A method and system for magnetic resonance spectroscopy based on CEST effect enhancement

CN122592300APending Publication Date: 2026-08-18WUHAN UNITED IMAGING LIFE SCIENCE INSTRUMENT CO LTD
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Patent Information

Application Number
CN202610424938.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-04-01
Publication Date
2026-08-18

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Technical Problem

两者虽然同属磁共振技术分支,但在以下方面存在根本性差异:研究对象(前者为谱线,后者为图像)、信号处理对象(前者为代谢物峰,后者为水信号强度)以及技术手段(前者为水压制,后者为水利用)

Benefits of technology

显著提升检测灵敏度:通过将微弱的代谢物信号转换为可检测的水信号变化,检测灵敏度可提升数百至数千倍,使得原本难以检测的低浓度代谢物能够被准确量化。

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Abstract

The application discloses a kind of based on CEST effect enhanced magnetic resonance spectroscopy detection method and system.The method first applies CEST pre-saturation module, and the exchangeable proton in target analyte is selectively saturated using frequency-selective saturation pulse;Immediately afterwards, magnetic resonance spectrum acquisition sequence is executed, and the water signal changed due to chemical exchange saturation transfer effect is collected;By changing saturation pulse frequency and repeating acquisition, Z spectrum is constructed;Finally, Z spectrum is analyzed, and signal change characteristics are extracted to determine the information of target analyte.The application introduces CEST effect into spectroscopy analysis, reversely uses the water signal that needs to be suppressed in conventional MRS as information carrier, and indirectly and high-sensitivity quantitatively detects low-concentration metabolites by detecting the change of water signal.The application can significantly improve detection sensitivity and signal-to-noise ratio, has the advantages of high specificity and quantitative accuracy, and can be used as a front-end module compatible with existing PRESS, STEAM and other standard spectroscopy sequences.
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Description

Technical Field

[0001] This invention belongs to the field of magnetic resonance imaging and spectral analysis technology, specifically relating to a method, sequence, and system for enhancing the detection sensitivity of magnetic resonance spectroscopy (MRS) by utilizing the Chemical Exchange Saturation Transfer (CEST) effect. Background Technology

[0002] Magnetic resonance spectroscopy (MRS) is currently the only technique capable of non-invasively detecting the concentration of metabolites in living tissues, playing a crucial role in neuroscience, oncology, and metabolic disease research. However, traditional MRS technology faces an inherent technical bottleneck: many physiologically significant metabolites (such as creatine, glutamate, glutamine, and glucose) have inherently low concentrations in tissues (typically in the millimole to micromolar range), resulting in very weak magnetic resonance signals. Especially in high-field (e.g., 9.4T) MRS systems, despite theoretically improved signal-to-noise ratios, the detection of low-concentration metabolites remains limited by insufficient SNR. Traditional spectral acquisition sequences, such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition (STEAM), while enabling spatial localization and signal acquisition, are primarily designed to extract weak metabolite signals against a strong water signal background. Therefore, these sequences typically require the integration of complex water signal suppression modules (such as CHESS or VAPOR) to maximally suppress water peaks, preventing them from overwhelming metabolite peaks and interfering with the spectral baseline. This technical approach, which focuses on "suppressing water signals," solves the problem of spectral visibility, but it does not fundamentally change the intensity of the metabolite signal itself. Therefore, it is difficult to meet the need for accurate monitoring of dynamic changes in extremely low concentrations of metabolites.

[0003] Chemical exchange saturation transfer (CEST) is a magnetic resonance contrast enhancement technique developed in recent years. This technique selectively saturates exchangeable protons on certain compounds by applying a saturating radio frequency pulse at a specific frequency. These saturated protons then chemically exchange with a large number of surrounding water protons, thereby altering the macroscopic magnetization vector of the water signal. Because the water proton pool is much larger than the metabolic proton pool, this exchange process can produce a significant signal amplification effect. Currently, CEST technology is mainly applied in the field of magnetic resonance imaging, generating molecularly specific image contrast by detecting changes in the saturated water signal at a single or multiple frequencies, such as amide proton transfer imaging (APT imaging) and glucose CEST imaging (glucoCEST). In CEST imaging, the water signal itself is the information carrier that constructs the image contrast.

