A system and method for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy

Through J editing spectroscopy technology, specific pulse sequences are designed to achieve targeted detection of glucose and lactate molecules, solving the problems of signal overlap and water peak interference in the existing technology, and achieving non-invasive and accurate detection of cerebrospinal fluid components, with clinical application potential for early diagnosis and treatment monitoring.

CN120044067BActive Publication Date: 2025-08-26SHANDONG PROVINCIAL HOSPITAL AFFILIATED TO SHANDONG FIRST MEDICAL UNIVERSITY (SHANDONG PROVINCIAL HOSPITAL)
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Patent Information

Application Number
CN202510510090.7
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-04-23
Publication Date
2025-08-26
Estimated Expiration
2045-04-23

AI Technical Summary

Technical Problem

The prior art is difficult to efficiently detect the magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid simultaneously and efficiently. Conventional MRS methods are limited by signal overlap and water peak interference, and cannot achieve non-invasive and accurate detection.

Method used

Using J-edit spectroscopy technology, by designing specific pulse sequences, including signal suppression, signal selection and magnetic resonance spectroscopy modules, J-edit technology is used to manipulate the quantum states of α-glucose and lactate molecules, and targeted detection of glucose and lactate molecules in cerebrospinal fluid.

Benefits of technology

It realizes rapid, non-invasive and radiation-free magnetic resonance signal detection of glucose and lactate molecules, with good accuracy and sensitivity, replaces invasive lumbar puncture, and has important clinical application value.

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Abstract

The present invention discloses a system and method for the targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-editing spectroscopy, which belongs to the field of magnetic resonance medicine technology. The present invention realizes the accurate detection of magnetic resonance signals of α-glucose and lactose in cerebrospinal fluid by precisely manipulating the quantum states of glucose and lactate molecules based on J-editing technology. The method of the present invention can measure the magnetic resonance signals of α-glucose and lactose molecules in the human brain rapidly, non-invasively and without radiation. The obtained data information has important application value in the early diagnosis, treatment monitoring and other aspects of diseases such as mitochondrial encephalomyopathy, meningitis and Alzheimer's disease.
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Description

Technical Field

[0001] The present invention belongs to the field of magnetic resonance medicine technology, and specifically relates to a system and method for detecting magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy. Background Art

[0002] The cerebrospinal fluid in the body contains a variety of inorganic ions, glucose, trace proteins and a small amount of lymphocytes at varying concentrations, which provide certain nutrients for brain cells and promptly clean up the metabolic products produced by the brain. Many neurological diseases are accompanied by changes in the concentration of metabolites in the cerebrospinal fluid, such as viral encephalitis, mitochondrial encephalomyopathy, Alzheimer's disease, diabetes, bacterial encephalitis and Parkinson's disease. Among these metabolites, glucose and lactate are key indicators in the cerebrospinal fluid. For example, in patients with bacterial encephalitis, bacteria consume a large amount of glucose in the cerebrospinal fluid, and the destruction of the blood-brain barrier restricts the entry of glucose, resulting in a significant decrease in glucose in the cerebrospinal fluid; bacterial infection causes increased hypoxia and anaerobic metabolism in brain tissue, and the lactate level in the cerebrospinal fluid is usually significantly elevated.

[0003] Lumbar puncture (LP) has become an important method for routine, biochemical, and bacteriological examinations, providing crucial evidence for the diagnosis of intracranial inflammation, tumors, hemorrhage, and white matter demyelinating diseases. Currently, this technique has become the primary means of analyzing CSF composition. However, due to its invasive nature, LP is often associated with complications such as CSF leakage, migraines, hemorrhage, and spinal cord injury. Furthermore, some patients, such as those with elevated intracranial pressure, lumbar deformities, and critical shock, are unable to undergo LP, leading to delayed diagnosis. Magnetic resonance spectroscopy (MRS), a noninvasive technique for detecting the type, structure, content, and spatial distribution of metabolites in living tissues and organs, is currently one of the most direct and effective methods for noninvasively monitoring in vivo metabolism due to its noninvasive and high sensitivity. Glucose in CSF is divided into two types: α-Glc and β-Glc. Due to their similar chemical structures, their magnetic resonance signals overlap, making them difficult to distinguish. In addition, the two sets of magnetic resonance signals of α-Glc and β-Glc are close to the water peak, which leads to the conventional 1 The HMRS method often interferes with these two groups of signals during the water peak suppression process. The signal of lactic acid (Lac) molecules easily overlaps with the signals of proteins, lipids and other molecules in the cerebrospinal fluid. 1 It is difficult to achieve targeted detection of glucose and Lac signals simultaneously using H MRS technology.

