CN103885013A - Method for obtaining nuclear magnetic resonance two-dimensional J-resolved spectroscopy in non-uniform magnetic field - Google Patents
Method for obtaining nuclear magnetic resonance two-dimensional J-resolved spectroscopy in non-uniform magnetic field Download PDFInfo
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Abstract
The invention discloses a method for obtaining nuclear magnetic resonance two-dimensional J-resolved spectroscopy in a non-uniform magnetic field, and relates to a nuclear magnetic resonance spectrometer. The method comprises the steps that a piece of one-dimensional spectroscopy is sampled through a general one-dimensional pulse sequence, the line width of a spectral line is obtained, the basis is provided for spectral width parameter setting, and the line width reflects the magnetic field environment uniformity condition; (2) an intermolecular single-quantum coherent two-dimensional J-resolved spectroscopy pulse sequence which is compiled in advance is led to the nuclear magnetic resonance spectrometer; (3) an intermolecular single-quantum coherent signal selection module, an indirect dimension evolution period t1 module, an indirect dimension evolution period t2 module and a signal sampling period t3 module of the intermolecular single-quantum coherent two-dimensional J-resolved spectroscopy pulse sequence are opened, and experiment parameters of the modules of the intermolecular single-quantum coherent two-dimensional J-resolved spectroscopy pulse sequence are set; (4) the intermolecular single-quantum coherent two-dimensional J-resolved spectroscopy pulse sequence with the experiment parameters set in the step (3) is executed, and data sampling is carried out; (5) after data sampling is accomplished, related data post-processing is carried out to obtain the high-resolution two-dimensional J-resolved spectroscopy free from influence of the non-uniform magnetic field.
Description
Technical field
The present invention relates to nuclear magnetic resonance (NMR, Nuclear Magnetic Resonance) spectrometer, especially relate to and under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling.
Background technology
It is that nuclear magnetic resonance field proposes one of two-dimentional spectrum method the earliest that two dimension J divides spectrum unscrambling (Two-dimensional J-resolved spectroscopy, 2D JRES).Its pulse train can be expressed as (pi/2)-t
1/ 2-(π /)-t
1/ 2+t
2, by a pi/2 pulse, a π pulse, a quilt is divided the indirect dimension evolution phase t of two halves equally
1an and sampling period t
2form.This conventional J divides Spectra Unfolding Methods to be proposed the earliest (Aue W.P. in 1976 by Ernst, Karhan J., and Ernst R.R.Two-dimensional spectroscopy application to nuclear magnetic resonance[J] .J.Chem.Phys., 1976,64,2229-2246).Divide in spectrum unscrambling at two-dimentional J, chemical shiftsum J coupling information lays respectively at two disalignments of spectrogram, i.e. F1 and F2 dimension.Therefore, utilize this technology can realize the separation of NMR signal chemical shiftsum J coupling information completely, solve the problem of traffic congestion in one-dimensional nuclear magnetic resonance spectrum, there is important application for biological tissue's metabolin and complicated chemical composition ownership and detection.Because the sampling time of J decomposition technique is depended on indirect dimension J coupling size, therefore its sampling efficiency is greatly better than other conventional two-dimensional spectrums and learns a skill, generally as long as divide spectrum unscrambling with the interior two-dimentional J of acquisition that just can sample in two minutes.Nowadays two-dimentional J divide Spectrum stripping techniques in analysis become a kind of important testing tool in metabolism group research (Ludwig C.and Viant M.R.Two-dimensional J-resolved NMR spectroscopy:review of a key methodology in the metabolomics toolbox[J] .Phytochem.Anal., 2010,21,22-32.).For example, the people such as Foxall (Foxall P.J.D., Parkinson J.A., Sadler I.H., Lindon J.C., and Nicholson J.K..Analysis of biological-fluids using600MHz proton NMR spectroscopy:application of homonuclear2-dimensional J-resolved spectroscopy to urine and blood-plasma for spectral simplification and assignment[J] .J.Pharmaceut.Biomed.Anal., 1993, 11, 21-31.) divide spectrum unscrambling to be applied to the research of human urine and plasma metabolism composition two-dimentional J, for analyzing the feature metabolin of specified disease.The people such as Lutz (Lutz N.W., Maillet S., Nicoli F., Viout P., and Cozzone P.J.Further assignment of resonances in
