CN117309924A - Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition - Google Patents
Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition Download PDFInfo
- Publication number
- CN117309924A CN117309924A CN202311044522.7A CN202311044522A CN117309924A CN 117309924 A CN117309924 A CN 117309924A CN 202311044522 A CN202311044522 A CN 202311044522A CN 117309924 A CN117309924 A CN 117309924A
- Authority
- CN
- China
- Prior art keywords
- cest
- gsh
- vdmp
- pulse
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 51
- 238000005516 engineering process Methods 0.000 title claims abstract description 19
- 238000001228 spectrum Methods 0.000 claims abstract description 39
- -1 GSH thiol Chemical class 0.000 claims abstract description 21
- 238000005070 sampling Methods 0.000 claims abstract description 18
- 238000012360 testing method Methods 0.000 claims abstract description 14
- 230000000694 effects Effects 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 239000000126 substance Substances 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 238000012546 transfer Methods 0.000 claims description 10
- 238000003384 imaging method Methods 0.000 claims description 7
- 238000011002 quantification Methods 0.000 claims description 5
- 238000000079 presaturation Methods 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 238000013139 quantization Methods 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
- 238000002592 echocardiography Methods 0.000 claims description 2
- 238000004590 computer program Methods 0.000 claims 2
- 238000000264 spin echo pulse sequence Methods 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 abstract description 9
- 238000001514 detection method Methods 0.000 abstract description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Natural products OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 74
- 229960003180 glutathione Drugs 0.000 description 55
- 125000003396 thiol group Chemical class [H]S* 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- OAVCWZUKQIEFGG-UHFFFAOYSA-O 2-(5-methyl-2H-tetrazol-1-ium-1-yl)-1,3-thiazole Chemical compound CC1=NN=N[NH+]1C1=NC=CS1 OAVCWZUKQIEFGG-UHFFFAOYSA-O 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000012805 post-processing Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 150000003573 thiols Chemical group 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 229960004308 acetylcysteine Drugs 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000033116 oxidation-reduction process Effects 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
- Y02A90/30—Assessment of water resources
Landscapes
- Physics & Mathematics (AREA)
- High Energy & Nuclear Physics (AREA)
- General Physics & Mathematics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Signal Processing (AREA)
- Health & Medical Sciences (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Abstract
The application provides a method for detecting GSH sulfhydryl based on a magnetic resonance sequence VDMP-CEST, aiming at realizing signal detection of GSH sulfhydryl under weak alkaline condition, which comprises the following steps: obtaining a VDMP-CEST magnetic resonance scanning sequence through programming; scanning the test tube model by using a VDMP-CEST sequence and a non-uniform sampling method; the obtained scanning data are subjected to fitting and drawing of a plurality of Chi Luolun pieces of Z spectra; signal intensity of GSH thiol was quantified on the Z spectrum by the three-shift method. The limitation that the conventional CEST technology can only detect GSH sulfhydryl signals under the acidic PH condition is eliminated; and meanwhile, the scanning time can be effectively shortened.
Description
Technical Field
The application relates to the technical field of magnetic resonance imaging, in particular to a method and a system for detecting GSH sulfhydryl based on a VDMP-CEST technology under a weak alkaline condition.
Background
The chemical exchange saturation transfer CEST (Chemical Exchange Saturation Transfer) imaging is a magnetic resonance molecular imaging technology, can noninvasively acquire microscopic information such as organism tissue energy metabolism, acid-base environment, metabolite content and the like based on the chemical exchange action of exchangeable protons and water molecules in endogenous or exogenous, and has important research value and application potential in disease identification, diagnosis and evaluation. The classical principle explanation about CEST technology is that a two-tank model comprises a free water tank (solution tank) and an exchangeable tank (solute tank), hydrogen protons in the exchangeable tank are saturated by pre-applying saturation pulses to the exchangeable tank, and then are subjected to chemical exchange with hydrogen protons in the surrounding free water tank, so that the magnetic resonance signal of water is reduced, and information such as the concentration of certain metabolites in the exchangeable tank can be indirectly obtained by measuring the change of the signal of water molecules. With the development of technology and the improvement of algorithms, the scholars have also proposed three-pool and multi-pool models to better analyze CEST.
