CN113466280B - Simulated nuclear magnetic resonance spectrum analysis method and system convenient for expanding molecular information base and application thereof - Google Patents
Simulated nuclear magnetic resonance spectrum analysis method and system convenient for expanding molecular information base and application thereof Download PDFInfo
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Abstract
The invention discloses a simulated nuclear magnetic resonance spectrum analysis method convenient for expanding a molecular information base, which comprises the steps of constructing a simulated sample molecular information model and a simulated sample molecular information base; constructing spectrometer hardware parameters; constructing a spectrum sequence physical model; constructing a physical mathematical model for acquiring original nuclear magnetic resonance spectrum data based on the constructed simulated sample molecular information model, the simulated sample molecular information base, relevant hardware parameters of a spectrometer and a spectrum sequence physical model, and realizing a simulated original data acquisition algorithm and a program to complete simulated acquisition of original data; and carrying out Fourier transformation on the original data acquired by the simulation to obtain a spectrogram. The method and the system can be applied to various aspects such as a matching virtual experiment training platform of a nuclear magnetic resonance spectrum application technology, self-learning of application personnel in the related technical field and the like, and have wide application prospects.
Description
Technical Field
The invention relates to the technical field of nuclear magnetic resonance, in particular to a simulated nuclear magnetic resonance spectrum analysis method and system convenient for expanding a molecular information base and application thereof.
Background
The nuclear magnetic resonance spectrum is an important tool for researching molecular and material structures in a chemical system, and is an analytical instrument with the lowest degree of localization; the equipment is expensive, the number of sets is limited, the arrangement of scientific research machines is compact, and the teaching experiment machine is very limited; the performance of equipment is worried about to be degraded by student experiment operation, and related parameters are damaged; the novice is easy to have misoperation to cause equipment damage; the experimental process is complex, the sample preparation, shimming, field locking and tuning matching need to be adjusted slowly and carefully, the occupied time is long, and the like, so that the spectrum experiment is weak in development.
Nuclear magnetic resonance spectroscopy is increasingly used in the related fields of organic chemistry, such as pharmaceuticals, petrochemicals, organic materials, rubber materials, biological medicines, etc.; more and more researchers need to use nuclear magnetic resonance spectroscopy analyzers to carry out related research and test work. However, the nmr spectroscopy involves many nmr bases, especially sequence techniques, and the complex variability of the sample to be measured, which makes the use of the instrument and interpretation of the results of the test data problematic. These results from the fact that practitioners in various fields do not know the fundamental principles of nmr spectroscopy, and the rules of influence on the operation flow of the spectrometer and the settings of relevant parameters on the spectrum are unclear. The invention can meet the requirement in order to enable related practitioners to better and quickly understand and master the principle of the nuclear magnetic resonance spectrum analysis technology and better set acquisition parameters and hardware adjustment, thereby quickly, efficiently and accurately operating experiments, acquiring data and processing spectrograms to carry out simulation training before real machine operation.
Disclosure of Invention
The invention provides a simulation nuclear magnetic resonance spectrum analysis method and system based on a numerical simulation technology, and solves the technical problems in the prior art.
The invention provides a simulation nuclear magnetic resonance spectrum analysis method based on a numerical simulation technology, which comprises the following steps:
constructing a simulation sample molecular information model and a simulation sample molecular information library;
constructing a hardware parameter of the spectrometer;
constructing a spectrum sequence physical model;
based on the constructed simulated sample molecular information model, the simulated sample molecular information base, related hardware parameters of a spectrometer instrument and a spectrum sequence physical model, combining to construct a nuclear magnetic resonance spectrum original data acquisition physical mathematical model, and implementing a simulated original data acquisition algorithm and a program to complete simulated acquisition of original data;
and performing FT conversion on the original data acquired in the simulation to obtain a spectrogram. I.e. to obtain a one/two or three dimensional distribution of the signal frequencies, i.e. a one/two or three dimensional spectrogram.
Further, the method of the invention also comprises the following steps: and (4) performing spectrogram processing on the spectrogram obtained in the last step. The spectrogram processing comprises spectrogram processing methods such as phase correction, baseline correction, peak searching, integration, distance measurement, chemical shift correction and the like.
Further, the method of the invention also comprises the following steps: and constructing a correction model and simulation adjustment of the hardware parameters of the spectrometer, and correcting the hardware system parameters to ensure the consistency with the operation of a real machine system. The analog adjustments include wobb (auto-tune match), shim, lock, P1 adjustments, and the like. The construction of the correction model involves the construction of a physical mathematical model. In the prior art, an instrument system needs to be corrected to an optimal state before a sample is tested, and the final spectrogram can be ensured to be effective by correcting before each experiment, and the steps are most time-consuming and difficult in a spectrum experiment. The invention solves the technical problems by constructing and simulating and adjusting the hardware parameter correction model based on the numerical simulation technology.
In the step 1, a simulation sample molecule information model and a simulation sample molecule information base are constructed, and an information model and an information base of common sample molecules to be analyzed are constructed. The molecular information of the sample is determined according to a spin system, which can be two spin systems: one is AmBnCd, A, B and C are three spin nuclei which are mutually coupled, and the number of nuclei is m, n and d respectively. The other is XpYqZw, X, Y and Z are other three spin nuclei which are mutually coupled, and the number of the nuclei is p, q and w respectively. In the present invention, the sample molecular information model is not limited to the foregoing two spin system, and may be a three, four or more spin system. The nuclear species in each spin system is not limited to three species, but may be four, five or more species. Preferably, only the nuclei between the spin systems are free of J indirect coupling.
Specifically, for AmBnCd, the chemical shift information is constructed as Wa, Wb and Wc, the chemical shift information respectively represents the chemical shift values of three nuclei of A, B and C, and the dimension is ppm; j coupling information between every two is constructed as Jab, Jbc and Jac, and respectively represents J coupling values between an AB nucleus, a BC nucleus and an AC nucleus, and the unit is Hz. D coupling information between every two is constructed as Dab, Dbc, Dac, and respectively represents direct mutual coupling values between AB nucleus, BC nucleus and AC nucleus, and the unit is Hz. XYZ or other spin regimes, and so on.
In the invention, in order to expand the molecular information base, a user can edit new molecular information according to the rule, and the new molecular information can become a new sample molecule after being added into the information base. Self-building molecular information can be added through an EXCEL database, or through software interface parameter addition or other forms of addition. Mainly including spin body coefficients (1, 2, 3, 4 or more), spin species (1, 2, 3 or 4), number of each spin, chemical shift, J-coupling and D-value; it is to be noted that the spin nuclei between two different spin systems are independent, i.e. there is no indirect coupling J or direct coupling D.
Wherein, the molecular sample can be liquid sample molecules and solid sample molecules. The solid sample molecules are mainly characterized by their D value differences.
The hardware parameters related to the relaxation analysis include a main magnetic field B0, a main magnetic field inhomogeneity deltaB0, a radio frequency field B1, a gradient field G, PL1W, P1 (or P90), P2 (or P180), and the like.
Wherein the spectrum sequences comprise a monopulse sequence, a decoupling sequence (comprising dept45, dept90, dept135 and the like), a nuclear chemical shift related two-dimensional spectrum COSY sequence, a nuclear chemical shift related overhause enhanced two-dimensional spectrum NOESY sequence, a heteronuclear chemical shift related spectrum (1H-13C HSQC sequence), a heteronuclear chemical shift related spectrum (1H-13C HMBC sequence) and the like.
