Low-cost NMR Research Articles

Abstract 18914: Metabolomic Biomarker Profiling Improves Cardiovascular Risk Assessment for Patients on Statins: Evidence From 35000 Individuals From the United Kingdom

Introduction: Identification of individuals at high cardiovascular risk even when using statins can guide second line therapy for primary prevention. Hypothesis: We addressed whether metabolomic biomarker profiling has utility in predicting onset of major adverse cardiovascular events (MACE) and heart failure among individuals already on statin therapy. Methods: Circulating lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers were measured by NMR metabolomics in ~275,000 individuals from UK Biobank. The study population was filtered to people using statins at blood sampling, comprising 34,971 individuals. During 10-year follow-up, 2156 first occurrence MACE events and 1753 heart failure hospitalisation events occured. Using multivariable regression modelling, we derived separate 10-year residual risk scores for the first onset of MACE and heart failure. We assessed the predictive improvements of adding the metabolomic biomarkers to established risk factors and routine cholesterol measurements. Results: Adding the metabolomic biomarkers to established risk factors and cholesterol measures improved AUC from 0.67 to 0.70 for 3-point MACE and from 0.68 to 0.71 for heart failure. Using only the metabolomic biomarkers from the low-cost NMR assay, along with age and sex, yielded a performance close to that of the full model, achieving AUC of 0.69 for 3-point MACE and 0.70 for heart failure. Substantial improvements were observed when looking at the high-risk tails of the risk scores. When comparing the highest risk decile to the remaining 90% of study population, adding the metabolomic biomarkers to established risk factors and cholesterols increased the hazard ratio from 2.2 (95% CI 1.9-2.6) to 2.8 (95% CI 2.4-3.3) for 3-point MACE and from 2.7 (95% CI 2.3-3.3) to 3.4 (95% CI 2.8-4.0) for heart failure, i.e. reaching comparable risk elevation as seen in familial hypercholesterolemia. Conclusions: Metabolomic biomarker profiling by a low-cost NMR assay enhanced prediction of incident MACE and heart failure beyond established risk factors for individuals already on statin therapy. This may complement the residual risk assessment in primary prevention settings and guide second line therapy to those with most benefit.

An open-source, low-cost NMR spectrometer operating in the mT field regime

In recent years, low field and ultra-low field NMR spectrometers have gained interest due to their portability, lower cost, and reduced subject-induced magnetic field inhomogeneities. Here, we describe the design of a low-cost multinuclear NMR spectrometer operating in the ultra-low field regime (ULF), which possesses high spectral resolution and enables arbitrary pulse programming. An inexpensive multifunction input/output (I/O) device is used to handle waveform generation and digitization in the kHz operating range. A home-built radio frequency (RF) mixing circuit is used to down-mix the NMR signals, allowing for the slower sampling rates and lower memory requirements needed to enable minute-long acquisitions using a standard Windows PC. The LabVIEW code, along with a bill of materials for all components used in the spectrometer, is included. As proof of concept, 1H relaxation measurements and the simultaneous detection of 1H with gas phase and dissolved 129Xe frequencies using the described low field NMR spectrometer are demonstrated.

Low-cost low-field NMR and MRI: Instrumentation and applications

While NMR and MRI are often thought of as expensive techniques requiring large institutional investment, opportunities for low-cost, low-field NMR and MRI abound. We discuss a number of approaches to performing magnetic resonance experiments with inexpensive, easy to find or build components, aimed at applications in industry, education, and research. Opportunities that aim to make NMR accessible to a broad community are highlighted. We describe and demonstrate some projects from our laboratory, including a new prototype instrument for measurements at frequencies up to ∼200 kHz and demonstrate its application to the study of the rapidly advancing technique known as inhomogeneous magnetization transfer imaging, a promising method for characterizing myelin in vivo.

Geometrically-differential NMR in a stripline front-end

A major challenge facing the development of portable, low-cost NMR is the development of robust yet sensitive transceivers, for which several trade-offs in scalability, performance and complexity are usually necessary. Here we report on a stripline-based NMR detector that overcomes previous limitations. It features a sensitivity of 5.7×10-4 TA−1Ω−0.5 over a sample volume of 10 mm × 10 mm × 3 mm, an exceptionally high B1 homogeneity of A450/A90=98.4%, intrinsic electromagnetic shielding of 27 dB from environmental influences, and a total signal gain of 68 dB in the presence of a noise factor of 1.28, without any exterior shielding. The new dual-coil arrangement offers a downscalable geometry optimised for gap magnets, and it is voltage-tunable and plug-in compatible with commercial software-defined radio spectrometer boards. Exceptionally, it features both common-mode and novel differential-mode NMR measurement abilities.

Compact, low-cost NMR spectrometer and probe for dissolution DNP.

The desire for higher magnetic resonance sensitivity has led to the development of multiple home-built and commercial dissolution dynamic nuclear polarization polarizers. The emergence of polarizers capable of variable magnetic field strengths desires a versatile standalone spectrometer and NMR circuit to fulfill detection needs at different frequencies. We present a benchtop NMR spectrometer with a duplexer capable of serving high-field solid and liquid state NMR applications up to 450 MHz. A detailed view of the employed probe is discussed. Tuning and matching schemes are investigated yielding and experimentally verifying closed-form equations to estimate the nutation frequency for a remotely tuned and matched sample coil.