1h NMR spectra of cerebrospinal fluid (CSF) [J] .Febs Lett., 1998,425,345-351.) the metabolin composition and the corresponding change procedure that utilize two-dimentional J to divide Spectrum stripping techniques in analysis to analyze human body cerebrospinal fluid.From these application, we find that these now conventional two-dimentional J divide the main application of Spectra Unfolding Methods to concentrate on chemical solution or biological fluid.For semi-solid biological tissue, as brain tissue, cartilaginous tissue, even musculature, conventional two-dimentional J divides the Spectra Unfolding Methods often cannot be for detection of analysis.Wherein chief reason is that conventional magnetic resonance detection has high requirement for magnetic field homogeneity, even if relatively uniform fluid sample often still needed to do very careful shimming process to guarantee the acquisition of high-resolution spectroscopy information before experiment.And for biological tissue, the factors such as its sample interior magnetic susceptibility can be introduced magnetic field bump, thereby cause conventional two-dimentional J to divide the signal peak of spectrum unscrambling, along chemical shift dimension (F1 dimension), inhomogeneous broadening occurs, cannot belong to metabolite signals.Although the impact that conventional two-dimentional J divides the J coupling dimension (F2 dimension) of spectrum unscrambling can not be subject to Magnetic field inhomogeneity effect, because signal causes the overlapping of each signal peak in the broadening meeting of chemical shift dimension, finally also cannot measure metabolin J coupling constant accurately.Visible, the Magnetic field inhomogeneity that sample interior magnetic susceptibility and actual measurement environment cause often causes conventional two-dimentional J to divide Spectra Unfolding Methods cannot obtain correct detection information, has seriously hindered the application of J decomposition technique, the particularly application aspect biological tissue.
A series of methods of improving and operate to improve magnetic field homogeneity by shimming hardware aspect are there are at present, and this need to expend considerable effort, comprise careful shimming, rotary sample, strictly remove paramagnetism or the graininess impurity in sample, and the container that mates with magnetic sample rate of employing etc.Also develop at present the method for utilizing radio-frequency field compensation B0 field unevenness, and obtained High Resolution Spectrum for non-uniform magnetic field.For example, for the outer nuclear magnetic resonance of magnet, Bl ü mich research group has designed monolateral movably magnetic resonance detection means (Perlo J. under a kind of downfield, Casanova F., and Blumich B.Exsitu NMR in highly homogeneous fields:H-1spectroscopy[J] .Science., 2007,315 (5815), 1110-1112); Pines research group utilizes " ex situ pulse " and " shimming pulse " technology to eliminate impact (the Meriles C.A. of nonuniform field, Sakellariou D., Heise H., Moule A.J., and Pines A.Approach to high-resolution ex situ NMR spectroscopy[J] .Science., 2001,293 (5527), 82-85); In addition, also having researcher to propose some from software aspect compensates by data post processing method or magnetic field for correcting inhomogeneous broadening effect.For example, the people such as Sersa (Sersa I., Macura S.Improvement of spectral resolution by spectroscopic imaging[J] .Appl Magn.Reson., 2004,27,259-266.) propose the post-processing approach that a kind of imaging deconvolutes and carried out compensating field inhomogeneous broadening effect.The existing method (comprising from hardware and software) that these improve magnetic field homogeneity has many restrictions in application, as needs obtain Distribution of Magnetic Field etc. in advance.
Although had the method for shimming of some row hardware or software to improve magnetic field homogeneity, because the current conventional two-dimentional J of limitation of himself divides Spectra Unfolding Methods still cannot be applied in undesirable magnetic field environment, particularly in the detection of biological tissue application.If can resolve this problem, do not need complicated hardware shimming operation not need to know in advance Distribution of Magnetic Field situation yet, and only from pulse train design angle, design the method that one can be divided spectrum unscrambling at the lower acquisition of non-uniform magnetic field environment (particularly biological tissue) high-resolution two dimension J, just can greatly improve two-dimentional J decomposition technique range of application.
Summary of the invention
The object of the present invention is to provide a kind ofly on nuclear magnetic resonance spectrometer, under non-uniform magnetic field, to obtain the method that high resolution nuclear magnetic resonance two dimension J divides spectrum unscrambling, and the method can be applicable to biological tissue and detects application.
