A continuous phase-modulated approach to spatial encoding in ultrafast 2D NMR spectroscopy

Ultrafast 2D NMR replaces the time-domain parametrization usually employed to monitor the indirect-domain spin evolution, with an equivalent encoding along a spatial geometry. When coupled to a gradient-assisted decoding during the acquisition, this enables the collection of complete 2D spectra within a single transient. We have presented elsewhere two strategies for carrying out the spatial encoding underlying ultrafast NMR: a discrete excitation protocol capable of imparting a phase-modulated encoding of the interactions, and a continuous protocol yielding amplitude-modulated signals. The former is general but has associated with it a number of practical complications; the latter is easier to implement but unsuitable for certain 2D NMR acquisitions. The present communication discusses a new protocol that incorporates attractive attributes from both alternatives, imparting a continuous spatial encoding of the interactions yet yielding a phase modulation of the signal. This in turn enables a number of basic experiments that have shown particularly useful in the context of in vivo 2D NMR, including 2D J-resolved and 2D H,H-COSY spectroscopies. It also provides a route to achieving sensitivity-enhanced acquisitions for other homonuclear correlation experiments, such as ultrafast 2D TOCSY. The main features underlying this new spatial encoding protocol are derived, and its potential demonstrated with a series of phase-modulated homonuclear single-scan 2D NMR examples.     

单扫描快速采样方法及其在NMR中的应用

单扫描快速采样方法利用空间编码技术,只需单次扫描就能获得二维及多维核磁共振(NMR)谱数据,极大地缩短了二维和多维核磁共振谱的采样时间,有望在NMR领域得到广泛的应用. 该文以离散编码单扫描快速采样方法为例阐明了单扫描快速采样方法的原理,介绍了连续幅度调制、连续相位调制等各种单扫描快速采样新方法及其在NMR领域中的应用, 指出了单扫描快速采样方法的局限性,并对其未来发展进行了展望.     

Spatial encoding and the single-scan acquisition of high definition MR images in inhomogeneous fields

We have recently proposed a protocol for retrieving multidimensional magnetic resonance spectra and images within a single scan, based on a spatial encoding of the spin interactions. The spatial selectivity of this encoding process also opens up new possibilities for compensating magnetic field inhomogeneities; not by demanding extreme uniformities from the B(0) fields, but by compensating for their effects at an excitation and/or refocusing level. This potential is hereby discussed and demonstrated in connection with the single-scan acquisition of high-definition multidimensional images. It is shown that in combination with time-dependent gradient and radiofrequency manipulations, the new compensation approach can be used to counteract substantial field inhomogenities at either global or local levels over relatively long periods of time. The new compensation scheme could find uses in areas where heterogeneities in magnetic fields present serious obstacles, including rapid studies in regions near tissue/air interfaces. The principles of the B(0) compensation method are reviewed for one- and higher-dimensional cases, and experimentally demonstrated on a series of 1D and 2D single-scan MRI experiments on simple phantoms.     

Spatially resolved multidimensional NMR spectroscopy within a single scan

We have recently demonstrated that the spatial encoding of internal nuclear magnetic resonance (NMR) spin interactions can be exploited to collect multidimensional NMR spectra within a single scan. Such experiments rely on an inhomogeneous spatial excitation of the spins throughout the sample, and lead to indirect-domain peaks via a constructive interference among the spatially resolved spin-packets that are thus created. The shape of the resulting indirect-domain echo peaks approaches a Sinc function when the chemical's distribution is uniform, but will depart from this function otherwise. It is hereby shown that a Fourier analysis of either the diagonal- or the cross-peaks resolved in these single-scan two-dimensional (2D) NMR experiments can in fact provide a weighted spatial distribution of the analyte originating such peak, thus opening up the possibility of completing spatially resolved multidimensional NMR measurements within a fraction of a second. Principles of this new mode of analysis are discussed, and examples where the potential of spatially resolved ultrafast 2D NMR spectroscopy is brought to bear are presented. Potential extensions of this approach to higher dimensions are also briefly addressed.     