For quantification of CEST effect, asymmetric susceptibility is typically used(Magnetization Transfer Asymmetry,MTR asym ) The height of the value is reflected, thereby reflecting the concentration of the corresponding metabolite, the formula is: MTR (methyl thiazolyl tetrazolium) asym (Δω)＝[I(-Δω)-I(Δω)]/I 0 ；I 0 The signal intensity obtained when the saturation pulse is not applied is I (Δω) which is the signal intensity obtained when the saturation pulse is applied, and I (- Δω) and I (Δω) represent the negative direction value and the positive direction value at the same bias frequency.
In terms of metabolite groups, amide (amide), amine (amino), hydroxyl (hydroxy) proton exchange have been widely used in CEST, but the related search for thio (mercapto) -SH proton exchange has been less. GSH contains two groups, amino and mercapto, GSH amino produces a 3.0ppm signal on the Z spectrum, which cannot be distinguished from the amino signal of glutamic acid, GSH mercapto produces a-2.5 ppm signal on the Z spectrum, although this signal slightly overlaps with the NOE effect, which can be attenuated by modulating the saturation energy, and MTC effects, which can also be minimized by the three-shift method, so that a-2.5 ppm mercapto signal is expected to be a characteristic signal of GSH. GSH is critical to maintaining redox homeostasis in vivo, which is closely related to cellular activity, and therefore has the potential to probe the redox environment. The scholars published a related article (Chen J, yadav NN, station-Gardner T, gupta a, price WS, zheng g.thio-water proton exchange of glutathione, cysteine, and N-acetylcysteine: implications for CEST mri.nmr biomed.2020 Jan;33 (1): e 4188) in journal NMR in Biomedicine), explored the rate of exchange of GSH with water at different pH and the pH dependence of the sulfhydryl effect by CEST technique, demonstrated that the rate of exchange of GSH sulfhydryl with water was accelerated after pH exceeded 4.7, thereby reducing saturation efficiency, resulting in a decrease in CEST effect; meanwhile, experiments also show that GSH mercapto group has no CEST effect after the pH is more than or equal to 5.9.
In the conventional CEST sequence scanning, a frequency range is generally selected to be symmetrical left and right, saturation pulses of different frequencies are applied incrementally at a predetermined step pitch, and this uniform sampling method of equal frequency pitch takes a long time to scan a living body,SAR values (electromagnetic wave absorption ratio) accumulate and may cause motion artifacts. With respect to analysis of CEST effect, asymmetric susceptibility (MTR asym ) Is a simple and effective quantization method commonly used at present, but the method has the following disadvantages: (1) is susceptible to B0 field inhomogeneity; (2) MTR (methyl thiazolyl tetrazolium) asym Is susceptible to various confounding parameters including tissue relaxation, MT, MTC and more importantly MTR asym The NOE effect cannot be distinguished from CEST comparison; (3) MTR (methyl thiazolyl tetrazolium) asym The longitudinal relaxation effect of water is not corrected, which is a major factor affecting CEST signal amplitude.
Disclosure of Invention
The application provides a method for detecting GSH sulfhydryl based on a magnetic resonance sequence VDMP-CEST, which is particularly aimed at realizing detection of GSH sulfhydryl signals under the weak alkaline condition (normal pH value of human body fluid), has good clinical application conversion value, and gets rid of the limitation that the conventional CEST technology can only detect GSH sulfhydryl signals under the acidic pH condition; meanwhile, the scanning time can be effectively shortened by combining a non-uniform sampling method. The method comprises the following steps: obtaining a VDMP-CEST magnetic resonance scanning sequence through programming; scanning the test tube model by using a VDMP-CEST sequence and a non-uniform sampling method; the obtained scanning data are subjected to fitting and drawing of a plurality of Chi Luolun pieces of Z spectra; signal intensity of GSH thiol was quantified on the Z spectrum by the three-shift method.
The VDMP-CEST is originally designed for separating fast exchange protons and slow exchange protons, and a saturation pulse module is designed into a form with variable pulse number and adjustable pulse interval.
