Non-diagnostic method for selectively detecting glycine molecules in mixed system based on magnetic resonance optimization control pulse and application

Abstract

The invention discloses a non-diagnostic method for selectively detecting glycine molecules in a mixed system based on magnetic resonance optimal control pulses, which is characterized in that the evolution of nuclear spin quantum states of mixed molecules including the glycine molecules is simultaneously controlled by utilizing broadband excited optimal control pulses; before and after the optimized pulse is applied, a magnetization vector of glycine molecule nuclear spinning is always in a z direction, and transverse magnetization vectors of other molecules are dispersed by applying gradient pulse, so that retention and selective detection of glycine magnetic resonance signals are realized. The method has a wide application scene.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of magnetic resonance technology, and in particular to a method for selectively detecting glycine molecules in a mixed system based on magnetic resonance optimized control pulses for non-diagnostic purposes, which realizes selective observation of the H signal of the glycine molecules. 1 H signal. BACKGROUND

[0002] Glycine is the simplest amino acid in the series of 20 members of amino acids, and is a non-essential amino acid in the human body. It has both acidic and basic functional groups in the molecule and is a strong electrolyte in aqueous solution. Glycine is the only amino acid that does not contain a chiral carbon atom, and therefore has no optical activity. Due to its special structure, glycine plays an irreplaceable role in the field of new drug synthesis and biochemical research. Glycine is not only one of the important synthetic substrates of life macromolecules such as proteins and nucleic acid molecules, but also can act as a neurotransmitter to transmit information, with a concentration often lower than 1 mmol / L in the normal human brain. Glycine can generate a carbon unit in the human body, which, combined with tetrahydrofolate, is a raw material for the synthesis of purines and pyrimidines. Reduced glutathione, which can be synthesized from glycine, is an important antioxidant in the body, which can protect some proteins containing sulfhydryl groups from oxidation and protect the integrity of cell membranes. As one of the most basic chemical substances in living organisms, glycine plays an indispensable physiological function in the body and is closely related to many important biological activities, metabolic activities, and organ functions. Recent scientific research has further proven that many tumor diseases in mammals, including humans, are closely related to abnormal glycine content in the corresponding organs or parts of the body, including kidney cancer, breast cancer, and brain tumors, which are related to cell proliferation and metastasis. Glycine usually accumulates at a higher concentration in its tumor tissue sites. According to relevant literature, the glycine concentration in the brain is higher than 2.5 mM, and the survival rate is lower. Therefore, glycine can be used as one of the detection methods for comprehensive judgment of tumors, and has the potential to be a metabolic molecular marker for cancer.

[0003] Currently, the main detection methods for glycine include high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), chemical methods, and ion chromatography, etc. These methods all require complex pretreatment processes, and cannot realize online non-destructive detection of glycine in more complex biological organisms. SUMMARY

[0004] In order to solve the problems in the prior art, the method for selectively detecting glycine molecules in a mixed system based on magnetic resonance with optimized control pulses for non-diagnostic purposes has good accuracy, sensitivity and selectivity. The signal intensity after selective detection by the method can reach 90% of the signal intensity in the original aqueous solution, and the minimum detectable concentration is 0.2 mmol / L. The selective detection method in the application can accurately detect the signal of glycine molecules from a complex system (such as a mixed solution system, a mixed gel system, etc.), while effectively eliminating the interference of other substances.