The sequence construction in the invention is realized by giving control parameters of different data acquisition modes. In addition to the use of the above-described conventional spectral sequences, new spectral sequence methods and models can be constructed on their own. The above sequence is the basic theory in the art. In the prior art, a sequencer (hardware) is adopted to generate a series of control signals to drive relevant hardware to complete relevant work.
Wherein the spectrogram is a one-dimensional spectrogram, a two-dimensional spectrogram or a three-dimensional spectrogram.
The invention also provides a simulation nuclear magnetic resonance spectrum analysis system based on the numerical simulation technology, which is used for realizing the simulation nuclear magnetic resonance spectrum analysis method based on the numerical simulation technology. The system comprises: the building module of the simulation sample molecular information model and the simulation sample molecular information base is used for building the simulation sample molecular information model and the simulation sample molecular information base; the construction module of the related hardware parameters of the spectrometer is used for constructing the related hardware parameters of the spectrometer; the building module of the spectrum sequence physical model is used for building different spectrum sequence physical models; the nuclear magnetic resonance FID data acquisition physical mathematical model building module is used for building a nuclear magnetic resonance FID data acquisition physical mathematical model and simulating and acquiring original data; and the spectrogram module is used for obtaining a one-dimensional, two-dimensional or three-dimensional spectrogram of the signal frequency.
The device further comprises a spectrogram processing module used for carrying out spectrogram processing on the obtained spectrogram, wherein the spectrogram processing comprises phase correction, baseline correction, peak searching, integration, distance measurement, chemical shift correction and the like.
The device further comprises a building module of a simulation adjustment and correction model of the spectrum hardware parameters, and the building module is used for building the simulation adjustment and correction model of the spectrum hardware parameters. The analog adjustment and correction module comprises modules for adjusting and correcting such as automatic tuning matching wobb, shimming shim, field locking, P1 adjustment and the like.
The invention also provides the application of the simulation nuclear magnetic resonance spectrum analysis system based on the numerical simulation technology, and the analysis system is applied to a matching virtual experiment training platform of the nuclear magnetic resonance spectrum application technology and can also be applied to the self-learning technical principle of application personnel in the technical field of related spectrum analysis. The invention also provides a simulation analyzer capable of developing the nuclear magnetic resonance relaxation spectrum analysis technology based on the content of the invention, and the simulation analyzer can be used as a matching virtual experiment training platform of a general nuclear magnetic resonance relaxation spectrum application technology or used for self-learning technical principles by application personnel in the technical field of related relaxation spectrum analysis. The analysis method and the system of the invention are a simulation analyzer which is a piece of software (except a computer carrier for software operation, the simulation analyzer does not contain any hardware). The invention can realize the data acquisition and processing functions which are completely the same as those of a wave spectrum analyzer (comprising hardware and software).
The basic function of the TopSpin2.0 of a Bruker nuclear magnetic resonance spectrometer is simulated, and the basic process of a liquid nuclear magnetic resonance spectrum experiment of common small organic molecules can be realized. The steps and functions include: 1, adopting common chemical shift and J coupling information of organic micromolecules as sample information; 2, the functions of the magnet cavity of entering (inject) and ejecting (eject) of the sample can be simulated; 3, the manual/automatic tuning matching process of the probe can be simulated; 4, a field locking/shimming adjusting process can be simulated; 5, the process of setting sampling parameters to collect sample signals can be simulated; and 6, basic spectrogram processing and analyzing functions can be simulated. And 7, completing data acquisition and spectrogram processing of the one-dimensional spectrum/two-dimensional spectrum.
The advantages and beneficial effects of the invention include: the experimental effect same as that of a nuclear magnetic resonance spectrometer can be obtained without the need of huge hardware matching, and the high requirement of a hardware imaging teaching instrument on hardware is avoided. Can be used as reference comparison and parameter setting understanding of the measurement effect of the actual sample. The invention has the advantages that the technical characteristics can be used for intuitively and quickly learning and understanding the principle of the nuclear magnetic resonance spectrum technology; the method can be used for early self-learning principle and operation of professionals related to the spectrum, and is familiar with setting rules of parameters; it can also be used to compare the signal and spectrum results of actual test samples with reference.
The present invention adopts a numerical simulation technology, which is different from the operation appearance of a common simulation instrument, and the simulation is essential and also comprises an operation process. Virtual simulation technology is a current development hotspot. The application of virtual technology to teaching and training of large expensive equipment and high and new technology is a necessary trend. Different from the visualization simulation virtual technology based on the structure and the process in the general sense, the project of the invention expresses the extremely abstract and obscure nuclear magnetic resonance spectrum theory by using a mathematical formula and realizes the visualization by a program. The final software can completely get rid of hardware, and the experimental effect which is the same as that of a hardware instrument is achieved. In other words, techniques based on animation and the like are mainly used for general virtual techniques. The invention is the perfect combination of the nuclear magnetic resonance theory essence and the computer program development technology. The digital simulation technology of the invention simulates that the simulation effect is focused on the same essence, but not on the visualization of the structure.
The invention can be applied to the experiment teaching and practice training of talents in related fields; the method has the advantages that hardware is not needed (the price of a single piece of hardware is 200-1000 thousands), the method is not limited by the hardware, low-cost and batch experimental operation and training are realized, and the influence rule of data acquisition parameters and a spectrum processing process on molecular spectrums of different samples is fully mastered, so that the technical theory of spectrum analysis is really mastered, the analysis and operation capabilities of the analysis technology are improved, and a foundation is laid for subsequent work.
The invention can be used for instrument development and test calibration; the actual spectroscopy instrument is affected by many factors such as electronic noise, eddy currents, system dead time, etc., which make it impossible to evaluate whether the final spectra are affected by the hardware of the device or actually reflect the characteristics of the sample. By applying the virtual system, the spectrum of a standard sample under an ideal hardware condition can be used as a test standard, so that hardware indexes can be evaluated or formulated.
The invention can be used as a spectrogram result reference of the same sample molecule under different devices; because the spectrometer equipment is expensive, it is difficult to obtain the spectrum performance of the same sample under different equipment (different field intensity, and possibly different uniformity). By adopting the virtual spectrometer, the spectrogram expressions of different uniformity (1ppm to 1ppb) of the same molecule under equipment with different field strengths (60MHz to 1.2GHz) can be rapidly given. To generate ideal spectrogram and spectrogram reference object under different equipment.
Drawings
FIG. 1A is a schematic flow chart of the method of the present invention, and FIG. 1B shows the information of the simulated sample molecules, including J-coupling, chemical shift, etc., by constructing different sample molecule information as input. FIG. 1C shows the output spectrum obtained according to the process of FIG. 1A, i.e., the output spectrum shown in FIG. 1C can be obtained after the virtual data acquisition and FT of the molecular information shown in FIG. 1B are performed by the method shown in FIG. 1A. FIG. 1D is a schematic flow chart of an embodiment of the present invention.
FIG. 2 is a schematic diagram of the system of the present invention.
FIG. 3 is a schematic diagram of the process of raw data acquisition simulation in the method of the present invention.
Fig. 4 is a VMRS main interface of the embodiment of the present invention, which is a simulation system interface after interface programming is performed by computer programming software (matlab software in the embodiment).
FIG. 5 is a schematic view of the wobb interface in an embodiment of the present invention.
FIG. 6 is a shim interface schematic in an embodiment of the present disclosure.
FIG. 7 is a schematic diagram of a PL1W tuning interface in an embodiment of the present invention.
FIG. 8 is a schematic view of the nutation spectrum effect in an embodiment of the present invention.
Fig. 9 is a schematic diagram of a spectrum after phase correction is successful in the embodiment of the present invention.