不均匀场下空间编码超快速高分辨NMR研究进展

二维核磁共振(2D NMR)的提出和发展,为NMR技术的研究和应用提供了广阔的空间. 然而当样品或磁场本身不均匀时,高分辨的2D NMR谱难以获得. 此外,常规2D NMR实验通常需要长的采样时间. 空间编码超快速采样方法利用空间编码技术,只需单次扫描即可获得2D甚至多维NMR谱,极大地缩短了采样时间. 目前相位补偿、相干转移和分子间多量子相干等技术与空间编码技术相结合,已成功实现不均匀场下超快速获得高分辨NMR谱. 该文对不均匀场下空间编码超快速NMR方法进行了介绍,对其未来发展进行了展望.     

Ultrafast 2D NMR spectroscopy using a continuous spatial encoding of the spin interactions

A new protocol for acquiring multidimensional NMR spectra within a single scan is introduced and illustrated. The approach relies on applying a pair of frequency-chirped excitation and storage pulses in combination with echoing magnetic field gradients, in order to impart the kind of linear spatial encoding of the NMR interactions that is required by ultrafast 2D NMR spectroscopy. It is found that when dealing with 2D NMR experiments involving a t1 amplitude-modulation of the spin evolution, such continuous encoding scheme presents a number of advantages over alternatives employing discrete excitation pulses. From an experimental standpoint this is mainly reflected by the use of a single pair of bipolar gradients during the course of the indirect-domain encoding, as opposed to the numerous (and more intense) gradient echoes required so far. In terms of the spectral outcome, main advantages of the continuous spatial encoding scheme are the avoidance of "ghost peaks" and of "enveloping effects" associated to the discrete excitation mode. The principles underlying this new spatial encoding protocol are derived, and its applicability is demonstrated with homo- and heteronuclear 2D ultrafast NMR applications on small molecule and on protein samples.     

Spatially encoded NMR and the acquisition of 2D magnetic resonance images within a single scan

An approach that enables the acquisition of multidimensional NMR spectra within a single scan has been recently proposed and demonstrated. The present paper explores the applicability of such ultrafast acquisition schemes toward the collection of two-dimensional magnetic resonance imaging (2D MRI) data. It is shown that ideas enabling the application of these spatially encoded schemes within a spectroscopic setting, can be extended in a straightforward manner to pure imaging. Furthermore, the reliance of the original scheme on a spatial encoding and subsequent decoding of the evolution frequencies endows imaging applications with a greater simplicity and flexibility than their spectroscopic counterparts. The new methodology also offers the possibility of implementing the single-scan acquisition of 2D MRI images using sinusoidal gradients, without having to resort to subsequent interpolation procedures or non-linear sampling of the data. Theoretical derivations on the operational principles and imaging characteristics of a number of sequences based on these ideas are derived, and experimentally validated with a series of 2D MRI results collected on a variety of model phantom samples.     

High-definition,single-scan 2D MRI in inhomogeneous fields using spatial encoding methods

An approach has been recently introduced for acquiring two-dimensional (2D) nuclear magnetic resonance images in a single scan, based on the spatial encoding of the spin interactions. This article explores the potential of integrating this spatial encoding together with conventional temporal encoding principles, to produce 2D single-shot images with moderate field of views. The resulting “hybrid” imaging scheme is shown to be superior to traditional schemes in non-homogeneous magnetic field environments. An enhancement of previously discussed pulse sequences is also proposed, whereby distortions affecting the image along the spatially encoded axis are eliminated. This new variant is also characterized by a refocusing of T₂^* effects, leading to a restoration of high-definition images for regions which would otherwise be highly dephased and thus not visible. These single-scan 2D images are characterized by improved signal-to-noise ratios and a genuine T₂ contrast, albeit not free from inhomogeneity distortions. Simple postprocessing algorithms relying on inhomogeneity phase maps of the imaged object can successfully remove most of these residual distortions. Initial results suggest that this acquisition scheme has the potential to overcome strong field inhomogeneities acting over extended acquisition durations, exceeding 100 ms for a single-shot image.     

