A temperature measurement method and device based on creatine chemical exchange saturation transfer imaging

Abstract

The present invention relates to a temperature measurement method and device based on creatine chemical exchange saturation transfer imaging, the method comprising the following steps: (1) performing chemical exchange saturation transfer imaging on a creatine phantom and analyzing the chemical shift of creatine relative to water in the creatine phantom; (2) fitting the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom; (3) performing chemical exchange saturation transfer imaging on creatine in a sample and analyzing the chemical shift of creatine relative to water in the sample, and calculating the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted in step (2). The measurement method uses creatine as an endogenous reference substance and utilizes the temperature dependence of the CEST effect of creatine and water to perform high spatial resolution, high sensitivity, and non-invasive absolute temperature measurement.

Description

[0001] This application claims priority to patent application number 202110540092.2 (the filing date of the prior application is May 18, 2021, and the name of the invention is A temperature measurement method and device based on creatine chemical exchange saturation transfer imaging). Technical Field

[0002] The present invention belongs to the technical field of non-invasive temperature measurement, and relates to a temperature measurement method and device based on creatine chemical exchange saturation transfer imaging. Background Art

[0003] Brain tissue temperature can fluctuate with neural activity and brain metabolism, and is regulated and influenced by body temperature through blood circulation. It is a comprehensive indicator of tissue physiological characteristics such as material metabolism, tissue perfusion, and vascular self-regulation. Most physical and chemical reactions during brain neuronal activity are temperature sensitive. Many diseases (such as brain trauma, stroke, tumors, multiple sclerosis, and epilepsy) can disrupt brain temperature homeostasis, leading to local brain temperature abnormalities, changes in the spatial distribution pattern of brain temperature, and a series of reactions such as abnormal cell metabolism, secondary neuronal damage, and vascular and blood-brain barrier damage. Therefore, non-invasive absolute temperature imaging technology is of great significance for exploring the brain temperature regulation mechanism under physiological and pathological conditions and for in-depth exploration of the complex pathological mechanisms of brain injury.

[0004] Magnetic resonance temperature measurement methods are mainly based on the temperature dependence of magnetic resonance parameters such as proton density, T1 and T2 relaxation time, diffusion coefficient, proton resonance frequency and magnetization transfer. The currently widely used technologies for measuring absolute temperature based on magnetic resonance are: (1) using water hydrogen protons 1The resonance frequency of H is temperature-dependent, while the chemical shift of some macromolecules is not easily affected by temperature, such as acetyl-aspartic acid (NAA). Magnetic resonance spectroscopy (MRS) imaging technology is used to measure the chemical shift of reference macromolecules relative to water hydrogen protons at different temperatures, and the relationship between the chemical shift of the reference substance and temperature is fitted to achieve non-invasive temperature measurement based on proton resonance frequency (PRF). However, the imaging resolution of this method is currently low, and the temperature measurement is easily affected by movement and magnetic field drift; (2) The absolute temperature of tissues such as cerebrospinal fluid is measured based on the relationship between the free diffusion coefficient of water molecules and temperature. However, this technology is currently only applicable to the detection of the temperature of pure water tissues and cannot be applied to tissues with limited water molecule diffusion; (3) Some studies have injected paramagnetic chelates as exogenous reference substances, measured the chemical shift of chelates at different temperatures in animals based on chemical exchange saturation transfer (CEST) imaging technology, and fitted its linear relationship with temperature (see: Zhang S, Malloy CR, ADSherry. MRI thermometry Based on PARACEST agents[J].Journal of the American Chemical Society,2005,127(50):17572.), however, the biosafety of paramagnetic chelates needs to be considered, and repeated injection and temperature measurement are not possible, which is not conducive to clinical promotion.