[0005] The specific technical scheme for achieving the object of the application is:

[0006] The method for selectively detecting glycine molecules in a mixed system based on magnetic resonance with optimized control pulses for non-diagnostic purposes, in the specific implementation process, the mixed system can include glycine molecules, inositol molecules, glutamic acid molecules, etc.; the selective detection method includes the following specific steps:

[0007] Step i, the magnetic resonance signals of glycine molecules, inositol molecules and glutamic acid molecules in the mixed system are excited by the first optimized control pulse OC pulse I and the second optimized control pulse OC pulse II at the same time, the nuclear spins of other molecules including inositol molecules and glutamic acid molecules are completely converted from longitudinal magnetization to transverse magnetization, and the nuclear spins of glycine molecules are kept in longitudinal magnetization after the application of the optimized control pulse;

[0008] Step ii, a gradient pulse is applied, and the transverse magnetization vectors of other molecules except glycine molecules converted by the optimized control pulse are scattered, that is, the magnetic resonance signals of other molecules including inositol molecules and glutamic acid molecules rapidly decay to zero due to the action of the gradient pulse, while the magnetic resonance signals of glycine molecules are retained;

[0009] Step iii, the glycine molecules retaining the magnetic resonance signals are converted into an observable state by applying a PRESS positioning pulse, and the magnetic resonance signals are collected, so as to realize the selective detection of the magnetic resonance signals of glycine molecules.

[0010] In one specific embodiment, the step i can further include the step of applying a water suppression module to resonate and saturate the hydrogen protons in the aqueous solution, thereby suppressing the water signal in the magnetic resonance signal; the frequency bandwidth of the water suppression module is set to 35 Hz.

[0011] In the step i, the spin evolution of the multi-spin system composed of inositol-glycine-glutamic acid (the six methylene hydrogens of inositol are labeled as H1, H2, H3, H4, H5 and H6, respectively, the two equivalent methylene hydrogens of glycine are labeled as H7, and the methine and methylene hydrogens of glutamic acid are labeled as H8, H9, H10, H11 and H12, respectively) is controlled by an optimized control pulse, so that the thermal equilibrium state of the nuclear spins of inositol-glycine-glutamic acid (ρ(0)=I 1z +I 2z +I 3z +I 4z +I 5z +I 6z +I 7z +I 8z +I 9z +I 10z +I 11z +I 12z ) is converted into a combination of multiple spin states (ρ(1)=I 1x +I 2x +I 3x +I 4x +I 5x +I 6x +I 7z +I 8x +I 9x +I 10x +I 11x +I 12x ); wherein, after the optimized control pulse, the signals of the hydrogens of inositol and glutamic acid are in transverse magnetization, and the methylene hydrogen of the glycine molecule is still in longitudinal magnetization.

[0012] In the step ii, the states of the 11 nuclear spins contained in the inositol-glutamic acid molecule are rapidly dephased by applying a gradient pulse, and only the magnetic resonance signal of glycine is retained.

[0013] The gradient pulse includes a first gradient pulse g1 and a second gradient pulse g2, the intensity of the first gradient pulse is 5 mT / s, and the application time is 2 ms; the intensity of the second gradient pulse is 20 mT / s, and the application time is 2 ms.

[0014] In the step iii, a PRESS pulse is applied to selectively detect the glycine proton signal. The present application simultaneously considers the suppression of the signals of glutamic acid and inositol molecules, and compared with the method reported in the literature, the suppression effect of inositol and glutamic acid is better, the retention efficiency of glycine is higher, the sensitivity of the method of the present application is high, and the quantification is more accurate; at the same time, compared with the method reported in the literature, the suppression effect on choline is also better.

[0015] The PRESS pulse consists of a 90°, two 180° pulses for spin excitation and spatial localization;

[0016] The parameters of the PRESS pulse are as follows:

[0017] Repetition time (TR) = 2s;

[0018] Echo time (TE) = 30ms;

[0019] Acquisition points (TD) = 1024;

[0020] Spectrum width (SW) = 1024Hz;

[0021] Average times = 64;

[0022] In one embodiment, the average times can be increased appropriately; the size of the voxel selected in the detection space is based on the area of the region or lesion area to be detected.