Meanwhile, unlike the conventional CEST sampling mode, the method provided by the application innovatively applies the non-uniform sampling method in scanningThe frequency range of (1) is provided with uneven frequency intervals, dense sampling is adopted near the concerned frequency point, and sparse sampling is adopted in other frequency intervals, so that the number of sampled images can be reduced, the scanning time is effectively reduced, the accumulation of SAR values is also reduced, motion artifacts are avoided, smooth Z spectrums with reliable precision can be obtained through post-processing fitting, and the method is simple and has good practical value. In addition, in the quantification of the thiol signal of GSH-2.5ppm, the three-offset method is adopted, so that the error influence of the amino signal of GSH 3.0ppm on the quantification of the thiol signal of-2.5 ppm (the distance of 3.0ppm from 2.5ppm is too close, and MTR can be influenced) can be avoided when an asymmetric magnetic transfer rate analysis method is adopted asym (-2.5ppm)＝[I(2.5ppm)-I(-2.5ppm)]/I 0 As a result of (c), while avoiding other deficiencies of the asymmetric susceptibility analysis, in addition to the three-shift approach, the effect of MTC can be minimized.
The so-called three-shift method, i.e. selecting three shift frequencies on the Z spectrum, wherein-2.5 ppm is the center frequency of GSH mercapto effect, -3.0ppm and-2.0 ppm is the frequency of GSH mercapto effect upper and lower limits, the calculation formula of GSH mercapto signal intensity is as follows:
wherein S0 refers to the signal intensity acquired without the presaturation pulse.
In terms of experimental verification, test tubes of GSH solutions were scanned with the conventional CEST sequence and VDMP-CEST sequence, respectively, which showed effects of 3.0ppm amino and-2.5 ppm mercapto on the Z spectra, both under acidic conditions at ph=5.4, as seen on the Z spectra drawn after collection; under weakly alkaline conditions at ph=7.4, the effect of 3.0ppm amino groups is present on both the Z spectrum of conventional CEST and on the Z spectrum of VDMP-CEST, but the effect of-2.5 ppm mercapto groups is only present on the Z spectrum of VDMP-CEST. In the above, the present application provides a method for detecting GSH thiol based on the magnetic resonance sequence VDMP-CEST, which can detect GSH thiol effect under both acidic and weakly basic conditions of pH. Because the pH value of the normal pH value of the body fluid of a human body is 7.35-7.44, the GSH sulfhydryl signal cannot be detected under the condition by the conventional CEST, and the VDMP-CEST technology can be realized, the method has good clinical conversion value and is expected to provide practical and effective technical support for detecting in-vivo oxidation-reduction related information.
Drawings
FIG. 1 is a schematic diagram of a VDMP-CEST sequence
FIG. 2 is the effect of GSH thiol at different pH values in the literature (Z spectrum of CEST)
FIG. 3 is a graph showing CEST signal of GSH thiol with pH at different saturation energies in the literature
FIG. 4 is a pseudo-color plot of CEST and VDMP-CEST scanned Z-spectra comparison of GSH solutions at different concentrations at pH=5.4
FIG. 5 is a pseudo-color plot of CEST and VDMP-CEST scanned Z-spectra comparison of GSH solutions at different concentrations at pH=7.4
FIG. 6 is a flow chart of a method for detecting GSH thiol under weakly alkaline conditions based on VDMP-CEST technique
Detailed Description
The following describes in further detail the embodiments of the present invention with reference to the drawings and examples. The following examples are illustrative of the invention and are not intended to limit the scope of the invention.
The magnetic resonance sequence VDMP-CEST is obtained by programming on an Agilent 7T magnetic resonance VnmrJ software platform (according to the same design scheme, the magnetic resonance of other brands and different field strengths can be realized), a sequence time chart is shown in figure 1, and the specific design scheme comprises the following steps:
a saturation pulse module is added into a conventional water imaging sequence rapid spin echo FSE (Fast Spin Echo), the saturation pulse module is designed into a plurality of pairs of pulses before 90-degree excitation pulses of an FSE sequence, each pair of pulses consists of two square waves, the pulse logarithm is variable, the pulse pair spacing is adjustable, and simultaneously, the pulse energy and the center frequency can be self-determined and assigned; a gradient of X, Y, Z is applied between pulse pairs simultaneously (the gradient is a type of gradient pulse), the duration of the gradient fills the whole pulse interval and the intensity is one thousandth of the pulse interval value (the unit is gauss/cm), and the variable delay multi-pulse-chemical exchange saturation transfer sequence VDMP-CEST (Variable Delay Multi Pulse-Chemical Exchange Saturation Transfer) can be obtained through the design.
