Intermolecular Zero-quantum Coherences Research Articles

High-resolution diffusion-order NMR spectroscopy in inhomogeneous magnetic fields via intermolecular zero-quantum coherences

Diffusion-order NMR spectroscopy (DOSY) presents a powerful tool for studying solution mixtures by recording diffusion coefficients of individual components and separating their signals into respective 1D NMR spectra. Existing DOSY experiments, however, are generally unsuitable for measurements under adverse magnetic field conditions, because calculations for diffusion coefficients strictly rely on resolved resonances in the 1D NMR spectral domain. Herein, we propose a general DOSY method by introducing intermolecular zero-quantum coherence mechanism into molecular diffusion evolution to overcome the challenge of magnetic field inhomogeneity and to record high-resolution DOSY spectra free of magnetic field inhomogeneity. Our experimental results and theoretical interpretation suggest that the proposed method allows to diffusion analysis and component discrimination on solution mixtures under externally inhomogeneous magnetic field conditions and on intact biological tissues with field inhomogeneity internally caused by magnetic susceptibility variations. This study provides a previously unreported NMR protocol for high-resolution DOSY measurements in inhomogeneous magnetic fields, thus broadening the scope of DOSY applications and showing the promising prospect for studies on chemical and biological mixture samples.

Correlation distance dependence of the resonance frequency of intermolecular zero quantum coherences and its implication for MR thermometry

Correlation distance dependence of the resonance frequency of intermolecular zero quantum coherences and its implication for MR thermometry

Correlation distance dependence of the resonance frequency of intermolecular zero quantum coherences and its implication for MR thermometry.

Because the resonance frequency of water-fat intermolecular zero-quantum coherences (iZQCs) reflects the water-fat frequency separation at the microscopic scale, these frequencies have been proposed and used as a mean to obtain more accurate temperature information. The purpose of this work was to investigate the dependence of the water-fat iZQC resonance frequency on sample microstructure and on the specific choice of the correlation distance. The effect of water-fat susceptibility gradients on the water-methylene iZQC resonance frequency was first computed and then measured for different water-fat emulsions and for a mixture of porcine muscle and fat. Similar measurements were also performed for mixed heteronuclear spin systems. A strong dependence of the iZQC resonance frequency on the sample microstructure and on the specific choice of the correlation distance was found for spin systems like water and fat that do not mix, but not for spin systems that mix at the molecular level. Because water and fat spins do not mix at the molecular level, the water-fat iZQC resonance frequency and its temperature coefficient are not only affected by sample microstructure but also by the specific choice of the correlation distance. Magn Reson Med 79:1429-1438, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution nuclear magnetic resonance measurements in inhomogeneous magnetic fields: A fast two-dimensional J-resolved experiment.

High spectral resolution in nuclear magnetic resonance (NMR) is a prerequisite for achieving accurate information relevant to molecular structures and composition assignments. The continuous development of superconducting magnets guarantees strong and homogeneous static magnetic fields for satisfactory spectral resolution. However, there exist circumstances, such as measurements on biological tissues and heterogeneous chemical samples, where the field homogeneity is degraded and spectral line broadening seems inevitable. Here we propose an NMR method, named intermolecular zero-quantum coherence J-resolved spectroscopy (iZQC-JRES), to face the challenge of field inhomogeneity and obtain desired high-resolution two-dimensional J-resolved spectra with fast acquisition. Theoretical analyses for this method are given according to the intermolecular multiple-quantum coherence treatment. Experiments on (a) a simple chemical solution and (b) an aqueous solution of mixed metabolites under externally deshimmed fields, and on (c) a table grape sample with intrinsic field inhomogeneity from magnetic susceptibility variations demonstrate the feasibility and applicability of the iZQC-JRES method. The application of this method to inhomogeneous chemical and biological samples, maybe in vivo samples, appears promising.

Establishing resolution-improved NMR spectroscopy in high magnetic fields with unknown spatiotemporal variations.

