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.     

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%.     

Ultrafast hetero-nuclear 2D J-resolved spectroscopy

Ultrafast techniques enable the acquisition of 2D NMR spectra in a single scan. In this study, we propose a new ultrafast experiment designed to record hetero-nuclear (1)H-(13)C J-resolved spectra in a fraction of a second. The approach is based on continuous constant-time phase modulated spatial encoding followed by a J-resolved detection scheme. An optional isotopic filter is implemented to remove the signal arising from (1)H bound to (12)C. While the most evident application of the technique proposed in this paper is the direct measurement of one bond scalar (13)C-(1)H couplings for structural elucidation purposes, it also offers interesting potentialities for measuring (13)C isotopic enrichments in metabolic samples. The main features of this methodology are presented, and the analytical performances of the ultrafast hetero-nuclear J-resolved pulse sequence are evaluated on model 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.     

多维核磁共振数据在通用计算机上的处理与三维谱的观测

本文分析、讨论了利用外部通用计算机处理核磁共振数据的方法及程序,包括数据格式转换,一维、二维、三维谱的数据处理,谱图的显示及输出,并以VAX机为例实现了三维谱的观测。文中还详细讨论了编程的原理和一些技术细节。     

TopSpin核磁共振软件中集成的DOSY采集／处理模块DOSYmTM

Bruker TopSpinTM核磁共振软件中集成的DOSY数据采集和处理模块DOSYm^TM,可以方便简单地进行DOSY实验的在线数据采集与处理,并已很好地应用于复杂混合物的定性和定量分析,如天然混合物、石油产品、医药产品、食品工业及质量控制等领域．本文介绍了DOSY实验的原理,数据采集和处理的方法及DOSYm^TM模块的应用．     

Modeling of NMR processing, toward efficient unattended processing of NMR experiments

Many alternative processing techniques have recently been proposed in the literature. Most of these techniques rely on specific acquisition protocols as well as on specific data processing techniques, the need for an efficient versatile and expandable NMR processing tool would be a particularly timely addition to the modern NMR spectroscopy laboratory. The work presented here consists in a modeling of the various possible NMR data processing approaches. This modeling presents a common working frame for most of the modern acquisition/processing protocols. Two different data modeling approaches are presented, strong modeling and weak modeling, depending whether the system under study or the measurement is modeled. The emphasis is placed on the weak modeling approach. This modeling is implemented in a computer program developed in python and called NPK standing (standing for NMR Processing Kernel), organized in four logical layers (i) mathematical kernel; (ii) elementary actions; (iii) processing phases; (iv) processing strategies. This organisation, along with default values for most processing parameters allows the use of the program in an unattended manner, producing close to optimal spectra. Examples are shown for 1D and 2D processing, and liquid and solid NMR spectroscopy. NPK is available from the site: http://abcis.cbs.cnrs.fr/NPK.     

Progress on the two-dimensional filter diagonalization method. An efficient doubling scheme for two-dimensional constant-time NMR

An efficient way to treat two-dimensional (2D) constant-time (CT) NMR data using the filter diagonalization method (FDM) is presented. In this scheme a pair of N- and P-type data sets from a 2D CT NMR experiment are processed jointly by FDM as a single data set, twice as large, in which the signal effectively evolves in time for twice as long. This scheme is related to "mirror-image" linear prediction, but with the distinction that the data are directly used, without any preprocessing such as Fourier transformation along one dimension, or point-by-point reflection. As the signal has nearly perfect Lorentzian line shape in the CT dimension, it can be efficiently handled by the FDM approach. Applied to model and experimental signals, the scheme shows significant resolution improvement, and appears to tolerate noise reasonably well. Other complex aspects of multidimensional FDM are discussed and illustrated.     

2D separated-local-field spectra from projections of 1D experiments

A novel procedure for reconstruction of 2D separated-local-field (SLF) NMR spectra from projections of 1D NMR data is presented. The technique, dubbed SLF projection reconstruction from one-dimensional spectra (SLF-PRODI), is particularly useful for uniaxially oriented membrane protein samples and represents a fast and robust alternative to the popular PISEMA experiment which correlates (1)H-(15)N dipole-dipole couplings with (15)N chemical shifts. The different 1D projections in the SLF-PRODI experiment are obtained from 1D spectra recorded under influence of homonuclear decoupling sequences with different scaling factors for the heteronuclear dipolar couplings. We demonstrate experimentally and numerically that as few as 2-4 1D projections will normally be sufficient to reconstruct a 2D SLF-PRODI spectrum with a quality resembling typical PISEMA spectra, leading to significant reduction of the acquisition time.     

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.     

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.     

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.     

Double-quantum biased covariance spectroscopy: application to the 2D INADEQUATE experiment

A novel processing scheme is presented that converts a two-dimensional double-quantum NMR spectrum into a single-quantum correlation spectrum. The covariance-like spectrum is computed from the 2D Fourier transform spectrum by emphasizing contributions that fulfill the double-quantum condition resulting in a symmetric spectrum that is easier to analyze. The method is demonstrated for the 2D INADEQUATE experiment.     

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.     