FIG. 10 is a diagram illustrating the effect of spectrum integration in the embodiment of the present invention.
FIG. 11 is a diagram illustrating an automatic peak finding effect of a spectrogram in an embodiment of the present invention.
Fig. 12 is a schematic diagram of a two-dimensional spectrogram contourr format display obtained by applying virtual acquisition of the present invention.
Fig. 13 is a schematic diagram showing a mesh format of a two-dimensional spectrogram obtained by virtual acquisition according to the present invention.
Fig. 14 shows (part of) two-dimensional spectral data obtained by virtual acquisition according to the present invention after one-dimensional FT, where the phase change of different spectral peaks can be seen. The figure shows only 25 pieces of data after one-dimensional FT (one-dimensional array), and the total data of this example is 100 pieces. The total number of data pieces is num _ t 1.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples and the accompanying drawings. The procedures, conditions, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
The invention relates to a simulation nuclear magnetic resonance spectrum analysis method based on numerical simulation technology, which is shown by reference to figures 1A and 1D and comprises the following steps:
and 4, combining the sample molecular information model and the molecular information base constructed in the steps 1, 2 and 3, spectrometer equipment hardware parameters and physical mathematical model sequence parameters of different spectrum pulse sequences, constructing a nuclear magnetic resonance spectrum original data acquisition physical mathematical model, realizing a simulated data acquisition algorithm and a program, and completing simulated acquisition of original FID data.
And step 5, performing Fourier transform (FT transform) on the original data acquired in the simulation of the step 4 to obtain a one-dimensional/two-dimensional/three-dimensional spectrogram.
Further, step 6, performing spectrogram processing such as phase correction, baseline correction, peak searching, integration, distance measurement, chemical shift correction and the like on the spectrogram obtained in the step 5;
further, a correction and simulation adjustment model of the spectrometer hardware parameters is established; the correction and analog adjustments include auto-tune matching wobb, shimming shim, lock field lock, P1 adjustments, and the like.
Some information of the simulated sample molecules, including information such as J coupling, chemical shift and the like, is input by constructing different sample molecule information, as shown in FIG. 1B, and the molecular information shown in FIG. 1B can be output as shown in FIG. 1C after virtual data acquisition and FT by the method of the invention shown in FIG. 1A and FIG. 1D.
As shown in fig. 2, the present invention further provides a simulated nuclear magnetic resonance spectrum analysis system based on the numerical simulation technology, which is used for implementing the simulated nuclear magnetic resonance spectrum analysis method based on the numerical simulation technology. The system comprises: the building module of the simulation sample molecular information model and the simulation sample molecular information base is used for building the simulation sample molecular information model and the simulation sample molecular information base; the construction module of the related hardware parameters of the spectrometer is used for constructing the related hardware parameters of the spectrometer; the building module of the spectrum sequence physical model is used for building different spectrum sequence physical models; the nuclear magnetic resonance FID data acquisition physical mathematical model building module is used for building a nuclear magnetic resonance FID data acquisition physical mathematical model and simulating and acquiring original data; and the spectrogram module is used for obtaining a one-dimensional, two-dimensional or three-dimensional spectrogram of the signal frequency.
The device further comprises a spectrogram processing module used for carrying out spectrogram processing on the obtained spectrogram, wherein the spectrogram processing comprises spectrogram processing such as phase correction, baseline correction, peak searching, integration, distance measurement, chemical shift correction and the like.
Further, the system also comprises a construction module of a simulation adjustment and correction model of the spectrum hardware parameters, and the construction module is used for constructing the simulation adjustment and correction model of the spectrum hardware parameters. The analog adjustment and correction module comprises modules for adjusting and correcting such as automatic tuning matching wobb, shimming shim, field locking lock, P1 adjustment and the like.
Specifically, for step 1, the invention provides a molecular information construction model, but is not limited to such a model, and the construction of other sample models for achieving the purpose of the invention is based on the inventive concept and falls into the scope of the invention.
And constructing a common molecular information model and a molecular information library of the sample to be analyzed. The molecular information is determined according to a spin system, and can be two spin systems, wherein one spin system is AmBnCd, and the other spin system is XpYqZw; ABC are three spin nuclei with coupling between them, and the number of nuclei is subscripts m, n, d. XYZ are the other three spin nuclei with couplings between them, the number of nuclei being the subscripts p, q, w, respectively. The specific molecular information model is not limited to the two spin system, but may be three, four or more. The number of nuclear species in each spin system is not limited to three, and may be four, five or more. Except that the nuclei between the spin systems can be considered to be free of J-coupling.
Constructing chemical shift information Wa, Wb and Wc of the AmBnCd, respectively representing the chemical shift values of three nuclei of A, B and C, and the dimension is ppm; j coupling information between every two is constructed as Jab, Jbc and Jac, and respectively represents J coupling values between an AB nucleus, a BC nucleus and an AC nucleus, and the unit is Hz. D coupling information between every two is constructed as Dab, Dbc and Dac, and direct mutual coupling values among the AB nucleus, the BC nucleus and the AC nucleus are respectively represented in Hz. Similarly, XYZ or other spin regime is analogized.
Furthermore, in order to expand the molecular information base, a user can edit new molecular information according to the rules, and the new molecular information can become new sample molecular information after being added into the information base. Self-building molecular information can be added through an EXCEL database, or through software interface parameter addition or other forms of addition. The sample molecular information library mainly includes spin body coefficients (1, 2, 3, 4 or more), spin species (1, 2, 3 or 4), the number of each spin, chemical shifts, J-coupling and D-values. It is to be noted that the spin nuclei between two different spin systems are independent, i.e. there is no indirect coupling J or direct coupling D.
In step 2, hardware parameters related to the relaxation analyzer are constructed, including a main magnetic field B0, a main magnetic field inhomogeneity deltaB0, a radio frequency field B1, a gradient field G, PL1W (radio frequency power), and the like.
In step 3, physical models of different spectrum sequences are constructed, wherein the physical models comprise a single pulse sequence, a decoupling sequence (dept45, dept90, dept135 and the like), a two-dimensional spectrum COSY sequence related to nuclear chemical shift, an overhause enhanced two-dimensional spectrum NOESY sequence related to nuclear chemical shift, a heteronuclear chemical shift related spectrum (1H-13C HSQC sequence), a heteronuclear chemical shift related spectrum (1H-13C HMBC sequence) and the like. Not limited to these sequences; the specific spectrum sequence model comprises pulse types, pulse numbers, pulse time, pulse amplitude, interval time, gradient application time and interval time, gradient amplitude, gradient stepping values, stepping times, data acquisition time, sampling intervals, sampling point numbers, reverse time intervals and times, time sequence of events and the like.
The spectrum sequence is a basic theory, and a practical instrument adopts a sequence generator (hardware) to generate a series of control signals to drive related hardware to complete related work. The sequence construction of the invention is realized by giving control parameters of different data acquisition modes. The invention does not protect the basic sequence theory, but the construction of the sequence (including parameter) pattern for virtual acquisition based on the object of the invention is the protection content of the invention.
For example, a single pulse sequence, the following parameters are respectively constructed to realize the following steps: d0 (repetition time), SW (sampling bandwidth), TD (number of sampling points), TDeff (number of effective sampling points), DS (number of idle sampling), P90 (90-degree pulse width), P180 (180-degree pulse width), NS (number of accumulation), DE, D1 (delay sampling time), NUC1(H channel); these parameters are relevant to the acquisition of single pulse sequence data and are used in the subsequent integrated data acquisition.
