A chip-based C-band ODNP platform.

In this paper, we present a chip-based C-band ODNP platform centered around an NMR-on-a-chip transceiver and a printed microwave (MW) Alderman-Grant (AG) coil with a broadband tunable frequency range of 528MHz. The printable ODNP probe is optimized for a high input-power-to-magnetic-field conversion-efficiency, achieving a measured ODNP enhancement factor of -151 at microwave power levels of 33.3dBm corresponding to 2.1W. NMR measurements with and without microwave irradiation verify the functionality and the state-of-the-art performance of the proposed ODNP platform. The wide tuning range of the system allows for indirect measurements of the EPR signal of the DNP agent by sweeping the microwave excitation frequency and recording the resulting NMR signal. This feature can, e.g., be used to detect line broadening of the DNP agent. Moreover, we demonstrate experimentally that the wide tuning range of the new ODNP platform can be used to perform multi-tone microwave excitation for further signal enhancement: Using a 10mM TEMPOL solution, we improved the enhancement by a factor of two.

Asymmetry in three-site relaxation exchange NMR.

The asymmetry of peak integrals in 2D relaxation maps of exchange between three sites indicates circular flow between the relaxation sites. This disagrees with the detailed balance according to which the exchange between any pair of sites must be balanced in terms of thermodynamic equilibrium. Confined diffusion of particles jumping randomly on a 2D checkerboard grid to any of their eight neighbor positions and confined gas diffusion were modeled in Monte Carlo simulations to explore the impact of topological constraints on particle exchange between three pools. Both models produce density variations across the pore and reveal that up to 1 % of the molecules move in circular paths between the relaxation pools. This motion is driven by different features of either algorithm. It is silent in terms of thermodynamic equilibrium, confirming that multi-site exchange maps are symmetric in this case. The coherent flux is argued to result from stochastic pore resonance related to diffusion eigenmodes. If it can be driven experimentally by external time-varying electric, magnetic, or ultrasonic fields, this may be a way to enhance heterogeneous catalysis.

A Portable Chip-Based NMR Relaxometry System With Arbitrary Phase Control for Point-of-Care Blood Analysis.

In this article, we present a portable NMR relaxometry system optimized for the point-of-care analysis of body liquids such as blood. The presented system is centered on an NMR-on-a-chip transceiver ASIC, a reference frequency generator with arbitrary phase control, and a custom-designed miniaturized NMR magnet with a field strength of 0.29 T and a total weight of 330 g. The NMR-ASIC co-integrates a low-IF receiver, a power amplifier, and a PLL-based frequency synthesizer on a total chip area of 1100 × 900 µm 2. The arbitrary reference frequency generator enables the use of conventional CPMG and inversion sequences, as well as modified water-suppression sequences. Moreover, it is used to implement an automatic frequency lock to correct temperature-induced magnetic field drifts. Proof-of-concept measurements on NMR phantoms and human blood samples show an excellent concentration sensitivity of v[Formula: see text] = 2.2 mM/[Formula: see text]. This very good performance renders the presented system an ideal candidate for the future NMR-based point-of-care detection of biomarkers such as the blood glucose concentration.

Quantitative stray-field T1 relaxometry with the matrix pencil method.

The matrix pencil method (MPM) is tested as an approach to quantitatively process multiexponential low-field nuclear magnetic resonance T1 relaxometry data. The data is obtained by measuring T1 saturation recovery curves in the highly inhomogeneous magnetic field of a stray-field sensor. 0.9% brine solutions, doped with different concentrations of a Gd3+ containing contrast agent, serve as test liquids. Relaxation-times as a function of contrast-agent concentration along with the T1 relaxation curves for combinations of multiple different test liquids are measured, and the results from processing using MPM as well as inverse Laplace transformation as a benchmark are compared. The relaxation-time resolution limits of both procedures are probed by gradually reducing the difference between the relaxation-times of two liquids measured simultaneously. The sensitivity to quantify the relative contribution of each component to the magnetization build-up curve is explored by changing their volume ratio. Furthermore, the potential to resolve systems with more than two components is tested. For the systems under test, MPM shows superior performance in separating two or three relaxation components, respectively and effectively quantifying the time constants.

Analysis of Aging Products from Biofuels in Long-Term Storage.