In subsequent experimental scans, specific VDMP-CEST scan parameters were set as follows:
for a saturated pulse module, setting 16 pairs of pulses, wherein the duration time of a single square wave in each pair of pulses is 21ms, the two square waves have no delay time and consistent phase, the interval time of the pulse pairs is 40ms, the pulse energy is 2 mu T (NOE effect is suitable for low saturated energy lower than 2 mu T on a living body, and NOE effect can be greatly weakened under the saturated energy of 2 mu T), and the scanning frequency range is +/-6 ppm (+ -1800 Hz); in combination with the non-uniform sampling method, a non-uniform frequency interval is set in the scanning frequency range, wherein the vicinity of the frequency point of the mercapto group-2.5 ppm of interest adopts dense sampling, namely, the interval of the center frequency of the saturation pulse in the interval of-3.0 ppm to-2.0 pmm (-900 Hz to-600 Hz) is set to 0.1ppm (30 Hz), and the interval of the center frequency of the saturation pulse in the interval of-6 ppm to-3 ppm (-1800 Hz to-900 Hz) and-2 ppm to 6ppm (-600 Hz to 1800 Hz) is set to 0.2ppm (60 Hz), and the sampling point with the frequency of 10000Hz is added, and the scanning totally acquires images with different center frequencies of 67 pairs of saturation pulses (on MRI with the field intensity of 7T, 1 ppm=300 Hz). For the water imaging module, i.e. the FSE parameters are set to 16 echoes, the echo spacing is 8ms, the signal of the first echo is acquired, and the repetition time TR (time of repetition) is 3500ms.
In the comparison experiments, the scanning parameters of the CEST sequences employed were set as follows:
for the saturation pulse module, a single continuous wave pulse is used, the pulse type is square wave, the duration of the pulse is 2000ms (2 s), the saturation energy is 2 mu T, and the scanning frequency range is +/-6 ppm (+ -1800 Hz); and combining a conventional uniform sampling method, setting uniform frequency spacing of 0.1ppm in a scanning frequency range, and adding sampling points with the frequency of 10000Hz, and scanning to obtain 122 images with different center frequencies of the saturation pulses. For the water imaging module, a plane echo EPI (Echo Planar Imaging) is used to acquire the signal, the repetition time TR (time of repetition) is 6000ms and the echo time TE (time of echo) is 24.31ms.
The principle of the chemical exchange saturation transfer CEST technology is that a specific off-resonance saturation pulse is utilized to fully presaturate a specific substance, because H on the group of the specific substance can exchange with H of free water (namely chemical exchange), the saturated H can be transferred to the free water (namely saturation transfer), and the saturation influences the signal intensity of the free water through the chemical exchange, so that the information such as the concentration of the specific substance can be indirectly reflected by detecting the signal change of the water.
To quantify the intensity of the CEST signal, at least three images are obtained by the CEST scanning sequence, an image I without presaturation pulse 0 (typically, a saturation pulse with a relatively large center frequency is applied as an image for capturing unsaturated images, and the setting is 10000Hz as described in the previous paragraph), an image I (Δω) with a saturation pulse with a specific off-resonance frequency is applied at the mark position (for example, 3.0ppm for amino group of GSH, 2.5ppm for thiol group of GSH, 1 ppm=300 Hz on 7T MRI, namely, 900Hz and 750Hz respectively), and an image I (- Δω) with a saturation pulse is applied at the mark position symmetrical with respect to water (for example, -3.0ppm or 2.5 ppm), the signal intensity can be quantified by using the asymmetric magnetic susceptibility, and the calculation formula is: MTR (methyl thiazolyl tetrazolium) asym (Δω)＝[I(-Δω)-I(Δω)]/I 0 . In order to obtain the best-known and most simplified CEST scan, a frequency range of bilateral symmetry is generally selected, saturated pulses are incrementally applied at a certain interval, and images with different center frequencies of multiple saturated pulses are obtained, wherein the Z spectrum is a curve drawn by taking the resonance frequency of free water H as a center zero point, the off-resonance saturation frequency as an abscissa, and the water signal intensity as an ordinate. The method of the present application does not utilize an asymmetric susceptibility analysis, but rather utilizes three offsets in quantifying GSH thiol signals, as will be described in detail below.