For example, a two-dimensional COSY sequence, the parameters to be constructed are: t1-step (first dimension time step value), t1-num (first dimension number), D0 (repetition time), SW (sampling bandwidth), TD (sampling point number), P90 (90-degree pulse width), P180 (180-degree pulse width), t2(t2 dimension time array).
Such as the HSQC sequence, NUC2(C channel) is added, as with the parameters described above.
Such as DEPT decoupling sequences, increasing decoupling frequency, decoupling pulse width, decoupling pulse shape, etc.
And 4, combining the molecular information and the molecular information base of the simulation sample, hardware parameters and spectrum sequence parameters which are constructed in the steps 1, 2 and 3, constructing a physical mathematical model for acquiring original data of the nuclear magnetic resonance spectrum FID, and realizing a simulation data acquisition algorithm and a program to finish the simulation acquisition of the original data. The innovation of the present invention is that the above steps are proposed, which are substantially significantly different and have unexpected benefits compared to the prior art practice that requires the use of nmr spectrometer hardware.
The actual hardware components used in the actual spectrometer of the prior art perform signal acquisition on the actual sample according to the instructions generated by the sequencer, but what the specific acquired signals are and what the signal follows is not a concern for the hardware of the prior art.
Instead, the signals of the present invention are generated virtually by means of a physical mathematical model. In the present invention, the raw data generated virtually will be different for different spectral sequences. In addition, the invention can simulate a one-dimensional spectrum (single pulse, decoupling dept90 and the like), a two-dimensional spectrum (homonuclear chemical shift correlation spectrum, heteronuclear chemical shift correlation spectrum) or a three-dimensional spectrum.
As shown in fig. 3, in step 4, a physical mathematical model for simulating and collecting comprehensive raw data is constructed, specifically:
the one-dimensional spectrum acquisition mode is characterized in that for each spin nucleus in each spin system, the amplitude item and the frequency item of spectral line splitting caused by J coupling factors of all spin nuclei in each spin system (namely, the amplitude item of J coupling splitting peaks and the frequency item of J coupling splitting peaks), the frequency item caused by self chemical shift (namely, the chemical shift item), a rotating coordinate system data acquisition item, a T2 relaxation item, a T1 relaxation item, a magnetization vector inversion item (magnetization vector inversion) are calculated, the items are multiplied to obtain each spin nucleus signal respectively, and then a plurality of spin nucleus signals under each spin nucleus system are added to obtain each accumulated spin nucleus system signal. And then, continuously adding a plurality of spin nuclear system signals, and then superimposing analog random noise to obtain the analog-collected nuclear magnetic resonance spectrum original data. The raw data obtained is displayed and stored.
For example, under a first spin nuclear system (ABC), the terms are multiplied together to obtain a spin nuclear signal a, a spin nuclear signal B, and a spin nuclear signal C, which are added together to obtain an accumulated first spin nuclear system signal. Similarly, under the second spin nuclear system (XYZ), the items are multiplied to obtain a spin nuclear signal X, a spin nuclear signal Y and a spin nuclear signal Z, and the signals are added to obtain an accumulated second spin nuclear system signal. And then, the first spinning nuclear system signal and the second spinning nuclear system signal are added in succession, and then the simulated random noise is superposed, so that the simulated and collected nuclear magnetic resonance spectrum original data can be obtained.
The number of the spin nuclear system and the spin nuclear can be positive integers of 1-n, and n is more than 1.
Under a two-dimensional spectrum acquisition mode, on the basis of a one-dimensional spectrum, a diagonal peak frequency item (corresponding to a quantum operator Ix) and a cross peak frequency item (corresponding to a quantum operator Izy) caused by a t 1-dimensional evolution period of each spin disaster in each spin system are considered; taking the diagonal peak frequency term as the product factor of the spin nucleus; the cross-peak frequency term is then used as a factor of the product of the spin nuclei of the other side of the J-coupling, i.e. the manifestation of polarization transfer.
For decoupling, J-couplings corresponding to or within the decoupling frequency range can be set to 0 by the decoupling frequency and frequency range.
As shown in FIG. 3, the amplitude term Na of the split peak caused by J coupling can be obtained by the following double cycle (taking the A nucleus of AmBnCd spin system as an example, the numbers of the A, B and C spin nuclei are m, n and d respectively, and adjacent J couplings are Jab, Jac and Jbc respectively):
For i＝1:n+1
For j＝1:d+1
Na＝m/n/d*A0(n+1，i)*A0(d+1，j)；
End
End
as shown in FIG. 3, the frequency term Ja of the split peak due to J coupling can be obtained by the following double cycle (taking the A nucleus of AmBnCd spin system as an example, the numbers of the A, B, C spin nuclei are m, n, d, respectively, and the adjacent J couplings are Jab, Jac, Jbc, respectively)
For i＝1:n+1
For j＝1:d+1
exp(-i*Ja*t)＝exp(-i*(I0(n+1，I)*Jab)+I0(d+1，j)*Jac)*t)；
End
End
I0, a0 are respectively constructed two-dimensional matrices of 7 × 7;
in the above calculation, if the spin nuclear species exceed 3, for example, 4, 3-fold (4-1-fold) cycles are required; and so on.
Specifically, analog data acquisition of a single pulse sequence as a one-dimensional spectrogram measurement: as shown in the figure 3 of the drawings,
the first step is as follows: firstly, a data sampling model is constructed, namely a one-dimensional discrete time array comprises a plurality of parameters such as sampling point number, null scan times, delay sampling time, sampling bandwidth, echo time, sampling time t and the like, for example, t ═ is (DE:1/SW (DE + TD/SW)), a sampling rule determined for a sequence comprises the sampling bandwidth SW, the delay time DE and the sampling point number TD, and an example of an analog sampling data algorithm is as follows:
and secondly, respectively constructing a peak number array I0 of spectral line splits with different coupling nucleus numbers, wherein I0 is a two-dimensional array (matrix), the number of rows corresponds to different J coupling numbers, and the value of each row represents the number of spectral peak splits and the relative amount of frequency deviation. One specific example matrix of I0 is a 7 x 7 two-dimensional matrix:
I0＝【0，0，0，0，0，0，0；-1/2，1/2，0，0，0，0，0；-1，0，1，0，0，0，0，0；-3/2，-1/2，1/2，3/2，0，0，0；-2，-1，0，1，2，0，0；-5/2，-3/2，-1/2，1/2，3/2，5/2，0；-3，-2，-1，0，1，2，3；】
the first row indicates that there are no J-coupled kernels around, the frequency split score is 0, and the frequency offset value is 0; the second row shows 1J-coupled nucleus around, with a split number of 2 and relative amounts of frequency shift-1/2 and 1/2, respectively; the third row shows 2J-coupled nuclei around the cycle with a split number of 3 and relative amounts of frequency shift of-1, 0, 1; and so on. The matrix can simulate the condition that 6J-coupled nuclei surround at most, and basically covers the common molecular condition;
and thirdly, respectively constructing an amplitude array A0 of peaks of spectral line splits with different coupling nucleus numbers, wherein A0 is a two-dimensional array (matrix), the number of lines corresponds to different J coupling numbers, and the number of each line represents the number and the amplitude of the spectral peak splits. One specific a0 example matrix is a 7 × 7 two-dimensional matrix:
I0＝【1，0，0，0，0，0，0；1，1，0，0，0，0，0；1，2，1，0，0，0，0，0；1，3，3，1，0，0，0；1，4，6，4，1，0，0；1，5，10，10，5，1，0；1，6，15，20，15，6，1；】
the first row indicates that there are no J-coupled nuclei around, the frequency split fraction is 0, and the amplitude of the original peak is 1; the second row shows that 1J coupling nucleus exists around the second row, the splitting number is 2, and the amplitudes of splitting peaks are 1 and 1 respectively; the third row shows that 2J-coupled nuclei are around, the split number is 3, and the amplitudes of the split peaks are 1, 2 and 1 respectively; and so on. The matrix can simulate the condition that 6J-coupled nuclei surround at most, and basically covers the common molecular condition;
fourthly, calculating basic amplitude information of each spin nucleus (such as the A, B, C and the like) in each spin system, and considering factors such as a radio frequency excitation effect, a sample T1 relaxation effect, a sample intrinsic T2 relaxation effect, a sample actual T2 relaxation effect and the like, wherein the final amplitude is the product of the factors; the relaxation effect of T1 is 1-exp (-TR/T1).