White noise nonlinear system analysis in nuclear magnetic resonance spectroscopy

Nonlinear noise excitation in nuclear magnetic resonance is a form of nonlinear spectroscopy which exploits the nonlinear susceptibilities in a very direct way. The nonlinear susceptibilities are defined by perturbation theory in the frequency domain. In nonlinear system analysis, on the other hand, the system response is described by a Volterra series in the time domain. The kernels of the Volterra functionals carry the information about the system and are to be determined by experiment.The series expansion of a molecular, atomic or nuclear system response is derived in quantum mechanics by time dependent perturbation theory, leading to a Volterra series with time ordered, triangular kernels. The kernels are multi-dimensional products of decaying exponentials, which describe coherence decays of particular density matrix elements. The Fourier transforms of the triangular Volterra kernels are the susceptibilies, which are formally identical in NMR spectroscopy and nonlinear optical spectroscopy. The nonlinear susceptibilities are multi-dimensional spectra, which in NMR spectroscopy reveal the spin communication pathways. These are established by various forms of single quantum coherence connectivities, such as indirect coupling, chemical exchange, cross-relaxation, dipolar and quadrupolar coupling.If the functionals of the Volterra series are orthogonalized with respect to Gaussian white noise excitation, the Wiener series results. The Wiener kernels can be derived by multi-dimensional cross-correlation of the system response with different powers of the Gaussian white noise excitation.Cross-correlation of the transverse magnetization response to noise excitation in NMR leads to multi-dimensional time functions, the Fourier transforms of which closely resemble the nonlinear susceptibilities. The cross-correlation spectra differ from the susceptibilities in the governing Liouvillean and the dynamic density matrix, which are affected by saturation for continuous excitation. Cross-correlation spectra and susceptibilities converge for vanishing excitation power. Therefore the cross-correlation spectra are referred to as stochastic susceptibilities.In stochastic NMR spectroscopy only odd order susceptibilities exist for transverse magnetization. The first nonlinear order is the third, and the nonlinear spectral information is derived from the third order susceptibility. Higher order susceptibilities are not feasible to derive from experimental data. An important share of the nonlinear information is found on the six subdiagonal 2D cross-sections through the third order susceptibility. These cross-sections arise in three pairs, which carry distinct information, separated according to longitudinal magnetization and population effects, zero quantum coherences, and double quantum coherences.In practice a nonlinear 3D spectrum is computed from experimental data by an algorithm in the frequency domain, which yields access to selected regions in the 3D spectrum. This spectrum is the symmetrized stochastic third order susceptibility. All its sub-diagonal 2D cross-sections are equivalent. They are the average of the six different sub-diagonal 2D cross-sections through the asymmetric third order susceptibility.The stochastic excitation technique in NMR is characterized by several unique attributes. (1) There is no minimum time for a data acquisition cycle, so that, at the expense of signal-to-noise ratio, strong samples can be investigated faster with stochastic NMR than with pulsed FT NMR. (2) Stochastic excitation tests the sample extensively, and measures a maximum amount of information in a single experiment. This feature is of particular interest for investigation of short-lived samples and of samples with little a priori information. (3) An experiment with stochastic excitation is simple to perform, but the data processing is more complex than in FT spectroscopy. (4) The nonlinear information about spin communication pathways is derived for individual frequency regions only, which are identified in the stochastic ID spectrum. This information is located primarily on the sub-diagonal 2D cross-sections through the third order susceptibility. (5) Stochastic NMR spectra derived from random noise excitation are contaminated by systematic noise. In the sub-diagonal 2D cross-sections the noise is reduced by filtering and symmetrization during data processing. (6) Sub-diagonal 2D cross-sections are sensitive to experimental phase distortions in one direction only. They are readily adjusted in phase with the same parameters as the ID spectrum. (7) Stochastic multi-dimensional spectra can be computed at variable resolution from one and the same set of raw data.So far stochastic NMR spectroscopy is not applied routinely in analytical spectroscopy. More practical experience is needed to evaluate its merits in comparison with Fourier transform NMR.Stochastic excitation is distinguished from continuous wave and sparsely pulsed excitation by low input power in connection with large bandwidth. This important property cannot be exploited in high resolution NMR in liquids, because excitation power is not a restricting factor in this case. The situation is different in NMR imaging, where large field gradients require large bandwidths and the excitation power becomes a point of concern. For this reason stochastic RF excitation is being investigated in NMR imaging.The multi-dimensional cross-correlation functions obtained from random noise excitation generally are contaminated by systematic noise. The occurrence of systematic noise can be avoided if pseudo-random excitation is used in combination with a transformation of the system response to obtain the kernels. This technique is used successfully in Hadamard spectroscopy, where the linear Volterra kernel is the Hadamard transform of the linear response functional. Nonlinear transformations^(220,221) for retrieval of nonlinear kernels have not yet been realized in NMR spectroscopy.The cross-correlation technique underlying the data evaluation in stochastic nonlinear system analysis is equivalent to interferometry in optical spectroscopy. The Michelson interferometer is the most prominent optical correlator. The time resolution of the kernels derived by cross-correlation is determined by the inverse bandwidth of the excitation. With the Michelson interferometer a time resolution of 10⁻¹⁴ s is achieved in IR spectroscopy. Since the IR correlogramm is Fourier transformed for spectral analysis, the time resolution cannot be exploited otherwise. For analysis of fast time dependent processes a two-dimensional interferometer should be constructed, which performs a 2D cross-correlation of the system response to two in general different noise inputs. One input pumps the time dependent process, the other is used to investigate the time dependence spectroscopically. This technique is introduced by the name of ‘two-dimensional interferometry’. It uses low excitation power, but provides high time resolution at large response energy. Related work is pursued in nonlinear optical spectroscopy with incoherent excitation. In this area the use of broad band lasers is investigated for generation of echoes and for correlation based measurements of relaxation times.     