The long-term aging processes during storage of different heating oils and their blends with biofuels including fatty acid methyl ester, hydrogenated vegetable oil, and power-to-liquids products were followed by different analytical techniques, and the aging products were analyzed. While most standard techniques are time-consuming and labor-intensive and specify only a single property, analyses by benchtop nuclear magnetic resonance spectroscopy proved to be effortless and fast. Moreover, only 0.4 mL of the sample is required for nondestructive NMR measurements. White and waxlike precipitates were found in FAME stored at a cold temperature and identified as esters of glycerol with saturated side chains by chromatographic, thermal, and spectroscopic analyses. At colder temperatures, they reversibly precipitate and can lead to system failure.

Magnetic Resonance Imaging of Water Content and Flow Processes in Natural Soils by Pulse Sequences with Ultrashort Detection.

Magnetic resonance imaging is a valuable tool for three-dimensional mapping of soil water processes due to its sensitivity to the substance of interest: water. Since conventional gradient- or spin-echo based pulse sequences do not detect rapidly relaxing fractions of water in natural porous media with transverse relaxation times in the millisecond range, pulse sequences with ultrafast detection open a way out. In this work, we compare a spin-echo multislice pulse sequence with ultrashort (UTE) and zero-TE (ZTE) sequences for their suitability to map water content and its changes in 3D in natural soil materials. Longitudinal and transverse relaxation times were found in the ranges around 80 ms and 1 to 50 ms, respectively, so that the spin echo sequence misses larger fractions of water. In contrast, ZTE and UTE could detect all water, if the excitation and detection bandwidths were set sufficiently broad. More precisely, with ZTE we could map water contents down to 0.1 cm3/cm3. Finally, we employed ZTE to monitor the development of film flow in a natural soil core with high temporal resolution. This opens the route for further quantitative imaging of soil water processes.

Versatile high-pressure gas apparatus for benchtop NMR: Design and selected applications.

A simple, yet highly versatile setup is presented for benchtop NMR analyses of gases at high-pressure. It consists mostly of commercial parts and includes multiple safety features while maintaining a small size to fit into a 1.20 m wide fume hood. Pressures up to 200 bar can be adjusted independently of the sample gas-bottle pressure in a matter of seconds. Mixtures of multiple gases can be produced in situ in a mixing chamber, which also serves to adjust the pressure. The high-pressure hardware and benchtop NMR spectrometer have been tested for long-term stability and repeatability of the measurements. The versatility of the setup is demonstrated by analyzing hydrocarbon-gas with attention to linewidths as well as their 1H relaxation times, by improving the resolution of 1H NMR spectra from solid polymers with pressurized CO2, and by visualizing the ingress of gaseous and supercritical methane into liquid benzene.

Mapping Cell Viability Quantitatively and Independently From Cell Density in 3D Gels Noninvasively.

OBJECTIVE: In biomanufacturing there is a need for quantitative methods to map cell viability and density inside 3D bioreactors to assess health and proliferation over time. Recently, noninvasive MRI readouts of cell density have been achieved. However, the ratio of live to dead cells was not varied. Herein we present an approach for measuring the viability of cells embedded in a hydrogel independently from cell density to map cell number and health. METHODS: Independent quantification of cell viability and density was achieved by calibrating the 1H magnetization transfer- (MT) and diffusion-weighted NMR signals to samples of known cell density and viability using a multivariate approach. Maps of cell viability and density were generated by weighting NMR images by these parameters post-calibration. RESULTS: Using this method, the limits of detection (LODs) of total cell density and viable cell density were found to be 3.88 ×108 cells · mL -1· Hz -1/2 and 2.36 ×109 viable cells · mL -1· Hz -1/2 respectively. CONCLUSION: This mapping technique provides a noninvasive means of visualizing cell viability and number density within optically opaque bioreactors. SIGNIFICANCE: We anticipate that such nondestructive readouts will provide valuable feedback for monitoring and controlling cell populations in bioreactors.

When the MOUSE leaves the house.

Change is inherent to time being transient. With the NMR-MOUSE (MObile Universal Surface Explorer) having matured into an established NMR tool for nondestructive testing of materials, this forward-looking retrospective assesses the challenges the NMR-MOUSE faced when deployed outside a protected laboratory and how its performance quality can be maintained and improved when operated under adverse conditions in foreign environments. This work is dedicated to my dear colleague and friend Geoffrey Bodenhausen on the occasion of his crossing an honorable timeline in appreciation of his ever-continuing success of fueling the dynamics of magnetic resonance.