[0004] The patent application "A method for distinguishing tuberculous meningitis from viral meningitis based on nuclear magnetic resonance technology and its application" (Announcement No.: CN105943048B) provides a technical solution for analyzing the results of cerebrospinal fluid of patients to be tested using nuclear magnetic resonance imaging to determine whether the patient is or is a candidate for tuberculous meningitis. However, it is also unable to achieve simultaneous targeted detection of glucose and lactate molecular signals. Summary of the Invention

[0005] To overcome the shortcomings of existing technologies, the present invention proposes a system and method for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid (CSF) using J-editing spectroscopy. This method utilizes J-editing technology for non-diagnostic purposes. By simultaneously manipulating the quantum states of α-glucose and lactate molecules, J-editing allows for targeted detection of α-glucose and lactate signals while effectively suppressing the water peak. Experiments have demonstrated the advantages of this method's rapidity and non-invasiveness.

[0006] In order to achieve the above technical objectives, the technical solutions implemented by the present invention are:

[0007] As a first aspect of the present invention, a system for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy is provided, comprising:

[0008] An acquisition module, configured to acquire magnetic resonance images; the magnetic resonance images may be acquired from an in vitro sample or a living organism;

[0009] a pulse sequence applying module, used for applying a pulse sequence and displaying a magnetic resonance spectrum;

[0010] Among them, the acquisition module and the pulse sequence application module realize information transmission through communication;

[0011] The pulse sequence application module includes: a signal suppression module, a signal selection module and a magnetic resonance spectroscopy module; wherein the signal suppression module mainly includes two parts: an outer volume suppression (OVS) module and a water suppression (WS) module;

[0012] The signal selection module includes saturation pulse and gradient pulse;

[0013] The magnetic resonance spectroscopy module includes several slice selection pulses and gradient pulses.

[0014] Furthermore, the glucose is α-glucose.

[0015] Furthermore, the acquisition module uses a T1 or T2 magnetic resonance weighted sequence to locate the position of the body tissue in the magnetic field and select a region of interest.

[0016] As a second aspect of the present invention, a method for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy for non-diagnostic purposes is also proposed, the method comprising:

[0017] Step i: using water suppression technology to suppress the water signal in the cerebrospinal fluid;

[0018] Step ii: Using the saturation pulse in the J-editing technique to further suppress the signal of water molecules and precisely manipulate the quantum state evolution of the glucose and lactate molecular spin systems;

[0019] Step iii: Targeted detection of glucose and lactic acid molecular signals in the region of interest is achieved using slice selection pulses and gradient pulses to obtain magnetic resonance signals of glucose and lactic acid molecules.

[0020] Specifically, the present invention designs a specific pulse sequence based on the spin coupling characteristics and chemical shifts between protons in α-glucose and lactic acid molecules. The pulse sequence is functionally composed of "signal suppression", "signal selection" and "magnetic resonance spectroscopy" modules, among which the signal suppression module mainly includes outer volume suppression (OVS) and water suppression (WS) parts, the signal selection module mainly consists of two saturation pulses of specific frequencies and gradient pulses, and the magnetic resonance spectroscopy module consists of multiple layer selection pulses and gradient pulses.

[0021] In the embodiment of the present invention, in step i, the signal outside the region of interest is suppressed by using extra-volume suppression; the extra-volume suppression includes 8 saturation pulses, each of which has a duration of 8 ms and an amplitude of 160 Hz.

