized E-Field for Ultra-High-Field MRI

In this work, we demonstrate an approach for local reduction of the electric field amplitude of the transmitted radio-frequency signal in ultrahigh-field magnetic resonance imaging (MRI). We excite a suitable combination of three coupled dipole hybrid resonances composing a single transmit antenna array element. Using numerical optimization, we designed a feeding network for three coupled dipoles placed over an electromagnetic phantom mimicking a human body. This network of discrete elements provides the appropriate amplitudes and phases of three dipole currents excited by a single input port. It allows controlling the electric field distribution in the vicinity of the antenna. Our goal was to obtain a minimum of the electric field at the given relatively small depth inside the phantom, where body implants are typically located while keeping a tolerable level of the magnetic field toward the phantom’s center. We designed and manufactured a three-dipole antenna prototype optimized for MRI of the human body at 7 T (proton Larmor frequency of 298 MHz). The experimental validation showed a 40 dB reduction of the electric field amplitude at a depth of 4 cm compared to a conventional single-dipole antenna. The coupling network can be rearranged to target different depths. Therefore, a principle of electric field minimization at a controllable position inside the body has been shown, which may be useful for designing transmit MRI antennas with improved safety of implants.

Development and Optimization of Surface and Volume Radiofrequency Coils Suitable for Fast-Field-Cycling Magnetic Resonance Imaging (FFC-MRI)


 
 
 
 
 Objective: To evaluate a modelling and design methodology employed in constructing and optimizing radiofrequency (RF) coils suitable for use with the whole-body fast-field-cycling Magnetic Resonance Imaging (FFC-MRI). It is also aimed at comparing the sensitivity and the signal-to-noise ratio (SNR) of the various types of surface RF coils constructed at the initial and final stages of this research.
 Methodology: An experimental study carried out at Biomedical MRI Laboratory at University of Aberdeen. Various designs of RF coil were constructed, optimized and tested with network/signal analyser for use with an experimental FFC - MRI scanner, operating at a detection magnetic field of 0.2 T (proton Larmor frequency of 8.5 MHz). The coils comprised circular loop (CL) RF – receive surface coil and a birdcage RF – transmit volume coil. The intrinsic parameters of the CL coils were measured using a search-coil field probe and a network/signal analyser.
 Results: The CL surface coil constructed with copper wire had resonant frequency of 8.46 MHz and Quality factor (Q – factor) of 47.1 while the resonant frequency of the one constructed with litz wire was 8.54 MHz and Q - factor of 85.4 MHz. The intrinsic parameter of the birdcage volume coil was 8.48 MHz and Q - factor of 102.
 Conclusion: Bench testing of the coils showed promise as receiver and transmit coils for the FFC-MRI system
 
 
 
 

Modest Offset Difference Internuclear Selective Transfer via Homonuclear Dipolar Coupling.

Homonuclear dipolar recoupling is routinely used for magic-angle spinning NMR-based structure determination. In fully protonated samples, only short proton–proton distances are accessible to broadband recoupling approaches because of high proton density. Selective methods allow detection of longer distances by directing polarization to a subset of spins. Here we introduce the selective pulse sequence MODIST, which recouples spins that have a modest chemical shift offset difference, and demonstrate it to selectively record correlations between amide protons. The sequence was selected for good retention of total signal, leading to up to twice the intensity for proton–proton correlations compared with other selective methods. The sequence is effective across a range of spinning conditions and magnetic fields, here tested at 55.555 and 100 kHz magic-angle spinning and at proton Larmor frequencies from 600 to 1200 MHz. For influenza A M2 in lipid bilayers, cross-peaks characteristic of a helical conformation are observed.

Measuring hydrological connectivity inside soils with different texture by fast field cycling nuclear magnetic resonance relaxometry

The locution “hydrological connectivity inside the soil” is generally used to disclose how the spatial patterns inside the soil affect the physical–chemical processes at a molecular level to influence water transfer into the soil, the surface runoff and related sediment transport. Fast Field Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry has been used to measure both structural and functional connectivity by two indexes indicated as structural (SCI) and functional (FCI) connectivity index. Here, FFC-NMR relaxometry has been applied to analyze three samples: two non-degraded soils, having different grain-size distribution, and a degraded soil sampled in a badland area. Proton Larmor frequencies (νL) ranging in the 0.015–35 MHz interval were used on water suspended samples. The relaxograms (i.e., the distributions of the longitudinal relaxation times, T1) obtained by the FFC-NMR investigations were integrated. The resulting S-shaped curves were handled to obtain the aforementioned FCI and SCI parameters. Results showed that the empirical frequency distribution of the SCI index is related to soil texture and structure, while soils having similar SCI revealed different functional connectivity values. This approach allowed (i) to distinguish SCI values of degraded soils from those of non-degraded ones and (ii) to verify whether the structural connectivity index is related to soil texture and structure. The analysis also showed that the variation coefficient of SCI and FCI, achieved from the measurements done at different νL values, is minimum in the measurement range 0.015–1 MHz. The frequency of 1 MHz can be considered the optimal value to have accurate measured connectivity indexes. For the investigated samples, the obtained relationship between FCI and SCI allowed to conclude that high structural connectivity values correspond to a better functional connectivity. Finally, the hydrological connectivity inside a soil was defined as the sum of the two components representing structural and functional perspective.