The number of spin nuclei (m, n, d, etc. as mentioned above), TR, TE, T1, T2, B1, tau, deltaB0, etc. are mentioned;
fifthly, carrying out dot product on the frequency splitting information of each spin nucleus (such as the A, B, C and the like) in each spin system, specifically the frequency effect of chemical shift, and the frequency splitting effect Jab of the spin nucleus, namely I0A 0 Jab, with the J coupling effect on the periphery, and multiplying the elements in the matrix I0 and A0 corresponding to the number of the spin nuclei on the periphery by Jab;
wherein, model and molecular information such as I0, A0, J, W and the like are involved;
sixthly, multiplying the effects of the 4-5 steps, and then considering the data acquisition process under a rotating coordinate system to obtain a signal of a certain spin nucleus;
seventhly, repeating the steps 4-6, repeatedly calculating all spin nuclear signals and accumulating to obtain signals in a spin system;
and eighthly, repeating the steps 4-7 to obtain the acquisition signal of the other spinning system and then superposing the acquisition signals. Meanwhile, random noise is increased; the final analog acquisition data of the single pulse sequence can be obtained;
ninth, if there are more than 2 molecules of spin system, repeat eighth step.
Specifically, as a simulation data acquisition model of the COSY two-dimensional spectrum:
the first step is as follows: firstly, constructing a t 2-dimensional data sampling model, namely a one-dimensional discrete time array, which comprises a plurality of parameters such as sampling point number, null scan times, delay sampling time, sampling bandwidth, echo time, sampling time t and the like, such as t ═ (DE:1/SW (DE + TD/SW);
secondly, constructing a t 1-dimensional (evolution period) data acquisition model which is also a discrete time array; step values including t1, step number t 1; as a specific example, t1 ═ 0, step _ t1, num _ t1 ═ step _ t 1; wherein step _ t1 is an evolution period stepping value; num _ t1 is the evolution period step number; a specific example is step _ t1 ═ 1 ms; num _ t 1-128; other values are possible.
And thirdly, respectively constructing a peak number array I0 of spectral line splits with different coupling nucleus numbers, wherein I0 is a two-dimensional array (matrix), the number of rows corresponds to different J coupling numbers, and the numerical value of each row represents the number of spectral peak splits and the relative amount of frequency deviation. One specific example matrix of I0 is a 7 x 7 two-dimensional matrix:
I0＝【0，0，0，0，0，0，0；-1/2，1/2，0，0，0，0，0；-1，0，1，0，0，0，0，0；-3/2，-1/2，1/2，3/2，0，0，0；-2，-1，0，1，2，0，0；-5/2，-3/2，-1/2，1/2，3/2，5/2，0；-3，-2，-1，0，1，2，3；】
the first row indicates that there are no J-coupled kernels around, the frequency split score is 0, and the frequency offset value is 0; the second row shows 1J-coupled nucleus around, with a split number of 2 and relative amounts of frequency shift-1/2 and 1/2, respectively; the third row shows 2J-coupled nuclei around the cycle with a split number of 3 and relative amounts of frequency shift of-1, 0, 1; and so on. The matrix can simulate the condition that 6J-coupled nuclei surround at most, and basically covers the common molecular condition;
and fourthly, respectively constructing an amplitude array A0 of peaks of spectral line splitting with different coupling nucleus numbers, wherein A0 is a two-dimensional array (matrix), the line numbers correspond to different J coupling numbers, and the numerical value of each line represents the number and the amplitude of the spectral peak splitting. One specific example a0 matrix is a 7 x 7 two-dimensional matrix:
I0＝【1，0，0，0，0，0，0；1，1，0，0，0，0，0；1，2，1，0，0，0，0，0；1，3，3，1，0，0，0；1，4，6，4，1，0，0；1，5，10，10，5，1，0；1，6，15，20，15，6，1；】
the first row indicates that there are no J-coupled nuclei around, the frequency split fraction is 0, and the amplitude of the original peak is 1; the second row shows that 1J coupling nucleus exists around the second row, the splitting number is 2, and the amplitudes of splitting peaks are 1 and 1 respectively; the third row shows that 2J-coupled nuclei are around, the split number is 3, and the amplitudes of the split peaks are 1, 2 and 1 respectively; and so on. The matrix can simulate the condition that 6J-coupled nuclei surround at most, and basically covers the common molecular condition;
fifthly, calculating a self-evolution (corresponding to an angular peak) model of each spin nuclear in each spin system and a polarization transfer (corresponding to a cross peak) model of each other nuclear;
sixthly, calculating basic amplitude information of each spin nucleus (such as A, B, C and the like) in each spin system, and considering factors such as a radio frequency excitation effect, a sample T1 relaxation effect, a sample intrinsic T2 relaxation effect, a sample actual T2 relaxation effect and the like, wherein the final amplitude is the product of the factors; the T1 relaxation effect is 1-exp (-TR/T1).
The number of spin nuclei (such as m, n, d, etc. mentioned above), TR, TE, T1, T2, B1, tau, deltaB0, the number of echoes, etc. are referred to the model parameters constructed above;
seventhly, performing dot product on the frequency splitting information, specifically the frequency effect of chemical shift, of each spin nucleus (such as the aforementioned a, B, C and the like) in each spin system, namely the frequency splitting effect J of the spin nucleus with the J coupling effect around, namely I0 a 0J, and multiplying the frequency splitting effect J by the elements in the matrix of I0 and a0 corresponding to the number of the surrounding spin nuclei one by one;
wherein, model and molecular information such as I0, A0, J, W and the like are involved;
eighthly, multiplying the effects of the six-seven steps, and then considering the data acquisition process under a rotating coordinate system to obtain a t2 dimensional acquisition signal of a certain spin nucleus;
and a ninth step, after the t1 dimension self-evolution information obtained in the fifth step and the polarization transfer information of the nuclear core are expressed in complex number by other spin cores, the complex number is multiplied by the result of the eighth step to be used as the final signal of a certain spin nuclear.
The tenth step, repeating the sixth to ninth steps, and accumulating after repeatedly calculating all spin nuclear signals to obtain signals in a spin system;
and step eleven, repeating the step six to the step ten to obtain an acquisition signal of another spin system, and then performing superposition. Meanwhile, random noise is increased; the final analog acquisition data of the single pulse sequence can be obtained;
and a tenth step, if there are molecules of more than 2 spin systems, repeating the tenth step.
And 5, performing FT conversion on the original data acquired in the step 4 to obtain a real part, an imaginary part or a mode spectrum of a frequency spectrum, namely spectrum output. Since the bottom baseline of the real part is narrower and the resolution is better, the real part spectrogram is generally output. The invention can obtain a one-dimensional spectrogram/two-dimensional spectrogram or a three-dimensional spectrogram.