[0022] In the embodiment of the present invention, in step ii, the echo time is set to between 90 ms and 130 ms, and a 180-degree slice-selective pulse and a saturation pulse of water peak resonance are used;

[0023] Preferably, two saturation pulses are used, both of which have Gaussian shapes, 15 ms durations, and frequencies centered at 4.7 ppm.

[0024] In the embodiment of the present invention, in step iii, three sinc-type layer selection pulses are used, the layer selection pulse durations are 2.5 ms, 5 ms, and 5 ms, and the flip angles are 90 degrees, 180 degrees, and 180 degrees, respectively.

[0025] In an embodiment of the present invention, in step iii, a conventional T1 or T2 weighted sequence is used to locate the position of the living organism in the magnetic field and select a region of interest.

[0026] In an embodiment of the present invention, in step iii, the magnetic resonance signals of glucose and lactic acid molecules include their J coupling values, chemical shifts of protons on methyl groups, and signal intensities.

[0027] The present invention provides a system for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-editing spectroscopy, which implements the method for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-editing spectroscopy.

[0028] The beneficial effects of the present invention are:

[0029] 1. The present invention provides a system for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-editing spectroscopy. This system is based on magnetic resonance technology and has a significant feature and innovation that distinguishes it from other previous magnetic resonance spectroscopy technologies: J-editing technology is used to target the detection of α-glucose and lactate molecular signals in cerebrospinal fluid in vivo, which is expected to replace lumbar puncture in clinical practice and become a routine clinical examination.

[0030] 2. The method of the present invention can measure the magnetic resonance signals of α-glucose and lactic acid molecules in the body rapidly, non-invasively and without radiation, with good accuracy, sensitivity and stability; it has important application value in biology and medicine, and provides a new detection idea.

[0031] 3. The data information obtained based on the detection method of the present invention has important application value in the early diagnosis and treatment monitoring of diseases such as mitochondrial encephalomyopathy, meningitis and Alzheimer's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. 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 paying any creative work.

[0033] Figure 1 Schematic diagrams of the molecular structures of Lac, α-Glc and β-Glc involved in the present invention, respectively; wherein (a) is the molecular structural formula of lactic acid, (b) is the structural formula of α-Glc, and (c) is the structural formula of β-Glc.

[0034] Figure 2 The figure is a specific implementation flow chart of the method of the present invention.

[0035] Figure 3 Schematic diagram of the pulse sequence for accurately observing α-Glc and Lac magnetic resonance signals in cerebrospinal fluid according to the present invention, wherein Gx , G y and G z Represents the pulse gradient channels in the x, y, and z directions, 90 x , 180 y , 180 y Medium 90, 180, 180 and x 、 y 、 y are the flip angle and phase of the pulse used for layer selection respectively.

[0036] Figure 4 Schematic diagram of the main steps of the specific implementation of the present invention.

[0037] Figure 5 The test results of the water film sample in Example 1 of the present invention are shown in FIG. 1 ; wherein (a) is a conventional T1-weighted image of the water film sample, (b) above is a conventional magnetic resonance spectrum, and (b) below is a conventional magnetic resonance spectrum using Figure 3 The pulse magnetic resonance spectrum was obtained; α-Glc refers to the magnetic resonance signal of the protons on the α-Glc methine group around 5.2 ppm.

[0038] Figure 6 The test results of the 12-year-old mitochondrial encephalomyopathy subject in Example 2 of the present invention; wherein, (a) is the conventional T1-weighted image of the patient, (b) above is the conventional magnetic resonance spectroscopy image of the subject, and (b) below is the image of the subject using Figure 3 Pulse magnetic resonance spectroscopy was obtained.