[0004] In summary, current technologies in the MRS field focus on suppressing water signals to expose metabolite peaks, while the CEST imaging field focuses on utilizing changes in water signals to generate image contrast. Although both belong to the magnetic resonance imaging (MRI) branch, they differ fundamentally in the following aspects: the object of study (spectral lines for the former, images for the latter), the object of signal processing (metabolite peaks for the former, water signal intensity for the latter), and the technical means (water suppression for the former, water utilization for the latter). Furthermore, introducing the CEST effect into spectral analysis requires redesigning pulse sequence timing and coordinating the parameter requirements of both techniques. Currently, there is no publicly available technical solution for systematically introducing the CEST effect into the field of spectral analysis to enhance the spectral detection sensitivity of specific metabolites. Summary of the Invention

[0005] This invention aims to address the problems existing in the prior art by providing a magnetic resonance spectroscopy detection method and system based on the CEST effect enhancement, significantly improving the detection sensitivity and signal-to-noise ratio for low-concentration metabolites. This invention reverses the traditional MRS method by utilizing the water signal that needs to be suppressed, introducing the CEST effect from the traditional imaging field to the spectral analysis field. By combining a CEST pre-saturation module with a traditional MRS acquisition module, the weak metabolite signal is "amplified" into a detectable water signal change using the CEST effect, thereby indirectly and with high sensitivity quantification of metabolite concentration.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: Firstly, a magnetic resonance spectroscopy detection method based on the CEST effect enhancement includes the following steps: Step A: Apply the CEST presaturation module, which includes at least one frequency-selective saturation pulse, the frequency of which is set to correspond to the resonance frequency of the exchangeable protons in the target analyte, so as to selectively saturate the exchangeable protons; Step B: After applying the CEST presaturation module, a magnetic resonance spectroscopy acquisition sequence is executed to acquire water signals from the region of interest, the water signals exhibiting detectable changes due to the chemical exchange saturation transfer effect between the exchangeable protons and water protons; Step C: Change the frequency of the saturation pulse, repeat steps A and B to obtain water signals at different saturation frequencies, and construct a Z-spectrum based on the water signals at different saturation frequencies; Step D: Analyze the Z-spectrum, extract the signal change features corresponding to the target analyte by fitting or calculation, the signal change features characterize the detectable changes in the water signal, and determine the information of the target analyte based on the signal change features.

[0007] Preferably, the target analyte includes endogenous metabolites or exogenous compounds. Endogenous metabolites include, but are not limited to, naturally occurring metabolites in the body such as creatine, glutamate, and glutamine; exogenous compounds include, but are not limited to, glucose as an exogenous contrast agent, and drug molecules with exchangeable protons.

[0008] Preferably, the signal variation characteristics include the signal drop depth at a specific frequency on the Z spectrum, the signal drop integral area within a specific frequency range, or the magnetization transfer rate asymmetry analysis value calculated based on the Z spectrum.

[0009] Preferably, the magnetic resonance spectroscopy acquisition sequence is a point-resolved spectroscopy sequence (PRESS) or a stimulated echo acquisition mode sequence (STEAM).

[0010] Preferably, the parameters of the saturation pulse include pulse intensity and / or pulse duration, which are optimized based on the chemical exchange rate of the target analyte and / or the relaxation time of water protons. Specifically, to achieve the best CEST enhancement effect, the intensity B1 of the saturation pulse should be selected within the matching range of the chemical exchange rate k_ex of the target analyte, typically satisfying B1≈k_ex / 2π, to maximize the saturation transfer efficiency; the duration T_sat of the saturation pulse is typically set to 1.5-3 times the longitudinal relaxation time T1 of water protons to ensure steady-state saturation is achieved.