Further comprising a step 6, the general information of the real part spectrogram is not enough, and further processing is needed to give more useful information prompts. Such as performing phase correction, baseline correction, peak finding, integration, ranging, chemical shift correction, and other spectral processing. Spectrogram processing can be achieved by the prior art.
Further comprises a hardware parameter adjustment correction step. Effective results of nuclear magnetic resonance spectroscopy rely on a highly uniform and stable main magnetic field, well-matched tuning of the probe coils, and accuracy of the radio frequency angle. The deficiency of any link can have a great influence on the result. Therefore, in actual operation experiments, hardware adjustment and correction are respectively carried out on all links. The invention can also adopt the numerical simulation technology to realize the adjustment and correction functions, including modules such as wobb, shim, lock and PL1W adjustment and the like and adjustment and correction.
A wobb module:
firstly, constructing a probe coil resonance circuit model; the resonance mode can be a series resonance mode or a parallel resonance mode; one example of the present invention is a series resonance model; the series resonance circuit model comprises a coil equivalent inductor L (6nH), an equivalent resistor r (0.2 ohm), a matching capacitor cm (13pf is adjustable), and a tuning capacitor ct (120pf is adjustable);
secondly, calculating the power reflection coefficient of the circuit model in the tuning frequency range (580 MHz-620 MHz);
thirdly, displaying the difference between the reflection coefficient and the working frequency to be tuned;
fourthly, respectively adjusting the matching capacitor cm and the tuning capacitor ct to enable the peak frequency of the reflection coefficient to be consistent with the working frequency (tuning is successful); and the value of the reflection coefficient is minimal (best match); this step is consistent with the manual tuning matching process of the actual spectrometer, which requires a certain time to adjust;
step five, the fourth step can also be skipped, the tuning capacitance value and the matching capacitance value required by the optimal tuning matching are directly calculated through an automatic tuning matching theory calculation model, and the system can reach the optimal tuning matching state at once; the step is completely consistent with the automatic tuning matching process of the actual spectrometer, and the adjusting time is short;
in the embodiment of the present invention, as shown in fig. 5, after the target tuning frequency can be set, a red vertical line is displayed at the target frequency; tuning capacitance and matching capacitance are adjusted (coarse/fine) separately and resonance pad shift and reflection curve sharpness adjustment are observed. Carefully and slowly adjusting 2 capacitors to enable the sharp peak point of the reflection curve to be on a red line, simultaneously, the sharp degree of the curve is the highest, the displayed decibel value is the minimum (such as-140 dB and the like), and an automatic tuning button can be clicked, so that the optimal tuning capacitor and the optimal matching capacitor can be automatically calculated, and the reflection curve is displayed in the optimal state;
a shim module: as shown in the figure 6 of the drawings,
firstly, constructing a main magnetic field inhomogeneous field model; two models are constructed, wherein one model is to construct non-uniform terms of different orders according to the spatial position of a magnetic field; however, the model needs to perform point-by-point calculation during actual shimming operation, is long in time, and is not consistent with the operation process of an actual instrument. The present invention does not employ such a modeling approach. The construction model adopted by the invention is that 20 random numbers between-0.5 and 0.5 are constructed through a random function, meanwhile, the weight factor is multiplied according to the uneven weight in the actual instrument, and the method of randomly constructing uneven items each time is more consistent with the work of actual equipment, because different magnetic field inhomogeneities can be formed after different samples are placed into a magnet.
And secondly, respectively constructing weight factors of 20 groups of shimming items. Such as the Z term multiplied by 200, representing a maximum deviation of + -100 Hz; the method comprises the following specific steps:
[x,y,z,z2,z3,z4,z5,z6,xz,yz,xy,z2y2,xyz,x3,y3,xz2,yz2,x2y2z,yz3,xz3]
-50, 200,100,60,20,10,2,16,16,20,24,10,6,6,2,2,2,2, 2; the left array of the equation represents 20 groups of non-uniform terms, and the currents are respectively adjusted corresponding to 20 groups of shimming coils; to the right of the equation is the non-uniform weight of each non-uniform term.
Thirdly, adjusting one group of currents of the 20 groups of shimming coils, correspondingly giving out magnetic field components generated by the currents, and successively and correspondingly accumulating the magnetic field components with the original random differential inhomogeneous terms; after the remaining non-uniformity is modulo, the display FID signal is output, and the integral value of the FID signal is also output. When the magnetic field generated by the adjusting current is opposite to the originally set non-uniformity value, the magnetic field becomes uniform after superposition, the FID signal trailing becomes long, and the integral area becomes large.
Fourthly, sequentially and repeatedly adjusting the current of 20 groups of coils, wherein the adjustment principle of each group of coils is to increase the integral area; the specific adjustment is provided with three levels of coarse adjustment/fine adjustment, wherein coarse adjustment, fine adjustment and fine adjustment can be carried out firstly.
And fifthly, after the optimal adjustment is carried out in the fourth step, performing FT conversion on the FID signal, measuring and evaluating the full width at half maximum of the FID signal, and thus completing the adjustment and evaluation of the main magnetic field uniformity.
Specific example effects, as shown in fig. 6, the shim interface schematic: before shimming, an Acquire button can be clicked to Acquire an FID signal, and after FT, the observation frequency spectrum width is wider, which indicates that the uniformity is poor; if the sample-in button is not displayed in green, the situation that no standard sample is placed is indicated, and the FID signal is 0; sample-in can be clicked at this time to place the sample.
Clicking the shim coil z, wherein a button of the z turns green to indicate that the coil is being adjusted; while the adjustment slider below the interface is shown as z, the actual adjustment value is also shown as the actual adjustment current of the z-coil. At the moment, the sliding bar is adjusted (coarse adjustment/fine adjustment three-gear switching can be carried out), the tail of the FID signal slightly changes along with current adjustment, and meanwhile, the integral area value of the FID signal correspondingly increases and decreases. If the numerical value is increased to indicate that the magnetic field is uniform in the optimized direction, continuing the current regulation in the direction; otherwise, the field homogeneity is degraded, and the adjustment is reversed. Adjustment until the z current fails to increase the integral value indicates that z has reached a temporary optimum.
Clicking the x button again to turn green, which indicates that the current of the x coil is effectively adjusted. Similar to the above adjustment, the FID integration area is maximized; thereafter the remaining 18 sets of coils are adjusted in sequence. Then the x, y, z and the like are adjusted in a return way; when the integral value is maximum, the spectrum broadening is observed by FT again, and the resolution is improved.
If spin on/off is clicked to turn green, the nonuniformity in the x and y directions is 0 directly. Any x, y modulation degrades the magnetic field.
A lock module:
firstly, constructing lock field sample information including gyromagnetic ratio gama, T1, T2 and the like;
secondly, constructing a magnetic field time drift curve;
thirdly, constructing field locking current information including current regulation precision;
fourthly, setting a field locking frequency value and outputting center frequency drift; calculating the frequency deviation between the current and the current, calculating the required field locking current according to the current-magnetic field ratio, and tracking the frequency;
and fifthly, continuously repeating the step 4 every time according to 0.5s under the field locking state, so that the actual frequency is stabilized on the required frequency value.
P1 regulation module:
firstly, constructing a radio frequency power value regulating range (0-200W) of PL1W and a radio frequency pulse width P1 regulating range (0-100 us);
and secondly, constructing a physical mathematical model from the radio frequency power to the coil current to the radio frequency field B1, and establishing a conversion relation between the radio frequency power and the radio frequency field strength B1, wherein the final relation adopted by the invention is that B1 is 2.6 sqrt (PL1W)/1000 (Gs). The coefficient of 2.6 can be different according to different coil diameters, coil wire diameters and coil material differences;
thirdly, constructing a radio frequency flip angle calculation mathematical model, wherein theta is gama and B1 and p 1; gama is the gyromagnetic ratio;
fourthly, constructing a signal acquisition mathematical model, namely S ═ sin (theta) × exp (-1i × w × T) × exp (-T/T2);
fifthly, regulating PL1W or p1 respectively, and observing the change rule of the signal amplitude; the pulse width of 90 degrees and 180 degrees at different PL1W is determined according to the relevant theory.