Selective magnetic resonance signal suppression by colored Frank excitation.

Inspired by the growing interest in miniaturized NMR devices and their applications in material science as well as in chemical and biological research, low power rf excitation is explored. 1H NMR spectra have been measured with low power Frank excitation and are compared to spectra obtained by single-pulse excitation. Frank excitation consists of a large number of phase-modulated, constant-amplitude rf-pulses. A Frank sequence is divided into packages of discrete phase wavelets that correspond to a scan across a spectral frequency range. The largely coherent excitation is found experimentally to require less power than white noise excitation. The package structure suggests that individual wavelets can be omitted to skip individual frequency regions in the excitation, converting the white Frank excitation into colored Frank excitation. This work explores different approaches of colored, selective Frank excitation for spectroscopy and imaging. It is motivated by the aim to eliminate the rf amplifier from the NMR spectrometer so as to enable further miniaturization of NMR instruments. Colored Frank excitation bears promise as a low-power modality for solvent signal suppression in spectroscopy and motion tagging in magnetic resonance imaging.

Analysis of three-site T2-T2 exchange NMR.

T2-T2 exchange NMR is a unique method to investigate the pore space and fluid dynamics in porous media. While two-site relaxation exchange is well understood, three-site exchange is not. We analyze the solutions for three-site T2-T2 exchange NMR analytically and by computer simulation. Three main results are obtained. First, the exchange map can be asymmetric in the case of microscale vortex motion in violation of the principle of detailed balance. Second, the apparent longitudinal relaxation times and/or apparent transverse relaxation times can be complex valued. In the case of complex apparent transverse relaxation times, the three-site exchange map coalesces to a two-site exchange map with characteristic oscillations in the time domain. As a result of the oscillations, the shorter relaxation time is less than expected. Third, there can be negative cross-peaks in the exchange map for certain combinations of longitudinal and transverse relaxation times or if the mixing period is shorter than the evolution and detection periods. In view of these results experimental exchange maps may need to be reevaluated.

SABRE polarized low field rare-spin spectroscopy.

High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR instruments operating at low magnetic fields are emerging as a compact, inexpensive, and highly accessible alternative but suffer from low thermal polarization at a low field strength and consequently a low signal. However, certain hyperpolarization techniques create high polarization levels on target molecules independent of magnetic fields, giving low-field NMR a significant sensitivity boost. In this study, SABRE (Signal Amplification By Reversible Exchange) was combined with high homogeneity electromagnets operating at mT fields, enabling high resolution 1H, 13C, 15N, and 19F spectra to be detected with a single scan at magnetic fields between 1 mT and 10 mT. Chemical specificity is attained at mT magnetic fields with complex, highly resolved spectra. Most spectra are in the strong coupling regime where J-couplings are on the order of chemical shift differences. The spectra and the hyperpolarization spin dynamics are simulated with SPINACH. The simulations start from the parahydrogen singlet in the bound complex and include both chemical exchange and spin evolution at these mT fields. The simulations qualitatively match the experimental spectra and are used to identify the spin order terms formed during mT SABRE. The combination of low field NMR instruments with SABRE polarization results in sensitive measurements, even for rare spins with low gyromagnetic ratios at low magnetic fields.

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

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 4-hydroxy-TEMPO solution. Additionally, 1H spectroscopic resolution and significant enhancements are demonstrated on acetic acid as a solvent.

NMR relaxometry of oil paint binders.