[0023] During the operation sequence of the present application, the relevant parameters include:

[0024] B0 magnetic field: 0-11.7T, preferably 3T;

[0025] Nuclear spin state

[0026] Initial state: p(0) = I 1z +I 2z +I 3z +I 4z +I 5z +I 6z +I 7z +I 8z +I 9z +I 10z +I 11z +I 12z (Number 7 represents the hydrogen proton of glycine)

[0027] Final state: p(1) = I 1x +I 2x +I 3x +I 4x +I 5x +I 6x +I 7z +I 8x +I 9x +I 10x +I 11x +I 12x

[0028] First and second optimized pulse power: 0-200Hz, preferably 180Hz;

[0029] The first and second optimized pulse lengths: 0-300 ms, preferably 120 ms;

[0030] The wideband interpolation points: 0-6, preferably 3;

[0031] The bandwidth: 0-50 Hz, preferably 10 Hz;

[0032] In the specific implementation process, the application introduces the concept of wideband excitation in the optimized pulse, when the narrowband sequence is run, the computer only performs digital pulse calculation and preparation on the radio frequency center (zero interpolation is 0 and the bandwidth is 0), and only one solution is obtained. The application considers running the pulse in a larger interpolation and a larger bandwidth range; in a specific implementation mode, when the wideband sequence is run, the optimal zero interpolation is 3 and the bandwidth is 10; the computer obtains seven optimal (2*3+1) solutions in ±10 Hz (2*10), the calculation amount is larger, but the pulse is more stable, and in the actual application, the optimized control pulse can still be good in the radio frequency center ±10 Hz, and the tolerance to the magnetic field inhomogeneity is higher. The efficiency of the pulse is not sensitive to the change of the radio frequency pulse excitation center, and when the experiment is implemented, the effect of the detection can be good in a larger frequency range, the center frequency of the pulse does not need to be adjusted, and the time of the whole experiment can be greatly shortened.

[0033] The magnetic resonance pulse sequence of the application is as shown in the figure Figure 2 In addition to the preparation and detection pulses, the pulse sequence also includes a water suppression module and a conventional localization sequence PRESS (Point Resolved Spectroscopy) module; specifically, first, a water suppression pulse based on the pre-saturation principle is applied, then a preparation pulse is applied, and finally a spatially localized PRESS pulse is applied. Wherein g1 and g2 are two gradient fields with different strengths, in the Siemens 3T Prisma system, the strengths of the two groups of gradients are 5 mT / m and 20 mT / m respectively, and the application time is 2 ms.

[0034] In the specific implementation process of the application, complete 6-spin calculation is performed on the two pairs of hydrogen protons in the inositol molecule which are chemically equivalent but not magnetically equivalent, so that the technical solution in the application has better inositol peak suppression effect.

[0035] The application also provides application of the above method in selective observation of glycine molecule signals in complex systems for non-diagnostic purposes and the like.

[0036] Compared with the prior art, the application has the beneficial effects including:

[0037] The pulse sequence of the present application can well suppress the signals of myo-inositol and glutamate, and selectively stimulate the signal of glycine, and the efficiency of the pulse is not dependent on the radio frequency excitation center to a certain extent. Meanwhile, the pulse sequence has the advantages of simple operation, painlessness and non-invasiveness, and can be used for monitoring the content and distribution of glycine in vivo, and has important application value in the fields of biology and medicine.

[0038] Compared with the prior art, the present application has the following advantages: high specificity, only the signal of glycine molecule is selectively observed, and the signal of other compounds with similar molecular structure is not interfered; simple method, the glycine in the sample to be tested does not need to be separated, and the method can be directly applied to the detection of glycine in a mixed sample; rapid measurement, only the sample needs to be placed in a nuclear magnetic device, and a complete set of pulse sequences for glycine molecules is run, and the magnetic resonance spectrum can be obtained in a few minutes, and the detection is completed; non-destructive to the sample, the nature of the sample or the structure of the glycine molecule does not need to be changed, and only a specific pulse is applied by using a nuclear magnetic resonance instrument to selectively detect the glycine molecules contained in the sample; no dependence on field strength, suitable for different specifications of magnetic resonance spectrometers, as long as the liquid nuclear magnetic hydrogen spectrum of glycine molecules is obtained, the J coupling size and the chemical shift difference between the two hydrogen protons in the molecule and the protons in the myo-inositol molecule are obtained, and the required pulse parameters can be calculated by SPINACH for selective detection of glycine; can be applied to living bodies, and a probe molecule does not need to be injected into the living body, and the glycine molecules can be detected in real time without damaging the cells of the tissue. BRIEF DESCRIPTION OF DRAWINGS