[0011] Secondly, the present invention provides a magnetic resonance spectroscopy detection system based on CEST effect enhancement, comprising: A magnetic resonance scanner is used to apply a main magnetic field, gradient field, and radio frequency pulses, and to acquire magnetic resonance signals. A sequence generator, communicatively connected to the magnetic resonance scanner, is configured to generate and execute pulse sequences, the pulse sequences comprising: The CEST presaturation module is configured to apply a frequency-selective saturation pulse to saturate the exchangeable protons in the target analyte before magnetic resonance spectroscopy acquisition. The magnetic resonance spectroscopy acquisition module is configured to acquire water signals from the region of interest after the CEST presaturation module; The data processing unit is communicatively connected to the magnetic resonance scanner and is used to receive water signals acquired by the magnetic resonance scanner, construct a Z-spectrum based on the water signals, extract signal change features corresponding to the target analyte by analyzing the Z-spectrum, and determine the information of the target analyte based on the signal change features. An output unit, connected to the data processing unit, is used to output information about the target analyte.

[0012] Preferably, the data processing unit is further configured to perform Lorentz fitting on the Z-spectrum to subtract the contribution of the direct water saturation effect and / or magnetization transfer effect to the Z-spectrum, and extract the magnetization transfer rate asymmetry analysis value of the target analyte.

[0013] Thirdly, the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein the computer program, when executed by a processor, implements the steps of the method described in any of the first aspects above.

[0014] Fourthly, the present invention provides a magnetic resonance spectroscopy acquisition sequence, the sequence comprising: The CEST pre-saturation module, located at the beginning of the sequence, is used to apply at least one frequency-selective saturation pulse, the frequency of which is set to correspond to the resonance frequency of exchangeable protons in the target analyte. The magnetic resonance spectroscopy acquisition module, which follows the CEST presaturation module, is used to acquire water signals from the region of interest after the CEST effect occurs. The sequence is configured to be repeated at multiple different saturation frequencies to generate Z-spectrum data for determining information about the target analyte.

[0015] Preferably, the magnetic resonance spectroscopy acquisition module is a point-resolved spectral sequence module or a stimulated echo acquisition mode sequence module.

[0016] Compared with the prior art, the present invention has the following beneficial effects: Significantly improves detection sensitivity: By converting weak metabolite signals into detectable changes in water signals, detection sensitivity can be improved by hundreds to thousands of times, enabling the accurate quantification of low-concentration metabolites that were previously difficult to detect.

[0017] High specificity: Frequency-selective saturation using the unique chemical shifts of metabolites can effectively distinguish different metabolites, reduce interference from overlapping spectral lines, and achieve accurate detection of specific metabolites.

[0018] High compatibility: It can be integrated as a front-end module into existing standard waveforms such as PRESS and STEAM without major hardware modifications, making it easy to promote in preclinical and clinical MRI systems.

[0019] Accurate quantification: Through Z-spectrum analysis and magnetization transfer rate asymmetry analysis, background interferences such as direct water saturation effect and magnetization transfer effect can be effectively eliminated, achieving accurate quantification. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic flowchart of the magnetic resonance spectroscopy detection method based on CEST enhancement in an embodiment of the present invention; Figure 2 This is a pulse sequence timing diagram in an embodiment of the present invention, illustrating the connection relationship between the CEST pre-saturation module and the traditional PRESS module; Figure 3 This is a schematic diagram of the Z-spectrum of the hippocampus in a mouse brain in an embodiment of the present invention; Figure 4 This is a structural block diagram of the magnetic resonance spectroscopy detection system based on CEST enhancement according to the present invention.

[0022] The following are the labeling elements in the figure: 10: Magnetic Resonance Scanner; 20: Sequence Generator; 30: Data Processing Unit; 40: Output Unit; 50: Control Console. Detailed Implementation

[0023] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0024] Although MRS technology has been developed for decades and plays an irreplaceable role in clinical and research fields, it has always faced several inherent technical bottlenecks that limit its application in the detection and dynamic monitoring of low-concentration metabolites. Problems such as insufficient detection sensitivity, signal loss and interference caused by water pressing techniques, severe spectral line overlap interference, and the fact that some metabolites are "invisible" in conventional MRS have consistently constrained the development of MRS technology.