Time domain DNP at 1.2 T

We present the results of an experimental pulsed DNP study at 1.2 T (33.5 GHz/51 MHz electron and 1H Larmor frequencies, respectively). The results include a comparison of constant-amplitude NOVEL (CA-NOVEL), ramped-amplitude NOVEL (RA-NOVEL) and the frequency-swept integrated solid effect (FS-ISE) experiments all of which were performed at the NOVEL matching condition, ω1S=ω0I, where ω1S is the electron Rabi frequency andω0I the proton Larmor frequency. To the best of our knowledge, this is the first pulsed DNP study carried out at field higher than X-band (0.35 T) using the NOVEL condition. A combination of high microwave power (∼150 W) and a microwave cavity with a high Q (∼500) allowed us to satisfy the NOVEL matching condition. We also observed stretched solid effect (S2E) contributions in the Zeeman field profiles when chirped pulses are applied. Furthermore, the high quality factor of the cavity limits the concentration of the radical to ∼5 mM and generates a hysteresis in the FS-ISE experiments. Nevertheless, we observe very high DNP enhancements that are comparable to the results at X-band. These promising outcomes suggest the importance of further studies at even higher fields that delineate the instrumentation and methods required for time domain DNP.

An 8-dipole transceive and 24-loop receive array for non-human primate head imaging at 10.5 T.

A 32-channel RF coil was developed for brain imaging of anesthetized non-human primates (rhesus macaque) at 10.5 T. The coil is composed of an 8-channel dipole transmit/receive array, close-fitting 16-channel loop receive array headcap, and 8-channel loop receive array lower insert. The transceiver dipole array is composed of eight end-loaded dipole elements self-resonant at the 10.5 T proton Larmor frequency. These dipole elements were arranged on a plastic cylindrical former, which was split into two to allow for convenient animal positioning. Nested into the bottom of the dipole array former is located an 8-channel loop receive array, which contains 5 × 10 cm2 square loops arranged in two rows of four loops. Arranged in a close-fitting plastic headcap is located a high-density 16-channel loop receive array. This array is composed of 14 round loops 37 mm in diameter and 2 partially detachable, irregularly shaped loops that encircle the ears. Imaging experiments were performed on anesthetized non-human primates on a 10.5 T MRI system equipped with body gradients with a 60 cm open bore. The coil enabled submillimeter (0.58 mm isotropic) high-resolution anatomical and functional imaging as well as tractography of fasciculated axonal bundles. The combination of a close-fitting loop receive array and dipole transceiver array allowed for a higher-channel-count receiver and consequent higher signal-to-noise ratio and parallel imaging gains. Parallel imaging performance supports high-resolution functional MRI and diffusion MRI with a factor of three reduction in sampling. The transceive array elements during reception contributed approximately one-quarter of the signal-to-noise ratio in the lower half of the brain, which was farthest from the close-fitting headcap receive array.

Analytical Approach for MRI RF Array Coils Decoupling by Using Counter-Coupled Passive Resonators

We introduce an analytical approach to design decoupling filters for MRI radiofrequency array elements, adopting counter-coupled passive resonators as unit-cells. Specifically, our method is based on a magneto-static hypothesis, thus a deep comprehension of the physical interactions between all the elements in the system and design guidelines can be achieved. In particular, the couplings between adjacent and next-nearest neighbors coils pairs are both modeled, hence addressing the requirements for MRI arrays. The analytically-obtained filter solution is subsequently refined resorting to targeted full-wave simulations, reducing the computational effort. To prove the validity of the proposed approach, we conceived a test-case consisting of three planar RF coils, tuned at the 7T proton Larmor frequency. We demonstrated through full-wave simulations that the analytical design method is accurate and effective. Moreover, we fabricated a prototype and we performed benchtop measurements, both in unloaded conditions and in the presence of a biological phantom, resulting in excellent agreement with simulations. The developed analytical framework can be useful to model and control the mutual interactions between the various elements of an RF MRI system. In addition, the possibility to print the decoupling elements and the RF coils on the same dielectric substrate leads to a mechanically robust prototype.