Line shape considerations in ultrafast 2D NMR

We have recently proposed and demonstrated an approach that enables the acquisition of 2D nuclear magnetic resonance (NMR) spectra within a single scan. The approach is based on spatially encoding the spins' evolution along the indirect domain with the aid of a magnetic field gradient, and subsequently decoding this information numerous times over the course of the signal acquisition while spins are subject to a train of gradient echoes. The present paper discusses further considerations pertaining the 2D line shapes arising from this new way of collecting NMR data. Specific issues that are hereby addressed include (i) the effects introduced by fast relaxation onto the spatial encoding process, particularly the line widths and line shapes that will then arise in the frequency domain; (ii) approaches capable of correcting for the mixed-phase kernels resulting in these fast-relaxation cases, corresponding in essence to spatially encoded analogs of the TPPI and hypercomplex time-domain acquisition procedures; (iii) the enveloping characteristics imposed by the use of discrete excitation pulses on the attainable spectral widths along the indirect domain; and (iv) an analysis of the signal-to-noise characteristics of the methodology, with experimental corroborations of theoretical predictions and an illustration of the method's capabilities to analyze protein solutions in the mM-range concentration.     

J-modulation effects in DOSY experiments and their suppression: the Oneshot45 experiment

Diffusion-ordered spectroscopy (DOSY) is a powerful NMR method for identifying compounds in mixtures. DOSY experiments are very demanding of spectral quality; even small deviations from expected behaviour in NMR signals can cause significant distortions in the diffusion domain. This is a particular problem when signals overlap, so it is very important to be able to acquire clean data with as little overlap as possible. DOSY experiments all suffer to a greater or lesser extent from multiplet phase distortions caused by J-modulation, requiring a trade-off between such distortions and gradient pulse width. Multiplet distortions increase spectral overlap and may cause unexpected and misleading apparent diffusion coefficients in DOSY spectra. These effects are described here and a simple and effective remedy, the addition of a 45° purging pulse immediately before the onset of acquisition to remove the unwanted anti-phase terms, is demonstrated. As well as affording significantly cleaner results, the new method allows much longer diffusion-encoding pulses to be used without problems from J-modulation, and hence greatly increases the range of molecular sizes that can be studied for coupled spin systems. The sensitivity loss is negligible and the added phase cycling is modest. The new method is illustrated for a widely-used general purpose DOSY pulse sequence, Oneshot.     

Spectroscopic imaging from spatially-encoded single-scan multidimensional MRI data

We have recently proposed a protocol for retrieving multidimensional magnetic resonance images within a single scan, based on a spatial encoding of the spin interactions. This methodology relies on progressively dephasing spin coherences throughout a sample; for instance, by sweeping a radiofrequency pulse in the presence of a magnetic field gradient. When spins are suitably refocused by a second (acquisition) field gradient, this yields a time-domain signal reflecting in its magnitude the spatial distribution of spins throughout the sample. It is hereby shown that whereas the absolute value of the resulting signals conveys such imaging information, the hitherto unutilized phase modulation of the signal encodes the chemical shift offsets of the present speciae. Spectroscopically-resolved multidimensional images can thereby be retrieved in this fashion at no additional expense in either experimental complexity, sensitivity or acquisition time--simply by performing an additional analysis of the collected data. The resulting approach to single-scan spectroscopic imaging can also incorporate "RF shimming" compensating abilities, capable of providing high-resolution spectral and high-definition imaging data even under the presence of substantial magnetic field inhomogeneities. The principles of these methodologies as applied to spectroscopic imaging are briefly reviewed and compared against the background of traditional Fourier-based single-scan spectroscopic imaging protocols. Demonstrations of these new multidimensional spectroscopic MRI experiments on simple phantoms are also given.     