The present invention includes following steps:
1) by one dimension spectrum of conventional one dimension pulse train sampling, obtain the live width of spectral line, for the setting of spectrum width parameter provides foundation, line width values has reflected magnetic field environment homogeneity situation simultaneously;
2) on nuclear magnetic resonance spectrometer, import in advance compiled intermolecular single quantum coherent two dimension J and divide spectrum unscrambling pulse train;
3) opening intermolecular single quantum coherent two dimension J divides intermolecular single quantum coherent signal selection module of spectrum unscrambling pulse train, indirectly ties up evolution phase t
1module, indirectly tie up evolution phase t
2module, signal sampling phase t
3module, arranges the experiment parameter of this pulse train modules;
4) execution step 3) the two-dimentional J that arranges after experiment parameter divides spectrum unscrambling pulse train, carries out data sampling;
5) after data sampling completes, carry out relevant Data Post, the high resolution 2 d J that obtaining avoiding non-uniform magnetic field affects divides spectrum unscrambling.
In step 1), described conventional one dimension pulse train is the one dimension pulse train that nuclear magnetic resonance spectrometer carries, formed by a non-selective pi/2 radio-frequency pulse and sampling period, be followed by signal sampling after the effect of non-selective pi/2 radio-frequency pulse, object is in order to check without any shimming in the situation that, magnetic field homogeneity situation in experiment, simultaneously for the setting of spectrum width parameter provides foundation.
In step 2) in, described intermolecular single quantum coherent two dimension J divides spectrum unscrambling pulse train to use intermolecular single quantum coherent signal selection module, indirectly tie up evolution phase t
1module, indirectly tie up evolution phase t
2module, directly tie up sampling period t
3module;
Described intermolecular single quantum coherent signal selection module is by the pulse of a non-selective rectangle pi/2, non-selective rectangle π pulse, two solvent selectivity gaussian shapes (pi/2)
ipulse, and three linear magnetic field gradients formations in the z-direction, can select desired intermolecular single quantum coherent signal by intermolecular single quantum coherent signal selection module; Because intermolecular single quantum coherent signal comes from long-range dipolar interaction, the coverage of this dipolar interaction is 10～100 μ m, this scope is far smaller than the yardstick of sample under normal circumstances, and under this small yardstick the homogeneity in magnetic field all very high energy meet the requirement of High Resolution Spectrum, therefore the selected signal out of intermolecular single quantum coherent signal selection module has immune characteristic to non-uniform magnetic field;
Described indirect dimension evolution phase t
1module is a supper-fast space encoding process, is made up of the adiabatic π pulse of a pair of sinc shape and corresponding encode gradient field; Selected go out intermolecular single quantum coherent signal after this module develops, just can encode to magnetic field bump, formed information (the F1 dimension corresponding indirectly dimension evolution phase t of three-dimensional sampled signal along F1 dimension
1).
Indirectly tie up evolution phase t with routine
1different, this module space encoding process is once sampled and just can be realized signal evolution, without carrying out signal evolution according to specific time increment, greatly improves sampling efficiency.
Described indirect dimension evolution phase t
2module is two parts t being equated by front and back
2/ 2 formations, and two t
2the signal that inserts a non-selective π pulse shaping spin echo in the middle of/2 develops.
This is a conventional indirect dimension evolutionary process, need carry out signal evolution according to specific time increment; Selected go out intermolecular single quantum coherent signal at indirect dimension evolution phase t
2after interior evolution, eliminate chemical shift completely and only retained J coupling information, formed information (the F2 dimension corresponding indirectly dimension evolution phase t of three-dimensional sampled signal along F2 dimension
2), two-dimentional J divides the J coupling Information Dimension of spectrum unscrambling.Dimension evolution phase t indirectly
2only comprise J coupling information and develop, in three dimensional signal sampling process, F2 dimension spectrum width size only need to cover J coupling constant and without covering chemical shift width, therefore greatly improve three-dimensional sampling efficiency.
Described direct dimension sampling period t
3module is that a space decoding forms, with indirect dimension evolution phase t
1the cataloged procedure of module is corresponding, and this module is to be made up of a pair of decoding gradient fields, finally realizes the sampling of three dimensional signal.Meanwhile, it has also formed information (the F3 dimension corresponding directly dimension sampling period t of three dimensional signal in F3 dimension
3).