A half-century quest for higher magnetic fields has been an integral part of the progress undergone in the Nuclear Magnetic Resonance (NMR) study of materials' structure and dynamics. Because 2D NMR relies on systematic changes in coherences' phases as a function of an encoding time varied over a series of independent experiments, it generally cannot be applied in temporally unstable fields. This precludes most NMR methods from being used to characterize samples situated in hybrid or resistive magnets that are capable of achieving extremely high magnetic field strength. Recently, "ultrafast" NMR has been developed into an effective and widely applicable methodology enabling the acquisition of a multidimensional NMR spectrum in a single scan; it can therefore be used to partially mitigate the effects of temporally varying magnetic fields. Nevertheless, the strong interference of fluctuating fields with the spatial encoding of ultrafast NMR still severely restricts measurement sensitivity and resolution. Here, we introduce a strategy for obtaining high resolution NMR spectra that exploits the immunity of intermolecular zero-quantum coherences (iZQCs) to field instabilities and inhomogeneities. The spatial encoding of iZQCs is combined with a J-modulated detection scheme that removes the influence of arbitrary field inhomogeneities during acquisition. This new method can acquire high-resolution one-dimensional NMR spectra in large inhomogeneous and fluctuating fields, and it is tested with fields experimentally modeled to mimic those of resistive and resistive-superconducting hybrid magnets.

Multi-spin echo spatial encoding provides three-fold improvement of temperature precision during intermolecular zero quantum thermometry.

Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR. A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples. MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C. MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow.

Fast high-resolution J-resolved correlation spectroscopy in inhomogeneous fields

Multi-dimensional NMR spectroscopy alleviates the jam or even overlaps of peaks in one-dimensional spectra of complicated samples, extending the application of NMR spectroscopy. However, the acquisition of high-resolution NMR spectra relies on high homogeneity of magnetic field, which is difficult to achieve in many cases. In this study, we present a fast NMR approach for acquiring high-resolution 3D spectrum in inhomogeneous fields via intermolecular zero-quantum coherence and spatial encoding technique, providing J-resolved spectrum and correlation spectrum information simultaneously within the acquisition time scale for a conventional two-dimensional spectrum.

Intermolecular zero quantum coherences enable accurate temperature imaging in red bone marrow.

Red bone marrow metastases are common in breast and prostate cancer patients, but those metastases are currently incurable. Recent developments show that hyperthermia could be a successful treatment for bone metastasis, but thermometry remains difficult or inaccurate in red marrow. The technique evaluated in this study measures the evolution frequency of intermolecular zero quantum coherences (iZQCs) between fat and water. The iZQC evolution frequency was mapped linearly to temperature. The temperature accuracy and coherence lifetime of the iZQC method were evaluated against other thermometry methods that are based on localized spectroscopy and multiple gradient echo imaging. The temperature coefficient (α) was 9.8 ± 0.7 ppb/°C with the iZQC method and 2 ± 7 ppb/°C with traditional localized spectroscopy. Because the accuracy of thermometry is limited by the reproducibility of α between samples, iZQCs provide nearly a 10-fold accuracy improvement in red marrow (0.7 ppb/°C for iZQCs versus 7 ppb/°C for localized spectroscopy.) The iZQC technique in this study will for the first time allow accurate and quantitative thermal imaging of red marrow. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 74:63-70, 2015. © 2014 Wiley Periodicals, Inc.

HRJCOSY: A three-dimensional NMR method for measuring complex samples in inhomogeneous magnetic fields

Three-dimensional (3D) NMR plays an important role in structural elucidations of complex samples, whereas difficulty remains in its applications to inhomogeneous fields. Here, we propose an NMR approach based on intermolecular zero-quantum coherences (iZQCs) to obtain high-resolution 3D J-resolved-COSY spectra in inhomogeneous fields. Theoretical analyses are presented for verifying the proposed method. Experiments on a simple chemical solution and a complex brain phantom are performed under non-ideal field conditions to show the ability of the proposed method. This method is an application of iZQCs to high-resolution 3D NMR, and is useful for studies of complex samples in inhomogeneous fields.