The literature published by scholars prior to this citation is illustrative of the relevant exploration of GSH thiol CEST effects. This article published in journal NMR in Biomedicine: chen J, yadav NN, station-Gardner T, gupta A, price WS, zheng G.thio-water proton exchange of glutathione, cysteine, and N-acetylcysteine: implications for CEST MRI NMR biomed 2020 Jan;33 E4188, explored the exchange rate of the thiol-water and the pH dependence of the thiol effect of GSH at different pH by CEST technique, demonstrated that the exchange rate of the thiol-water is accelerated after the pH exceeds 4.7, thereby reducing the saturation efficiency and leading to the decrease of CEST effect; meanwhile, experiments also show that GSH mercapto group has no CEST effect after the pH is more than or equal to 5.9. In this document, the effect of GSH thiol at different pH values (Z spectrum of CEST) is shown in FIG. 2, which shows the Z spectrum of a 20mM GSH solution (solvent PBS) at different pH values at a saturation energy of 3. Mu.T, after a pH of 5.9 or more, since the exchange rate of thio-water is too fast, there is essentially no CEST effect of GSH thiol anymore; the change of CEST signal of GSH sulfhydryl with pH value under different saturation energies is shown in FIG. 3, which shows that the CEST signal of sulfhydryl with pH value is almost zero under the saturation energies of 1 mu T, 3 mu T and 5 mu T of 20mM GSH solution (solvent is PBS) respectively. Thus, it is demonstrated that CEST technology can only detect signal of GSH thiol under acidic conditions with pH < 5.9.
The experimental scanning and post-processing modes of this embodiment are specifically described below:
eight 2ml nuclear magnetic tubes were filled with GSH solutions (40 mM, 20mM, 10mM, 5 mM) of different concentrations at pH values of 5.4 and 7.4, respectively, as test tube models, and four test tubes at pH values of 5.4 and four test tubes at pH value of 7.4 were fixed in two plastic containers filled with agarose gel, respectively, using PBS buffer as solvent (the filling of the periphery of the test tubes with agarose gel was for fixation of the position, on the other hand was advantageous for shimming during magnetic resonance scanning). And selecting a layer surface (cross section) with the thickness of 2mm of the middle layer of the test tube, and respectively carrying out experimental scanning according to the parameters of the CEST sequence and the VDMP-CEST sequence to acquire experimental data.
Post-processing experimental data obtained by scanning a CEST sequence and a VDMP-CEST sequence, fitting by using a three Chi Luolun-Z model, and drawing a Z spectrum, wherein the three-pool model is as follows: water pool with a center frequency of 0ppm, amine pool with a center frequency of 3.0ppm, thio pool with a center frequency of-2.5 ppm.
Lorentz fitting is a simpler quantization method of least squares Z-spectrum fitting, and is defined as follows:
wherein Δw represents the offset frequency relative to water, S (Δw) represents the CEST signal at Δw, S 0 Representing unsaturated signals, A i 、w i Sum sigma i Respectively representing the amplitude, the offset frequency and the line width of the ith proton pool, wherein N represents the number of fitting pools, and the general Lorentz fitting refers to the condition that N=1, and if N is greater than 1, the fitting is more than Chi Luolun z; the difference between the fit result and the Z-spectrum data is used as the CEST signal for quantification.
The ROI analysis of the test tube selects a circular area with the diameter about 5mm identical to that of the nuclear magnetic resonance tube, the result obtained by post-treatment is separated according to the pH value and the sequence type, and the Z spectra of GSH solutions with different concentrations corresponding to the result are drawn in the same graph. As shown in fig. 4, which shows a comparison of the Z spectra of CEST and VDMP-CEST scanned with GSH solutions of different concentrations at ph=5.4, it can be seen that both conventional CEST and VDMP-CEST show an effect of 3.0ppm amino and-2.5 ppm mercapto on the Z spectra at acidic conditions at ph=5.4; as shown in fig. 5, which shows a comparison of the Z spectra of CEST and VDMP-CEST scanned with different concentrations of GSH solution at ph=7.4, it can be seen that the effect of 3.0ppm of amino groups is present on both the Z spectrum of conventional CEST and the Z spectrum of VDMP-CEST, but the effect of-2.5 ppm of mercapto groups is only present on the Z spectrum of VDMP-CEST, at a slightly alkaline condition at ph=7.4.
From the above experimental results, CEST technology can only detect GSH thiol signals under pH acidic conditions, but not under pH acidic conditions, which is consistent with the results of previous literature studies; the VDMP-CEST technology can detect GSH sulfhydryl signals under the conditions of pH acidity and alkalescence, and the limitation that the conventional CEST technology can only detect GSH sulfhydryl signals under the condition of acidic pH is eliminated.