Due to the characteristic of intermolecular single quantum coherent signal, Magnetic field inhomogeneity effect is to be associated along F1 and F3 dimension, therefore can make the Magnetic field inhomogeneity effect of F1 peacekeeping F3 dimension mutually compensate through specific data rotation processing, finally be eliminated and formed two-dimentional J along F3 dimension Magnetic field inhomogeneity effect and divide the chemical shift information of spectrum unscrambling to tie up.
In step 3), described experiment parameter comprise direct dimension spectrum width SW, first indirectly dimension spectrum width SW1, second indirectly dimension spectrum width SW2, sampling time at, indirectly tie up evolution phase t
2the ni2 that counts, sequence delays time RD, constant time lag 2 Δs, the time of the non-selective rect.p. of pi/2, the time of the non-selective rect.p. of π, (pi/2)
ithe time of selectivity Gauss pulse, the time of the adiabatic π pulse of sinc shape, linear coherent gradient field strength and action time thereof, space encoding gradient fields intensity and action time thereof, space decoding gradient strength degree and action time thereof; The setting range of described constant time lag 2 Δs can be 40～120ms.
In step 4), described in carry out data sampling concrete grammar can be: sequence implementation each time, first, the time of one section of RD of sequence delays, object is in order to allow magnetization vector relaxation recover; Then, the modules of pulse train develops to sample effect successively, selects corresponding intermolecular single quantum coherent signal, is indirectly tieing up evolution phase t
1cataloged procedure carries out signal evolution, is indirectly tieing up evolution phase t
2carry out signal evolution according to specific time increment; Finally, directly tieing up sampling period t
3carry out space decoding collection signal; Above-mentioned sequence implementation is just to indirect dimension t once
2the sampling of counting, need to repeat ni2 time above-mentioned sequence implementation for a whole three-dimensional data.
In step 5), described in carry out relevant Data Post, first, obtained three-dimensional data is carried out to three-dimensional Fourier transform one time, obtain an initial three-dimensional plot; Then, initial three-dimensional plot is implemented to a three-dimensional rotation processing, three-dimensional rotation processing is along being rotated counterclockwise 45 ° on F1-F3 in-plane, the three-dimensional plot that processing obtains has been eliminated the impact of Magnetic field inhomogeneity effect completely along F2 peacekeeping F3, and has formed along this bidimensional the information that two-dimentional J divides spectrum unscrambling; Finally, handled three-dimensional plot is carried out to the once two-dimentional accumulation projection along F2 and F3 dimension.
The present invention utilizes intermolecular single quantum coherent signal selection module and three-dimensional sampling dimension evolution phase t indirectly by the design of pulse train
1and t
2module, carries out signal evolution and samples and do corresponding Data Post, and the high-resolution two dimension J that finally obtaining avoiding Magnetic field inhomogeneity affects divides spectrum unscrambling.Although need to carrying out three-dimensional sampling, described pulse train obtains required signal, but because F1 and F3 dimension has been utilized respectively ultrafast Code And Decode process to realize signal to develop, the whole three-dimensional sampling time is only relevant with J coupling size in F2 dimension, it is identical that the sampling time of this pulse train is divided the sampling time of spectrum unscrambling with conventional two-dimentional J, generally in two minutes, can obtain a high-resolution two dimension J and divide spectrum unscrambling.High-resolution two-dimensional correlation spectrum has important application for biological tissue's metabolin and complicated chemical sample attribution analysis, but often magnetic field bump has affected spectrum analysis, therefore each experiment all will be by regulating shim coil electric current to carry out shimming to sample, requirement in operating experience, the homogeneity of some sample (for example biological tissue) is difficult to realize by this shimming mode.The present invention can overcome the impact of various Magnetic field inhomogeneities on nuclear magnetic resonance spectrometer and obtain high-resolution two dimension J and divide spectrum unscrambling, without shimming operation, for biological tissue's metabolin and complicated chemical sample analysis provide a kind of simple and effective method.The present invention makes any change without the hardware to nuclear magnetic resonance spectrometer, only need on spectrometer, import compiled pulse train and corresponding Data Post code with text formatting, and therefore the method can be applicable to the nuclear magnetic resonance spectrometer of all routines.