A new detection scheme for ultrafast 2D J-resolved spectroscopy

Recent ultrafast techniques enable 2D NMR spectra to be obtained in a single scan. A modification of the detection scheme involved in this technique is proposed, permitting the achievement of 2D 1H J-resolved spectra in 500 ms. The detection gradient echoes are substituted by spin echoes to obtain spectra where the coupling constants are encoded along the direct nu2 domain. The use of this new J-resolved detection block after continuous phase-encoding excitation schemes is discussed in terms of resolution and sensitivity. J-resolved spectra obtained on cinnamic acid and 3-ethyl bromopropionate are presented, revealing the expected 2D J-patterns with coupling constants as small as 2 Hz.     

Nearly 10-fold enhancements in intermolecular H double-quantum NMR experiments by nuclear hyperpolarization

Intermolecular Multiple-Quantum Coherences (iMQCs) can yield interesting NMR information of high potential usefulness in spectroscopy and imaging – provided their associated sensitivity limitations can be overcome. A recent study demonstrated that ex situ dynamic nuclear polarization (DNP) could assist in overcoming sensitivity problems for iMQC-based experiments on ¹³C nuclei. In the present work we show that a similar approach is possible when targeting the protons of a hyperpolarized solvent. It was found that although the DNP procedure enhances single-quantum ¹H signals by about 600, which is significantly less than in optimized low-γ liquid-state counterparts, the non-linear dependence of iMQC-derived signals on polarization can yield very large enhancements approaching 10⁶. Cleary no practical amount of data averaging can match this kind of sensitivity gains. The fact that DNP endows iMQC-based ¹H NMR spectra with a sensitivity that amply exceeds that of their thermally polarized single-quantum counterpart, is confirmed in a number of simple single-scan 2D imaging experiments.     

Compressed sensing and the reconstruction of ultrafast 2D NMR data: Principles and biomolecular applications

A topic of active investigation in 2D NMR relates to the minimum number of scans required for acquiring this kind of spectra, particularly when these are dictated by sampling rather than by sensitivity considerations. Reductions in this minimum number of scans have been achieved by departing from the regular sampling used to monitor the indirect domain, and relying instead on non-uniform sampling and iterative reconstruction algorithms. Alternatively, so-called "ultrafast" methods can compress the minimum number of scans involved in 2D NMR all the way to a minimum number of one, by spatially encoding the indirect domain information and subsequently recovering it via oscillating field gradients. Given ultrafast NMR's simultaneous recording of the indirect- and direct-domain data, this experiment couples the spectral constraints of these orthogonal domains - often calling for the use of strong acquisition gradients and large filter widths to fulfill the desired bandwidth and resolution demands along all spectral dimensions. This study discusses a way to alleviate these demands, and thereby enhance the method's performance and applicability, by combining spatial encoding with iterative reconstruction approaches. Examples of these new principles are given based on the compressed-sensed reconstruction of biomolecular 2D HSQC ultrafast NMR data, an approach that we show enables a decrease of the gradient strengths demanded in this type of experiments by up to 80%.     

Arrayed acquisition of 2D exchange NMR spectra within a single scan experiment

We have recently demonstrated that magnetic field gradients in combination with frequency selective pulses, can be employed to collect a complete multi-dimensional NMR spectrum within a single scan. Following similar guidelines, field gradients could also be exploited to parallelize other types of NMR experiments where the final results arise from the collection and analysis of a series of time-incremented spectra. The present Communication exemplifies this concept by showing how a combination of gradients can be employed to monitor within a single continuous acquisition, a slow dynamic process which is in turn followed by systematic increments in the duration of a magnetization transfer time. Further, since 2D exchange NMR spectra can nowadays be themselves collected within one scan, the acquisition of a complete set of mixing-incremented 2D exchange patterns could be achieved within a single experiment entailing a total time of approximately 1 s.     