Further, the signal intensity of GSH sulfhydryl is quantified on the Z spectrum of VDMP-CEST by a three-offset method, the intensity of the signal is presented in the form of a pseudo-color chart, and the color scale can be adjusted by self-setting, such as the pseudo-color chart of the test tube shown in fig. 4 and 5. The so-called three-shift method, i.e. selecting three shift frequencies on the Z spectrum, wherein-2.5 ppm is the center frequency of GSH mercapto effect, -3.0ppm and-2.0 ppm is the frequency of GSH mercapto effect upper and lower limits, the calculation formula of GSH mercapto signal intensity is as follows:
wherein S0 refers to the signal intensity acquired without the presaturation pulse.
In the above, the present application provides a method for detecting GSH thiol based on VDMP-CEST technology, which can realize detection of GSH thiol signal in a wider pH range. Because the pH value of the normal pH value of the body fluid of a human body is 7.35-7.44, the GSH sulfhydryl signal cannot be detected under the condition by the conventional CEST, and the VDMP-CEST technology can be realized, the application has good clinical conversion value, and is expected to provide practical and effective technical support for detecting in-vivo oxidation-reduction related information. In addition, the application has the further innovation point that the non-uniform sampling method is adopted, so that the number of sampled images is reduced, the scanning time is shortened, the accumulation of SAR values is reduced, the precision is reliable, the method is simple, the method is applicable to scanning by the conventional CEST technology, and the method has good practical value.
Claims (9)
1. A method for detecting GSH mercapto groups under weakly alkaline conditions based on VDMP-CEST technology, comprising the steps of:
obtaining a VDMP-CEST magnetic resonance scanning sequence through programming;
scanning the test tube model by using a VDMP-CEST sequence and a non-uniform sampling method;
the obtained scanning data are subjected to fitting and drawing of a plurality of Chi Luolun pieces of Z spectra;
signal intensity of GSH thiol was quantified on the Z spectrum by the three-shift method.
2. The method of claim 1, wherein the programming to obtain a VDMP-CEST magnetic resonance scan sequence comprises:
the code programming and compiling test of the magnetic resonance scanning sequence are carried out through the VnmrJ software platform of Agilent, a saturation pulse module is added into the rapid spin echo sequence FSE (Fast Spin Echo), the saturation pulse module is designed into a plurality of pairs of pulses, one pair of pulses consists of two square waves, the pulse logarithm is variable, the pulse pair spacing is adjustable, the pulse energy and the center frequency can be assigned by self-determination, and the required variable delay multi-pulse-chemical exchange saturation transfer sequence VDMP-CEST is obtained (VariableDelay Multi Pulse-Chemical Exchange Saturation Transfer).
3. The method of claim 1, wherein scanning the cuvette model using a VDMP-CEST sequence in combination with a non-uniform sampling method comprises:
for a VDMP-CEST sequence, parameters of a saturated pulse module are set to 16 pairs of pulses, each pair of pulses consists of two square waves, the duration of a single square wave is 21ms, the pulse interval is 40ms, the saturated energy is 2 mu T, the scanning frequency range is +/-6 ppm (+ -1800 Hz), a water imaging module acquires signals by adopting a fast spin echo FSE (Fast Spin Echo), the repetition time TR (time of repetition) is 3500ms, 16 echoes are used, the echo interval is 8ms, and the signals of the first echo are acquired;
the non-uniform sampling method is to set a non-uniform frequency interval in a scanning frequency range, and to adopt dense sampling in the vicinity of mercapto-2.5 ppm frequency points, namely, the interval of saturated pulse center frequencies in the interval of-3.0 ppm to-2.0 pmm (-900 Hz to-600 Hz) is set to 0.1ppm (30 Hz), and the interval of saturated pulse center frequencies in the interval of-6 ppm to-3 ppm (-1800 Hz to-900 Hz) and-2 ppm to 6ppm (-600 Hz to 1800 Hz) is set to 0.2ppm (60 Hz).
4. A method according to claim 1 or 3, characterized in that the test tube model is:
the test tube model was prepared as follows: GSH solutions (40 mM, 20mM, 10mM, 5 mM) of different concentrations having pH values of 5.4 and 7.4, respectively, were filled into 2ml nuclear magnetic tubes, respectively, for a total of 8 nuclear magnetic tubes.