Accompanying drawing explanation
Fig. 1 is applied under non-uniform magnetic field to obtain the pulse train that high-resolution two dimension J divides spectrum unscrambling, and wherein rectangular strip is non-selective pi/2 and π radio-frequency pulse, and the bar shaped of gaussian shape is solvent selectivity (pi/2)
iand solvent selectivity (pi/2)
sradio-frequency pulse, sinc shape bar is adiabatic π pulse, and the rectangular block that oblique line is filled is that space rectangles piece is space encoding and decoding gradient along the linear relevant gradient of selecting of Gz direction, and I represents solvent, and S represents solute, N
edimension space coding number of times, N
dfor space decoding number of times.
Fig. 2 is the conventional one dimension spectrum of pig brain tissue, and line width is 120Hz.Wherein, in one dimension spectrogram, 0.7～4.2ppm part comprises pig brain tissue's metabolite signals, and its intensity is amplified to 400 times and be presented at the top of one dimension spectrum corresponding part.
Fig. 3 result that intermolecular single quantum coherent two dimension J divides Spectra Unfolding Methods to obtain for pig brain tissue utilizes in the situation of same magnetic field.
Embodiment
Intermolecular single quantum two dimension J proposed by the invention divides Spectra Unfolding Methods can overcome the impact of Magnetic field inhomogeneity on nuclear magnetic resonance spectrometer and tissue sample inner magnet rate inhomogeneous broadening effect and obtains high resolution 2 d J and divide spectrum unscrambling, save the operation of artificial shimming, for biological tissue's metabolin and complicated chemical sample analysis provide a kind of simple and effective method.Each step in specific implementation process of the present invention is as follows:
Step 1, the sampling of conventional one dimension spectrum
First conventional one dimension pulse train (i.e. non-selective pi/2 radio-frequency pulse effect is afterwards followed by the signal sampling) sampling carrying with nuclear magnetic resonance spectrometer obtains an one dimension spectrum, obtained the live width of spectral line by one dimension spectrum, line width values has reflected magnetic field homogeneity situation, and this line width values is also for the setting of spectrum width parameter provides foundation simultaneously.
Step 2, the importing of pulse train
On nuclear magnetic resonance spectrometer operator's console, open the corresponding function software of spectrometer, import in advance compiled intermolecular single quantum two dimension J and divide spectrum unscrambling pulse train (as shown in Figure 1), select specific test block, then call in above-mentioned pulse train, for next step operation is prepared.
Step 3, intermolecular single quantum two dimension J divides the setting of spectrum unscrambling pulse train parameter
First open each correlation module of this pulse train, comprise intermolecular single quantum coherent signal selection module, indirectly tie up evolution phase t
1module, indirectly tie up evolution phase t
2module, directly tie up sampling period t
3module.Then according to detecting sample actual conditions, corresponding experiment parameter is set, comprises direct dimension spectrum width SW, first ties up spectrum width SW1 indirectly, the second indirect dimension spectrum width SW2, and sampling time at, ties up evolution phase t indirectly
2the ni2 that counts, constant time lag 2 Δs, non-selective rect.p. time of pi/2 and π, (pi/2)
ithe selectivity Gauss pulse time, the time of the adiabatic π pulse of sinc shape, linear coherent gradient field strength and action time thereof, space encoding gradient fields intensity and action time thereof, space decoding gradient strength degree and action time thereof.Wherein, the setting of space encoding decoding gradient and the adiabatic π pulse of sinc shape can the conventional one dimension spectrum of refer step 1 line width values that obtains.
Step 4, intermolecular single quantum two dimension J divides spectrum unscrambling pulse train data sampling
Be different from conventional two-dimentional J and divide Spectra Unfolding Methods or other spectroscopy sequences, the present invention can skip the shimming process of sample, directly carries out the pulse train setting, and carries out data sampling.In sequence implementation, the first time of one section of RD of sequence delays, object is in order to allow magnetization vector relaxation recover each time; Then, the modules of pulse train develops to sample effect successively, selects corresponding intermolecular single quantum coherent signal, is indirectly tieing up evolution phase t
1cataloged procedure carries out signal evolution, is indirectly tieing up evolution phase t
2carry out signal evolution according to specific time increment, finally directly tieing up sampling period t
3carry out space decoding collection signal; Above-mentioned sequence implementation is just to indirect dimension t once
2the sampling of counting, need to repeat ni2 time above-mentioned sequence implementation for a whole three-dimensional data.After data sampling completes, carry out next step, otherwise continue sampling until sampled.