High-resolution absorptive intermolecular multiple-quantum coherence NMR spectroscopy under inhomogeneous fields

Intermolecular multiple-quantum coherence (iMQC) is capable of improving NMR spectral resolution using a 2D shearing manipulation method. A pulse sequence termed CT-iDH, which combines intermolecular double-quantum filter (iDQF) with a modified constant-time (CT) scheme, is designed to achieve fast acquisition of high-resolution intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) spectra without strong coupling artifacts. Furthermore, double-absorption lineshapes are first realized in 2D intermolecular multi-quantum coherences (iMQCs) spectra under inhomogeneous fields through a combination of iZQC and iDQC signals to double the resolution without loss of sensitivity. Theoretically the spectral linewidth can be further reduced by half compared to original iMQC high-resolution spectra. Several experiments were performed to test the feasibility of the new method and the improvements are evaluated quantitatively. The study suggests potential applications for in vivo spectroscopy.

Apparent diffusion behaviors of spins in the presence of distant dipolar field in two-component solution NMR

The diffusion behaviors of spins in the presence of distant dipolar field in two-component spin systems during the second evolution period of a modified CRAZED sequence before acquisition were investigated. Theoretical formulas were deduced based on the distant dipolar field model. The simulation results and experimental observations are consistent with the theoretical predictions. This study shows that the relative intensities of signals from intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) have the same diffusion attenuation characteristic under the combined effect of diffusion weighting gradients and distant dipolar field during the second evolution period. This diffusion attenuation may be different from that of conventional single-quantum coherence signal, depending on the relative orientation of the diffusion weighting gradients to the coherence selection gradients. The results presented herein are helpful for understanding the effect of distant dipolar field from a spin system on the diffusion behavior of other spin system and the signal properties in the iZQC or iDQC magnetic resonance imaging.

High-Resolution 2D J-Resolved Spectroscopy in Inhomogeneous Fields with Two Scans

A scheme via spatially encoded intermolecular zero-quantum coherences was proposed for high-resolution 2D J-resolved spectra in inhomogeneous fields with high acquisition efficiency. Compared to a recent paper (Pelupessy et al. Science, 2009, 324, 1693-1697), the novel method can obtain chemical shifts and J multiplicity patterns directly.

High-resolution NMR spectroscopy in unstable and inhomogeneous fields via stroboscopic acquisition

In this paper, we demonstrated that despite the insensitivity of intermolecular zero-quantum coherences (iZQCs) to B 0 variations, the influence of unstable fields on the observable single-quantum coherence signals causes strong t 1 noises in the high-resolution iZQC projection spectra. Stroboscopic acquisition was then proposed for noise suppression. The feasibility of the modified sequences with the proposed acquisition scheme was verified by computer simulations and experiments in different unstable fields generated by the Z0 and Z1 coil current oscillations, which mimic the unstable fields of NMR using externally powered magnets and MRS in the presence of physiological motions, respectively.

In vivo brown adipose tissue detection and characterization using water-lipid intermolecular zero-quantum coherences

In vivo brown adipose tissue detection and characterization using water-lipid intermolecular zero-quantum coherences

In vivo brown adipose tissue detection and characterization using water–lipid intermolecular zero‐quantum coherences

Brown adipose tissue and white adipose tissue depots are noninvasively characterized in vitro and in vivo in healthy and obese mice using intermolecular zero-quantum coherence transitions between lipid and water spins. Intermolecular zero-quantum coherences enable selective detection of spatial correlation between water and lipid spins and thereby the hydration of fatty deposits with subvoxel resolution. At about a 100 mm distance scale, the major observed peaks are between water, methylene protons at 1.3 ppm, and olefinic protons at 5.3 ppm. Our in vitro results show that the methylene-olefinic intermolecular zero-quantum coherence signal is strong both in brown and white adipose tissues, but that the water-methylene intermolecular zero-quantum coherence signal is characteristic only of brown adipose tissue. In vivo, the ratio of these peaks is substantially higher in lean or young mice than in old or obese mice.