[0025] Chemical exchange saturation transfer (CEST) is a magnetic resonance contrast enhancement technique developed in recent years. Its core lies in utilizing the dynamic chemical exchange process between exchangeable protons on certain compounds and protons in the surrounding water, producing a significant signal amplification effect. Theoretically, it can improve detection sensitivity by hundreds to thousands of times. Currently, CEST technology is mainly applied in the field of magnetic resonance imaging, and there are no publicly available technical solutions for systematically introducing it into the field of spectral analysis to enhance the spectral detection sensitivity of specific metabolites.

[0026] This invention is the first to systematically introduce the CEST effect from the traditional imaging field into the field of spectral analysis, and proposes a technical solution of "CEST-enhanced magnetic resonance spectroscopy detection". By reversely utilizing the water signal that needs to be suppressed in traditional MRS, the CEST effect is used as a front-end signal enhancement module, and the concentration of metabolites can be indirectly and with high sensitivity quantified by detecting changes in the water signal.

[0027] In magnetic resonance spectroscopy, the region of interest is typically a monochromatin, which is a cubic or cuboid volume selected from tissue or phantom as the analyte. A monochromatin usually contains multiple coexisting metabolites. For example, in monochromatins of the mouse hippocampus, multiple metabolites such as glutamate, creatine, N-acetylaspartate, choline, and taurine are present simultaneously. These metabolites have different chemical shifts and exchangeable protons. When a saturation pulse of a specific frequency is applied, the exchangeable protons of the target analyte are primarily saturated, but other metabolites may produce weak, non-specific contributions. This invention effectively eliminates these interferences through Z-spectrum analysis and background subtraction techniques.

[0028] For phantom experiments, phantoms containing a single metabolite can be prepared for method validation, or mixed phantoms containing multiple metabolites can be prepared to simulate the real tissue environment.

[0029] Example 1: Detection of glutamate in the hippocampus of mouse brain This embodiment uses the hippocampus of a mouse brain as the research object to verify the detection specificity and quantitative accuracy of the method of the present invention in the complex metabolic environment of the brain of a live small animal, corresponding to the results shown in Figure 2 (pulse sequence timing) and Figure 3 (Z spectrum of mouse hippocampus) in the specification.

[0030] Eight-week-old male C57BL / 6 mice, weighing 20–25 g, were selected and anesthetized with 1.5%–2% isoflurane inhalation. The respiratory rate was maintained at 40–60 breaths / minute, and the rectal temperature was controlled at 37 ± 0.5℃ using a thermostat. The mouse head was fixed at the center of the surface coil of a 9.4T small animal MRI scanner to obtain coronal, sagittal, and horizontal localization images.

[0031] Referring to the stereotaxic atlas of the mouse brain, regions of interest (ROIs) of monomorphons were selected in the CA1 region of the bilateral hippocampus. The coordinates were set as follows: origin at the anterior fontanelle, 2.0 mm posteriorly, 1.5 mm laterally, and 2.0 mm deep. The monomorphon size was 2 mm × 2 mm × 2 mm to ensure that the volume was confined within the gray matter of the hippocampus and to avoid contamination of the cortex, white matter, and cerebrospinal fluid.

[0032] The uniformity of the magnetic field within the monomer was optimized using the FASTMAP local shimming program, resulting in a water peak half-width of less than 20 Hz. The longitudinal relaxation time of water protons in the hippocampus region was approximately 1.9 s, as measured by the inversion recovery sequence.

[0033] Based on the chemical exchange characteristics of glutamate protons (exchange rate kex ≈ 1000 s), - ¹) and tissue T1 value, optimize CEST pre-saturation pulse parameters: use continuous wave saturation pulse, intensity B1=3.6μT, duration Tsat=3.5 s (about 1.8 times T1) to achieve steady-state saturation.