Sixthly, in order to simulate the radio frequency field nonuniformity in the probe coil more truly, a B1 nonuniformity attenuation term can be constructed, wherein the B1(p1) is exp (-p 1/0.0005); the non-uniform decay exponential time for B1 was 500us, a value that can vary depending on probe coil specifications.
Step seven, setting an automatic step p1, sequentially collecting signals, displaying a peak value after FT, and obtaining a nutation spectrogram (shown in figure 8); the p1 values of different angles can be obtained at one time. The degree of non-uniformity of B1 was also observed;
examples are shown in FIG. 7 for the effects of PL1W and P1 modulation: adjusting the power value of a radio frequency field power PL1W sliding bar, wherein the power value changes, the frequency spectrum amplitude of a right signal also changes, and the frequency spectrum amplitude changes according to the transformation rule between the radio frequency turnover angle and the signal amplitude;
adjusting a radio frequency pulse width P1 sliding strip, wherein the pulse width value of the sliding strip changes, the frequency spectrum amplitude of a right signal also changes, and the frequency spectrum amplitude changes according to the change rule between the radio frequency flip angle and the signal amplitude;
the nutation spectrum effect in the embodiment of the invention is as shown in fig. 8: after min-p1, max-p1 and the step value are set, click the go button. The peaks of the spectra at different values of p1 appear on the right. The peak value change is consistent with the change rule of the change rule between the radio frequency turning angle and the signal amplitude, and the change rule follows the sine change rule, namely the nutation spectrum;
the whole adjusting process is the same as the real machine adjusting process and parameter setting.
The phase correction effect in the embodiment of the present invention is as shown in fig. 9: after data acquisition and FT are carried out on ethanol molecules, dispersion components appear in a part of spectrogram, and the part of spectrogram is not completely in an absorption line shape. After clicking the phase correction button on the main interface, a cross line appears, and the purpose is to determine the pivot to be adjusted (0-order correction main peak). Clicking a left key at a certain group of peaks to complete the pivot setting;
thereafter, the zeroth order phase PL0 is adjusted up/down, and the change of the peak shape of pivot is observed until the peak shape of pivot shows a standard absorption line shape; thereafter, the first-order phase PL1 was adjusted up/down to observe changes in the peak shape outside the pivot until all peak shapes exhibited the standard absorption profile. During the process of PL1 knots, the pivot peak shape remains unchanged;
the principle of pivot setting is that the vicinity of the highest peak is set as a common practice. In practice, different peaks can be set as the pivot, and the final perfect phase correction can be achieved.
The adjusting process and the adjusting effect realized on the system are the same as those of a real spectrometer.
If the automatic integration button is clicked on the spectrogram after phase correction, the integral spectrum effect of the spectrogram appears, such as the automatic integral effect of the spectrogram in the embodiment of the present invention shown in fig. 10.
For the spectrogram after phase correction, the automatic peak searching button is clicked, so that the automatic peak searching and peak position marking effects of the product of the spectrogram appear, as shown in fig. 11, in the embodiment of the invention, the automatic peak searching effect of the spectrogram appears.
In an embodiment, two-dimensional data acquisition is performed on ethanol (which may also be directed to any other molecule in the molecule library), and a two-dimensional spectrogram display effect of an ethanol molecule is obtained after 2DFT, as shown in fig. 12, the two-dimensional spectrogram contour display effect obtained by acquisition is obtained. In the embodiment, the two-dimensional spectrogram obtained by virtual acquisition by applying the method disclosed by the invention has a mesh display effect as shown in fig. 13.
Fig. 14 shows an intermediate effect of the two-dimensional spectrogram of fig. 12, and shows an effect obtained by performing FT only on the t 2-dimensional data. Fig. 14 shows (part of) two-dimensional spectral data obtained by virtual acquisition according to the present invention after one-dimensional FT, where the phase change of different spectral peaks can be seen. Fig. 14 shows only 25 pieces of data after one-dimensional FT (one-dimensional array), and the total data of this example is 100 pieces. The total number of data is num _ t 1.
The protection content of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, which is set forth in the following claims.
Claims (9)
1. A method for simulated nuclear magnetic resonance spectroscopy to facilitate expansion of a library of molecular information, the method comprising:
building a simulation sample molecular information model and a simulation sample molecular information base; the constructed molecular information of the sample is added through an EXCEl database or through software interface parameters, and comprises the following steps: spin body coefficient, spin species, number of each spin, chemical shift, J-coupling, and D value; there is no indirect coupling J or direct coupling D between spin nuclei between different spin systems; the molecular information of the sample is determined according to two or more spin systems, and the nuclear species in each spin system are three, four, five or more; the spin regime includes: spin systems AmBnCd and XpYqZw, wherein ABC are three spin nuclei which are mutually coupled, and the number of the nuclei is m, n and d respectively; XYZ is another three kinds of coupled spin nuclei, and the number of nuclei is p, q and w respectively;
constructing a hardware parameter of the spectrometer; the hardware parameters of the spectrometer comprise a main magnetic field B0, offset, main magnetic field inhomogeneity deltaB0, a radio frequency field B1, a gradient field G, radio frequency power PL1W, P1 and P2;
adjusting and correcting hardware parameters; adjusting and correcting are achieved by adopting a numerical simulation technology, and the adjusting and correcting method comprises automatic tuning matching wobb, shimming shim, lock field lock and P1 adjustment;
constructing a spectrum sequence physical model, wherein the spectrum sequence comprises a single pulse sequence, a decoupling sequence, a same-nucleus chemical shift related two-dimensional spectrum COSY sequence, a same-nucleus chemical shift related overhause enhanced two-dimensional spectrum NOESY sequence, a heteronuclear chemical shift related spectrum and a heteronuclear chemical shift related spectrum; the decoupling sequence comprises dept45, dept90 and dept 135;
constructing a nuclear magnetic resonance spectrum data acquisition physical mathematical model based on the constructed sample molecular information model and information base, the spectrometer hardware parameters and the spectrum sequence physical model, and performing simulation data acquisition algorithm and program realization to complete simulation acquisition of original data; in the step of constructing original data by the physical and mathematical model for acquiring the nuclear magnetic resonance spectrum data, respectively calculating an amplitude item and a frequency item of spectral line splitting caused by J coupling factors of all spin nuclei in each spin system, a frequency item caused by self chemical shift, a data acquisition item under a rotating coordinate system, a T2 relaxation item, a T1 relaxation item and a magnetization vector overturning item for each spin nucleus in each spin system in a one-dimensional spectrum acquisition mode, multiplying the items to obtain each spin nucleus signal, and then adding each spin nucleus and all spin nucleus signals in each spin nucleus system to obtain each accumulated spin nucleus system signal; then, adding the spin system signals of all spin systems in succession, and then superimposing analog random noise to obtain analog collected nuclear magnetic resonance spectrum original data; in the step of constructing the physical and mathematical model for acquiring the nuclear magnetic resonance spectrum data, under a two-dimensional spectrum acquisition mode, on the basis of a one-dimensional spectrum, a frequency term of a diagonal peak caused by a t 1-dimensional evolution period of each spin nucleus in each spin system is used as a multiplication factor of the spin nucleus; taking the cross-peak frequency term caused by each spin nucleus in each spin system in the t 1-dimensional evolution period as a product factor of the other spin nucleus of the J coupling;
and carrying out Fourier transformation on the original data acquired in the last step to obtain a spectrogram.