[0039] Figure 7 The test results of the 55-year-old ventriculomegaly patient in Example 3 of the present invention are shown in FIG. 1 , wherein (a) is a conventional T1-weighted image, (b) above is a conventional magnetic resonance spectroscopy image of the subject, and (b) below is a conventional magnetic resonance spectroscopy image of the subject. Figure 3 Pulse magnetic resonance spectroscopy was obtained. DETAILED DESCRIPTION

[0040] The present invention is further described below with reference to specific embodiments and accompanying drawings. The processes, conditions, experimental methods, etc. for implementing the present invention, except for those specifically mentioned below, are common knowledge and common common sense in the art and are not particularly limited by the present invention.

[0041] Figure 1 Schematic diagrams of the molecular structures of Lac, α-Glc, and β-Glc, respectively, according to the present invention; (a) is the molecular formula of lactic acid, (b) is the structural formula of α-Glc, and (c) is the structural formula of β-Glc. Due to the similar structures of α-Glc and β-Glc, their nuclear magnetic resonance (NMR) signals overlap in cerebrospinal fluid, making them difficult to distinguish. Accurate detection of lactic acid molecules is also difficult in existing technologies.

[0042] The present invention provides a system and method for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-editing spectroscopy. Targeted detection of α-glucose and lactate molecules in cerebrospinal fluid can be achieved using J-editing technology.

[0043] Example 1: A system for targeted detection of magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy

[0044] including an acquisition module for acquiring magnetic resonance images of the brain;

[0045] a pulse sequence applying module, used for applying a pulse sequence and displaying a magnetic resonance spectrum;

[0046] Among them, the acquisition module and the pulse sequence application module realize information transmission through communication;

[0047] The pulse sequence application module includes a "signal suppression" module, a "signal selection" module and a "magnetic resonance spectroscopy" module; wherein the signal suppression module mainly includes two parts: an outer volume suppression (OVS) module and a water suppression (WS) module;

[0048] The signal selection module includes two saturation pulses and gradient pulses of specific frequencies;

[0049] The magnetic resonance spectroscopy module includes multiple slice selection pulses and gradient pulses.

[0050] In one or more embodiments of the present invention, the acquisition module uses a T1 or T2 magnetic resonance weighted sequence to locate the position of the tissue in the body in the magnetic field and select a region of interest.

[0051] In one or more embodiments of the present invention, the water suppression module is used to suppress the signal of water molecules in a selected region of interest. This technique utilizes VAPOR (VAriable Power Radiofrequency Pulses with Optimized Relaxation Delays), a technique consisting of multiple RF pulses, evolution times, and gradient pulses. This method, which includes multiple small-angle RF pulses and optimized evolution times, achieves a narrow suppression range in the spectrum, suppressing the water peak while avoiding impacting the α-glucose signal. In this embodiment, eight RF pulses were used, with flip angles of α, α, 1.78α, α, 1.59α, α, 1.78α, and 1.78α, where α is 80 degrees. The inter-pulse evolution times were 150 ms, 100 ms, 122 ms, 105 ms, 102 ms, 61 ms, 67 ms, and 14 ms, respectively.

[0052] Furthermore, an out-of-volume suppression module is embedded within the VAPOR pulse to suppress MRI signals outside the region of interest, while ensuring a short recovery time (TR) and water peak suppression, minimizing the likelihood that the selected voxels represent cerebrospinal fluid rather than brain tissue. In this invention, the out-of-volume suppression module includes eight saturation pulses, each lasting 8 ms.

[0053] A method for detecting the magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy. Figure 2 As shown, the method includes the following steps:

[0054] Step i: using water suppression technology to suppress the water signal in the cerebrospinal fluid;

[0055] Step ii: Using the saturation pulse in the J-editing technique to further suppress the signal of water molecules and precisely manipulate the quantum state evolution of the α-glucose and lactate molecular spin systems;

[0056] Step iii: Targeted detection of glucose and lactate signals in the region of interest is achieved using slice selection pulses and gradient pulses to obtain magnetic resonance signals of glucose and lactate molecules.