NMR Separation of Intra- and Extracellular Compounds Based on Intermolecular Coherences

NMR spectroscopy is a powerful tool for detection and characterization of chemical compounds in biological systems. Its application in pharmaceutical studies in cell cultures, however, has been hampered by the enormous technical challenges in separating intra- from extracellular amounts of one substance. We introduce a novel approach to separate intra- from extracellular NMR signal based on the detection of intermolecular zero-quantum coherences in presence of a chemical shift agent. In a sample of large cells in culture, the investigation of cellular uptake of pharmacological substances becomes feasible. The addition of 10 mM Tm-DOTP to a suspension of 100 Xenopus laevis oocytes resulted in sufficient separation of resonance frequencies between intra- and extracellular water. Upon selective excitation of either intra- or extracellular water signal, only intra- or extracellular components were observed, respectively. The presented localization technique provides intrinsic averaging over a large number of cells, resulting in a significant signal gain. The method works on standard NMR spectrometers, which are available at most scientific research institutions today. On a high-resolution NMR system with a cryoprobe, a 20-fold sensitivity gain was observed as compared to conventionally localized NMR spectroscopy of a single X. laevis oocyte on dedicated NMR microscopes.

High-resolution NMR spectra in inhomogeneous and unstable fields via the three-pulse method

In modern solution nuclear magnetic resonance (NMR), the spectral resolution is mainly dependent on the spatial homogeneity and temporal stability of the magnetic field. The spectral linewidths are usually proportional to the overall field homogeneity and the stability experienced by the sample. Many high-resolution NMR methods have been developed, but few are applicable in inhomogeneous and unstable fields. In this paper, a high-resolution three-pulse method based on intermolecular zero-quantum coherences (iZQCs) is proposed. Since this method is insensitive to field inhomogeneity and instability, spectral information such as the chemical shift can be retained in the resulting spectra. In comparison with the CPMG-HOMOGENIZED method, the new method provides almost pure solvent–solute iZQC signals.

High-resolution two-dimensional correlation spectroscopy in inhomogeneous fields: New application of intermolecular zero-quantum coherences

A new pulse sequence is proposed based on intermolecular zero-quantum coherences (iZQCs) to obtain high-resolution two-dimensional (2D) correlation spectroscopy (COSY) in inhomogeneous fields via three-dimensional (3D) acquisition. This sequence extends the high-resolution iZQC approaches from one dimension to two dimensions. Since the iZQC evolution periods in the new sequence are insensitive to the field inhomogeneities, high-resolution COSY spectra can be recovered from inhomogeneous fields by projecting the 3D data onto the indirectly acquired 2D plane. Theoretical expressions were derived according to the distant dipolar field treatment combined with product operator formalism. Both the experimental observations and computer simulations are consistent with the theoretical predictions. The new sequence thus provides an attractive way to eliminate the influences of field inhomogeneity on the conventional COSY methods, which may be useful for the study of chemical and biological materials.

High-resolution magnetic resonance spectroscopy in unstable fields via intermolecular zero-quantum coherences

Intermolecular zero-quantum coherences (iZQCs) have been utilized to achieve high-resolution nuclear magnetic resonance (NMR) proton spectra under inhomogeneous and/or unstable fields. In this paper, we demonstrated that despite the insensitivity of iZQCs to B(0) variations, the influence of unstable fields on the observable single-quantum coherence signals causes strong t(1) noises in the high-resolution iZQC spectra. Short-time acquisition (STA) and phase spectrum schemes were proposed for noise suppression in in vivo iZQC magnetic resonance spectroscopy (MRS) under temporal B(0) variations. The feasibility of these schemes were verified by localized spectroscopic studies under B(0) variations generated by the Z0 coil current oscillations and by voxel position variations in the presence of field gradients, which simulate the field conditions of MRS in the presence of physiological motions. The phase scheme not only improves the signal-to-noise ratio but also further reduces the linewidth by half.

High-resolution NMR spectroscopy in inhomogeneous fields via heteronuclear intermolecular multiple-quantum coherences

A heteronuclear CRAZED pulse sequence was utilized to obtain high-resolution NMR spectra via heteronuclear intermolecular zero-quantum coherences (iZQCs) or intermolecular double-quantum coherences (iDQCs) in inhomogeneous fields. It overcomes the difficulty of selective excitation in homonuclear CRAZED experiments when the chemical shifts of solvent and solute are close to each other. In the 1D spectrum extracted from the 2D data, chemical shifts, coupling constants, multiplet patterns, and relative peak areas are almost independent of the magnetic field inhomogeneity. Theoretical predictions were verified by experimental observations.