Extending a birdcage coil for magnetic resonance imaging of a human head with an artificial magnetic shield

In magnetic resonance imaging, a birdcage coil is the most commonly used volumetric resonator creating a highly homogeneous radiofrequency magnetic field in a conductive sample. An artificial magnetic radiofrequency shield was recently shown to improve the magnetic field amplitude per unit power (transmit efficiency) of a preclinical birdcage coil by reducing the intrinsic losses in the coil and increasing power absorbed by the sample. In this paper, we propose a new application of an artificial shield in clinical MRI. Thanks to the proposed artificial shield a birdcage coil for human brain imaging operating at 300 MHz (Larmor frequency of protons at static fields of 7 T) can be expanded to increase free space. As a result, the coil becomes more comfortable for the patient and keeping comparable transmit efficiency. The same extended coil with a conventional copper shield would have at least 10% lower efficiency. The proposed artificial shield is implemented as an annular-ring cavity-backed slot in a copper cylinder that tightly surrounds the birdcage. To demonstrate the effect, radiofrequency magnetic field and specific absorption rate distributions were compared numerically and experimentally for the initial and extended coils with different shields.

Design and performance of an in-vacuum, magnetic field mapping system for the Muon g-2 experiment

The Muon g−2 experiment at Fermilab (E989) aims to measure the anomalous magnetic moment, aμ, of the muon with a precision of 140 parts-per-billion. This requires a precise measurement of both the anomalous spin precession frequency, ωa, of muons stored in a magnetic field of 1.45 T, and a precise measurement of that magnetic field in terms of the shielded proton Larmor frequency, ω′p. The measurement of ω′p with a total systematic uncertainty of 70 parts-per-billion involves a combination of various nuclear magnetic resonance (NMR) probes. There are 378 probes mounted in fixed locations that constantly monitor field drifts. A water-based, cylindrical calibration probe provides the calibration in terms of the shielded proton Larmor frequency. A crucial element for the multi-step measurement of ω′p is the regular mapping of the magnetic field over the muon storage region. The former experiment at Brookhaven National Laboratory (BNL) employed an in-vacuum field mapping system equipped with 17 NMR probes, which was developed by the University of Heidelberg. We have refurbished and upgraded this system with new probes and electronics. The upgrades include the addition of 16-bit, 1 MSPS digitization of the NMR signals, which replaced the hardware-implemented zero-crossing counting of the system at Brookhaven. The digitized signals offer new capabilities in the NMR frequency analysis and its related systematic uncertainties. To sustain the higher data rates, a new communication scheme with time-division multiplexing was implemented to separate the important NMR reference clock from the data communication in order to reach the specifications for the accuracy and stability of the reference clock. A new barcode reader provides more precise azimuthal position determination during the measurement and calibration. While the mechanical systems that move the field mapper inside the storage ring have been mostly refurbished from BNL, the motion control system was completely replaced with a custom-built electronics centered around a commercial Galil motion controller. Both the field mapping NMR system and its motion control were successfully commissioned at Fermilab and have been in reliable operation during the first three data taking periods of the experiment at Fermilab. This article will provide the details of the upgrades of the field mapper and its performance.

Use of 2.1 MHz MRI scanner for brain imaging and its preliminary results in stroke

Cerebral stroke greatly contributes to death and disability rates in China and the whole world. Effective non-invasive imaging device for bedside monitoring of stroke is critically needed in clinically. This study developed a lightweight (350 kg) and low-footprint magnetic resonance imaging (MRI) system for brain imaging. Static magnetic field was built using an H-typed permanent magnet, which has 50.9 mT magnetic field strength (corresponding to 2.167 MHz proton Larmor frequency). Biplanar gradient coils were designed using the target field method based on dipole equivalent. Radio-frequency coils were optimized by particle swarm optimization. The 2 MHz MRI system was deployed in the Department of Neurology of hospital to test its performance in stroke imaging detection. Gradient recall echo and fast spin echo sequences were utilized to acquire T1- and T2-weighted MR images, respectively. Brain images of a healthy volunteer, a patient with hemorrhagic stroke, a patient of ischemic stroke, and a patient with ischemic stroke and images from 17-day long-term monitoring of hemorrhagic stroke were obtained with a 1.5 mm * 2.0 mm spatial resolution in plane, and a 10 mm thickness.

Calibration Transfer of Partial Least Squares Regression Models between Desktop Nuclear Magnetic Resonance Spectrometers.