Step 5, Data Post
After data sampling completes, carry out relevant Data Post, first be that obtained three-dimensional data is carried out to three-dimensional Fourier transform one time, obtain an initial three-dimensional plot, and then this three-dimensional plot is implemented to a three-dimensional rotation processing, this process is along being rotated counterclockwise 45 ° on F1-F3 in-plane, last, handled three-dimensional plot is carried out once along the two-dimentional accumulation projection of F2 and F3 dimension, obtain high-resolution two dimension J and decompose Correlated Spectroscopy.
Below provide specific embodiment:
This new method is scanned to a kind of biological tissue as an embodiment, verified the feasibility of particularly applying of the present invention by this specific embodiment under non-uniform magnetic field environment in biological tissue.The sample that experiment adopts is pig brain tissue, and experiment test is to carry out under a Varian500MHz NMR spectrum view (Varian, Palo Alto, CA), and whole experimentation does not carry out artificial shimming operation.The operating process of dividing Spectra Unfolding Methods according to above-mentioned intermolecular single quantum two dimension J, first obtains an one dimension spectrum with conventional simple one dimension pulse train sampling, and the sampling time is 2s, and as shown in Figure 2, can obtain line width from this one dimension spectrum is 120Hz to result.Owing to directly sample being sampled and do not carried out shimming operation, magnetic field homogeneity is lower.The part that one dimension spectrum 0.7～4.2ppm is comprised to brain tissue metabolism thing is carried out the amplification of 400 times of signal intensities, can find out that metabolite signals peak still cannot differentiate.In addition, powerful water peak-to-peak signal has also further hindered the analysis of spectrogram.Then, import compiled intermolecular single quantum two dimension J as shown in Figure 1 and divide spectrum unscrambling pulse train, open each correlation module of pulse train, comprise intermolecular single quantum coherent signal selection module, indirectly tie up evolution phase t
1module, indirectly tie up evolution phase t
2module, directly tie up sampling period t
3module, arranges experiment parameter, the sample specifically adopting for the present embodiment, its experiment parameter arranges as follows: directly tieing up spectrum width SW is 3000Hz, and the first indirect dimension spectrum width SW1 is 200Hz, and the second indirect dimension spectrum width SW2 is 60Hz, sampling time at is 0.4s, indirectly ties up evolution phase t
2the ni2 that counts be 40, pulse delay time, RD was 2s, the non-selective rect.p. time of pi/2 and π is 10s and 20s, (pi/2)
iselectivity Gaussian Pulse Width is 6ms, the time of the adiabatic π pulse of sinc shape is 10ms, 2 Δs are 60ms, linear coherent gradient field strength and time are respectively 0.1T/m and 1.2ms, space encoding gradient fields intensity and time are respectively 0.039T/m and 10ms, and space decoding gradient strength degree and time are respectively 0.042T/m and 0.13ms.Skip shimming process and directly click beginning, carry out the sequence setting, sequence implementation each time, just can obtain indirect dimension t once
2institute's respective signal of counting, will repeat 40 times this sample signal sampling, and the whole sampling time is 80s.
After data sampling completes, according to the processing procedure of above-mentioned steps 5, obtained data are carried out to aftertreatment, first do three-dimensional Fourier transform one time, obtain an initial three-dimensional plot, this three-dimensional plot is implemented to a three-dimensional rotation processing, the three-dimensional plot that obtains processing.In the three-dimensional plot of processing at this, F2 peacekeeping F3 dimension has jointly formed two-dimentional J and has decomposed spectrum information, and the impact of non-uniform magnetic field broadening is eliminated, carry out along F1 peacekeeping F3 dimension the high resolution 2 d J that two-dimentional accumulation projection just can obtain the present embodiment and divide spectrum unscrambling, net result as shown in Figure 3, therefrom can find out, even in the situation that organization internal magnetic susceptibility is inhomogeneous and magnetic field is undesirable, the present invention can make two-dimentional J divide spectrum unscrambling to be reduced to 20Hz along the live width of chemical shift dimension by 120Hz, and this is conducive to metabolite signals ownership; Live width along J coupling dimension drops to 3Hz by 120Hz, and this is conducive to the detection of metabolin J coupling information.As can be seen here, utilize method of the present invention can in pig brain tissue, recover high resolution 2 d J and decompose spectrum information, various metabolin ownership and J coupling information can obtain, and solvent peak is also effectively suppressed.