[0034] The pulse sequence used in this embodiment is shown in the attached figure. Figure 2 As shown, it consists of two cascaded parts: the CEST presaturation module and the PRESS spectral acquisition module, with a clearly discernible timing structure. The CEST presaturation module is located at the very beginning of the sequence and consists of frequency-selective continuous wave saturation pulses. The center frequency of the pulses is set to +3.0 ppm, corresponding to the glutamate proton resonance frequency, and is used to selectively saturate the exchangeable protons of the target metabolite. A short delay of 100 μs is set after the saturation pulse to avoid interference from gradient switching on subsequent signal acquisition. The PRESS spectral acquisition module follows immediately after the delay interval and includes one 90° excitation pulse and two 180° refocusing pulses to achieve spatial localization of monomers and water signal acquisition, fully preserving the water signal changes induced by the CEST effect.

[0035] This sequence design can be directly used as a front-end module compatible with existing standard spectral sequences, without requiring modification to the magnetic resonance system hardware, and is compatible with attached... Figure 2 The pulse sequence shown corresponds perfectly in timing.

[0036] Step A: Apply the CEST presaturation module, which includes at least one frequency-selective saturation pulse. The frequency of the saturation pulse is set to correspond to the resonance frequency of the exchangeable protons in the target analyte, so as to selectively saturate the exchangeable protons. (See Appendix) Figure 2 The timing sequence shown applies a CEST presaturation module before the PRESS sequence, setting the saturation pulse center frequency to +3.0 ppm, which corresponds to the resonance frequency of the glutamate proton, selectively saturating the glutamate exchangeable proton.

[0037] Step B: After applying the CEST pre-saturation module, a magnetic resonance spectroscopy acquisition sequence is executed to acquire water signals from the region of interest. These water signals exhibit detectable changes due to the chemical exchange saturation transfer effect between the exchangeable protons and water protons. Immediately after a 100 μs delay following the saturation pulse, a PRESS sequence is executed to acquire the water signal. The parameters are set as follows: TR = 6 s (to ensure sufficient magnetization recovery), TE = 15 ms (to reduce T2 relaxation loss), acquisition bandwidth 5 kHz, and 2048 data points. The water signal intensity after saturation is recorded as Ssat(Δω), and a reference signal S0 without a saturation pulse is acquired simultaneously.

[0038] Step C: Change the frequency of the saturation pulse and repeat steps A and B to obtain water signals at different saturation frequencies, and construct a Z-spectrum based on the water signals at different saturation frequencies. Keeping other parameters constant, systematically change the saturation pulse frequency offset in a step size of 0.5 ppm within the range of -6 ppm to +6 ppm, and repeatedly collect water signals at different frequencies. Normalize Ssat(Δω) and S0 at each frequency to obtain the Z-spectrum: Z(Δω) = Ssat(Δω) / S0. The Z-spectrum of the mouse hippocampus region obtained is shown in the attached figure. Figure 3 As shown.

[0039] Step D: Analyze the Z-spectrum, extract the signal change features corresponding to the target analyte by fitting or calculation, the signal change features characterize the detectable changes in the water signal, and determine the information of the target analyte based on the signal change features.

[0040] The Levenberg-Marquardt algorithm was used to perform multi-peak Lorentz fitting on the Z-spectrum shown in Figure 3 to decompose the direct water saturation, magnetization transfer (MT) background, and the signal contributions of each metabolite. After removing the background interference, the magnetization transfer rate asymmetry value corresponding to glutamate was extracted according to the formula MTLRasym(3.0 ppm) = Z(-3.0 ppm) - Z(+3.0 ppm), and the result was MTLRasym=0.03±0.001.