[0039] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0040] Figure 1 is a MRS spectrum graph collected by a mixed aqueous solution in different sequences.

[0041] Figure 2 is a selective detection pulse sequence graph used in the present application.

[0042] Figure 3is a schematic diagram of peak retention efficiency of glycine under different radio frequency centers in narrowband excitation.

[0043] Figure 4 is a schematic diagram of peak retention efficiency of glycine under different radio frequency centers in wideband excitation of the application.

[0044] Figure 5 is a schematic diagram of molecular structure and spin numbering of myo-inositol, glycine and glutamic acid.

[0045] Figure 6 is a graph of experimental results of the application.a) is a MRI positioning graph of a plastic bottle filled with an aqueous glycine solution in the application;b) is a MRS spectrum of sensitivity test of the aqueous glycine solution in the application;c) is a standard curve of peak intensity at different concentrations.

[0046] Figure 7 is a) a T2-Flair MRI image of a brain of a glioma patient and b) a spectrum obtained by a conventional PRESS acquisition.

[0047] Figure 8 is a) a T2-Flair MRI image of a brain of a glioma patient, b) a MRS spectrum obtained by a glycine-targeted sequence acquisition and c) a MRS spectrum obtained by a conventional PRESS acquisition. DETAILED DESCRIPTION

[0048] The application will be further described in conjunction with the following specific examples and drawings. The process, conditions, experimental methods and the like for implementing the application are the general knowledge and common sense in the art, and the application does not have special limitations.

[0049] The application provides a magnetic resonance pulse sequence method for selectively detecting glycine in a mixed system based on magnetic resonance optimized control pulses for non-diagnostic purposes. The method uses the characteristics of glycine chemical shift and J-coupling, the differences between glutamic acid and myo-inositol molecular chemical shift and J-coupling, and designs an optimized control pulse for wideband excitation to control the evolution of multiple molecular spins, so as to selectively detect the glycine signal in a complex system. The application detects glycine molecules based on the principle and equipment of magnetic resonance, has high glycine signal retention, suppresses the myo-inositol and glutamic acid peaks that affect the quantification of glycine, introduces a wideband design into the optimized control pulse, so that the optimized control pulse has certain tolerance to radio frequency center inaccuracy and field inhomogeneity, can simply and effectively eliminate the interference of other substances in the system without damaging the sample or changing the properties of the sample, and accurately discovers and verifies the signal of glycine from a complex test system. At the same time, the application also has the advantages of simple operation, rapid time efficiency, painless and non-invasive, and can be applied to monitor the content and distribution of glycine in vivo, and has important application value in biological research, industrial production and medical field.

[0050] Specifically, the application provides a method for selectively detecting glycine in a mixed system based on magnetic resonance for non-diagnostic purposes, the method comprising the following steps:

[0051] Step i, exciting glycine molecules, inositol molecules and glutamic acid molecules simultaneously by a first optimal control pulse and a second optimal control pulse, completely converting the nuclear spins of the inositol molecules and the glutamic acid molecules from longitudinal magnetization to transverse magnetization, and ensuring that the nuclear spins of the glycine molecules remain in longitudinal magnetization after the optimal control pulses are applied;

[0052] Step ii, applying gradient pulses to the mixed system of the glycine molecules, the inositol molecules and the glutamic acid molecules, scattering the transverse magnetization vectors of the inositol molecules and the glutamic acid molecules, and rapidly decaying the magnetic resonance signals of the inositol molecules and the glutamic acid molecules to 0 due to the effect of the gradient pulses, while retaining the magnetic resonance signals of the glycine molecules;

[0053] Step iii, converting the quantum state and the magnetic resonance signals of the glycine molecules into observable states by a PRESS positioning pulse and collecting signals, to achieve selective detection of the glycine molecules.