Mobile nuclear magnetic resonance (NMR) is a flexible technique for nondestructive characterization of water in plants, the physical properties of polymers, moisture in porous walls, or the binder in paintings by relaxation measurements. NMR relaxation data report material properties and therefore can also help to characterize the state of tangible cultural heritage. In this work, we discuss the relaxation behavior in two series of naturally aged paint mock-up samples. First, paints with different pigment concentrations were prepared and investigated in terms of the longitudinal and transverse relaxation-time distributions. We document the evolution of both relaxation-time distributions during the initial drying stage and demonstrate the heightened importance of transverse over longitudinal relaxation measurements. Second, we observe nonlinear dependences of the relaxation times on the pigment concentration in a typical oil binder. Third, in a study of naturally aged paint samples prepared in the years between 1914 and 1951 and subsequently aged under controlled conditions, we explore the possibility of determining the age of paintings using partial least square regression (PLS) by fitting T1 -T2 data with the sample age. Our results suggest some correlation, albeit with significant scatter. Estimating the age of a painting stored under unknown conditions from NMR relaxation data is therefore not feasible, as the cumulative effects of light irradiation, humidity, and biological degradation further obfuscate the chemical and physical impact of aging on the relaxation times in addition to the impact of pigment concentration.

In-situ MRI velocimetry of the magnetohydrodynamic effect in electrochemical cells.

Electrochemical reactions have become increasingly important in a large number of processes and applications. The use of NMR (Nuclear Magnetic Resonance) techniques to follow in situ electrochemistry processes has been gaining increasing attention from the scientific community because they allow the identification and quantification of the products and reagents, whereas electrochemistry measurements alone are not able to do so. However, when an electrochemical reaction is performed in situ the reaction rate can be increased by action of the Lorentz force, which is equal to the cross product between the current density and the magnetic field applied. This phenomenon is called the magnetohydrodynamic (MHD) effect. Although this process is beneficial because it accelerates the reaction, it needs to be well understood and taken into account during the in situ electrochemical measurements. The MHD effect is based on increased mass transfer, which is shown by in situ MRI velocimetry here. Images had to be acquired in a rapid manner since current was not pulsed. Significant velocities in a plane parallel to the electrodes alongside with complex flow patterns were detected.

Elucidating the ionic liquid distribution in monolithic SILP hydroformylation catalysts by magnetic resonance imaging.

Monolithic silicon carbide supported ionic liquid-phase (SILP) Rh-catalysts have very recently been introduced for gas-phase hydroformylation as an important step toward industrial upscaling. This study investigates the monolithic catalyst system in combination with different impregnation procedures with non-invasive magnetic resonance imaging (MRI). The findings were supported by X-ray microtomography (micro-CT) data of the monolithic pore structure and a catalytic performance test of the catalyst system for 1-butene gas-phase hydroformylation. MRI confirmed a homogeneous impregnation of the liquid phase throughout the full cross-section of the cylindrical monoliths. Consistent impregnations from one side to the other of the monoliths were achieved with a stabilizer in the system that helped preventing inhomogeneous rim formation. External influences relevant for industrial application, such as long-term storage and temperature exposure, did not affect the homogeneous liquid-phase distribution of the catalyst. The work elucidates important parameters to improve liquid-phase catalyst impregnation to obtain efficient monolithic catalysts for industrial exploitation in gas-phase hydroformylation as well as other important industrial processes.

Production of highly concentrated and hyperpolarized metabolites within seconds in high and low magnetic fields.

Hyperpolarized metabolites are very attractive contrast agents for in vivo magnetic resonance imaging studies enabling early diagnosis of cancer, for example. Real-time production of concentrated solutions of metabolites is a desired goal that will enable new applications such as the continuous investigation of metabolic changes. To this end, we are introducing two NMR experiments that allow us to deliver high levels of polarization at high concentrations (50 mM) of an acetate precursor (55% 13C polarization) and acetate (17% 13C polarization) utilizing 83% para-state enriched hydrogen within seconds at high magnetic field (7 T). Furthermore, we have translated these experiments to a portable low-field spectrometer with a permanent magnet operating at 1 T. The presented developments pave the way for a rapid and affordable production of hyperpolarized metabolites that can be implemented in e.g. metabolomics labs and for medical diagnosis.

Single-shot velocity mapping by rewinding of velocity encoding with Echo-Planar Imaging.

The ability of single-shot NMR imaging methods to follow the time evolution of a velocity distribution within an object is strongly limited by the phase errors accumulated as velocity maps are acquired. In the particular case of Carr-Purcell based sequences combined with Echo Planar Imaging acquisition, phase accumulates through subsequent images, hampering the possibility to acquire several velocity maps, which would be useful to determine transient behavior. In this work, we propose the use of a rewinding velocity encoding module applied after the acquisition of each image during the CPMG echo train. In this way, the first velocity module imparts a velocity dependent phase prior to the image acquisition and the second pair cancels this phase out before the next refocusing radiofrequency pulse is applied. The performance and limits of this method are studied by acquiring 100 images of a co-rotating Couette cell over a period of 1.6 s as a function of the rotation speed. The method is applied to determine the kinematic viscosity of a water/alcohol mixture, which is a relevant topic in many physical, chemical and biological processes.

