Method for detecting sodium ions through ultra-sensitive magnetic resonance

By combining hyperpolarized 129Xe magnetic resonance technology and spin exchange saturation technology with cucurbituril (CB7) and viologen complex, the problem of low sensitivity in magnetic resonance detection of sodium ions was solved, and a highly sensitive sodium ion detection effect was achieved.

CN121612913APending Publication Date: 2026-03-06INNOVATION ACAD FOR PRECISION MEASUREMENT SCI & TECH CAS
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Patent Information

Application Number
CN202411182296.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-08-27
Publication Date
2026-03-06

AI Technical Summary

Technical Problem

Existing magnetic resonance imaging methods for detecting sodium ions (Na+) have low sensitivity, which limits their effectiveness in assessing physiological changes, especially in brain magnetic resonance imaging where the signal-to-noise ratio is insufficient.

Method used

The hyperpolarized 129Xe magnetic resonance technique was used in combination with a complex of cucurbituril (CB7) and viologen as a Na+ probe. Na+ was detected by spin exchange saturation (CEST) technique. The change of 129Xe magnetic resonance signal in the viologen@CB7 complex cavity was detected.

Benefits of technology

It significantly improves the sensitivity of magnetic resonance detection of sodium ions, enhances the signal-to-noise ratio, and is suitable for highly sensitive targeted detection, enabling accurate detection of Na+ in complex biological environments.

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Abstract

The invention discloses a method for detecting sodium ions through ultra-sensitive magnetic resonance, hyperpolarized 129Xe is used as an ultra-sensitive magnetic resonance signal source, a viologen-coated CB7 compound is used as a carrier of the hyperpolarized 129Xe, viologen-coated CB7 probes are respectively dispersed in a solution which does not contain Na < + > and a solution which contains Na < + >, and due to the interaction between Na < + > and a viologen-coated CB7 cavity structure, the sodium ions can be detected through the ultra-sensitive magnetic resonance signal source and the viologen-coated CB7 compound. A chemical microenvironment sensed by 129Xe atoms in a viologen-coated CB7 cavity is changed, so that a characteristic magnetic resonance signal of 129Xe in the viologen-coated CB7 cavity is changed, and magnetic resonance signals of different hyperpolarized 129Xe carriers in two sample solutions are obtained through 129Xe CEST detection. The invention provides a novel ultra-sensitive magnetic resonance method for Na < + > detection, since 129Xe is an exogenous element and has no background signal influence in a living body, the method is expected to obtain a higher signal-to-noise ratio, the sensitivity of magnetic resonance is improved by more than 10000 times through a hyperpolarization method, and the method is more suitable for high-sensitivity targeted detection research and is expected to be used in the field of biological medicine.
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Description

Technical Field

[0001] This invention relates to the field of magnetic resonance spectroscopy, specifically to an ultrasensitive magnetic resonance detection method for sodium ions, applicable to the detection of sodium ions. Background Technology

[0002] Sodium is an essential element in the human body, playing a central role in maintaining homeostasis, cellular metabolism, osmotic regulation, and numerous physiological activities. For example, as a component of blood electrolytes, sodium plays a crucial role in regulating nerve and muscle function and maintaining acid-base and fluid balance. Hypernatremia (high sodium levels in the brain) can lead to abnormal brain function such as confusion, muscle twitching, seizures, and coma, while hyponatremia (low sodium levels in the brain) can cause slowed thinking and impaired consciousness. Malignant tumors such as gliomas, breast cancer, and prostate cancer are associated with sodium deficiency at the lesion site. + A significant increase in sodium content. This is due to sodium's crucial role in the human body. + The detection of these substances is of great significance for assessing (patho)physiological changes.

[0003] As a spin-3 / 2 nuclide, sodium can be directly used as a signal source for magnetic resonance imaging (MRI) in living organisms / human bodies. + Detection and research. Due to the non-invasive and non-radioactive nature of magnetic resonance imaging, 23 Na MRI has become one of the most important clinical assessment tools for evaluating changes in the physiological environment. However, 23 The gyromagnetic ratio of Na (γ) 23Na =11.25MHz / T) is more powerful than the protons most commonly used in conventional magnetic resonance imaging (MRI). 1 H) signal source (γ) 1H =42.58MHz / T) is about 3.8 times lower, 23 The magnetic resonance sensitivity of Na is only 1 H accounts for approximately 9.2%. Taking the brain as an example, Na+ in the white matter... + The concentration is 10–300 mM, while H + The concentration was 80 M. Therefore, in brain magnetic resonance imaging (MRI), 23 The signal-to-noise ratio of Na is only 1 The sensitivity of Na is 1 / 10000 to 1 / 1000. This low sensitivity has become a bottleneck limiting the detection of Na by magnetic resonance methods. + And key factors for assessing related physiological changes.