基于超快超声多普勒的三维脑损伤成像方法研究

三维超声微血管成像可直观呈现血流信息,对于脑血管疾病诊断和治疗具有重要意义。本文旨在将超快超声成像技术、超快超声功率多普勒技术和机械扫描相结合,实现脑血管三维成像和脑缺血区域评价。通过工程实现,完成了可同步控制微型线性位移平台移动和超声阵列超快发射、高速采集与压缩存储的三维扫描数据采集序列与系统。利用GPU并行运算,高效实现了超声图像波束合成方法,对原始射频超声数据完成重建。进而,基于SVD杂波滤除技术,从重建三维超声数据中提取了脑部的动态小血管信号,并获得了各切面的功率多普勒成像和冠状面彩色多普勒超声小血管成像。最后,采用体素方法对三维脑血管进行重建。大鼠在体实验结果表明,该成像系统可用于三维脑血管网络在体成像,以及脑血管损伤区域定位与量化评价。本工作对脑病检测技术发展与诊断方法研究具有一定的借鉴意义。此外,相关检测系统和成像算法具有一定普适性,对其他富含微血流血管的组织检测也有一定的参考价值。     

Multidimensional dipolar exchange-assisted recoupling measurements in solid-state NMR

Aseries of uni- and multidimensional variants of the dipolar exchange-assisted recoupling (DEAR) NMR experiment is described and applied to determinations of (13)C-(14)N dipolar local field spectra in amino acids and dipeptides. The DEAR protocol recouples nearby nuclei by relying on differences in their relative rates of longitudinal relaxation, and has the potential to give quantitative geometric results without requiring radiofrequency pulsing on both members of a coupled spin pair. One- and two-dimensional variants of this recoupling strategy on generic I-S pairs are discussed, and measurements of (13)C-(14)N distances and 2D local field experiments sensitive to the relative orientation of CN vectors with respect to the (13)C shielding tensor are presented. Since these measurements did not involve pulsing on the broad nitrogen resonance, their results were independent of the quadrupolar parameters of this nucleus. High-resolution 3D NMR versions of the 2D experiments were also implemented in order to separate their resulting local field patterns according to the isotropic shifts of inequivalent (13)C sites. These high-resolution 3D acquisitions involved collecting a series of 2D DEAR NMR data sets on rotating samples as a function of spinning angle, and then subjecting the resulting data to a processing akin to that involved in variable-angle correlation NMR. Once successfully tested on l-alanine this experiment was applied to the analysis of a series of dipeptides, allowing us to extract separate local field (13)C-(14)N spectra from this type of multisite systems.     

一种基于组分补偿的二维核磁共振测井数据高精度处理方法

二维核磁共振技术能够对储层中各类含氢流体进行无损、快速、定量的测量和表征，但受限于采集方式和参数，核磁共振设备在对页岩油等致密储层中的有机质、沥青等超快弛豫组分进行检测时，经常出现由于信号采集不完整所导致的二维谱中流体组分缺失或不准的问题.本文提出了基于超快弛豫组分补偿技术的T₂-T₁二维谱高精度反演方法，该方法将一维核磁共振前端信号补偿技术进行推广，通过在二维核磁数据反演前对回波数据进行组分补偿，能够有效解决二维核磁共振测井前端信号漏失的问题.实验及测井数据的应用表明，该方法在页岩油等富含快弛豫组分信号的储层中，可以得到更加精准和完整的储层信息.     

基于C#的二维核磁共振测井观测模式设计软件的开发

二维核磁共振测井观测模式是以获取特定地层信息为目标的数据采集方式，它直接决定着核磁共振谱仪对不同类型储层的适应性以及获取原始数据的可信度．本文从观测模式的组成元素以及工作机理出发，采用C#语言开发了一套具有可视化功能的二维核磁共振测井观测模式设计软件．该软件支持二维核磁共振测井以及核磁共振岩心分析仪的观测模式设计，同时提供了三种采集参数编辑方式、观测模式优化机制以及图形化显示等功能，实现了观测模式的灵活调整，解决了当前主流二维核磁共振测井观测模式中存在的采集参数固定、不宜灵活调整从而导致所采集的原始数据信噪比低下、储层中流体弛豫特性加载不完全等问题．此外，软件还提供了观测模式的采集参数信息以及采集时序信息的输出功能等．     

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.