[0041] To directly quantify glutamate concentration from Z-chromatograms, a multi-pool exchange model based on the Bloch-McConnell equation was employed for the analysis of glutamate. Figure 3Nonlinear fitting was performed on the Z-spectrum. The fitting model included a water proton pool, a semi-solid macromolecule pool (MT effect), and an exchangeable proton pool for glutamate. During the fitting process, the water proton exchange intervals were fixed at T1 = 1.9 s (measured by inversion recovery sequence) and T2 = 50 ms (obtained by CPMG sequence, using TR = 6 s, 16 echo times, acquiring and fitting data from the same region of interest). All these parameters were pre-determined under the same experimental conditions and used as known constants input into the multi-pool exchange model. The glutamate exchange rate was fixed at kex = 1000 s. - ¹, with B1 fixed at 3.6 μT, glutamate concentration [Glu] and semi-solid cell size were used as free parameters. The Levenberg-Marquardt algorithm was used to minimize the residual between the fitted curve and the experimental Z-spectrum, and the optimal solution for glutamate concentration was directly output as 10.2 mM, with a standard deviation of 1.1 mM reflecting the goodness of fit.

[0042] Example 2: Detection of glutamate in the gray matter of normal rat brain Male Sprague-Dawley rats, weighing 250-300g, were used in the experiment and provided by the experimental animal center. Anesthesia was administered using isoflurane inhalation: an induction concentration of 5% and a maintenance concentration of 1.5-2%, controlled by a precision vaporizer. After anesthesia, the rats were fixed in a prone position to a specialized rat adapter, with their heads positioned at the center of the surface coil, ensuring the region of interest was within the coil's sensitive range. A respiratory sensor was used to monitor the animals' respiratory rate, which was maintained within the normal physiological range of 40-60 breaths / minute by adjusting the depth of anesthesia. A rectal temperature probe was used to monitor body temperature in real time, and a circulating water bath heating system was used to maintain the body temperature at 37±0.5℃ to avoid the effects of hypothermia on physiological state and metabolite concentration. Vital signs were continuously monitored throughout the experiment to ensure stable physiological function under anesthesia.

[0043] First, a fast spin-echo sequence scan was performed to obtain localization images in three directions: coronal, sagittal, and horizontal, for subsequent precise localization of the monochromatin. Referring to the stereotaxic atlas of the Paxinos-Watson rat brain, the monochromatin was selected from the left sensorimotor cortex. The specific coordinates were set as follows: 1.0 mm posterior to the anterior fontanelle, 2.5 mm lateral to the left, and 2.0 mm deep (from the cortical surface downwards). This location corresponds to the primary sensorimotor cortex, a region densely populated with glutamatergic neurons. The monochromatin size was set to 3 mm × 3 mm × 3 mm. This size ensured sufficient signal intensity while effectively confining it within the gray matter, avoiding contamination from adjacent white matter and cerebrospinal fluid.

[0044] Homogenization and parameter optimization were performed. Local shimming was conducted using the FASTMAP program, which calculates and optimizes the magnetic field homogeneity within a single element by acquiring projection data from multiple orthogonal directions. After shimming, the full width at half maximum (FWHM) of the water peak was measured using a single-pulse sequence, requiring it to be less than 18 Hz. This standard is sufficient to ensure the frequency resolution of subsequent CEST measurements.

[0045] The longitudinal relaxation time (T1) of water protons in the region of interest (ROI) was measured using inversion recovery sequence (IRS). The IRS parameters were set as follows: 12 inversion times (TI) ranging from 50 ms to 5000 ms, TR = 10 s, and each TI point was averaged four times. Single-exponential fitting was performed on the collected data, and the measured T1 value for the gray matter region was approximately 2.1 s, consistent with the typical T1 value of brain tissue under a 9.4T field strength.

[0046] Based on the chemical exchange properties of glutamate (approximately 1000 s Kex), - ¹) Based on the measured tissue T1 value, the CEST pre-saturation pulse parameters were optimized. The saturation pulse intensity B1 was set to 1.0 μT. The saturation pulse duration was set to 3.5 seconds, approximately 1.7 times the T1 value (2.1 s). This duration allows the saturation effect to reach a steady state while avoiding excessively long scan times. The pulse sequence timing still refers to... Figure 2 The structure shown is modified by adjusting only the specific parameters.

[0047] The detection method of the present invention was performed according to steps A to D as described in Example 1. Specific parameter adjustments were as follows: the saturation pulse frequency offset step size was set to 0.2 ppm, and the scan range was -5 ppm to +5 ppm; the PRESS sequence parameters remained consistent with those in Example 1 (TR=6 s, TE=15 ms). The acquired live-cell Z-spectrum also presented the following... Figure 3 The spectrum exhibits typical characteristics, but due to the coexistence of multiple metabolites, the spectral lines are more complex.