[0057] Specifically, the present invention designs a specific pulse sequence based on the spin coupling characteristics and chemical shifts between protons in α-glucose and lactic acid molecules; the pulse sequence is functionally composed of "signal suppression", "signal selection" and "magnetic resonance spectroscopy" modules, wherein the signal suppression module mainly includes outer volume suppression (OVS) and water suppression (WS) parts; the signal selection module mainly consists of two saturation pulses of specific frequencies and gradient pulses, where the gradient pulse refers to Figure 3 The six trapezoidal gradient pulses near the two saturation pulses have an amplitude ranging from 5 mT / m to 40 mT / m and a duration ranging from 1 ms to 5 ms. The amplitude and duration of the trapezoidal gradient pulses used in the embodiment of the present invention are 15 mT / m and 2.5 ms, respectively. The magnetic resonance spectroscopy module is composed of multiple slice selection pulses and gradient pulses.

[0058] In one or more embodiments of the present invention, in step i, to suppress the water peak while avoiding affecting the α-glucose signal, the present invention employs VAPOR (VAriable Power radiofrequency pulses with optimized relaxation delays) technology, consisting of multiple radiofrequency pulses, evolution times, and gradient pulses, to suppress the water molecule signal in the selected region of interest. In this embodiment, eight radiofrequency pulses were used, with flip angles of α, α, 1.78α, α, 1.59α, α, 1.78α, and 1.78α, where α is 80 degrees. The inter-pulse evolution times were 150 ms, 100 ms, 122 ms, 105 ms, 102 ms, 61 ms, 67 ms, and 14 ms, respectively. In VAPOR, the first three gradient pulses have a duration of 4 ms and an amplitude of 15 mT / m; the fourth to sixth gradient pulses have a duration of 3 ms and an amplitude of 10 mT / m; the sixth to tenth gradient pulses have a duration of 2 ms and an amplitude of 10 mT / m; and the eleventh to thirteenth gradient pulses have a duration of 2 ms and an amplitude of 8 mT / m. Furthermore, an out-of-volume suppression module is embedded within the VAPOR pulses to suppress magnetic resonance signals outside the region of interest, while ensuring a short recovery time (TR) and water peak suppression. In the present invention, the out-of-volume suppression module contains eight saturation pulses, each of which has a duration of 8 ms and an amplitude of 160 Hz.

[0059] In step ii, the present invention simultaneously considers the evolution of the four-spin system of lactate molecules and the seven-spin system of α-glucose. Because the VAPOR and OVS in step i significantly suppress the signal of water molecules in the cerebrospinal fluid (CSF) signal, the concentration of α-glucose in the CSF is only about one ten-thousandth of that of water molecules. Therefore, the residual water signal caused by VAPOR water suppression is generally much higher than that of α-glucose. To further suppress water molecules, the present invention aligns the frequency of the saturation pulse in the signal selection module with the water peak to further suppress the residual water peak. The quantum state evolution of the seven-spin system of α-glucose molecules is as follows: Under the action of radio frequency pulses and gradient pulses, the quantum state of the seven-spin system of α-glucose molecules is transformed from the thermal equilibrium state S1z+S2z+S3z+S4z+S5z+S6z+S7z to S1x, while other signals are destroyed by the saturation pulse and gradient pulse. At this time, the signal of α-glucose near 5.25 ppm is a positive doublet, where Sjx and Sjz (j=1~7) refer to the product operators of the j-th nuclear spin of the α-glucose molecule in the x and z directions, respectively; in addition, under the action of the long echo time pulse, the fat signal is suppressed; in general, through J editing technology, while suppressing the water peak and other metabolite signals, the targeted detection of lactate molecules and α-glucose signals in cerebrospinal fluid is achieved at the same time.

[0060] In step ii, the echo time (TE) is set between 90 ms and 130 ms. Under the action of the radio frequency pulse and the gradient pulse, the quantum state of the lactic acid molecule will be transformed from the thermal equilibrium state I1z+I2z+I3z+I4z to - (I1x+I2x+I3x+I4x), where is the transfer efficiency of the lactic acid molecule from the thermal equilibrium state to the single quantum state. At this time, the lactic acid molecule signal near 1.33 ppm is an inverted doublet, where Ijx and Ijz (j = 1~4) refer to the product operators of the j-th nuclear spin of the lactic acid molecule in the x and z directions, respectively.