[0054] The magnetic resonance pulse sequence used in the application is as shown in the following figure, comprising a water suppression module, a signal selection module, an excitation and positioning module, and a signal collection module. Figure 2 The water suppression module suppresses the water signals in the magnetic resonance signals by applying the water suppression module to the system to cause resonance saturation of the hydrogen protons in the aqueous solution.

[0055] The signal selection module comprises a first optimal control pulse, a second optimal control pulse, and two gradient pulses, which completely convert the nuclear spins of other molecules including the inositol molecules and the glutamic acid molecules from longitudinal magnetization to transverse magnetization, while ensuring that the nuclear spins of the glycine molecules are in longitudinal magnetization after the pulses are applied; then scattering the transverse magnetization vectors of other molecules except the glycine molecules, i.e., the magnetic resonance signals of other molecules including the inositol molecules and the glutamic acid molecules rapidly decay to 0 due to the effect of the gradient pulses, while the magnetic resonance signals of the glycine molecules are retained.

[0056] The excitation and positioning module converts the magnetic resonance signals of the glycine molecules into observable states by using a PRESS pulse.

[0057] The signal collection module is used for detecting and collecting the magnetic resonance signals of the glycine molecules.

[0058] The signal collection module is used for detecting and collecting the magnetic resonance signals of the glycine molecules.

[0059] Example 1

[0060] The mixture system of glycine, inositol and glutamic acid is used in the embodiment, and a multi-self-selected system is formed. Six methylene hydrogen protons of inositol are labeled as H1, H2, H3, H4, H5 and H6 respectively, two equivalent hydrogen protons in the methylene of a glycine molecule are labeled as H7, and one methine hydrogen proton and two methylene hydrogen protons in a glutamic acid molecule are labeled as H8, H9, H10, H11 and H12 respectively. The structures of the glycine, the inositol and the glutamic acid are as shown in Figure 5 .

[0061] The embodiment is a technical detail of glycine targeting sequence on Siemens PRISMA 3.0T imager and a water model filtering effect display, and the specific steps are as follows:

[0062] Step 1: In the embodiment, glycine, glutamic acid and inositol are dissolved in water, and a water solution with a mass fraction of 0.5% glycine, 2.0% inositol and 2.0% glutamic acid is prepared and placed in a magnetic resonance imager to obtain Figure 1 glycine, glutamic acid and inositol shown in a) of 1 H MRS spectrum, wherein the glycine hydrogen proton chemical shift is 3.55ppm, the hydrogen protons of the inositol molecule are 4.05ppm, 3.61ppm, 3.61ppm, 3.52ppm, 3.52ppm and 3.27ppm respectively, and the glutamic acid hydrogen protons are 2.05ppm, 2.12ppm, 2.33ppm, 2.35ppm and 3.75ppm respectively;

[0063] Step 2: Based on the differences in the chemical shifts and J-coupling of glycine and inositol hydrogen protons, the initial state and the final state of twelve spins are set, and the operator form is expressed as follows:

[0064]

[0065] The duration setting range of the optimized control pulse is 5ms-3000ms, and the number range of the optimized pulse is 500-3000.