[0004] Hyperpolarization technology offers a feasible solution to the sensitivity problem of magnetic resonance imaging (MRI). Specifically, hyperpolarization technology can improve the sensitivity of MRI by tens to tens of thousands of times by breaking the Boltzmann distribution of nuclear spin and establishing a new highly polarized equilibrium state of nuclear spin. Hyperpolarization... 129 Xe technology can increase the sensitivity of magnetic resonance imaging by 10,000 to 100,000 times. It is the only hyperpolarization MRI method currently approved for clinical use. In addition, the hyperpolarization method greatly improves the sensitivity of magnetic resonance imaging and is also known as ultrasensitive magnetic resonance imaging technology.

[0005] Furthermore, as an emerging field in magnetic resonance imaging (MRI), chemical exchange saturation transfer (CEST) technology amplifies the magnetic resonance signal of a target spin nucleus by separately detecting the magnetic resonance signals of freely exchangeable spin nuclei and all spin nuclei in the environment, and then subtracting the two. This method can improve MRI sensitivity by 2–3 orders of magnitude and has been used in in vivo / human metabolic studies. The application of CEST technology to hyperpolarization... 129 Xe magnetic resonance detection, combined with molecular probe technology, hyperpolarization 129 The detection limit of Xe magnetic resonance has reached the nM level. Summary of the Invention

[0006] To solve the existing Na + To address the low sensitivity of conventional magnetic resonance imaging (MRI) methods, a hyperpolarized method is proposed. 129 Xe magnetic resonance technology detects Na + The method introduces a complex of cucurbit[7]uril (CB7) and viologen, where viologen@CB7 is Na + After the probe CB7 and viologen molecules form a viologen@CB7 complex through host-guest interactions, the remaining space inside the viologen@CB7 complex is just enough to enable hyperpolarization. 129 Xe atoms pass through, and free Xe in the environment exchanges with Xe in the complex. The resulting exchange can be detected by the CEST method. 129 Xe is located within the complex and emits a unique magnetic resonance signal. When Na is present... + When it exists, Na + It interacts with the -OH group in the viologen@CB7 cavity, altering the chemical microenvironment of viologen@CB7, thus... 129 The magnetic resonance signal of Xe in the Violet@CB7 cavity changes.

[0007] The technical solution adopted to achieve the above-mentioned objectives of this invention is as follows:

[0008] A method for detecting sodium ions using ultrasensitive magnetic resonance imaging, characterized by comprising the following steps:

[0009] First, cucurbituril 7 and viologen molecules were mixed in a molar ratio of 3:1 to 1:1 and then self-assembled through host-guest interactions to obtain the viologen@CB7 complex.

[0010] With hyperpolarization 129 Xe was used as the signal source for magnetic resonance imaging, with the viologen@CB7 complex as the hyperpolarization source. 129 Xe carriers disperse the viologen@CB7 complex in a Na-free environment. + In the sample solution and the test sample solution, to make the superoxide dismutase present... 129 After Xe gas flows through the polarization device, it is directly introduced into both sample solutions. After the gas flow is stopped and air bubbles are removed, the process is carried out. 129 Xe CEST assays revealed the different hyperpolarizations in the two sample solutions. 129 Magnetic resonance signal of Xe carrier;

[0011] If the sample solution to be tested 129 Xe characteristic magnetic resonance signal relative to Na-free + The sample solution 129 If the characteristic magnetic resonance signal of Xe shifts to a lower field and its intensity decreases, it can be determined that the sample solution contains Na. + .