[0048] Analysis of the collected in vivo Z-ray spectra revealed signal decreases around +3.0 ppm, +1.9 ppm, and 2.5 ppm due to the coexistence of multiple metabolites within the monomeric material. To separate the CEST signal of glutamate, the Levenberg-Marquardt algorithm was used to perform multi-peak Lorentz fitting on the Z-ray spectra, decomposing the direct water saturation peak, magnetization transfer background, and characteristic peaks of each metabolite. After subtracting background interference, the glutamate peak amplitude was obtained. Simultaneously, MTLRasym (3.0 ppm) was calculated using magnetization transfer rate asymmetry analysis. The results from both methods were consistent, and the calculated glutamate concentration in the rat cortical gray matter was 11.5 ± 1.2 mM.

[0049] Reference Figure 4The CEST-enhanced magnetic resonance spectroscopy detection system of the present invention comprises five main components: a magnetic resonance scanner, a sequence generator, a data processing unit, an output unit, and a control console.

[0050] The magnetic resonance scanner 10 is used to apply a main magnetic field, a gradient field, and radio frequency pulses, and to acquire magnetic resonance signals. Specifically, it includes a superconducting main magnet (9.4T), a triaxial active shielded gradient coil with a maximum gradient of 600 mT / m, and a radio frequency coil system, wherein the volume coil is used for transmission and the surface coil is used for reception.

[0051] Sequence generator 20 is communicatively connected to magnetic resonance scanner 10 and is configured to generate and execute magnetic resonance spectroscopy acquisition sequences for implementing the method of the present invention. For example... Figure 2 As shown, the magnetic resonance spectroscopy acquisition sequence includes two core parts: The CEST presaturation module is located at the beginning of the sequence and is used to apply at least one frequency-selective saturation pulse. The frequency of the saturation pulse is set to correspond to the resonance frequency of the exchangeable protons in the target analyte, so as to selectively saturate the target analyte. The magnetic resonance spectroscopy acquisition module follows the CEST presaturation module and is used to acquire water signals in the region of interest immediately after the CEST effect occurs. The sequence is configured to be repeatedly executed at multiple different saturation frequencies. That is, while keeping other parameters constant, the frequency offset of the saturation pulse is systematically changed to scan within a range that includes the resonance frequency of the target analyte, thereby generating a series of water signals at different saturation frequencies for constructing Z-spectrum data. This sequence can be directly stored in the pulse sequence library of the magnetic resonance system and, when executed, can automatically complete the entire process of CEST pre-saturation, water signal acquisition, frequency scanning, and Z-spectrum data generation.

[0052] Preferably, the magnetic resonance spectroscopy acquisition module is a point-resolved spectroscopy sequence module (PRESS module) or a stimulated echo acquisition mode sequence module (STEAM module). The PRESS module contains one 90° excitation pulse and two 180° refocusing pulses, which can achieve high signal-to-noise ratio monomorphic signal acquisition; the STEAM module consists of three 90° pulses, which can achieve a shorter echo time and is suitable for detecting short T2 metabolites.

[0053] The data processing unit 30 is communicatively connected to the magnetic resonance scanner 10 and is used to receive the acquired water signals and construct a Z-spectrum based on the water signals at different saturation frequencies (e.g., Figure 3 The typical Z-spectrum shown is used to calculate the MTLRasym value at the target frequency by fitting and subtracting background interference. This value is then compared with a pre-established standard curve to convert it into the concentration of the target analyte. The data processing unit 30 includes a memory and a processor for storing data and executing calculation programs.

[0054] The output unit 40 is connected to the data processing unit 30 and is used to output information about the target analyte, including a display, printer, and network interface.

[0055] The console 50 is connected to the sequence generator 20, the data processing unit 30, and the output unit 40, allowing operators to input scanning parameters and monitor the system's operating status.