[0066] Step 3: Based on the pre-created script file and the SPINACH program opened by the program command symbol window, finally, the pulse file for converting the rho0 quantum state into the rho1 quantum state is obtained, and the operator expression is as follows:

[0067] The Hamiltonian H J based on J-coupling evolution is:

[0068]

[0069] The Hamiltonian H w based on chemical shift evolution is:

[0070]

[0071] Hamiltonian H0 under the Zeeman effect:

[0072] H0= H J + H w

[0073] Consider the total Hamiltonian H after optimizing the pulse:

[0074] H = H0 + 2*pi*power(k)*(rho0*sin(phase(k)) + rho0*cos(phase(k)))

[0075] rho1 = expm(-1*i*H*tau)*rho0*expm(1*i*H*tau)

[0076] Where: phase(k) represents the phase of the optimized control pulse, power(k) represents the power of the optimized control pulse. The generated pulse document is represented in a 2000*2 matrix, 2000 represents the number of pulses, and 2 represents the power and phase.

[0077] After the evolution of the operation operator and the Hamiltonian under the hard pulse, the final state rho1 is obtained by multiplying the target operator Q and taking the trace, that is, the preparation efficiency of the optimized pulse:

[0078]

[0079] S = trace(rho1*Q) / trace(Q*Q)

[0080] S represents the conversion rate of the designed quantum state. In order to maximize the conversion rate, SPINACH fitting is used to modify the pulse duration and pulse number in the script, so that the optimal value of the thermal equilibrium state term (the absolute value of S) is obtained.

[0081] In the specific implementation process of the embodiment, the detection system and the optimized pulse are optimized. Before optimization, only inositol and glycine molecules are considered, and inositol is only considered as a 4-spin system (complete 6-spin system), and glutamic acid molecules are not added, and narrow-band pulses with interpolation point number 0 and bandwidth 0 are used; After optimization, a twelve-spin system containing inositol, glycine and glutamic acid is considered, and a broadband pulse is used; the number of pulses is 2000, the pulse duration is 120 ms, and the number of points set for the broadband pulse is 7. At this time, the thermal equilibrium state efficiency can take the optimal value.

[0082] Step 4: The complete pulse obtained in step 3 is written into the computer in the language of the nuclear magnetic resonance instrument, and then glycine, glutamic acid, inositol and their mixture solutions are respectively placed in the magnet, and then field locking, tuning and shimming operations are performed, finally the radio frequency center of the transmitter is aligned in the middle of two non-exchangeable H atoms in the glycine molecule (at 37℃, the chemical shift is 3.54ppm, and at 22℃, the chemical shift is 3.45ppm), and the complete pulse written into the computer is applied to prepare and detect the thermal equilibrium state of the glycine molecule. The MRS spectrum collected based on the glycine targeting sequence is shown in Figure 1 c) of FIG. 6, compared with the conventional MRS spectrum, it can be seen that the glycine proton signal loss is small, and the hydrogen proton signals of inositol and glutamic acid adjacent to the glycine signal are almost completely suppressed. The results show that the glycine targeting magnetic resonance sequence has good preparation efficiency and selectivity of glycine on a 3.0T magnetic resonance imaging instrument.

[0083] Figure 1 a) of FIG. 6 is a spectrum obtained by collecting a mixed aqueous solution of glycine, glutamic acid and inositol by using a conventional PRESS (TE=30ms) at room temperature, wherein the glycine peak and the inositol peak overlap at 3.45ppm, and the glutamic acid peak is at 3.68ppm; b) is a spectrum collected by using PRESS (TE=135ms), and the inositol peak at 3.45ppm is suppressed to a certain extent, but the effect is limited, and the glutamic acid peak is still retained [1] ; c) is a spectrum collected by using the targeting sequence, and the inositol and glutamic acid peaks are suppressed.

[0084] Figure 3 is the influence of bias on the retention of the glycine peak under the condition of narrow-band excitation, and the peak retention value changes obviously under different center frequency bias conditions. In the range of -30 to 30Hz, the peak retention value fluctuates three times, and the peak retention values at -19Hz, 3Hz and 25Hz reach the highest, which are 68%, 69% and 31% respectively. The retention efficiency is low, the fluctuation is large, and the tolerance is low.