Low-field proton nuclear magnetic resonance (LF-1H NMR) devices based on permanent magnets are a promising analytical tool to be extensively applied to the process analytical chemistry scenario. To enhance its analytical applicability in samples where the spectral resolution is compromised, multivariate regression methods are required. However, building a robust calibration model, such as partial least squares (PLS) regression, is a laborious task because (1) the number of measurements required during the calibration process is large and (2) the procedure must be repeated when the instrument is changed or after a certain period due to the long-term stability of the instrument. Thus, the present work describes the application of calibration transfer methodologies (direct standardization (DS), piece-wise direct standardization (PDS), and double-window piece-wise direct standardization (DWPDS)) on LF-1H NMR to exempt the necessity of a recalibration procedure when moving from the original spectrometer to a second one with the same, lower, or higher magnetic field. These calibration transfer methodologies were tested with PLS models built on a 60 MHz (for the proton Larmor frequency) spectrometer to predict the specific gravity (SG), distillation temperature (T50%), and final boiling point (FBP) of commercial gasoline. The results showed that the DWPDS method applying only 2 to 7 transference samples enables the transference of all PLS models built on the primary instrument (60 MHz) to other (43, 60, and 80 MHz) different instruments, reaching the same RMSEP values as the primary instrument: 1.2 kg/m3 for SG, 5.1 °C for FBP, and 1.1 °C for T50%.

Fast field-cycling magnetic resonance detection of intracellular ultra-small iron oxide particles in vitro: Proof-of-concept

PurposeInflammation is central in disease pathophysiology and accurate methods for its detection and quantification are increasingly required to guide diagnosis and therapy. Here we explored the ability of Fast Field-Cycling Magnetic Resonance (FFC-MR) in quantifying the signal of ultra-small superparamagnetic iron oxide particles (USPIO) phagocytosed by J774 macrophage-like cells as a proof-of-principle. MethodsRelaxation rates were measured in suspensions of J774 macrophage-like cells loaded with USPIO (0–200 μg/ml Fe as ferumoxytol), using a 0.25 T FFC benchtop relaxometer and a human whole-body, in-house built 0.2 T FFC-MR prototype system with a custom test tube coil. Identical non-imaging, saturation recovery pulse sequence with 90° flip angle and 20 different evolution fields selected logarithmically between 80 μT and 0.2 T (3.4 kHz and 8.51 MHz proton Larmor frequency [PLF] respectively). Results were compared with imaging flow cytometry quantification of side scatter intensity and USPIO-occupied cell area. A reference colorimetric iron assay was used. ResultsThe T1 dispersion curves derived from FFC-MR were excellent in detecting USPIO at all concentrations examined (0–200 μg/ml Fe as ferumoxytol) vs. control cells, p ≤ 0.001. FFC-NMR was capable of reliably detecting cellular iron content as low as 1.12 ng/µg cell protein, validated using a colorimetric assay. FFC-MR was comparable to imaging flow cytometry quantification of side scatter intensity but superior to USPIO-occupied cell area, the latter being only sensitive at exposures ≥ 10 µg/ml USPIO. ConclusionsWe demonstrated for the first time that FFC-MR is capable of quantitative assessment of intra-cellular iron which will have important implications for the use of USPIO in a variety of biological applications, including the study of inflammation.

A fast field-cycling MRI relaxometer for physical contrasts design and pre-clinical studies in small animals

We present a fast field-cycling NMR relaxometer with added magnetic resonance imaging capabilities. The instrument operates at a maximum proton Larmor frequency of 5 MHz for a sample volume of 35 mL. The magnetic field homogeneity across the sample is 1400 ppm. The main field is generated with a notch-coil electromagnet of own design, fed with a current whose stability is 220 ppm. We show that images of reasonable quality can still be produced under such conditions. The machine is being designed for concept testing of the involved instrumentation and specific contrast agents aimed for field-cycling magnetic resonance imaging applications. The general performance of the prototype was tested through localized relaxometry experiments, T1-dispersion weighted images, temperature maps and T1-weighted images at different magnetic field intensities. We introduce the concept of positive and negative contrast depending on the use of pre-polarized or non-polarized sequences. The system is being improved for pre-clinical studies in small animals.

Protein Dynamics from Accurate Low-Field Site-Specific Longitudinal and Transverse Nuclear Spin Relaxation.

Nuclear magnetic relaxation provides invaluable quantitative site-specific information on the dynamics of complex systems. Determining dynamics on nanosecond time scales requires relaxation measurements at low magnetic fields incompatible with high-resolution NMR. Here, we use a two-field NMR spectrometer to measure carbon-13 transverse and longitudinal relaxation rates at a field as low as 0.33 T (proton Larmor frequency 14 MHz) in specifically labeled side chains of the protein ubiquitin. The use of radiofrequency pulses enhances the accuracy of measurements as compared to high-resolution relaxometry approaches, where the sample is moved in the stray field of the superconducting magnet. Importantly, we demonstrate that accurate measurements at a single low magnetic field provide enough information to characterize complex motions on low nanosecond time scales, which opens a new window for the determination of site-specific nanosecond motions in complex systems such as proteins.