[0056] Accordingly, the present invention also protects a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the detection method described in any of the above embodiments.

[0057] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A magnetic resonance spectroscopy detection method based on CEST effect enhancement, characterized in that, Includes the following steps: Step A: Apply the CEST presaturation module, which includes at least one frequency-selective saturation pulse, the frequency of which is set to correspond to the resonance frequency of the exchangeable protons in the target analyte, so as to selectively saturate the exchangeable protons; Step B: After applying the CEST presaturation module, a magnetic resonance spectroscopy acquisition sequence is executed to acquire water signals from the region of interest, the water signals exhibiting detectable changes due to the chemical exchange saturation transfer effect between the exchangeable protons and water protons; Step C: Change the frequency of the saturation pulse, repeat steps A and B to obtain water signals at different saturation frequencies, and construct a Z-spectrum based on the water signals at different saturation frequencies; Step D: Analyze the Z-spectrum, extract the signal change features corresponding to the target analyte by fitting or calculation, the signal change features characterize the detectable changes in the water signal, and determine the information of the target analyte based on the signal change features.

2. The method according to claim 1, characterized in that, The target analytes include endogenous metabolites or exogenous compounds.

3. The method according to claim 1, characterized in that, The signal variation characteristics include the signal drop depth at a specific frequency on the Z-spectrum, the signal drop integral area within a specific frequency range, or the magnetization transfer rate asymmetry analysis value calculated based on the Z-spectrum.

4. The method according to claim 1, characterized in that, The magnetic resonance spectroscopy acquisition sequence is a point-resolved spectroscopy sequence or a stimulated echo acquisition mode sequence.

5. The method according to claim 1, characterized in that, The parameters of the saturation pulse include pulse intensity and / or pulse duration, which are optimized based on the chemical exchange rate of the target analyte and / or the relaxation time of water protons.

6. A magnetic resonance spectroscopy detection system based on CEST effect enhancement, characterized in that, include: A magnetic resonance scanner is used to apply a main magnetic field, gradient field, and radio frequency pulses, and to acquire magnetic resonance signals. A sequence generator, communicatively connected to the magnetic resonance scanner, is configured to generate and execute pulse sequences, the pulse sequences comprising: The CEST presaturation module is configured to apply a frequency-selective saturation pulse to saturate the exchangeable protons in the target analyte before magnetic resonance spectroscopy acquisition. The magnetic resonance spectroscopy acquisition module is configured to acquire water signals from the region of interest after the CEST presaturation module; The data processing unit is communicatively connected to the magnetic resonance scanner and is used to receive water signals acquired by the magnetic resonance scanner, construct a Z-spectrum based on the water signals, extract signal change features corresponding to the target analyte by analyzing the Z-spectrum, and determine the information of the target analyte based on the signal change features. An output unit, connected to the data processing unit, is used to output information about the target analyte.

7. The system according to claim 6, characterized in that, The data processing unit is further configured to perform Lorentz fitting on the Z-spectrum to deduct the contribution of the direct water saturation effect and / or magnetization transfer effect to the Z-spectrum, and extract the magnetization transfer rate asymmetry analysis value of the target analyte.

8. A magnetic resonance spectroscopy acquisition sequence, characterized in that, The sequence includes: The CEST pre-saturation module, located at the beginning of the sequence, is used to apply at least one frequency-selective saturation pulse, the frequency of which is set to correspond to the resonance frequency of exchangeable protons in the target analyte. The magnetic resonance spectroscopy acquisition module, which follows the CEST presaturation module, is used to acquire water signals from the region of interest after the CEST effect occurs. The sequence is configured to be repeated at multiple different saturation frequencies to generate Z-spectrum data for determining information about the target analyte.

9. The magnetic resonance spectroscopy acquisition sequence according to claim 8, characterized in that, The magnetic resonance spectroscopy acquisition module is either a point-resolved spectral sequence module or a stimulated echo acquisition mode sequence module.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the steps of the magnetic resonance spectroscopy detection method based on the CEST effect enhancement as described in any one of claims 1 to 5.