[0012] Preferably, perform 129 Xe CEST detection involves applying a continuous wave (CW) saturation pulse to the sample solution, using... 129 Xe and 1 The H-dual resonance probe acquires the spectrum, which will be in gaseous state. 129 The Xe signal was defined as 0 ppm, the chemical shift was collected from 30 ppm to 260 ppm, and the signal data was processed to obtain the NMR CEST spectrum.

[0013] Preferably, it contains super-enhanced 129 Xe is a mixture of gases containing the following volume fractions: 10% N2, 88% He, and 2% Xe, where Xe is of natural abundance. 129 Xe.

[0014] Preferably, the obtained signal data is processed by CEST effect = (Off-Resonance - On-Resonance) / Off-Resonance.

[0015] Preferably, the saturation power of the continuous wave (CW) saturated pulse is 6.5 μT, and the duration is 20 seconds.

[0016] An application of a viologen@CB7 complex in the preparation of a probe for ultrasensitive magnetic resonance detection of sodium ions, wherein the viologen@CB7 complex is obtained by self-assembly of cucurbituril 7 and viologen molecules at a molar ratio of 30:1 through host-guest interactions; the viologen@CB7 complex is dispersed in solution and subjected to super-sensitive magnetic resonance detection. 129 Gas polarization of Xe.

[0017] An in vivo method for magnetic resonance imaging includes injecting a solution containing a viologen@CB7 complex into an individual; followed by inhalation of oxygen and superoxide dismutation. 129 The mixture of Xe ventilates the subject while forming a superoxide dismutase-containing compound. 129 Xe's viologen@CB7 complex xenon cage, viologen@CB7 complex xenon cage and Na in the subject's body + effect;

[0018] conduct 129 Xe CEST assays obtained intra-individual correlations with Na + The magnetic resonance signal of the viologen@CB7 complex xenon cage acts on the individual's Na+. + The position of the viologen@CB7 complex xenon cage was imaged.

[0019] Preferably, oxygen and superoxide 129 The mixture of Xe does not exceed 80% of the superoxide dismutase. 129 Xe and at least 20% oxygen.

[0020] Preferably, perform 129 Xe CEST detection involves applying a continuous wave (CW) saturation pulse to the sample solution, using... 129 Xe and 1 The H-dual resonance probe acquires the spectrum, which will be in gaseous state. 129 The Xe signal was defined as 0 ppm, the chemical shift was collected from 30 ppm to 260 ppm, and the signal data was processed to obtain the NMR CEST spectrum.

[0021] Compared with the prior art, the beneficial effects and advantages of the present invention are as follows:

[0022] 1. Comparison with traditional magnetic resonance methods for detecting Na + Using a 23Na signal source directly, this method is highly sensitive. 129 Xe, as a magnetic resonance signal source, can increase the sensitivity of magnetic resonance by more than 10,000 times through hyperpolarization, making it more suitable for high-sensitivity targeted detection research.

[0023] 2. This method introduces the viologen@CB7 complex as Na + Probe, using Na +The chemical microenvironment of the viologen@CB7 complex cavity is affected, causing changes in the viologen@CB7 complex cavity. 129 The characteristic magnetic resonance signal of Xe changes. Due to 129 Xe is an exogenous element and is not affected by background signals in organisms. Therefore, this method is expected to achieve a higher signal-to-noise ratio. Attached Figure Description

[0024] Figure 1 Ultrasensitive magnetic resonance method for Na + Schematic diagram: Na + The presence of [something] affects the cavity microenvironment of Violet@CB7, thereby altering [something]. 129 Xe is located in the magnetic resonance signal of Violet@CB7;

[0025] Figure 2 129 Schematic diagram of Xe CEST pulse sequence;

[0026] Figure 3 UV-Vis absorption spectra of CB7 reacted with viologen at different times;

[0027] Figure 4 Hyperpolarization of Violet@CB7 in Pure Water 129 Xe CEST spectrum;

[0028] Figure 5 Violet@CB7 and Na + Hyperpolarization of the mixture 129 Xe CEST spectrum;

[0029] Figure 6 Violet@CB7 and Na + The mixture contains physiological concentrations of K + Hyperpolarization under existing conditions 129 Xe CEST spectrum;

[0030] Figure 7 Violet@CB7 and Na + The mixture contains physiological concentrations of Ca 2+ Hyperpolarization under existing conditions 129 Xe CEST spectrum;

[0031] Figure 8 Violet@CB7 and Na + The mixture contains physiological concentrations of Mg 2+ Hyperpolarization under existing conditions 129 Xe CEST spectrum;

[0032] Figure 9 Violet@CB7 and Na + The mixture contains physiological concentrations of Zn2+ Hyperpolarization under existing conditions 129 Xe CEST spectrum. Detailed Implementation

[0033] The present invention is further illustrated below with specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0034] The main instruments used in the following embodiments are as follows:

[0035] Nuclear magnetic resonance spectrometer (400MHz Bruker AV400 wide bore spectrometer).