[0061] In one or more embodiments of the present invention, in step ii, under the action of a long TE pulse sequence, the signals of fat and protein molecules are suppressed under the action of spin-spin relaxation; in general, through J editing technology, while suppressing water peaks and fat signals, targeted detection of lactic acid molecules and α-glucose is achieved.

[0062] In one or more embodiments of the present invention, in step ii, the saturation pulse of water peak resonance means that the coverage of the saturation pulse is centered on the chemical shift of the water molecule, so that the spin system of the molecule evolves under the action of the saturation pulse. The saturation pulse can be composed of one or more long hard pulses or shaped pulses. The frequencies of multiple saturation pulses are all set near the resonance frequency of the water molecules to further suppress the signals of the water molecules. In order to avoid affecting the α-glucose signal, the time of the saturation pulse of the water peak resonance needs to be as long as possible within a specific TE time. The present invention uses two saturation pulses, both of which are Gaussian in shape, 15 ms in time, and 4.7 ppm in frequency center.

[0063] In one or more embodiments of the present invention, in step iii, the present invention uses three sinc-type layer selection pulses, the layer selection pulse durations are 2.5 ms, 5 ms, and 5 ms, and the flip angles are 90 degrees, 180 degrees, and 180 degrees, respectively; the gradient pulse duration is the same as the layer selection pulse duration.

[0064] In one or more embodiments of the present invention, in step iii, to detect the magnetic resonance signals of α-glucose and lactate molecules in the cerebrospinal fluid, a conventional T1- or T2-weighted sequence can be used to locate the position of the living organism in the magnetic field. This knowledge is common knowledge in the field and will not be further elaborated in the present invention.

[0065] In one or more embodiments of the present invention, in step iii, the magnetic resonance signals of α-glucose and lactic acid molecules include a J coupling value on the α-glucose methine near 5.2 ppm ( =7.0±0.2 Hz) and chemical shift ( =5.2±0.3 ppm), J coupling value of proton on methyl group of lactic acid molecule near 1.33 ppm ( =6.9±0.2 Hz) and chemical shift ( =1.33±0.3 ppm) and their signal intensities.

[0066] In step iii, the main steps of the implementation method are as follows Figure 4 As shown:

[0067] 1. Use T1- or T2-weighted MRI sequences to locate the position of tissue in the magnetic field and select a region of interest. Specifically, acquire conventional T1- or T2-weighted images of the brain or coccyx of a living person and select a region of interest at the location of the cerebrospinal fluid.

[0068] 2. Apply Figure 3 The pulses shown are used to accurately observe the magnetic resonance signals of α-glucose and lactate molecules in the cerebrospinal fluid of actual organisms.

[0069] Experimental Example 1

[0070] Experimental subjects: Mixed solution of α-Glc and Lac, their concentrations were both 20 mmol / L, and the sample volume was 45 ml.

[0071] Measurement instrument: Siemens 3T Skyra nuclear magnetic resonance instrument, the detection coil used is Siemens 64-channel head and neck combined coil.

[0072] Determination method: Figure 3 Pulse sequence shown.

[0073] The experimental steps are as follows:

[0074] 1. Use conventional T1-weighted sequences to locate the position of the water film sample in the magnetic field and select the water film sample area to be tested. See the water film magnetic resonance image and selected area. Figure 5 Middle (a).

[0075] 2. Apply Figure 3 The pulse sequence shown here has the following experimental parameters: spin recovery time (TR) of 2000 ms, echo time (TE) of 110 ms, averaging of 128, flip angle of 90°, region of interest of 30 × 10 × 10 mm³, Gaussian saturation pulses in the signal selection module with a duration of 15,000 μs and a radiofrequency center of 4.70 ppm. During the experiment, the saturation pulse center frequency and echo time were fine-tuned to optimize the magnetic resonance signals of α-glucose and lactate molecules.