[0085] Figure 4 is the influence of bias on the retention rate of the glycine peak under the condition of wide-band excitation in the sequence of the application. From -8Hz to 18Hz, the glycine peak retention rate is higher than 90%, the efficiency is high, the fluctuation is small, and the tolerance is high.

[0086] Figure 6 In FIG. 6, a) is an MRI positioning map of a plastic bottle filled with an aqueous solution of glycine according to the application, and the square region marked in the figure is the spectrum scanning region; b) is an MRS spectrum for testing the sensitivity of the aqueous glycine solution according to the application, and the minimum detection concentration of the glycine targeting sequence on a 3T MRI instrument is 0.2mmol / L; c) is a concentration-peak intensity standard curve according to the application, and the concentration and the peak intensity have a linear relationship, which serves as a quantitative curve.

[0087] Example 2

[0088] This example is a glycine-targeting sequence for a glioma patient for glycine-selective in vivo detection. Consultation with the hospital and approval by the medical ethics committee were carried out, and the following scanning process was carried out on the patient suitable for magnetic resonance acquisition:

[0089] Step 1: Write the pulse into the computer with the language of the nuclear magnetic resonance instrument, and write the computer code developed by Siemens engineers.

[0090] Step 2: After the sequence is successfully imported into the system, use the AAHead_Scout sequence for positioning image scanning, then use the 3D_AX sequence for acquisition and reconstruction of coronal and sagittal anatomical maps, next, use the T2_Flair sequence for acquisition, find the tumor entity position for spectral acquisition. The spectral sequence selected in sequence is SVS_SE (TR / TE = 2s / 30ms, VOI = 15*15*15mm 3 ) and glycine-targeting sequence GFOC (Glycine-Filtering based on Optical Control pulse, TR / TE = 2s / 30ms, VOI = 15*15*15mm 3 ). The spectral width is 1000Hz, the sampling point is 1024, and the sampling time is 1.024s. After completing the conventional steps of positioning, shimming, water compression, etc., spectral acquisition is carried out.

[0091] Step 3: Copy the spectral raw data in.rda format and the anatomical map in original.dcm format, open the raw data with jMRUI and MicroDicom DICOM Viewer software respectively, and obtain the in vivo MRS spectrum and imaging anatomical map. After obtaining the in vivo MRS spectrum, perform spectral post-processing - phase correction, zero filling 9216, exponential window 2; after exporting the.txt document, open and save the processed spectrum graph with origin software.

[0092] Figure 7 a) is a T2-Flair MRI image of the brain of a glioma patient, and the white box is the MRS scanning area. b) is a spectrum obtained by conventional PRESS (TE = 30ms) acquisition. Unlike in aqueous solution, the spectral line width in the human brain is wider, and for glioma patients, the baseline of the Glx (Glu / Gln) peak is raised relative to the glycine peak, so the Glx signal is considered in the present application.

[0093] Figure 8a) The T2-Flair MRI image of a glioma patient's brain, the red box is the spectrum acquisition area; b) The MRS spectrum obtained by glycine-targeted sequence acquisition, only a clear glycine peak appears at 3.54ppm, the non-interest peaks are effectively suppressed, the red peak line is the glycine MR signal peak fitted by Lorentz function; c) The MRS spectrum obtained by conventional PRESS (TE = 30ms) acquisition, the inositol peak and the glycine peak overlap at 3.54ppm, the sub-methylene peak of Glx appears at 3.78ppm, which raises the baseline of the glycine peak.

[0094] REFERENCES

[0095] [1] Choi C, Ganji S K, Deberardinis R J, et al. Measurement of glycine in the human brain in vivo by 1H-MRS at 3T: Application in brain tumors [J]. Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine, 2011 (3): 66.

[0096] The protection scope of the present application is not limited to the above-mentioned embodiments. Changes and advantages that can be thought of by those skilled in the art without departing from the spirit and scope of the present application are included in the present application, and are protected by the appended claims.