[0005] In summary, providing an accurate and non-invasive brain temperature measurement method is of great significance for exploring the brain temperature regulation mechanism under physiological and pathological conditions. Summary of the Invention

[0006] In response to the deficiencies of the existing technology and actual needs, the present invention provides a temperature measurement method and device based on creatine chemical exchange saturation transfer imaging. The method is based on the relationship between the chemical exchange saturation transfer effect of creatine and temperature, and is combined with magnetic resonance imaging technology to achieve high spatial resolution, high sensitivity, and non-invasive absolute temperature measurement.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a temperature measurement method based on creatine chemical exchange saturation transfer imaging, the method comprising the following steps:

[0009] (1) Perform chemical exchange saturation transfer imaging on the creatine mimetic to analyze the chemical shift of creatine relative to water in the creatine mimetic;

[0010] (2) fitting the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom;

[0011] (3) Performing chemical exchange saturation transfer imaging on creatine in the sample, analyzing the chemical shift of creatine relative to water in the sample, and calculating the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted in step (2).

[0012] In the present invention, creatine (Cr), as an important energy metabolite, has a stable concentration in the brain, and the creatine chemical exchange saturation transfer effect (Cr-CEST) is insensitive to non-temperature environmental factors such as pH. Moreover, its CEST exchange rate is approximately 7-8 times that of phosphocreatin (PCr) under physiological temperature and pH conditions. Therefore, the present invention uses creatine as an endogenous reference substance and utilizes the temperature dependence of the creatine-water CEST effect to perform high spatial resolution, high sensitivity, and non-invasive absolute temperature measurement.

[0013] The temperature measurement method based on creatine chemical exchange saturation transfer imaging of the present invention can be used for non-disease diagnosis or treatment purposes, or for scientific research.

[0014] Preferably, the raw materials for preparing the creatine mimetic include creatine, agar powder, phosphate buffer and deionized water.

[0015] In the present invention, the addition of agar powder can improve the strength of the creatine mimetic and avoid artifacts caused by heat conduction during detection.

[0016] Preferably, the concentration of creatine in the creatine mimetic is 10 to 120 mmol / L, including but not limited to 11 mmol / L, 12 mmol / L, 13 mmol / L, 15 mmol / L, 20 mmol / L, 30 mmol / L, 40 mmol / L, 50 mmol / L, 60 mmol / L, 70 mmol / L, 80 mmol / L, 90 mmol / L, 100 mmol / L, 105 mmol / L, 110 mmol / L, 112 mmol / L, 115 mmol / L, 118 mmol / L or 119 mmol / L.

[0017] Preferably, the purity of the creatine is greater than 98%.

[0018] Preferably, the pH of the creatine mimetic is 6.0-7.2, including but not limited to 6.1, 6.2, 6.3, 6.4, 6.6, 6.7, 6.8, 6.9 or 7.1.

[0019] Preferably, the temperature range of the creatine mimetic is 10-43°C, including but not limited to 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 25°C, 30°C, 35°C, 36°C, 37°C, 38°C or 39°C.

[0020] Preferably, the temperature measurement based on creatine chemical exchange saturation transfer imaging further includes the step of preparing a creatine mimetic.

[0021] Preferably, the preparation method of the creatine mimetic comprises:

[0022] Creatine, agar powder, phosphate buffer, and deionized water are mixed and heated, and the pH is adjusted to obtain the creatine mimetic. Specifically, creatine, agar powder, phosphate buffer, and deionized water are prepared into a creatine mimetic mixture of different concentrations, and a sodium hydroxide solution or a hydrochloric acid solution is added dropwise to adjust the pH value. The prepared mixture is heated until the agar powder is completely dissolved, stirred evenly, and then placed in a plastic container and cooled naturally.

[0023] Preferably, in step (1), chemical exchange saturation transfer imaging is performed on the creatine phantom, a constant temperature water bath device is set to a specific temperature, the prepared creatine phantoms with different pH values and different creatine concentrations are placed in the water bath, and an optical fiber temperature probe is inserted to monitor and record the real-time temperature of the creatine phantom. After the temperature of the phantom stabilizes, CEST scanning is started. First, a sequence without pre-saturation excitation pulses is used to scan a picture as a reference, and the signal intensity is recorded as S0. Then, a series of pre-saturation excitation pulse sequences with different bias frequencies Δω are used to scan to obtain a series of images, and the signal intensity is recorded as S sat (Δω), signal ratio S sat (Δω) / S0 is the signal attenuation under the action of a pre-saturation excitation pulse with a bias frequency of Δω, defined as the z-spectra. When the creatine phantom is excited and saturated by a pre-saturation pulse with a frequency of Δω, this saturation effect causes the water hydrogen protons to be saturated through the dynamic exchange of creatine's amino hydrogen protons with water hydrogen protons, resulting in a decrease in the magnetic resonance signal of the water hydrogen protons. When the pre-saturation excitation pulse frequency is equal to the water hydrogen proton resonance frequency, all water hydrogen protons are saturated and the signal acquisition approaches zero. As the bias frequency increases, the saturated water signal gradually decreases, while the magnetic resonance signal gradually increases. When the bias frequency is exactly the excitation frequency of creatine's amino hydrogen protons, the creatine's amino hydrogen protons are saturated and exchange with water hydrogen protons, and the signal intensity corresponding to this frequency shows a downward trend.