[0076] 3. Experimental results are as follows Figure 5 As shown, Figure 5 Middle a is a T1-weighted magnetic resonance image of a mixture of α-glucose and lactic acid molecules; Figure 5 (b) is the regular sequence (top) and the Figure 3 Magnetic resonance spectrum of the pulse sequence (bottom). As can be seen from the figure, the α-glucose signal near the water peak in the 1H MRS spectrum of the conventional sequence is suppressed, while the α-glucose and β-glucose at other frequencies overlap severely.

[0077] use Figure 3 The pulse sequence obtained a 1H MRS spectrum targeted at α-glucose. At this time, the signal of α-glucose was a positive doublet (near 5.2 ppm), while the signals of other metabolites were greatly suppressed. At the same time, the signal of the lactate molecule was an inverted peak.

[0078] Experimental Example 2

[0079] Experimental subjects: 12-year-old male patients clinically diagnosed with mitochondrial encephalomyopathy.

[0080] Measurement instrument: Siemens 3T Skyra nuclear magnetic resonance instrument, the detection coil used is Siemens 64-channel head and neck combined coil.

[0081] Determination method: Figure 3 Pulse sequence shown.

[0082] The experimental steps are as follows:

[0083] 1. Use conventional 3D T1-weighted sequences to acquire MRI images of the patient's brain and select the region of interest (cerebrospinal fluid). See the in vivo brain MRI images and regions of interest. Figure 6 Middle (a).

[0084] 2. Apply Figure 3 The pulse sequence shown here has the following experimental parameters: spin recovery time (TR) of 2000 ms, echo time (TE) of 110 ms, average count of 128, flip angle of 90°, region of interest of 20 × 20 × 20 mm³, Gaussian pulse shape in the signal editing module, pulse duration of 15,000 μs, and radiofrequency center of 4.70 ppm. During the experiment, the saturation pulse center frequency and echo time can be fine-tuned to optimize the magnetic resonance signals of α-glucose and lactate molecules.

[0085] 3. Experimental results are as follows Figure 6 As shown. Among them, Figure 6 (a) shows the T1-weighted MRI of the patient and the selected area (cerebrospinal fluid). Figure 6 The left side of (b) is the regular sequence (top) and the Figure 3 Magnetic resonance spectra collected in the region of interest using a pulse sequence (bottom). In the conventional 1H MRS spectrum, the magnetic resonance signals of α-glucose and β-glucose in the range of 3.0 ppm-4.5 ppm overlap severely, making them difficult to separate. In addition, the α-glucose signal near 5.20 ppm is partially saturated during water suppression, and the lactic acid signal near 1.33 ppm overlaps with a small amount of lipid and protein signals in the body. Figure 3 In the spectrum of the patient's cerebrospinal fluid acquired by pulse sequence, the magnetic resonance signals of α-glucose and β-glucose in the range of 3.0 ppm-4.5 ppm were greatly suppressed, and the signal near 5.20 ppm was clearly observed. The J coupling between the two peaks was close to that of the water film (both 7.0 Hz), and the signal of the lactic acid molecule showed an inverted peak.

[0086] Experimental Example 3

[0087] Experimental subjects: A 55-year-old male patient clinically diagnosed with ventriculomegaly.

[0088] Measurement instrument: Siemens 3T Skyra nuclear magnetic resonance instrument, the detection coil used is Siemens 64-channel head and neck combined coil.

[0089] Determination method: Figure 3 Pulse sequence shown.

[0090] The experimental steps are as follows:

[0091] 1. Use conventional 3D T1-weighted sequences to acquire MRI images of the patient's brain and select the region of interest (cerebrospinal fluid). See the in vivo brain MRI images and regions of interest. Figure 7 Middle (a).

[0092] 2. Apply Figure 3 The pulse sequence shown here has the following experimental parameters: spin recovery time (TR) of 2000 ms, echo time (TE) of 110 ms, average count of 128, flip angle of 90°, region of interest of 20 × 20 × 20 mm³, Gaussian pulse shape in the signal editing module, pulse duration of 15,000 μs, and radiofrequency center of 4.70 ppm. During the experiment, the saturation pulse center frequency and echo time can be fine-tuned to optimize the magnetic resonance signals of α-glucose and lactate molecules.