Claims

1. A method for selective detection of glycine molecules in a mixture system based on magnetic resonance optimized control pulse for non-diagnostic purposes, characterized in that, The method utilizes the optimized control pulse of wideband excitation to simultaneously control the evolution of the nuclear spin quantum state of the mixed molecules including glycine molecules, and the magnetization vector of the nuclear spin of the glycine molecules is always in the z direction before and after the application of the optimized pulse; the transverse magnetization vector of other molecules is dephased by applying a gradient pulse, so as to realize the preservation and selective detection of the glycine magnetic resonance signal. The mixed molecules include glycine molecules, inositol molecules and glutamic acid molecules.

2. The method of claim 1, wherein, The method comprises the following core steps: Step i, simultaneously exciting the magnetic resonance signal of the mixed molecules including glycine molecules by the first optimized control pulse and the second optimized control pulse, so that the nuclear spin of the glycine molecules is in longitudinal magnetization after the pulse application, and the nuclear spin of other molecules is converted from longitudinal magnetization to transverse magnetization; Step ii, applying a gradient pulse to dephase the transverse magnetization vector of other molecules converted by the optimized control pulse except the glycine molecules, so that the magnetic resonance signal is attenuated to zero, while the magnetic resonance signal of the glycine molecules is preserved; Step iii, applying a PRESS positioning pulse to convert the glycine molecules into an observable state, collecting the magnetic resonance signal, and realizing the selective detection of the magnetic resonance signal of the glycine molecules.

3. The method of claim 2, wherein, Before step i, a step of applying a water suppression module is further included, which resonantly saturates the hydrogen protons in the aqueous solution by applying a water suppression module to the system, so as to suppress the water signal in the magnetic resonance signal.

4. The method of claim 2, wherein, In the step i, the spin evolution of the multi-spin system composed of inositol-glycine-glutamic acid three molecules is controlled by the optimized control pulse, the multi-spin system includes six methylene hydrogen protons of inositol, two equivalent hydrogen protons in the methylene of glycine molecule, one methine and two methylene hydrogen protons in the glutamic acid molecule; the thermal equilibrium state of inositol-glycine-glutamic acid nuclear spin is converted into the combination of multiple spin states 1z +I 2z +I 3z +I 4z +I 5z +I 6z +I 7z +I 8z +I 9z +I 10z +I 11z +I 12z The thermal equilibrium state of inositol-glycine-glutamic acid nuclear spin is converted into the combination of multiple spin states 1x +I 2x +I 3x +I 4x +I 5x +I 6x +I 7z +I 8x +I 9x +I 10x +I 11x +I 12x ; wherein the signals of inositol and glutamic acid hydrogen protons are in transverse magnetization, and the methylene hydrogen protons of glycine molecule are still in longitudinal magnetization.

5. The method of claim 2, wherein, In step ii, the state of the 11 nuclear spins contained in the inositol-glutamic acid molecules is rapidly dephased by applying a gradient pulse, and only the magnetic resonance signal of the glycine is preserved; the gradient pulse comprises a first gradient pulse g1 and a second gradient pulse g2, the strength of the first gradient pulse is 5 mT / s, and the application time is 2 ms; the strength of the second gradient pulse is 20 mT / s, and the application time is 2 ms.

6. The method of claim 2, wherein, In step iii, the PRESS pulse is composed of one 90° pulse and two 180° pulses, which are used for spin excitation and spatial positioning; the PRESS pulse is applied to selectively detect the glycine proton signal; the parameters of the PRESS pulse include the following: The repetition time TR is 2 s; The echo time TE is 30 ms; The number of acquisition points TD is 1024; The spectral width SW is 1024 Hz; The number of averages is 64.

7. The method of claim 2, wherein, The optimized pulse is provided with wideband excitation; The number of interpolation points in the wideband excitation is 3, and the bandwidth is 10.

8. The method according to any one of claims 1-7 for the selective observation of glycine molecule signals in complex systems for non-diagnostic purposes.

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