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.     

超快速COSY类2D NMR实验弛豫假峰的抑制

在脉冲梯度场基础上研究了进一步缩短COSY类2D NMR实验数据采集时间的新方法.利用主动屏蔽梯度场线圈的梯度场恢复时间仅为100μs数量级这一特点,提出一类基于脉冲梯度场消除弛豫假峰的脉冲序列.并以DQF-COSY脉冲序列为例加以验证.实验结果表明:采用文中的方法,取序列重复时间远小于T₁和T₂是切实可行的;梯度场技术能很好地抑制弛豫假蜂以达到2D NMK数据的快速采集.     

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.     

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%.     

Single-scan 2D DOSY NMR spectroscopy

Spatial encoding is a particular kind of spin manipulation that enables the acquisition of multidimensional NMR spectra within a single scan. This encoding has been shown to possess a general applicability and to enable the completion of arbitrary nD NMR acquisitions within a single transient. The present study explores its potential towards the acquisition of 2D DOSY spectra, where the indirect dimension is meant to encode molecular displacements rather than a coherent spin evolution. We find that in its simplest form this extension shows similarities with methods that have been recently discussed for the single-scan acquisition of this kind of traces; still, a number of advantageous features are also evidenced by the “ultrafast” modality hereby introduced. The principles underlying the operation of this new single-scan 2D DOSY approach are discussed, its use is illustrated with a variety of sequences and of samples, the limitations of this new experiment are noted, and potential extensions of the methodology are mentioned.     

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.     

High-resolution MR spectroscopy via intermolecular double-quantum coherences in inhomogeneous B0 and B1 fields

Inhomogeneity in static field B₀ and/or RF field B₁ is inevitable under some circumstances. In this work, a method based on intermolecular double-quantum coherences is employed for high-resolution 1D MR spectroscopy via 2D acquisition under such a condition. High-resolution information on chemical shifts, multiplet patterns, J coupling constants and relative peak areas can be retained in the resulting 1D projected spectra, as shown with results from a narrow-bore NMR spectrometer and a whole-body clinical scanner.     

High-resolution heteronuclear correlation spectroscopy based on spatial encoding and coherence transfer in inhomogeneous fields

Two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy has been proven to be a powerful technique for chemical, biological, and medical studies. Heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) are two frequently used 2D NMR methods. In combination with spatially encoded techniques, a heteronuclear 2D NMR spectrum can be acquired in several seconds and may be applied to monitoring chemical reactions. However, it is difficult to obtain high-resolution NMR spectra in inhomogeneous fields. Inspired by the idea of tracing the difference of precession frequencies between two different spins to yield high-resolution spectra, we propose a method with correlation acquisition option and J-resolved-like acquisition option to ultrafast obtain high-resolution HSQC/HMBC spectra and heteronuclear J-resolved-like spectra in inhomogeneous fields.     

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.     

Fast multivoxel two-dimensional spectroscopic imaging at 3 T

The utility of multivoxel two-dimensional chemical shift imaging in the clinical environment will ultimately be determined by the imaging time and the metabolite peaks that can be detected. Different k-space sampling schemes can be characterized by their minimum required imaging time. The use of spiral-based readout gradients effectively reduces the minimum scan time required due to simultaneous data acquisition in three k-space dimensions (k(x), k(y) and k(f(2))). A 3-T spiral-based multivoxel two-dimensional spectroscopic imaging sequence using the PRESS excitation scheme was implemented. Good performance was demonstrated by acquiring preliminary in vivo data for applications, including brain glutamate imaging, metabolite T(2) quantification and high-spatial-resolution prostate spectroscopic imaging. All protocols were designed to acquire data within a 17-min scan time at a field strength of 3 T.     

基于近似l0范数最小化的NMR波谱稀疏重建算法

在核磁共振（NMR）波谱中,过长的数据采集时间会使很多化学以及分子生物学领域的高分辨率多维谱应用难以实现. 传统的解决办法是使用随机非均匀采样代替奈奎斯特采样,但这样会使谱图质量受损. 压缩传感的出现为此提供了更好的解决办法,合适的压缩传感重建算法可以通过很少的随机非均匀采样将谱图高质量的重建出来. 该文先介绍了一种可用于谱图重建的压缩传感重建算法,名为“平滑l₀范数最小化法”,然后针对该算法对采样噪声鲁棒性较差的缺点进行了改进. 通过将改进后的算法与原算法在一维实数域信号以及NMR波谱信号重建实验中进行对比后表明,改进后的算法对噪声的鲁棒性明显提高,并能获得更好的重建性能.     