[0093] 3. Experimental results are as follows Figure 7 As shown. Among them, Figure 7 (a) shows a T1-weighted MRI image of a patient with ventriculomegaly and a selected region (cerebrospinal fluid). Figure 7 The left side of (b) is the regular sequence (top) and the Figure 3 Magnetic resonance spectra collected in the region of interest using a pulse sequence (bottom). In the conventional 1H MRS spectrum, the magnetic resonance signals of α-glucose and β-glucose in the range of 3.0 ppm-4.5 ppm overlap severely, making them difficult to separate. In addition, the α-glucose signal near 5.20 ppm is partially saturated during water suppression, and the lactic acid signal near 1.33 ppm overlaps with a small amount of lipid and protein signals in the body. Figure 3 In the spectrum of the patient's cerebrospinal fluid acquired by pulse sequence, the magnetic resonance signals of α-glucose and β-glucose in the range of 3.0 ppm-4.5 ppm were greatly suppressed, and the signal near 5.20 ppm was clearly observed. The J coupling between the two peaks was close to that of the water film (both 7.0 Hz), and the signal of the lactic acid molecule showed an inverted peak.

[0094] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the appended claims.

Claims

1. A method for detecting the magnetic resonance signals of glucose and lactate molecules in cerebrospinal fluid based on J-edited spectroscopy for non-diagnostic purposes, characterized in that: The steps include: Step i: using water suppression technology to suppress the water signal in the cerebrospinal fluid; Step ii: Using the saturation pulse in the J-editing technique to further suppress the signal of water molecules and precisely manipulate the quantum state evolution of the glucose and lactate molecular spin systems; Step iii: using slice-selective pulses and gradient pulses to achieve targeted detection of glucose and lactate molecular signals in the region of interest, thereby obtaining magnetic resonance signals of glucose and lactate molecules; In step i, eight RF pulses were used, and the flip angles of each pulse were: α, α, 1.78α, α, 1.59α, α, 1.78α, 1.78α, where α was 80 degrees; the inter-pulse evolution times were: 150 ms, 100 ms, 122 ms, 105 ms, 102 ms, 61 ms, 67 ms, and 14 ms, respectively; Extravolumetric suppression was used to suppress signals outside the region of interest. This suppression consisted of eight saturation pulses, each lasting 8 ms and with an amplitude of 160 Hz. In step ii, the echo time was set between 90 ms and 130 ms, and gradient pulses and saturation pulses with water peak resonance were used; The saturation pulses for water peak resonance used two saturation pulses, both with Gaussian shape, 15 ms duration, and a frequency center of 4.7 ppm; At this time, the signal of α-glucose near 5.25 ppm is a positive doublet, and the signal of lactic acid molecules near 1.33 ppm is an inverted doublet; In step iii, three sinc-type slice selection pulses are used. The slice selection pulse durations are 2.5 ms, 5 ms, and 5 ms, and the flip angles are 90 degrees, 180 degrees, and 180 degrees, respectively. The gradient pulse duration is the same as the slice selection pulse duration. In step iii, the position of the living organism in the magnetic field is located using a conventional T1 or T2 weighted sequence, and a region of interest is selected; In step iii, the magnetic resonance signals of α-glucose and lactic acid molecules include the J coupling value and chemical shift of the methyl group of α-glucose near 5.2 ppm, the J coupling value and chemical shift of the proton on the methyl group of lactic acid molecule near 1.33 ppm and their signal intensities; the J coupling value of the methyl group of α-glucose is J α-Glc =7.0±0.2 Hz, chemical shift is δ α-Glc =5.2±0.3ppm, and the J coupling value of the proton on the methyl group of the lactic acid molecule is J Lac =6.9±0.2 Hz, chemical shift is δ Lac =1.33±0.3 ppm.

Citation Information

Patent Citations

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