Application of activated zeolite molecular sieve in ultra-sensitive magnetic resonance imaging

Abstract

The invention belongs to the technical field of magnetic resonance imaging, and particularly relates to application of an activated zeolite molecular sieve in ultra-sensitive magnetic resonance imaging. The activated zeolite molecular sieve material ZSM-5 has a special microporous structure and catalytic performance, and is a crystal composed of silicon, aluminum and oxygen atoms. The activated zeolite molecular sieve material ZSM-5 can be used as a novel Xe molecular cage for loading Xe, compared with a traditional magnetic resonance contrast agent, the contrast agent has the advantages of no background signal interference and high sensitivity, and a new idea is provided 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 ultra-sensitive 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. 1 The distribution of H has a strong background signal. 129 Xe magnetic resonance imaging has emerged as a new type of imaging technology. 129 As an exogenous gas, Xe does not cause interference from background signals in the body. With the help of spin exchange optical pumping (SEOP), hyperpolarization can be greatly enhanced. 129 Xe's magnetic resonance signal 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 by directly using Xe as a probe molecule. 129 Xe, then through targeted modification of the cage 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 on finding a variety of new cage molecules for constructing hyperpolarized 129 Xe imaging system, 129 Xe targeted imaging offers more possibilities.

[0004] Zeolite molecular sieve materials have a regular pore structure and have good adsorption effects on a variety of gases. In recent years, they have been used to a certain extent in many 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 Possibilities of Xe imaging systems. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention uses an activated zeolite molecular sieve material ZSM-5 for loading 129 Xe is a new type of magnetic resonance contrast agent with the advantages of no background signal interference and high sensitivity.

[0006] The technical solution adopted to achieve the above-mentioned purpose of the present invention is:

[0007] The present invention provides an activated zeolite molecular sieve material ZSM-5 as 129 The invention relates to 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 the zeolite molecular sieve ZSM-5 material.

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

[0009] The ZSM-5 material was placed in a porcelain boat, and the temperature was raised from room temperature to 550°C at a heating rate of 5°C / min in a static air atmosphere. After being calcined at 550°C for 5 hours, the mixture was naturally cooled to obtain the above-mentioned activated zeolite molecular sieve material ZSM-5.

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

[0011] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0012] 1. The present invention uses activated zeolite molecular sieve material ZSM-5 as 129 Xe carrier 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 hardly been developed. The present invention broadens the application scope of ZSM-5 and confirms the feasibility of the activated zeolite molecular sieve material ZSM-5 as a new type of magnetic resonance contrast agent. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 TEM image of the activated zeolite molecular sieve material ZSM-5 in Example 1;

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

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

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

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

[0019] The present invention is described in detail below with reference to specific embodiments.

[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 Sinopharm Chemical Reagent Co., Ltd.

[0022] The hyperpolarization instrument is an independently developed instrument (developed by the Institute of Precision Measurement Science and Technology Innovation, 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 materials

[0025] 1. Activation of ZSM-5

[0026] The ZSM-5 material was placed in a porcelain boat, and the temperature was raised from room temperature (room temperature in the present invention refers to 25°C) to 550°C at a heating rate of 5°C / min in a static air atmosphere. After constant temperature calcination at 550°C for 5 hours, the material was naturally cooled to obtain an activated zeolite molecular sieve material ZSM-5.

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

[0028] 1) Grind the activated zeolite molecular sieve material ZSM-5 obtained in step 1 above to obtain a powder sample, take 1 mg of the powder sample and add it into 1 mL of methanol, and perform ultrasonication at room temperature for 30 min to disperse it evenly to obtain a sample dispersion;

[0029] 2) Take 50 μL of the sample dispersion and drop it onto a clean ordinary carbon support film, let it dry naturally at room temperature, and place the carbon support film loaded with the dried sample under a transmission electron microscope (TEM) for scanning;

[0030] 3) Take 50 μL of the sample dispersion and drop it onto a clean silicon wafer, allow it to dry naturally at room temperature, and place the silicon wafer loaded with the dried sample under a scanning electron microscope (SEM) for scanning.

[0031] Experimental results:

[0032] The obtained TEM images are shown in 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, where a Cu target was used 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 no impurity phase.

[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, with a mother liquor concentration of 2 mg / mL;

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

[0042] 3) Take 2 mL of the above ZSM-5 test solution of each concentration into a 10 mm NMR sample tube for testing. The sequence used for the test is the CEST sequence. 129Xe was subjected to hyperpolarization treatment, and the composition of the mixed gas was 10% N2, 88% He, and 2% Xe (natural abundance Xe). After the mixed gas 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 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 129 The Xe signal was normalized and then normalized to the dissolved state 129 The Xe signal is used as the ordinate and the saturated irradiation site is used as the abscissa to 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 141 ppm 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 the concentration of the test solution, 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, with a mother liquor concentration of 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, 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 passed into the NMR sample tube at a flow rate of 0.1 slpm. After 20 seconds of ventilation, the ventilation was stopped for 3 seconds. After the bubbles disappeared, a 13μT saturation pulse was used to saturate the ZSM-5 pores. 129 Xe signal for 5s, then the RARE sequence is used to obtain a saturated image, and then the same pulse is used to saturate the channel. 129 The symmetric position of Xe signal (in dissolved state 129 Xe is the symmetry center), the unsaturated image is obtained by RARE sequence, and Matlab program is used for data processing and image reconstruction. The difference between the gray value of the unsaturated image and the saturated image is divided by the gray value of the unsaturated image to reconstruct the Hyper-CEST MRI image.

[0050] Experimental results:

[0051] The resulting MRI images are as follows Figure 5 As shown, 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 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 The invention relates to 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 the zeolite molecular sieve ZSM-5 material.

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.

3. The use according to claim 1 or 2, characterized in that: The activated zeolite molecular sieve material ZSM-5 is used as a hyperpolarized 129 Xe magnetic resonance contrast agent.

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