EASY: A simple tool for simultaneously removing background,deadtime and acoustic ringing in quantitative NMR spectroscopy—Part I: Basic principle and applications

Elimination of Artifacts in NMR SpectroscopY (EASY) is a simple but very effective tool to remove simultaneously any real NMR probe background signal, any spectral distortions due to deadtime ringdown effects and -specifically- severe acoustic ringing artifacts in NMR spectra of low-gamma nuclei. EASY enables and maintains quantitative NMR (qNMR) as only a single pulse (preferably 90°) is used for data acquisition. After the acquisition of the first scan (it contains the wanted NMR signal and the background/deadtime/ringing artifacts) the same experiment is repeated immediately afterwards before the T1 waiting delay. This second scan contains only the background/deadtime/ringing parts. Hence, the simple difference of both yields clean NMR line shapes free of artefacts.In this Part I various examples for complete ¹H, ¹¹B, ¹³C, ¹⁹F probe background removal due to construction parts of the NMR probes are presented. Furthermore, ²⁵Mg EASY of Mg(OH)₂ is presented and this example shows how extremely strong acoustic ringing can be suppressed (more than a factor of 200) such that phase and baseline correction for spectra acquired with a single pulse is no longer a problem. EASY is also a step towards deadtime-free data acquisition as these effects are also canceled completely. EASY can be combined with any other NMR experiment, including 2D NMR, if baseline distortions are a big problem.     

Fast high-resolution nuclear magnetic resonance spectroscopy through indirect zero-quantum coherence detection in inhomogeneous fields

In many cases, high-resolution nuclear magnetic resonance （NMR） spectra are virtually impossible to obtain by con- ventional nuclear magnetic resonance methods because of inhomogeneity of magnetic field and inherent heterogeneity of sample. Although conventional intramolecular zero-quantum coherence （ZQC） can be used to obtain high-resolution spectrum in inhomogeneous field, the acquisition takes rather long time. In this paper, a spatially encoded intramolecular ZQC technique is proposed to fast acquire high-resolution NMR spectrum in inhomogeneous field. For the first time, the gradient-driven decoding technique is employed to selectively acquire intramolecular ZQC signals. Theoretical analyses and experimental observations demonstrate that high-resolution NMR spectral information can be retrieved within several scans even when the field inhomogeneity is severe enough to erase most spectral information. This work provides a new way to enhance the acquisition efficiency of high-resolution intramolecular ZQC spectroscopy in inhomogeneous fields.     

Sequentially acquired two-dimensional NMR spectra from hyperpolarized sample

A scheme capable of acquiring heteronuclear 2D NMR spectra of hyperpolarized sample is described. Hyperpolarization, the preparation of nuclear spins in a polarized state far from thermal equilibrium, can increase the NMR signal by several orders of magnitude. It presents opportunities to apply NMR spectroscopy to dilute samples that would otherwise yield insufficient signal. However, conventional 2D NMR spectroscopy, which is commonly applied for the determination of molecular structure, relies on the recovery of the initial polarization after each transient. For this reason, it cannot be applied directly to a sample that has been hyperpolarized once. With appropriately modified pulse schemes, two-dimensional NMR spectra an however be acquired sequentially by utilizing a small portion of the hyperpolarized signal in every scan, while keeping the remaining polarization for future scans. We present heteronuclear multi-quantum spectra of single hyperpolarized samples using this technique, and discuss different options for distributing the polarization among different scans. This robust method takes full advantage of Fourier NMR to resolve overlapping chemical shifts, and may prove particularly useful for the structural elucidation of compounds in mass-limited samples.     

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.     

基于核磁共振的统计全相关谱在大鼠肾脏组织中的应用

生物组织是基于NMR的代谢组学研究的主要对象之一，广泛应用于分子病理学、毒理学、生物医学等众多领域. 但是，为了保证测定的准确，组织的NMR实验往往需要在较低的温度下和较短时间内完成，以防止由于组织内酶的降解和扩散而导致的某些代谢物质的分析信息被破坏. 统计全相关谱(Statistical Total Correlation Spectroscopy, STOCSY)是依靠一维谱来实现二维谱的一些功能的方法，不需要额外的实验时间，已经被广泛应用于代谢组学研究中. 本文采用STOCSY方法，通过对一系列¹H高分辨魔角旋转谱的统计分析和计算，得到了肾脏组织的准二维相关谱，其中共振峰之间的相关较为准确的反应了物质之间的耦合信息，为物质的归属提供了帮助.     

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.     

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.