[0036] Example 1

[0037] The specific experimental steps are as follows:

[0038] Step 1: Construction of CB7 composite nanoprobes

[0039] Weigh out 5.0 mg of CB7 (C 42 H 42 N 28 O 14 A solid powder (molecular weight 1162.96) was added to 4.30 mL of pure water to prepare a 1 mmol / L aqueous solution of CB7. 2.0 mg of viologen (C...) was weighed... 12 H 16 ClN₂O (molecular weight 239.7) solid powder was added to 8.34 mL of pure water to prepare a 1 mmol / L viologen aqueous solution. 1 mL of the prepared viologen solution was slowly added dropwise to 3 mL of CB₇ solution, and the mixture was sonicated at room temperature for 10–120 minutes to obtain a viologen@CB₇ complex solution. The host-guest reaction process between CB₇ and viologen was tested by ultraviolet absorption spectroscopy. After 60 minutes of sonication, the ultraviolet absorption no longer changed. Figure 3 As shown, this proves that all the viologen molecules have been "embedded" in CB7, and the reaction is complete.

[0040] Step 2, the ultra-sensitive Purple Essence@CB7 129 Xe magnetic resonance signal test

[0041] Take 0.2 mL of the prepared viologen@CB7 complex solution, add 1.8 mL of pure water, mix well, and then place the resulting sample solution in a 10 mm NMR sample tube.

[0042] Xe gas is hyperpolarized using a permanent magnet polarizer as described in CN102364333B to achieve a hyperpolarization of 10%. 129Xe gas. A mixture of the following gas volumes: 10% N2, 88% He, and 2% Xe (natural abundance). 129 Xe) was introduced into the polarization apparatus, and then the generated gas was introduced into a 400 MHz (9.4 T) Bruker AV400 nuclear magnetic resonance spectrometer, flowing directly into a sample tube containing 2 mL of viologen@CB7 complex solution at a flow rate of 0.1 L / min. Gas was continuously introduced for 15 seconds, followed by a 3-second delay to allow the bubbles to burst (e.g., ...). Figure 2 In the "bubble Xe" section, a continuous wave (CW) saturation pulse is applied. Figure 2 The “saturation pulse” in the text refers to the selective saturation of the Xe peak in the solution sample (saturation power 6.5 μT, duration 5 s), followed by a 10 mm dual resonance probe. 129 Xe and 1 H, PABBO 400W1 / S2 BB-HD-10Z) collected the spectrum, and the gaseous 129 The Xe signal was defined as 0 ppm, the chemical shift acquisition range was 30 ppm to 260 ppm, and the step size was 3 ppm. The sample was maintained at a pressure of 53 PSI and a temperature of 298 K. Figure 4 As shown, the obtained data is processed by CEST effect = (Off-Resonance - On-Resonance) / Off-Resonance to obtain the corresponding NMR CEST spectrum.

[0043] On-Resonance refers to the signal strength at the resonant frequency.

[0044] Off-Resonance refers to the signal strength at frequencies far from the resonant frequency.

[0045] Step 3, Na + For Violet@CB7 129 The effect of Xe magnetic resonance signal