2. The simulated nuclear magnetic resonance spectroscopy method of claim 1, further comprising subjecting the spectrogram obtained by the method of claim 1 to spectrogram processing, wherein the spectrogram processing method comprises phase correction, baseline correction, peak finding, integration, ranging, chemical shift correction.
3. The method of simulated nuclear magnetic resonance spectroscopy of claim 1 wherein the spectroscopic sequences comprise a single pulse sequence, a decoupling sequence, a nuclear chemical shift-related two-dimensional spectroscopy COSY sequence, a nuclear chemical shift-related overhause enhanced two-dimensional spectroscopy NOESY sequence, a heteronuclear chemical shift-related spectroscopy 1H-13C HSQC sequence, a heteronuclear chemical shift-related spectroscopy 1H-13C HMBC sequence.
4. A simulated nuclear magnetic resonance spectroscopy system for facilitating expansion of a library of molecular information, the system employing the method of simulated nuclear magnetic resonance spectroscopy for facilitating expansion of a library of molecular information of any one of claims 1 to 3, the system comprising:
the building module of the simulation sample molecular information model and the molecular information base is used for building the simulation sample molecular information model and the molecular information base;
the construction module of the hardware parameter of the spectrometer is used for constructing the relevant hardware parameter of the spectrometer;
the spectrometer hardware parameter adjusting and correcting module is used for constructing a simulation adjusting and correcting model of spectrometer hardware parameters; the adjusting and correcting module comprises an automatic tuning matching wobb module, a shimming shim module, a field locking lock module and a P1 adjusting module;
the building module of the spectrum sequence physical model is used for building physical models of different spectrum sequences;
the building module of the nuclear magnetic resonance spectrum data acquisition physical mathematical model is used for building the nuclear magnetic resonance spectrum data acquisition physical mathematical model, carrying out simulation data acquisition algorithm and program realization and realizing the simulation acquisition of the original data;
and the spectrum inversion module is used for performing FT conversion on the original data acquired by the simulation to obtain a spectrum.
5. The simulated nuclear magnetic resonance spectroscopy system of claim 4, further comprising a spectrogram processing module for performing spectrogram processing on the obtained spectrogram, including spectrogram processing such as phase correction, baseline correction, peak finding, integration, ranging, chemical shift correction, and the like.
6. Use of a simulated nmr spectroscopy system for expanding a library of molecular information according to claim 4 in a virtual experimental training platform for nmr spectroscopy applications.
7. Use of a simulated nuclear magnetic resonance spectroscopy system for facilitating expansion of a library of molecular information according to claim 4 in a self-learning principle for an individual skilled in the art of related spectroscopy.
8. Use of a simulated nuclear magnetic resonance spectroscopy system for facilitating expansion of a library of molecular information according to claim 4 in instrument development and test calibration.
9. A NMR relaxometry analysis technique simulation analyzer, the simulation analyzer comprising the NMR spectroscopy analysis system of claim 4, configured to facilitate expansion of the library of molecular information, and run on a computer carrier.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6052519A (en) * | 1996-12-20 | 2000-04-18 | The University Of Queensland | Computer simulation of magnetic resonance spectra employing homotopy |
| WO2014130813A1 (en) * | 2013-02-21 | 2014-08-28 | New York University | Method and device for accurate quantification of t2 relaxation times based on fast multi spin-echo nmr sequences |
| CN105241911A (en) * | 2015-09-23 | 2016-01-13 | 中国石油大学(北京) | LBM-based simulated low field nuclear magnetic resonance fluid analysis method and device |
| CN106814337A (en) * | 2017-01-21 | 2017-06-09 | 厦门大学 | A kind of nuclear magnetic resonance transverse relaxation measuring method without the interference of J coupling effects |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100346171C (en) * | 2004-07-23 | 2007-10-31 | 华东师范大学 | Receiving method of nuclear magnetic resonance imaging signal |
| WO2006134558A2 (en) * | 2005-06-16 | 2006-12-21 | Koninklijke Philips Electronics N.V. | Low power decoupling for multi-nuclear spectroscopy |
| CN1959427B (en) * | 2006-09-30 | 2010-05-12 | 上海卡勒幅磁共振技术有限公司 | Method for guaranteeing coherence between radio transmitting and receiving signals in magnetic resonance imaging spectrometer |
| CN101051075B (en) * | 2007-04-24 | 2010-04-14 | 骆建华 | Magnetic resonant part K data image re-establishing method based on compound strange spectrum analysis |
| CN101135722B (en) * | 2007-10-23 | 2010-10-06 | 骆建华 | Signal noise removing method based on reconstruction signal substituting frequency spectrum data |
| CN101847261B (en) * | 2010-05-10 | 2012-02-15 | 南京航空航天大学 | Obtaining method of rat head magnetic resonance image Monte Carlo simulation model |
| CN102258369A (en) * | 2010-05-31 | 2011-11-30 | 西门子公司 | Method and system for simulating magnetic resonance imaging (MRI) signal |
| CN103116148B (en) * | 2013-01-30 | 2015-04-01 | 上海理工大学 | Inversion method of nuclear magnetic resonance two-dimensional spectrum |
| US10614359B2 (en) * | 2014-04-19 | 2020-04-07 | Case Western Reserve University | Magnetic resonance fingerprinting (MRF) serial artificial neural network (ANN) sequence design |
| CN104021301B (en) * | 2014-06-18 | 2017-01-11 | 哈尔滨工业大学 | Magnetic resonance imaging simulating method for irrelevant movement in myocardial microcirculation perfusion voxel |
| US10551520B2 (en) * | 2014-11-13 | 2020-02-04 | Colorado School Of Mines | Surface relaxivity calculation using nuclear magnetic resonance (NMR) measurement, three dimensional (3D) rock model and NMR response simulation |
-
2018
- 2018-02-27 CN CN202110509302.1A patent/CN113466280B/en active Active
- 2018-02-27 CN CN201810161333.0A patent/CN108710092B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6052519A (en) * | 1996-12-20 | 2000-04-18 | The University Of Queensland | Computer simulation of magnetic resonance spectra employing homotopy |
| WO2014130813A1 (en) * | 2013-02-21 | 2014-08-28 | New York University | Method and device for accurate quantification of t2 relaxation times based on fast multi spin-echo nmr sequences |
| CN105241911A (en) * | 2015-09-23 | 2016-01-13 | 中国石油大学(北京) | LBM-based simulated low field nuclear magnetic resonance fluid analysis method and device |
| CN106814337A (en) * | 2017-01-21 | 2017-06-09 | 厦门大学 | A kind of nuclear magnetic resonance transverse relaxation measuring method without the interference of J coupling effects |
Non-Patent Citations (3)
| Title |
|---|
| The Virtual NMR Spectrometer: A Computer Program for Efficient Simulation of NMR Experiments Involving Pulsed Field Gradients;Peter Nicholas, David Fushman, Vladislav Ruchinsky, and David;《Journal of Magnetic Resonance》;20000831;全文 * |
| 基于Virtools与Flash的实时交互虚拟NMR实验室;付晓靓 张永策 林丛丛 刘志广;《计算机与应用化学》;20110928;全文 * |
| 核磁共振波谱分析的计算机模拟实验教学;彭惠琦 张亮;《实验室研究与探索》;20030615;全文 * |
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