Low-field and benchtop NMR.

NMR started at low field. Important discoveries like the first observation of NMR in condensed matter, the spin echo, NMR for chemical analysis, Fourier NMR spectroscopy, 2D NMR spectroscopy and magnetic resonance imaging happened at field strengths considered low today. With time the footprint of the NMR instruments at these field strengths shrunk from the laboratory floor to the tabletop. The first commercial tabletop NMR instruments were compact relaxometers for food analysis followed by mobile relaxometers for materials testing and oil-well exploration culminating in tabletop spectrometers for chemical analysis, capable of performing nearly the whole methodical portfolio of today's high-field instruments. The increasing sensitivity afforded by the lower noise of modern electronics and the unfolding richness of hyperpolarization scenarios along with detection schemes alternative to nuclear induction enable NMR at ultra-low field strengths down to zero applied field, where spin-spin couplings in local fields dominate the residual Zeeman interaction. Miniaturization and cost-reduction of NMR instruments outline current development goals along with the development of smart-phone-like apps to conduct standard NMR analyses.

Perfusion-related changes in intestinal diffusion detected by NMR-MOUSE® monitoring in minipigs.

OBJECTIVE: The aim was to investigate perfusion-related changes in the intestinal diffusion assessed by NMR-MOUSE monitoring in minipigs. This was a follow-up study of previous experiments on landrace pigs demonstrating the feasibility of NMR-MOUSE monitoring in large animals. METHODS: 5 mature female minipigs (mean body weight 50 ±â€¯2 kg) underwent laparotomy with exposition of several small intestinal loops and their feeding vessels. The loops were examined consecutively using NMR-MOUSE monitoring for assessment of intestinal proton diffusion (fast diffusion component [FC] and slow diffusion component [SC]) and oxygen to see monitoring (O2C, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory evaluation. Following a baseline measurement on each loop under physiological perfusion, measurements were continued as one of the following main treatments were performed per loop: method 1 - ischemia; method 2 - flow reduction; method 3 - intraluminal glucose followed by ischemia; method 4 - intraluminal glucose followed by flow reduction. Perioperative monitoring was supplemented by blood gas analyses and histopathological assessment of H.E. stained intestinal biopsies. RESULTS: The NMR-MOUSE measurement showed a significant difference in the change to baseline values in the FC during flow reduction compared to the other treatments according to the unadjusted (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0005, pM2 vs. M4 = 0.0005) and the adjusted p-values (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0030, pM2 vs. M4 = 0.0030). In the SC, the difference between ischemia and flow reduction was significant according to the unadjusted p-values (pM2 vs. M1 = 0.0397). Whereas the FC showed a trend towards ongoing increase during ischemia but towards ongoing decrease during flow reduction, the SC showed contrary trends. These effects seemed to be attenuated by prior glucose application. According to the results of O2C monitoring, ischemia as well as flow reduction caused a significant decrease of microcirculatory oxygen saturation (inner probe: methods 1-4 and outer probe methods 1, 2: p < 0.0001; outer probe: pM2 = 0.0001), velocity (inner probe: pM1 < 0.0001, pM2 = 0.0155, pM3 = 0.0027; outer probe: pM1 < 0.0001, pM2 = 0.0045, pM3 = 0.0047, pM4 = 0.0037) and serosal flow (outer probe, methods 1 and 2: p < 0.0001; pM3 = 0.0009, pM4 = 0.0008). The histopathological analysis showed a significant association with time (p = 0.003) but not with the experimental method (p = 0.1386). CONCLUSIONS: Intestinal diffusion is affected significantly by perfusion changes in mature minipigs. As shown by NMR-MOUSE monitoring, ischemia and flow reduction have contrary effects on intestinal diffusion and, additionally, the fast and slow diffusion components show opposite trends during each of those pathological perfusion states. Prior intraluminal glucose application seems to attenuate the effects of malperfusion on intestinal diffusion.