[0046] Take 0.3 mL of the prepared viologen@CB7 complex solution, add 2.7 mL of 25 mM / L NaCl aqueous solution, and sonicate for 5 minutes to prepare viologen@CB7 and NaCl. + A mixed solution was prepared. 2 mL of the prepared mixed solution was placed in a 10 mm NMR sample tube, which was then placed in a 400 MHz (9.4 T) Bruker AV400 NMR spectrometer. The following volume fractions of the mixed gas were used: 10% N2, 88% He, and 2% Xe (natural abundance). 129Xe was introduced into the polarization device, and then the generated gas was passed into the mixed solution inside the spectrometer at a flow rate of 0.1 L / min. The gas was continuously passed for 15 seconds, followed by a 3-second delay to allow the bubbles to burst. A continuous wave (CW) saturation pulse was then applied to selectively saturate the Xe peak in the solution sample (saturation power 6.5 μT, duration 20 seconds), followed by observation using a 10 mm dual resonance probe. 129 Xe and 1 H, PABBO 400W1 / S2BB-HD-10Z) to collect the spectrum, gaseous 129 The Xe signal was defined as 0 ppm, the chemical shift acquisition range was 30 ppm to 260 ppm, and the step size was 3 ppm. The sample was maintained at a pressure of 53 PSI and a temperature of 298 K. Figure 4 As shown, the obtained data is processed by CEST effect = (Off-Resonance - On-Resonance) / Off-Resonance to obtain the corresponding NMR CEST spectrum.

[0047] Example 2

[0048] Na + It is the most abundant cation in the human body, accounting for over 90%. In addition, K... + Ca 2+ Mg 2+ and Zn 2+ It is also an important cation in the human body. This example uses the median normal value of major cations in the body as an example to investigate the effect of the presence of cations on the viologen@CB7 probe constructed in Example 1 on Na+. + The impact of testing.

[0049] Step 1: Preparation of solutions of major cations in body fluids

[0050] K + Solution: The normal range for potassium in the human body is 3.5-5.5 mmol / L. Weigh 33.96 mg of KCl (molecular weight 75.46) solid, dissolve it in ultrapure water, and dilute to 10 mL in a volumetric flask to prepare a KCl aqueous solution with a concentration of 45.0 mmol / L (10 times the median normal value).

[0051] Ca 2+ Solution: The normal range for calcium in the human body is 2.1-2.6 mmol / L. Weigh 26.08 mg of CaCl2 (molecular weight 110.98) solid, dissolve it in ultrapure water, and dilute to 10 mL in a volumetric flask to prepare a CaCl2 aqueous solution with a concentration of 23.5 mmol / L (10 times the median normal value).

[0052] Mg 2+Solution: The normal range for magnesium in the human body is 0.7-1.0 mmol / L. Weigh 8.09 mg of MgCl2 (molecular weight 95.21) solid, dissolve it in ultrapure water, and dilute to 10 mL in a volumetric flask to prepare an 8.5 mmol / L MgCl2 aqueous solution (10 times the median normal value).

[0053] Zn 2+ Solution: The normal range for zinc in the human body is 7.65-23 μmol / L. Weigh 2.30 mg of ZnCl2 (molecular weight 75.46) solid, dissolve it in ultrapure water, and dilute to 200 mL in a volumetric flask to prepare a ZnCl2 aqueous solution with a concentration of 152.5 μmol / L (10 times the median normal value).

[0054] Step 2: The effect of cations in body fluids on viologen@CB7 129 The effect of Xe magnetic resonance signal

[0055] Take 0.3 mL of the viologen@CB7 complex solution prepared in step one of Example 1, add 2.4 mL of 25 mM / L NaCl aqueous solution, and sonicate for 5 minutes to prepare viologen@CB7 and NaCl. + The mixture was prepared by adding 0.3 mL of the KCl aqueous solution prepared in step one and mixing thoroughly. The potassium ion concentration in the prepared mixture was 4.50 mmol / L, which is the median normal potassium level in the human body. The prepared mixture is designated as sample ①.

[0056] Take 0.3 mL of the viologen@CB7 complex solution prepared in step one of Example 1, add 2.4 mL of 25 mM / L NaCl aqueous solution, and sonicate for 5 minutes to prepare viologen@CB7 and NaCl. + The mixture was prepared by adding 0.3 mL of the CaCl2 aqueous solution prepared in step one and mixing thoroughly. The calcium ion concentration in the prepared mixture was 2.35 mmol / L, which is the median normal value for human calcium. The prepared mixture is designated as sample ②.

[0057] Take 0.3 mL of the viologen@CB7 complex solution prepared in step one of Example 1, add 2.4 mL of 25 mM / L NaCl aqueous solution, and sonicate for 5 minutes to prepare viologen@CB7 and NaCl. + The mixture was prepared by adding 0.3 mL of the MgCl2 aqueous solution prepared in step one and mixing thoroughly. The magnesium ion concentration in the prepared mixture was 0.85 mmol / L, which is the median normal value for magnesium in the human body. This prepared mixture is designated as sample ③.

[0058] Take 0.3 mL of the viologen@CB7 complex solution prepared in step one of Example 1, add 2.4 mL of 25 mM / L NaCl aqueous solution, and sonicate for 5 minutes to prepare viologen@CB7 and NaCl. + The mixture was prepared by adding 0.3 mL of the ZnCl2 aqueous solution prepared in step one and mixing thoroughly. The zinc ion concentration in the prepared mixture was 15.25 μmol / L, which is the median normal value for zinc in the human body. This prepared mixture is designated as sample ④.

[0059] Take 2 mL of each of the prepared samples ①, ②, ③, or ④ and place them in 10 mm NMR sample tubes. Then, place the NMR sample tubes in a 400 MHz (9.4 T) Bruker AV400 NMR spectrometer. Mix the following gas mixtures by volume fraction: 10% N2, 88% He, and 2% Xe (natural abundance). 129 Xe was introduced into the polarization device, and then the generated gas was passed into the mixed solution inside the spectrometer at a flow rate of 0.1 L / min. The gas was continuously passed for 15 seconds, followed by a 3-second delay to allow the bubbles to burst. A continuous wave (CW) saturation pulse was then applied to selectively saturate the Xe peak in the solution sample (saturation power 6.5 μT, duration 20 seconds), followed by observation using a 10 mm dual resonance probe. 129 Xe and 1 H, PABBO 400W1 / S2 BB-HD-10Z) collected the spectrum, and the gaseous 129 The Xe signal was defined as 0 ppm, the chemical shift acquisition range was 30 ppm to 260 ppm, and the step size was 3 ppm. The sample was maintained at a pressure of 53 PSI and a temperature of 298 K. Figures 5-8 As shown, the obtained data were processed by CEST effect = (Off-Resonance - On-Resonance) / Off-Resonance to obtain the NMR CEST spectra corresponding to samples ①-④.

[0060] Experimental results: such as Figure 4 As shown, 129 Xe exhibits two magnetic resonance signals in the viologen@CB7 complex solution, with the signal at 193 ppm representing free radicals in the solution. 129 Xe production, 99.6 ppm 129 The characteristic signal of Xe in the cavity of the viologen@CB7 complex, and the viologen@CB7 complex 129 Xe signal is free 129 76.6% of the Xe signal. When Na is present... + When present, the hydroxyl group on CB7 reacts with Na. + The interaction altered the chemical microenvironment within the cavity of the viologen@CB7 complex. For example... Figure 5As shown, in viologen@CB7 and Na + In the mixed solution, the viologen@CB7 complex cavity 129 The characteristic Xe magnetic resonance signal shifts to a lower field, reaching a value of 117.8 ppm where its intensity is free. 129 Xe signal was 46.3%, compared to no Na + The presence of Xe decreased by approximately 30%. As shown in Table 1, further analysis of the obtained CEST spectra revealed that the exchange rate of Xe in the violet@CB7 cavity was 2442 ± 749 s. -1 When the solution contains Na + When present, the exchange rate of Xe increases to 5180±960 s. -1 The above results prove that Na + The presence of Xe altered the microenvironment of the viologen@CB7 complex pores, causing changes in the magnetic resonance signal of Xe within the pores. This demonstrates the effectiveness of the developed method in the magnetic resonance detection of Na. + Effectiveness in this regard.

[0061] To investigate the detection of Na+ by the viologen@CB7 complex probe developed for in vivo cation pairing. + The influence of the method, we found in the viologen@CB7 complex and Na + The mixture was further supplemented with the main cations, K+, at concentrations of the median normal value in the human body. + Ca 2+ Mg 2+ and Zn 2+ Then proceed 129 Xe CEST test. For example... Figures 6-9 As shown, when the above-mentioned cations are present, 129 Xe in the development of Na + The signals in the probe were located at 117.6 ppm (+K) + ), 117.2ppm (+Ca) 2+ ), 117.8 ppm (+Mg) 2+ ), 117.9ppm (+Zn) 2+ The addition of cations had no effect on the characteristic signal position at 117.8 ppm without the addition of cations, and the signal intensity did not change significantly. These results demonstrate that the main cations in body fluids do not change from those derived from Na+. + The chemical microenvironment created in the viologen@CB7 cavity will not cause characteristic 129 Changes in Xe magnetic resonance signals.

[0062] It should be noted that the embodiments described in this invention are merely illustrative of the spirit of the invention. Those skilled in the art to which this invention pertains can make various modifications or additions to the described embodiments or use similar methods to substitute them, without departing from the spirit of the invention or exceeding the scope defined by the appended claims.

[0063] Table 1

[0064]

Claims

1. A method of ultrasensitive magnetic resonance detection of sodium ions, characterized in that, Comprising the following steps: First, cucurbituril 7 is mixed with viologen molecules in a molar ratio of 3:1 to 1:1 and self-assembled into viologen@CB7 complex through host-guest interaction; with hyperpolarized 129 Xe as a signal source for magnetic resonance imaging, with the viologen@CB7 complex as a carrier of hyperpolarized 129 Xe, and dispersing the viologen@CB7 complex into a sample solution free of Na + and a sample solution to be tested, so that a gas containing hyperpolarized 129 Xe directly passes through the polarization device and is introduced into the two sample solutions, and after stopping the aeration, the bubbles are removed, and 129 Xe CEST detection is performed to obtain the magnetic resonance signals of the different hyperpolarized 129 Xe carriers in the two sample solutions; If the sample solution to be tested 129 Xe characteristic magnetic resonance signal relative to Na-free + The sample solution 129 If the characteristic magnetic resonance signal of Xe shifts to a lower field and its intensity decreases, it can be determined that the sample solution contains Na. + .

2. The method of claim 1, wherein, were performed 129 Xe CEST detection included applying a continuous wave (CW) saturation pulse to the sample solution, using 129 Xe and 1 H double resonance probe, acquiring spectra with gaseous 129 Xe signal defined as 0 ppm, chemical shift acquisition range 30 ppm to 260 ppm, and data processing of the signal data to obtain NMR CEST spectra.

3. The method of claim 1, wherein, containing super 129 The gas containing Xe was a mixture of various gases containing 10% N2, 88% He and 2% Xe, the Xe being of natural abundance 129 Xe.

4. The method of claim 2, wherein, The data processing comprises: performing CEST effect=(Off-Resonance-On-Resonance) / Off-Resonance processing on the obtained signal data.

5. The method of claim 2, wherein, The saturation power of the continuous wave (CW) saturation pulse is 6.5 muT, and the duration is 20 seconds.

6. Use of a viologen CB7 complex in the preparation of a probe for ultrasensitive magnetic resonance detection of sodium ions, characterized in that, The viologen@CB7 complex is obtained by mixing cucurbituril 7 and viologen molecules in a molar ratio of 3:1 and self-assembling after host-guest interaction, and the viologen@CB7 complex is dispersed into a solution and is contained in the super-sized 129 Gas polarization of Xe.

7. An in vivo method of magnetic resonance imaging, comprising, injecting a solution containing the purpurate CB7 complex into the individual; while ventilating the subject with oxygen and hyperpolarized 129 Xe, forming a hyperpolarized 129 Xe, purpurate CB7 complex xenon gas cages, purpurate CB7 complex xenon gas cages with Na + action; were performed 129 Xe CEST detection yields in vivo Na + the magnetic resonance signal of the Xe gas cage of the viologen CB7 complex in action, thereby imaging in vivo Na + the location of the viologen CB7 complex Xe gas cage in action.

8. The method of claim 7, wherein, Oxygen and hyperxidation 129 A mixture of Xe and no more than 80% hyperxidation 129 Xe and at least 20% oxygen.

9. The method of claim 1, wherein, were performed 129 Xe CEST detection included applying a continuous wave (CW) saturation pulse to the sample solution, using 129 Xe and 1 H double resonance probe, collecting spectra with gaseous 129 Xe signal defined as 0 ppm, chemical shift acquisition range 30 ppm to 260 ppm, and data processing of the signal data to obtain NMR CEST spectra.

Citation Information

Patent Citations

  • Permanent magnet polarizer

    CN102364333B