Claims (10)
1. under non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling, it is characterized in that comprising the steps:
1) by one dimension spectrum of conventional one dimension pulse train sampling, obtain the live width of spectral line, for the setting of spectrum width parameter provides foundation, line width values has reflected magnetic field environment homogeneity situation simultaneously;
2) on nuclear magnetic resonance spectrometer, import in advance compiled intermolecular single quantum coherent two dimension J and divide spectrum unscrambling pulse train;
3) opening intermolecular single quantum coherent two dimension J divides intermolecular single quantum coherent signal selection module of spectrum unscrambling pulse train, indirectly ties up evolution phase t
1module, indirectly tie up evolution phase t
2module, signal sampling phase t
3module, arranges the experiment parameter of this pulse train modules;
4) execution step 3) the two-dimentional J that arranges after experiment parameter divides spectrum unscrambling pulse train, carries out data sampling;
5) after data sampling completes, carry out relevant Data Post, the high resolution 2 d J that obtaining avoiding non-uniform magnetic field affects divides spectrum unscrambling.
2. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that in step 1), described conventional one dimension pulse train is the one dimension pulse train that nuclear magnetic resonance spectrometer carries, formed by a non-selective pi/2 radio-frequency pulse and sampling period, i.e. after non-selective pi/2 radio-frequency pulse effect followed by signal sampling.
3. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that in step 2) in, described intermolecular single quantum coherent two dimension J divides spectrum unscrambling pulse train to use intermolecular single quantum coherent signal selection module, indirectly tie up evolution phase t
1module, indirectly tie up evolution phase t
2module, directly tie up sampling period t
3module.
4. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 3, it is characterized in that described intermolecular single quantum coherent signal selection module is by the pulse of a non-selective rectangle pi/2, non-selective rectangle π pulse, two solvent selectivity gaussian shapes (pi/2)
ipulse, and three linear magnetic field gradients formations in the z-direction, can select desired intermolecular single quantum coherent signal by intermolecular single quantum coherent signal selection module; Because intermolecular single quantum coherent signal comes from long-range dipolar interaction, the coverage of this dipolar interaction is 10～100 μ m.
5. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 3, it is characterized in that described indirect dimension evolution phase t
1module is a supper-fast space encoding process, is made up of the adiabatic π pulse of a pair of sinc shape and corresponding encode gradient field; Selected go out intermolecular single quantum coherent signal after this module develops, just can encode to magnetic field bump, formed the information of three-dimensional sampled signal along F1 dimension, the corresponding dimension indirectly of F1 dimension evolution phase t
1.
6. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 3, it is characterized in that described indirect dimension evolution phase t
2module is two parts t being equated by front and back
2/ 2 formations, and two t
2the signal that inserts a non-selective π pulse shaping spin echo in the middle of/2 develops; Described evolution is conventional indirect dimension evolutionary process, need carry out signal evolution according to specific time increment; Selected go out intermolecular single quantum coherent signal at indirect dimension evolution phase t
2after interior evolution, eliminated chemical shift completely and only retained J coupling information, formed the information of three-dimensional sampled signal along F2 dimension, two-dimentional J divides the J coupling Information Dimension of spectrum unscrambling, the corresponding dimension indirectly of F2 dimension evolution phase t
2; Dimension evolution phase t indirectly
2only comprising J coupling information develops.
7. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that described direct dimension sampling period t
3module is that a space decoding forms, with indirect dimension evolution phase t
1the cataloged procedure of module is corresponding, and this module is to be made up of a pair of decoding gradient fields, finally realizes the sampling of three dimensional signal; Meanwhile, it also forms the information of three dimensional signal in F3 dimension, the corresponding directly dimension of F3 dimension sampling period t
3.
8. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that in step 3), described experiment parameter comprise direct dimension spectrum width SW, first indirectly dimension spectrum width SW1, second indirectly dimension spectrum width SW2, sampling time at, indirectly tie up evolution phase t
2the ni2 that counts, sequence delays time RD, constant time lag 2 Δs, the time of the non-selective rect.p. of pi/2, the time of the non-selective rect.p. of π, (pi/2)
ithe time of selectivity Gauss pulse, the time of the adiabatic π pulse of sinc shape, linear coherent gradient field strength and action time thereof, space encoding gradient fields intensity and action time thereof, space decoding gradient strength degree and action time thereof; The setting range of described constant time lag 2 Δs can be 40～120ms.
9. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that in step 4), the described concrete grammar that carries out data sampling is: sequence implementation each time, first, the time of one section of RD of sequence delays, object is in order to allow magnetization vector relaxation recover; Then, the modules of pulse train develops to sample effect successively, selects corresponding intermolecular single quantum coherent signal, is indirectly tieing up evolution phase t
1cataloged procedure carries out signal evolution, is indirectly tieing up evolution phase t
2carry out signal evolution according to specific time increment; Finally, directly tieing up sampling period t
3carry out space decoding collection signal; Above-mentioned sequence implementation is just to indirect dimension t once
2the sampling of counting, need to repeat ni2 time above-mentioned sequence implementation for a whole three-dimensional data.
10. under a kind of non-uniform magnetic field, obtain the method that nuclear magnetic resonance two dimension J divides spectrum unscrambling as claimed in claim 1, it is characterized in that in step 5), described in carry out relevant Data Post, first, obtained three-dimensional data is carried out to three-dimensional Fourier transform one time, obtain an initial three-dimensional plot; Then, initial three-dimensional plot is implemented to a three-dimensional rotation processing, three-dimensional rotation processing is along being rotated counterclockwise 45 ° on F1-F3 in-plane, the three-dimensional plot that processing obtains has been eliminated the impact of Magnetic field inhomogeneity effect completely along F2 peacekeeping F3, and has formed along this bidimensional the information that two-dimentional J divides spectrum unscrambling; Finally, handled three-dimensional plot is carried out to the once two-dimentional accumulation projection along F2 and F3 dimension.
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Cited By (14)
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| CN104237820A (en) * | 2014-09-26 | 2014-12-24 | 厦门大学 | Method for acquiring two-dimensional J-resolved spectroscopy of magnetic resonance by single sweeping |
| CN105092629A (en) * | 2015-08-05 | 2015-11-25 | 厦门大学 | Magnetic resonance two-dimensional spectrum method for measuring hydrogen-hydrogen J coupling constants |
| CN105158289A (en) * | 2015-10-28 | 2015-12-16 | 厦门大学 | Nuclear magnetic resonance detection method for biological tissue |
| CN106093099A (en) * | 2016-06-06 | 2016-11-09 | 厦门大学 | A kind of high-resolution two dimension J that obtains decomposes the method composed |
| CN106706694A (en) * | 2017-01-13 | 2017-05-24 | 厦门大学 | Nuclear magnetic resonance multi-spectral method for measuring hydrogen-hydrogen coupling constant of plurality of coupling networks |
| CN106841270A (en) * | 2017-01-21 | 2017-06-13 | 厦门大学 | A kind of method for obtaining nuclear magnetic resonance two dimension phase sensitivity J spectrums |
| CN106872506A (en) * | 2017-03-15 | 2017-06-20 | 厦门大学 | A kind of supper-fast nuclear magnetic resonance two dimension J spectral methods for resisting non-uniform magnetic field |
| CN107015181A (en) * | 2017-04-07 | 2017-08-04 | 厦门大学 | A kind of method that proton longitudinal relaxation time is measured under non-uniform magnetic field |
| CN107430178A (en) * | 2015-02-23 | 2017-12-01 | 圣纳普医疗(巴巴多斯)公司 | Differ the system and method for relaxation enhancing magnetic resonance imaging |
| CN107894436A (en) * | 2017-10-30 | 2018-04-10 | 厦门大学 | A kind of fast two-dimensional J spectral methods applied to non-uniform magnetic field |
| CN108732195A (en) * | 2018-04-19 | 2018-11-02 | 厦门大学 | A kind of high-resolution nuclear magnetic resonance spectral method for measuring hydrogen-hydrogen J coupling constants |
| CN110456294A (en) * | 2019-07-11 | 2019-11-15 | 厦门大学 | A kind of chemical shift amplification method improving nmr spectrum resolution ratio |
| CN110782452A (en) * | 2019-11-05 | 2020-02-11 | 厦门大学 | T2 quantitative image imaging method and system |
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