High-resolution NMR with resistive and hybrid magnets: deconvolution using a field-fluctuation signal

A method for compensating effect of field fluctuation is examined to attain high-resolution NMR spectra with resistive and hybrid magnets. In this method, time dependence of electromotive force induced for a pickup coil attached near a sample is measured synchronously with acquisition of NMR. Observed voltage across the pickup coil is converted to field fluctuation data, which is used to deconvolute NMR signals. The feasibility of the method is studied by (79)Br MAS NMR of KBr under a 30T magnetic field of a hybrid magnet. Twenty single-scan NMR signals were accumulated after the manipulation, resulting in a high-resolution NMR spectrum.     

Characterization of Mango Juice by High‐Resolution NMR,Hyphenated NMR,and Diffusion‐Ordered Spectroscopy

Abstract

The application of nuclear magnetic resonance (NMR) spectroscopy, hyphenated NMR, and diffusion‐ordered spectroscopy (DOSY) to the characterization of mango juice, as an example of a complex food mixture, is described. The compositional changes taking place as a function of ripening were followed, and selected metabolites were quantified by integration of the corresponding NMR peaks. In this way, an overall view of the metabolite changes is obtained, enabling the study of the biochemical mechanisms involved in the ripening process. More than 50 compounds were identified by 1D‐ and 2D‐NMR, but many ambiguous assignments remain due to spectral overlap or insufficient coupling information. The use of Liquid Chromatography (LC‐NMR) and LC‐NMR/Mass Spectrometry (MS) enables a fuller characterization of the soluble pectin fraction to be made; its dependence on ripening stage is discussed. Finally, DOSY adds information on the M_r of many metabolites, including the pectin fractions of ripe and unripe mango juices, and enables further peak assignments to be made.     

Improving pulse sequences for 3D DOSY: convection compensation

Signal overlap in the NMR dimension significantly complicates the construction and analysis of 2D diffusion-ordered (DOSY) spectra. Such problems can often be reduced or even eliminated by extending the NMR domain of a DOSY experiment into two dimensions, giving a 3D-DOSY spectrum. To date such experiments have generally sacrificed some signal-to-noise ratio and have required extensive and time-consuming phase cycling. A new family of pulse sequences with internal diffusion encoding (IDOSY) has been introduced which avoids both of these problems. It is often straightforward to incorporate convection compensation in such sequences at no cost in signal-to-noise ratio. Here, some of the problems caused by convection in DOSY are described and illustrated, and the efficacy of convection compensation in the 2DJ-IDOSY and COSY-IDOSY experiments is demonstrated.     

Improving resolution in single-scan 2D spectroscopy

New schemes are introduced that allow one to improve the resolution in the indirect dimension of single-scan ‘ultrafast’ two-dimensional NMR spectra. The methods combine undersampling with band-selective pulses to recover signals that lie outside the detection bandwidth. The efficiency is illustrated for homonuclear total correlation spectroscopy (TOCSY) of quinidine.     

Heteronuclear local field NMR spectroscopy under fast magic-angle sample spinning conditions

The acquisition of bidimensional heteronuclear nuclear magnetic resonance local field spectra under moderately fast magic-angle spinning (MAS) conditions is discussed. It is shown both experimentally and with the aid of numerical simulations on multispin systems that when sufficiently fast MAS rates are employed, quantitative dipolar sideband patterns from directly bonded spin pairs can be acquired in the absence of ¹H–¹H multiple-pulse homonuclear decoupling even for “real” organic solids. The MAS speeds involved are well within the range of commercially available systems (10–14 kHz) and provide sidebands with sufficient intensity to enable a reliable quantification of heteronuclear dipolar couplings from methine groups. Simulations and experiments show that useful information can be extracted in this manner even from more tightly coupled –CH₂– moieties, although the agreement with the patterns simulated solely on the basis of heteronuclear interactions is not in this case as satisfactory as for methines. Preliminary applications of this simple approach to the analysis of molecular motions in solids are presented; characteristics and potential extensions of the method are also discussed.