5. The method according to claim 1, wherein the scan data is plotted into a Z-spectrum by a multi Chi Luolun Z-fit, specifically:
the series of images obtained by the VDMP-CEST sequence scanning are fitted by using a three Chi Luolun-Z model, and a Z spectrum is drawn, wherein the three-pool model is as follows: water pool with a center frequency of 0ppm, amine pool with a center frequency of 3.0ppm, thio pool with a center frequency of-2.5 ppm.
6. The method according to claim 1 or 5, wherein the multiple Chi Luolun z fitting is specifically:
lorentz fitting is a quantization method of least square Z-spectrum fitting, and the definition of Lorentz fitting is as follows:
wherein Δw represents the offset frequency relative to water, S (Δw) represents the CEST signal at Δw, S 0 Representing unsaturated signals, A i 、w i Sum sigma i Respectively representing the amplitude, the offset frequency and the line width of the ith proton pool, wherein N represents the number of fitting pools, and the general Lorentz fitting refers to the condition that N=1, and if N is greater than 1, the fitting is more than Chi Luolun z; the difference between the fit result and the Z-spectrum data is used as the CEST signal for quantification.
7. The method according to claim 1, wherein the signal intensity of GSH thiol groups is quantified on the Z spectrum by a three-shift method, in particular:
three offset frequencies were selected on the Z spectrum, where-2.5 ppm is the center frequency of GSH mercapto effect, -3.0ppm and-2.0 ppm is the frequency of GSH mercapto effect upper and lower limits, the GSH mercapto signal intensity was calculated as follows:
wherein S0 refers to the signal intensity acquired without the presaturation pulse.
8. A system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition, which is characterized by comprising a memory and a processor; the memory is used for storing a computer program; the processor, when executing the computer program, is adapted to carry out the method of detecting GSH thiol groups under weakly basic conditions as claimed in any one of claims 1 to 7.
9. The system of claim 8, wherein the magnetic resonance sequence VDMP-CEST is programmed on an Agilent 7T magnetic resonance VnmrJ software platform.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311044522.7A CN117309924B (en) | 2023-08-18 | 2023-08-18 | Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311044522.7A CN117309924B (en) | 2023-08-18 | 2023-08-18 | Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN117309924A true CN117309924A (en) | 2023-12-29 |
| CN117309924B CN117309924B (en) | 2024-05-14 |
Family
ID=89283739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311044522.7A Active CN117309924B (en) | 2023-08-18 | 2023-08-18 | Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117309924B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104997511A (en) * | 2015-06-01 | 2015-10-28 | 中国科学院深圳先进技术研究院 | CESTR measuring method and system for magnetic resonance chemical exchange saturation transfer imaging |
| US20190011516A1 (en) * | 2017-07-05 | 2019-01-10 | The General Hospital Corporation | System and method for direct saturation-corrected chemical exchange saturation transfer (disc-cest) |
| CN110068780A (en) * | 2019-05-07 | 2019-07-30 | 上海东软医疗科技有限公司 | A kind of adaptive approach of magnetic resonance imaging, device and magnetic resonance imaging system |
| CN112748381A (en) * | 2020-12-07 | 2021-05-04 | 中国科学院深圳先进技术研究院 | Chemical exchange saturation transfer quantitative method, device and medium for magnetic resonance |
| CN114216920A (en) * | 2021-10-29 | 2022-03-22 | 清华大学 | Magnetic resonance molecular imaging method and system for dynamically reading CEST signal accumulation |
| CN116879338A (en) * | 2023-06-12 | 2023-10-13 | 汕头大学医学院第二附属医院 | Method and system for detecting GABA by combining VDMP-CEST with nonlinear fitting |
-
2023
- 2023-08-18 CN CN202311044522.7A patent/CN117309924B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104997511A (en) * | 2015-06-01 | 2015-10-28 | 中国科学院深圳先进技术研究院 | CESTR measuring method and system for magnetic resonance chemical exchange saturation transfer imaging |