A low-cost home-built NMR using Halbach magnet

The objective of this work is to develop a low-cost compact desktop NMR system based on Halbach magnets with the advantages of small size and ability to generate relatively high field strength. Considering the cost of manufacturing and assembling the magnetic blocks, the system utilized a 3-layer Halbach magnet and a wedge-shaped mechanical structure, which was designed for magnet rapid assembling. The comparison between simulation and calculation results of the initial magnetic field strength distribution showed that design theory and practice were in accordance. The initial homogeneity was 576 ppm in a square with a length of 5 mm. After passive shimming with two magnetic blocks and steel pieces, the uniformity reached 120 ppm in the same area. We developed and tested a compact single board spectrometer with digital modulation and demodulation in order to enhance the system mobility and improve the SNR. A self-made probe was used to carry out experiments with the spectrometer, and the spectral width at half-height reached 20 ppm in a cylinder with a diameter of 1.5 mm and a length of 1 mm. Compact structure and low cost of the system will facilitate and extend the application of desktop NMR system.

Simple and low-cost tabletop NMR system for chemical-shift-resolution spectra measurements

We have been working on developing a low-cost tabletop NMR system. We reported that a field homogeneity as high as 50 ppm was achieved with a simple NMR magnet by employing two facing ferrite magnets with iron disks in between (Chonlathep et al., 2017). In this paper, we report two improvements added to our previous system: (1) an FPGA based signal processing unit to improve the S/N ratio and (2) a simple shimming mechanism to improve the field homogeneity. We obtained as high as 1 ppm field homogeneity in the best case. The signals from hydrogen nuclear spins in a methyl and carboxy group in acetic acid were resolved in NMR spectra.

A simple low-cost single-crystal NMR setup

A low-cost single-crystal NMR kit is presented along with a web-based post-processing software. The kit consists of a piezo-crystal motor and a goniometer for the crystal, both embedded in a standard wide-bore NMR probe with a 3D printed scaffold. The NMR pulse program controls the angle setting automatically, and the post-processing software incorporates a range of orientation-angle discrepancies present in the kit and other single-crystal setups. Results with a NaNO3 single-crystal show a high degree of reproducibility and excellent agreement with previous findings for the anisotropic quadrupolar interaction.

Fast measurements of average flow velocity by Low-Field 1H NMR

In this paper, we describe a method for measuring the average flow velocity of a sample by means of Nuclear Magnetic Resonance. This method is based on the Carr–Purcell–Meiboom–Gill (CPMG) sequence and does not require the application of any additional static or pulsed magnetic field gradients to the background magnetic field. The technique is based on analyzing the early-time behavior of the echo amplitudes of the CPMG sequence. Measurements of average flow velocity of water are presented. The experimental results show a linear relationship between the slope/ y-intercept ratio of a linear fit of the first echoes in the CPMG sequence, and the average flow velocity of the flowing fluid. The proposed method can be implemented in low-cost Low-Field NMR spectrometers allowing a continuous monitoring of the average velocity of a fluid in almost real-time, even if the flow velocity changes rapidly.

Tracer diffusion measurements in solid lithium: a test case for the comparison between NMR in static and pulsed magnetic field gradients after upgrading a standard solid state NMR spectrometer

This paper reports on the upgrading of a standard solid state NMR spectrometer, which has been used in combination with a field variable 7 T cryomagnet, to a low-cost combined SFG and PFG NMR spectrometer. Both methods are applied to solid lithium as a simple test case. The results show that under the given conditions SFG NMR and PFG NMR can provide tracer diffusion coefficients for 7 Li diffusion down to about 10 −14 and 10 −13 m 2/ s , respectively. SFG and PFG NMR are complementary methods. The paper demonstrates advantages and disadvantages of each method with a concrete example and why it is desirable to be able to apply both methods to the same sample.

A simple, ultralow magnetic field NMR imaging system

The construction of a simple, low-cost NMR imaging system including a 0.3 m diameter electromagnet is described. The system operates at the unusually low frequency of 680 kHz and can be readily scaled-up to a full body machine. In spite of the inherently poor signal-to-noise ratio at this frequency, potentially useful results may be obtained using very simple and inexpensive equipment and a home-built approach.

An efficient, low-cost NMR imaging machine

An efficient, low-cost NMR imaging machine

The installation of a commercial resistive NMR imager.

It has been demonstrated that a relatively low-cost resistive NMR imager can be installed in a normal hospital environment without many major or expensive modifications. The magnet can be adjusted to give adequate uniformity and there is sufficient RF shielding to give good quality clinical images (Fig. 3). The fringe field of the magnet of this system, which operates at the lowest field strength of any commercial NMR imager, does not present a problem to imaging unit staff (NRPB, 1984). The long term reliability and detailed specifications with regard to image quality have yet to be determined. These will be determined whilst the imager is being used for clinical studies as part of the national clinical evaluation of NMR imaging supported by the Medical Research Council.

Utilization of a microprocessor in a pulsed NMR spectrometer

We have built a low-cost pulsed NMR system designed around the Intel 8080 microprocessor. The general block diagrams, some hardware details, and the software concepts of the system are presented together with its basic operation. This system was designed to provide the major sequences used in pulsed NMR experiments to measure T 1, T 2, T 1 ϱ relaxation times. In addition to instrument control, the microprocessor supervises the process of data acquisition. The data acquired are stored in RAM memory and can be transferred over telephone lines to a remote time-shared computer for further processing. The use of a programmable device such as a microprocessor allows future extensions to more sophisticated pulse sequences to be achieved easily via software modifications.