[0024] The z-spectra is symmetrical with respect to the water hydrogen proton resonance frequency data S sat (+Δω) and S satSubtract (-Δω) and divide by S sat (-Δω), as shown in formula (1), the result can characterize the asymmetry of each point of the proton resonance frequency spectrum curve, recorded as CEST asym , CEST asym The offset frequency corresponding to the maximum value is the chemical shift of the amino hydrogen proton of creatine.

[0025]

[0026] The temperature of the constant temperature water bath was changed, and the above process was repeated after the temperature of the creatine mimetic stabilized, and the chemical shifts of the creatine amino hydrogen protons measured at different temperatures were recorded.

[0027] Preferably, the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine mimetic is fitted to obtain the mathematical relationship shown in formula (2):

[0028] T(℃)=126.821×Δω-220.811 (2),

[0029] Where Δω represents the chemical shift of the amino hydrogen proton of creatine relative to water (ppm), the formula R 2 The p-value is 0.893 and less than 0.001.

[0030] In addition, the z-spectra of water hydrogen protons and creatine amino hydrogen protons can be fitted according to the multi-pool Lorentzian fitting method, as shown in formula (3), to improve the accuracy of calculating the chemical shift of creatine amino hydrogen protons.

[0031]

[0032] Among them, A i ,ω i and σ i represent the amplitude, chemical shift, and line width of the z spectrum of the i-th proton pool, respectively, and N represents the total number of proton pools.

[0033] The mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine mimetic was fitted according to the calculation result of formula (3), and the mathematical relationship was obtained as shown in formula (4):

[0034] T(℃)=169.519×Δω-302.907 (4),

[0035] Where Δω represents the chemical shift of the amino hydrogen proton of creatine relative to water (ppm), the formula R 2 The p-value is 0.956, and the p-value is less than 0.001. This formula has a higher fitting accuracy.

[0036] In the present invention, the chemical exchange saturation transfer imaging method includes using a pre-saturation excitation pulse in combination with a spin echo-planar echo sequence or a gradient echo sequence to collect signals and perform interval imaging.

[0037] Preferably, the pre-saturation excitation pulse includes 10 rectangular pulses.

[0038] Preferably, the duration of the rectangular pulse is 90-110 ms (eg, 91 ms, 92 ms, 93 ms, 95 ms, 98 ms, 100 ms, 105 ms, 106 ms, 108 ms, or 109 ms), and B1 = 0.1-0.3 μT.

[0039] Preferably, the interval imaging method includes interval imaging within a range of -3.0 ppm to +3.0 ppm offset of the frequency of the pre-saturation excitation pulse relative to the resonance frequency of water hydrogen protons, and the number of intervals is greater than 200 times.

[0040] As a preferred technical solution, the technical route of the temperature measurement method based on creatine chemical exchange saturation transfer imaging is as follows: Figure 1 As shown, the specific steps include:

[0041] (1) mixing creatine, agar powder, phosphate buffer and deionized water and heating them, adjusting the pH to 6.0-7.2 and the creatine concentration to 10-120 mmol / L, to obtain the creatine mimetic;

[0042] (2) Chemical exchange saturation transfer imaging is performed on the creatine mimetic. The CEST sequence consists of two parts: a pre-saturation excitation pulse and an image signal acquisition sequence. In a 3.0T magnetic resonance system, the pre-saturation excitation pulse consists of ten rectangular pulses, each of which lasts 90 to 110 milliseconds, and B1 = 0.1 to 0.3 μT. Signal acquisition is performed in combination with a spin echo-planar echo sequence or a gradient echo sequence. Imaging is performed at intervals in the range of -3.0 ppm to +3.0 ppm relative to the resonance frequency of water hydrogen protons, and the number of intervals is greater than 200 times. First, a sequence without a pre-saturation excitation pulse is used to scan an image as a reference, and the signal intensity is recorded as S0. Subsequently, a series of pre-saturation excitation pulse sequences with different offset frequencies Δω are used to scan a series of images, and the signal intensity is recorded as S. sat (Δω), signal ratio S sat (Δω) / S0 is the signal attenuation under the action of the pre-saturation excitation pulse with a bias frequency of Δω, which is defined as the z-spectra. The z-spectra is symmetrical with respect to the resonance frequency of water hydrogen protons. sat (+Δω) and S sat Subtract (-Δω) and divide by S sat(-Δω), the result can characterize the asymmetry of each point of the proton resonance frequency spectrum curve, recorded as CEST asym , CEST asym The bias frequency corresponding to the maximum value is the chemical shift of the creatine amino hydrogen proton relative to water. In addition, the z spectra of multiple proton pools can be fitted by the multi-pool Lorentz model to obtain the chemical shift of the creatine amino hydrogen proton relative to water.

[0043] (3) fitting the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom, and fitting the relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom based on the chemical shift of the creatine amino hydrogen proton relative to water measured at different temperatures and the temperature of the creatine phantom actually recorded by the optical fiber temperature measuring probe;

[0044] The above process can be repeated using creatine mimetics of different concentrations and pH values and the relationship between the chemical shift of creatine relative to water and temperature can be refitted to evaluate the reliability, repeatability and stability of the relationship between the chemical shift of creatine relative to water and temperature that is not easily affected by other environmental factors.

[0045] (4) Performing chemical exchange saturation transfer imaging on creatine in the sample, analyzing the chemical shift of creatine relative to water in the sample, and calculating the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted in step (3).

[0046] In a second aspect, the present invention provides a temperature measurement device based on creatine chemical exchange saturation transfer imaging, which is used in the temperature measurement method based on creatine chemical exchange saturation transfer imaging described in the first aspect. The temperature measurement device includes a creatine phantom test unit, a fitting unit and a sample test unit.

[0047] The creatine phantom testing unit is used to perform chemical exchange saturation transfer imaging on the creatine phantom and analyze the chemical shift of creatine relative to water in the creatine phantom. The fitting unit is used to fit the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom. The sample testing unit is used to perform chemical exchange saturation transfer imaging on the creatine in the sample and analyze the chemical shift of creatine relative to water in the sample. The sample temperature is calculated based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted by the fitting unit.

[0048] Preferably, the temperature measuring device further comprises a creatine mimetic unit.

[0049] The creatine mimetic preparation unit is used for mixing creatine, agar powder, phosphate buffer and deionized water, heating the mixture and adjusting the pH to obtain the creatine mimetic.

[0050] Preferably, the chemical exchange saturation transfer imaging method in the creatine phantom test unit includes using a pre-saturation excitation pulse in combination with a spin echo-planar echo sequence or a gradient echo sequence to collect signals and perform interval imaging.

[0051] Preferably, the pre-saturation excitation pulse includes 10 rectangular pulses.

[0052] Preferably, the duration of the rectangular pulse is 90-110 milliseconds, and B1 = 0.1-0.3 μT.

[0053] Preferably, the interval imaging method includes interval imaging within a range of -3.0 ppm to +3.0 ppm offset of the frequency of the pre-saturation excitation pulse relative to the resonance frequency of water hydrogen protons, and the number of intervals is greater than 200 times.

[0054] Compared with the prior art, the present invention has the following beneficial effects:

[0055] (1) The temperature measurement method based on creatine chemical exchange saturation transfer imaging of the present invention uses creatine as an endogenous reference substance and utilizes the temperature dependence of the creatine and water CEST effect to perform high spatial resolution, high sensitivity, and non-invasive absolute temperature measurement, which can be applied to non-invasive and label-free brain temperature measurement;

[0056] (2) The temperature measurement method based on creatine chemical exchange saturation transfer imaging of the present invention has high stability and accuracy, is simple to operate, is non-radioactive, and is conducive to promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] Figure 1 This is the technical roadmap of the present invention;

[0058] Figure 2 This is a scanning image of creatine mimetic (pH=6.0, 100mmol / L) at 38°C;

[0059] Figure 3 is the z-spectra of creatine mimetic (pH=6.0, 100 mmol / L) at 38°C;

[0060] Figure 4 This is a graph showing the relationship between the chemical shift of creatine relative to water and temperature, measured based on the symmetry analysis of the resonance frequency spectrum;

[0061] Figure 5 The z-spectra of the creatine CEST effect of pig brain sample at 28°C is fitted based on the multi-cell Lorentz method;

[0062] Figure 6 Figure 3 is a plot of the chemical shift of creatine relative to water versus temperature, measured based on multi-cell Lorentzian fitting. DETAILED DESCRIPTION

[0063] To further illustrate the technical means and effects of the present invention, the present invention is further described below with reference to the embodiments and drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention.

[0064] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0065] Example 1 Preparation of Creatine Mimetic

[0066] Use creatine monohydrate reagent (C4H 11 A 100 mL mixture of 1.4915 g of N3O3) (1.4915 g), agar powder (1.5 g), phosphate buffer (10 mL), and deionized water (90 mL) was prepared with a pH of 6.0 and a creatine concentration of 100 mmol / L. The solution was heated until the agar powder was completely dissolved, stirred evenly, and placed in a plastic test tube to cool naturally to obtain a creatine mimetic.

[0067] Example 2 Cr-CEST experiment

[0068] A constant temperature water bath was used and the temperature was set to 38°C (similar to the temperature of the human brain). The creatine phantom was placed in the water bath, and the real-time temperature of the phantom was monitored with a fiber optic thermometer. After the temperature stabilized, CEST imaging was performed (United Imaging uMR790, 3.0T, 32-channel head and neck coil). The CEST sequence consisted of a pre-saturation excitation pulse and a spin echo-planar echo imaging sequence. The pre-saturation excitation pulse consisted of ten rectangular pulses, each with a duration of 100 milliseconds, B1 = 0.1 / 0.15 μT, the spin echo-planar echo image acquisition sequence TR / TE = 4000 / 38.6 milliseconds, the imaging field of view FOV = 80 mm, the layer thickness was 8.0 mm, the FA was 160 degrees, and the pre-saturation excitation pulse frequency was offset by -3.0 relative to the water hydrogen proton resonance frequency. The imaging was performed in the range of ppm to +3.0ppm with an interval of 0.03ppm for 200 times. First, a sequence without pre-saturation excitation pulse was used to scan a picture as a reference, and the signal intensity was recorded as S0. Then, a series of pre-saturation excitation pulse sequences with different bias frequencies Δω were used to scan a series of images, such as Figure 2 As shown, the signal strength is recorded as S sat (Δω), signal ratio S sat (Δω) / S0 is the signal attenuation under the action of the pre-saturation excitation pulse with a bias frequency of Δω, which is defined as the z-spectra, as follows: Figure 3 As shown, the z-spectra is symmetrical with respect to the water hydrogen proton resonance frequency data S sat (+Δω) and S sat Subtract (-Δω) and divide by S sat (-Δω), the result can characterize the asymmetry of each point of the proton resonance frequency spectrum curve, recorded as CEST asym , CEST asym The offset frequency of 2.01 ppm corresponding to the maximum value is recorded as the chemical shift of the amino hydrogen proton of creatine relative to water at this temperature.

[0069] The temperature of the constant-temperature water bath was adjusted, and based on the symmetry analysis of z-spectra, the chemical shifts of the creatine amino hydrogen protons relative to water at temperatures of 15.1°C, 15.3°C, 16.3°C, 24.5°C, 32.0°C, 33.5°C, 34.5°C and 38.9°C were measured to be 1.89 ppm, 1.86 ppm, 1.89 ppm, 1.92 ppm, 1.95 ppm, 2.01 ppm, 2.04 ppm and 2.04 ppm, respectively. In addition, according to the multi-cell Lorentz fitting method, the chemical shifts of creatine amino hydrogen protons relative to water at temperatures of 13.8°C, 16.30°C, 18.30°C, 20.30°C, 23.56°C, 24.50°C, 29.30°C, 32.00°C, 32.07°C, 33.50°C, 34.50°C, 35.68°C, 38.10°C, and 38.9°C were measured to be 1.8770ppm, 1.8928ppm, 1.9016ppm, 1.8946ppm, 1.9127ppm, 1.9421ppm, 1.9615ppm, 1.9795ppm, 1.9615ppm, 1.9804ppm, 1.9832ppm, 2.0051ppm, 2.0263ppm, and 2.0032ppm, respectively.

[0070] Example 3 Fitting the relationship between Cr-CEST and temperature

[0071] SPSS 19.0 was used to perform linear fitting on the chemical shift of creatine amino hydrogen proton relative to water and temperature calculated by the above z-spectra-based symmetry analysis and the multi-cell Lorentz fitting method, as shown in the following figure: Figure 5 As shown, the mathematical relationships are shown in formulas (2) and (4):

[0072] T(℃)=126.821×Δω-220.811 (2),

[0073] Where Δω represents the chemical shift of the amino hydrogen proton of creatine relative to water (ppm), the formula R 2The p-value is 0.893 and less than 0.001.

[0074] T(℃)=169.519×Δω-302.907 (4),

[0075] Where Δω represents the chemical shift of the amino hydrogen proton of creatine relative to water (ppm), the formula R 2 The p-value is 0.956, and the p-value is less than 0.001. This formula has a higher fitting accuracy.

[0076] Example 4 Temperature Measurement of Biological Samples Based on Cr-CEST

[0077] A porcine brain tissue homogenate sample was prepared and scanned by CEST (Bruker Biospec, 9.4T) at 28.0°C, with B1 = 0.23 μT. Imaging was performed with a presaturation excitation pulse frequency offset from -5.0 ppm to +5.0 ppm relative to the water hydrogen proton resonance frequency, with 201 scans at 0.05 ppm intervals. Based on the multi-cell Lorentz fitting method (five-cell model: water hydrogen proton cell, creatine amino hydrogen proton cell, amide proton transfer cell, nuclear Ostwald effect cell, and magnetization transfer cell), the chemical shift of the creatine amino hydrogen proton relative to water at this temperature was measured to be 1.9423 ppm ( Figure 6 ), the calculated chemical shift is substituted into formula (2) to obtain a calculated temperature of 25.51°C, and into formula (4) to obtain a calculated temperature of 26.35°C, both of which are close to the calibration temperature of 28°C.

[0078] Because the number of creatine phantom CEST imaging times in the examples was limited, the data volume was small, and the experimental conditions were relatively simple, this may have affected the relationship between creatine chemical shift and temperature, thereby affecting the accuracy of temperature prediction. In practical applications, the accuracy of the mathematical relationship between Cr-CEST and temperature can be improved by increasing the number of phantom experiments, setting a variety of experimental conditions, optimizing the z-spectrum fitting strategy, and increasing the CEST scanning accuracy.

[0079] In summary, the temperature measurement method based on creatine chemical exchange saturation transfer imaging of the present invention uses creatine as an endogenous reference substance and utilizes the temperature dependence of the CEST effect of creatine and water to perform high spatial resolution, high sensitivity, and non-invasive absolute temperature measurement.

[0080] The applicant states that the present invention is intended to illustrate the detailed methods of the present invention through the above-described embodiments, but the present invention is not limited to the above-described detailed methods, that is, it does not mean that the present invention must rely on the above-described detailed methods in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for various raw materials in the products of the present invention, addition of auxiliary ingredients, and selection of specific methods, etc., are all within the scope of protection and disclosure of the present invention.

Claims

1. A temperature measurement method based on creatine chemical exchange saturation transfer imaging, characterized in that: The method comprises the following steps: (1) Perform chemical exchange saturation transfer imaging on the creatine mimetic to analyze the chemical shift of creatine relative to water in the creatine mimetic; (2) fitting the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom; (3) performing chemical exchange saturation transfer imaging on creatine in the sample, analyzing the chemical shift of creatine relative to water in the sample, and calculating the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted in step (2); The raw materials for preparing the creatine mimetic include creatine, agar powder and phosphate buffer.

2. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 1, characterized in that, The concentration of creatine in the creatine mimetic is 10-120 mmol / L.

3. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 1, characterized in that, The purity of the creatine is greater than 98%.

4. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 1, characterized in that, The pH of the creatine mimetic is 6.0-7.

2.

5. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 1, characterized in that, The temperature measurement range of the creatine mimetic is 10-43°C.

6. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 1, characterized in that, The method further comprises the steps of preparing a creatine mimetic; The preparation method of the creatine mimetic comprises: Creatine, agar powder, phosphate buffer and deionized water are mixed and heated, and the pH is adjusted to obtain the creatine mimetic.

7. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to any one of claims 1 to 6, characterized in that: The chemical exchange saturation transfer imaging method includes using a pre-saturation excitation pulse in combination with a spin echo-planar echo sequence or a gradient echo sequence to collect signals and perform interval imaging.

8. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 7, characterized in that: The pre-saturation excitation pulse includes 10 rectangular pulses; The duration of the rectangular pulse is 90-110 milliseconds, and B1 = 0.1-0.3 μT.

9. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 8, characterized in that: The interval imaging method includes interval imaging within a range of -3.0 ppm to +3.0 ppm offset of the pre-saturation excitation pulse frequency relative to the water hydrogen proton resonance frequency, with the number of intervals being greater than 200 times.

10. The temperature measurement method based on creatine chemical exchange saturation transfer imaging according to claim 9, characterized in that: The method comprises the following steps: (1) mixing creatine, agar powder, phosphate buffer and deionized water and heating them, adjusting the pH to 6.0-7.2 and the creatine concentration to 10-120 mmol / L, to obtain the creatine mimetic; (2) performing chemical exchange saturation transfer imaging on the creatine phantom, wherein each rectangular pulse in the pre-saturation excitation pulse lasts 90 to 110 milliseconds, B1 = 0.1 to 0.3 μT, and signal acquisition is performed in combination with a spin echo-planar echo sequence or a gradient echo sequence. Imaging is performed at intervals within a range of -3.0 ppm to +3.0 ppm relative to the resonance frequency of water hydrogen protons, with the number of intervals being greater than 200, and analyzing the chemical shift of creatine relative to water in the creatine phantom; (3) fitting the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine mimetic; (4) Performing chemical exchange saturation transfer imaging on creatine in the sample, analyzing the chemical shift of creatine relative to water in the sample, and calculating the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted in step (3).

11. A temperature measurement device based on creatine chemical exchange saturation transfer imaging, characterized in that: The temperature measuring device is used in the temperature measurement method based on creatine chemical exchange saturation transfer imaging according to any one of claims 1 to 10; The temperature measuring device includes a creatine phantom testing unit, a fitting unit and a sample testing unit; The creatine phantom testing unit is used to perform chemical exchange saturation transfer imaging on the creatine phantom and analyze the chemical shift of creatine relative to water in the creatine phantom; The fitting unit is used to fit the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom; The sample testing unit is used to perform chemical exchange saturation transfer imaging on creatine in the sample, and calculate the sample temperature based on the mathematical relationship between the chemical shift of creatine relative to water and the temperature of the creatine phantom fitted by the fitting unit.

12. The temperature measuring device according to claim 11, characterized in that: The temperature measuring device also includes a creatine phantom unit; The creatine mimetic preparation unit is used for mixing creatine, agar powder, phosphate buffer and deionized water, heating the mixture and adjusting the pH to obtain the creatine mimetic.

13. The temperature measuring device according to claim 11 or 12, characterized in that: The chemical exchange saturation transfer imaging method in the creatine phantom test unit includes using a pre-saturation excitation pulse in combination with a spin echo-planar echo sequence or a gradient echo sequence to perform signal acquisition and perform interval imaging.

14. The temperature measuring device according to claim 13, characterized in that: The pre-saturation excitation pulse includes 10 rectangular pulses; The duration of the rectangular pulse is 90-110 milliseconds, and B1 = 0.1-0.3 μT.

15. The temperature measuring device according to claim 14, characterized in that: The interval imaging method includes interval imaging within a range of -3.0 ppm to +3.0 ppm offset of the frequency of the pre-saturation excitation pulse relative to the resonance frequency of water hydrogen protons, with the number of intervals being greater than 200 times.

Images