| US20190011516A1 (en) * | 2017-07-05 | 2019-01-10 | The General Hospital Corporation | System and method for direct saturation-corrected chemical exchange saturation transfer (disc-cest) |
| CN110068780A (en) * | 2019-05-07 | 2019-07-30 | 上海东软医疗科技有限公司 | A kind of adaptive approach of magnetic resonance imaging, device and magnetic resonance imaging system |
| CN112748381A (en) * | 2020-12-07 | 2021-05-04 | 中国科学院深圳先进技术研究院 | Chemical exchange saturation transfer quantitative method, device and medium for magnetic resonance |
| CN114216920A (en) * | 2021-10-29 | 2022-03-22 | 清华大学 | Magnetic resonance molecular imaging method and system for dynamically reading CEST signal accumulation |
| CN116879338A (en) * | 2023-06-12 | 2023-10-13 | 汕头大学医学院第二附属医院 | Method and system for detecting GABA by combining VDMP-CEST with nonlinear fitting |
Non-Patent Citations (4)
| Title |
|---|
| JOHNNY CHEN等: "MRI Detection of Hepatic N-Acetylcysteine Uptake in Mice", 《BIOMEDICINES》, 31 August 2022 (2022-08-31) * |
| JOHNNY CHEN等: "Thiol-water proton exchange of glutathione, cysteine, and N-acetylcysteine: Implications for CEST MRI", 《NMR IN BIOMEDICINE》, 17 August 2019 (2019-08-17) * |
| XIAO-YONG ZHANG等: "Accuracy in the Quantification of Chemical Exchange Saturation Transfer (CEST) and relayed Nuclear Overhauser Enhancement (rNOE) saturation transfer effects", 《NMR BIOMED》, vol. 30, no. 7, 1 July 2018 (2018-07-01) * |
| 张利红;梁英波;: "化学交换饱和转移磁共振成像量化方法研究进展", 周口师范学院学报, no. 02, 15 March 2020 (2020-03-15) * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN117309924B (en) | 2024-05-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11169235B2 (en) | Method and apparatus for processing magnetic resonance data | |
| US10775462B2 (en) | System and method for direct saturation-corrected chemical exchange saturation transfer (DISC-CEST) | |
| Lutti et al. | Optimization and validation of methods for mapping of the radiofrequency transmit field at 3T | |
| US10726552B2 (en) | Quantification of magnetic resonance data by adaptive fitting of downsampled images | |
| US10663548B2 (en) | System and method for magnetic resonance imaging | |
| WO2021184471A1 (en) | Non-uniform field magnetic resonance system-based apparent diffusion coefficient measurment method | |
| CN108872897B (en) | Nuclear magnetic resonance T2 image imaging method | |
| CN116879338B (en) | Method and system for detecting GABA by VDMP-CEST combined with nonlinear fitting | |
| US5363042A (en) | Methods for measurement of longitudinal spin relaxation times in moving liquids | |
| US20240264257A1 (en) | Systems and methods for magnetic resonance imaging | |
| CN117309924B (en) | Method and system for detecting GSH sulfhydryl based on VDMP-CEST technology under weak alkaline condition | |
| CN112304811B (en) | Low-field nuclear magnetic resonance apparent diffusion coefficient measuring method insensitive to motion | |
| Deshpande et al. | MRI‐based quantification of whole‐organ renal metabolic rate of oxygen | |
| Lipp et al. | B 1+ B _1^+‐correction of magnetization transfer saturation maps optimized for 7T postmortem MRI of the brain | |
| CN113040744B (en) | Quantitative method for chemical exchange saturation transfer effect of living body | |
| Stabinska et al. | Two point Dixon-based chemical exchange saturation transfer (CEST) MRI in renal transplant patients on 3 T | |
| Kim et al. | Magnetization transfer | |
| WO2023216582A1 (en) | Magnetic resonance chemical exchange saturation transfer imaging method, system and device | |
| Cai | Diffusion-based mr methods for measuring water exchange | |
| JPH07148140A (en) | Method to measure spin-lattice relaxation period | |
| Dwork et al. | multiMap: A Gradient Spoiled Sequence for Simultaneously Measuring B1+, B0, T1/M0, T2, T2*, and Fat Fraction of a Slice | |
| Jiang | Probing Chemical Exchange Using Adiabatic Spin-Lock Magnetic Resonance Imaging | |
| Memhave | Multi-nuclear magnetic resonance imaging and spectroscopy of lithium in the brain | |
| Yang et al. | Diffusion measurement in phantoms and tissues using SLIM localization | |
| Johnson | Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |