Use of activated zeolite molecular sieves in ultra-sensitive magnetic resonance imaging

Abstract

The application belongs to the technical field of magnetic resonance imaging, and particularly relates to application of activated zeolite molecular sieve in super-sensitive magnetic resonance imaging. The activated zeolite molecular sieve material ZSM-5 has special microporous structure and catalytic performance, and is a crystal composed of silicon, aluminum and oxygen atoms. The application discloses that the activated zeolite molecular sieve material ZSM-5 can be used as a new Xe molecular cage for loading Xe, and compared with a traditional magnetic resonance contrast agent, the contrast agent has the advantages of no background signal interference and high sensitivity, and provides a new idea for development of the magnetic resonance contrast agent.

Description

Technical Field

[0001] The invention belongs to the technical field of magnetic resonance imaging, and in particular relates to the application of an activated zeolite molecular sieve in ultrasensitive magnetic resonance imaging. Background Art

[0002] Magnetic resonance imaging (MRI) is an important medical imaging technology. Due to its advantages such as no ionizing radiation, high resolution, and strong soft tissue penetration, it has been widely used in many fields such as clinical diagnosis and analytical testing. However, traditional proton MRI imaging relies on the 1 The distribution of H has a strong background signal. 129 Xe magnetic resonance imaging has emerged as a new imaging technology. 129 As an exogenous gas, Xe does not cause background signal interference in the body. With the help of spin exchange optical pumping technology (SEOP), hyperpolarization can be greatly enhanced. 129 Xe's magnetic resonance signal. This technology makes lung magnetic resonance imaging possible and can reveal detailed information about the structure and function of the lungs, providing a powerful tool for the clinical evaluation of lung diseases.

[0003] 129 Xe itself is not targeted. 129 It is difficult to achieve targeted imaging of the target area when Xe is used directly as a probe molecule. 129 Xe, then through targeted modification of the caged molecule can be conferred 129 Xe targeting. However, traditional cage molecules such as caveolin have problems such as complex synthesis, high price, poor water solubility and difficulty in modification, and some probe molecules have unclear responses to certain biomarkers. Therefore, scientists are currently working to find a variety of new cage molecules for the construction of hyperpolarized 129 Xe imaging system, 129 Xe targeted imaging offers more possibilities.

[0004] Zeolite molecular sieve materials have regular pore structures and have good adsorption effects on a variety of gases. In recent years, they have been used to a certain extent in various disciplines. 129 Xe builds hyperpolarization 129 Therefore, in this invention we will explore the use of activated zeolite molecular sieve materials to load 129 Xe, used to build hyperpolarized 129 The possibilities of Xe imaging systems. Summary of the Invention

[0005] In view of the deficiencies in the prior art, the application uses an activated zeolite molecular sieve material ZSM-5 to load 129 Xe is a new type of magnetic resonance contrast agent, which has the advantages of no background signal interference and high sensitivity.

[0006] The technical scheme adopted to achieve the above-mentioned purposes of the application is:

[0007] The application provides an activated zeolite molecular sieve material ZSM-5 as 129 The application of Xe molecular cage in Hyper-CEST NMR and MRI signal acquisition, the activated zeolite molecular sieve material ZSM-5 is obtained by high-temperature activation treatment of a zeolite molecular sieve ZSM-5 material.

[0008] Further, the high-temperature activation treatment comprises the following steps:

[0009] The ZSM-5 material is placed in a porcelain boat, and is programmed to be heated at a temperature increasing rate of 5 DEG C / min from room temperature to 550 DEG C in a static air atmosphere, and is naturally cooled after being baked at 550 DEG C for 5 h, so that the activated zeolite molecular sieve material ZSM-5 is obtained.

[0010] Further, the application is that the activated zeolite molecular sieve material ZSM-5 is used as a hyperpolarized 129 Xe magnetic resonance contrast agent.

[0011] Compared with the prior art, the application has the advantages and beneficial effects that:

[0012] 1. The application uses the activated zeolite molecular sieve material ZSM-5 as 129 Xe carrier, which has the advantages of simple synthesis, cheap raw materials and large-scale production;

[0013] 2. The application of ZSM-5 in the biomedical field has almost not been developed, the application widens the application range of ZSM-5, and proves the feasibility of the activated zeolite molecular sieve material ZSM-5 as a new type of magnetic resonance contrast agent. BRIEF DESCRIPTION OF DRAWINGS

[0014] Figure 1 It is a TEM graph of the activated zeolite molecular sieve material ZSM-5 in Example 1;

[0015] Figure 2 It is a SEM graph of the activated zeolite molecular sieve material ZSM-5 in Example 1;

[0016] Figure 3 It is an XRD spectrum of the activated zeolite molecular sieve material ZSM-5 in Example 1;

[0017] Figure 4Hyper-CEST NMR spectra of activated zeolite molecular sieve material ZSM-5 in Example 1 at different concentrations;

[0018] Figure 5 Hyper-CEST MRI spectra of activated zeolite molecular sieve material ZSM-5 in Example 1. DETAILED DESCRIPTION

[0019] The application will be described in detail below with specific examples.

[0020] The main reagents and instruments used in the following examples are as follows:

[0021] ZSM-5 was purchased from the Catalyst Factory of Nankai University, and methanol was purchased from the Chemical Reagent Co., Ltd. of China Pharmaceutical Group.

[0022] The hyperpolarization instrument is a self-developed instrument (developed by the Innovation Institute of Precise Measurement Science and Technology, Chinese Academy of Sciences);

[0023] Nuclear magnetic resonance instrument (400MHz Bruker AV400 wide bore spectrometer).

[0024] Example 1: Activation and characterization of zeolite molecular sieve material

[0025] 1. Activation of ZSM-5

[0026] The ZSM-5 material was placed in a porcelain boat and programmed to heat from room temperature (room temperature in the present application refers to 25℃) to 550℃ at a heating rate of 5℃ / min in a static air atmosphere, and then naturally cooled after constant temperature calcination at 550℃ for 5h to obtain the activated zeolite molecular sieve material ZSM-5.

[0027] 2. Morphological characterization of activated zeolite molecular sieve material ZSM-5

[0028] 1) The activated zeolite molecular sieve material ZSM-5 prepared in step 1 above was ground to obtain a powder sample, 1mg of the powder sample was added to 1mL of methanol, and ultrasonic dispersion was carried out at room temperature for 30min to obtain a sample dispersion liquid;

[0029] 2) 50μL of the sample dispersion liquid was dropped onto a clean ordinary carbon support film, and naturally dried at room temperature, and the carbon support film loaded with the dried sample was placed under a transmission electron microscope (TEM) for scanning;

[0030] 3) 50μL of the sample dispersion liquid was dropped onto a clean silicon wafer, and naturally dried at room temperature, and the silicon wafer loaded with the dried sample was placed under a scanning electron microscope (SEM) for scanning.

[0031] Experimental results:

[0032] The obtained TEM images are as follows Figure 1 The obtained SEM images are shown in Figure 2 As shown, according to Figure 2 The SEM image statistics show that the size of the activated zeolite molecular sieve material ZSM-5 obtained in the above step 1 is about 100 nm. It can be seen from the figure that the particles have a certain degree of agglomeration.

[0033] 3. Powder X-ray Diffraction Characterization of Activated Zeolite Molecular Sieve Material ZSM-5

[0034] 1) taking the powder sample obtained in step 2 and placing it in the sample cell of an X-ray diffractometer;

[0035] 2) PXRD data were collected on an X-ray diffractometer using a Cu target as the X-ray light source. The parallel light mode was used, and the scanning range was 2θ = 2 to 50°.

[0036] Experimental results:

[0037] The obtained PXRD pattern is as follows Figure 3 As shown, the powder X-ray diffraction peak of the activated zeolite molecular sieve material ZSM-5 obtained in step 1 is at the same position as the diffraction peak of the ZSM-5 before activation in the standard card, indicating that the activated zeolite molecular sieve material ZSM-5 obtained in step 1 has a complete crystal structure and is free of impurity phases.

[0038] Example 2 Magnetic Resonance Performance Test of Activated Zeolite Molecular Sieve Material ZSM-5

[0039] Test method:

[0040] 1) 4 mg of the activated zeolite molecular sieve material ZSM-5 obtained in Example 1 was added to 2 mL of ultrapure water and ultrasonically dispersed for 30 min to obtain a ZSM-5 mother liquor uniformly dispersed in water. The mother liquor concentration was 2 mg / mL;

[0041] 2) Take 50, 75, 100, 200, 300, and 400 μL of ZSM-5 mother solution, respectively, and dilute to 2 mL with ultrapure water to obtain ZSM-5 test solutions with concentrations of 50, 75, 100, 200, 300, and 400 μg / mL;

[0042] 3) Take 2mL of the above-mentioned ZSM-5 test solution of each concentration into a 10mm NMR sample tube for testing. The sequence used in the test is the CEST sequence. 129Xe was hyperpolarized, and the gas mixture was composed of 10% N2, 88% He, and 2% Xe (natural abundance Xe). After the gas mixture was polarized by the hyperpolarizer, it was directly introduced into the sample tube at a flow rate of 0.1 slpm. After ventilation for 15 seconds, ventilation was stopped for 3 seconds. After the bubbles disappeared, continuous wave selective pulses (pulse intensity of 6.5 μT, pulse length of 8 seconds) were used to saturate the ZSM-5 pores. 129 Xe signal, then excited with a 90° pulse 129 During the experiment, the saturation irradiation range was 100ppm-175ppm, and a point was taken every 2ppm. After obtaining a series of spectra, the dissolved state was 129 The Xe signal was normalized and then normalized to the dissolved state 129 The Xe signal is used as the vertical axis, and the saturated irradiation site is used as the horizontal axis to plot and obtain the Hyper-CEST spectrum.

[0043] Experimental results:

[0044] The resulting Hyper-CEST spectrum is as follows: Figure 4 As shown, from Figure 4 It can be seen that the signal near 141ppm comes from the pores of the activated zeolite molecular sieve material ZSM-5 obtained in Example 1. 129 The signal intensity of Hyper-CEST of Xe increases with the increase of test solution concentration, which shows that the activated zeolite molecular sieve material ZSM-5 obtained in Example 1 has a good Hyper-CEST effect. 129 Xe molecular cage has high signal sensitivity and is a new 129 Potential of Xe molecular cages.

[0045] Example 3 Magnetic Resonance Imaging Test of Activated Zeolite Molecular Sieve Material ZSM-5

[0046] Test method:

[0047] 1) 4 mg of the activated zeolite molecular sieve material ZSM-5 obtained in Example 1 was added to 2 mL of ultrapure water and ultrasonically dispersed for 30 min to obtain a ZSM-5 mother liquor uniformly dispersed in water. The mother liquor concentration was 2 mg / mL;

[0048] 2) Take 200 μL of ZSM-5 mother solution and dilute it to 2 mL with ultrapure water to obtain a ZSM-5 test solution with a concentration of 200 μg / mL;

[0049] 3) Take 2mL of ZSM-5 test solution and transfer it to a 10mm NMR sample tube for Hyper-CEST imaging. 129Xe was hyperpolarized, the composition of the mixed gas was 10% N2, 88% He, 2% Xe (natural abundance Xe). The mixed gas was polarized by the hyperpolarization device, and then was introduced into the nuclear magnetic sample tube at a flow rate of 0.1 slpm. After 20 s of aeration, aeration was stopped for 3 s, and after the bubbles disappeared, the ZSM-5 channels were saturated irradiated by using a saturation pulse of 13 μT 129 Xe signal for 5 s, then a saturation image was obtained by imaging using the RARE sequence, and then the channels were saturated irradiated by using the same pulse 129 Xe signal at the symmetrical position (dissolved state 129 Xe as the center of symmetry), an unsaturated image was obtained by using the RARE sequence, and data processing and image reconstruction were performed by using a Matlab program. The Hyper-CEST MRI image was reconstructed by dividing the difference between the gray values of the unsaturated image and the saturation image by the gray value of the unsaturated image.

[0050] Experimental results:

[0051] The obtained MRI image is shown in Figure 5 From Figure 5 it can be seen that the activated zeolite molecular sieve material ZSM-5 obtained in Example 1 has a good imaging effect in an aqueous solution, and the Hyper-CEST MRI signal intensity value is about 0.40.

Claims

1. An activated zeolite molecular sieve material ZSM-5 as 129 Application of Xe molecular cage in Hyper-CEST NMR and MRI contrast agents, wherein the activated zeolite molecular sieve material ZSM-5 is obtained by high-temperature activation treatment of the zeolite molecular sieve ZSM-5 material; In the application, the activated zeolite molecular sieve material ZSM-5 is prepared into a ZSM-5 test solution and put into use. The preparation method of the ZSM-5 test solution is as follows: 1) Add 4 mg of activated zeolite molecular sieve material ZSM-5 to 2 mL of ultrapure water and ultrasonically disperse for 30 min to obtain a ZSM-5 mother liquor uniformly dispersed in water with a mother liquor concentration of 2 mg / mL; 2) Take 200 μL of ZSM-5 mother solution and dilute it to 2 mL with ultrapure water to obtain a ZSM-5 test solution with a concentration of 200 μg / mL.

2. The use according to claim 1, characterized in that The high temperature activation treatment comprises the following steps: The ZSM-5 material was heated to 550°C in a static air atmosphere, calcined at 550°C for 5 h, and then naturally cooled to obtain an activated zeolite molecular sieve material ZSM-5.

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