Mixed gas for nuclear magnetic resonance and application thereof

Abstract

The invention discloses a mixed gas for nuclear magnetic resonance and application of the mixed gas. The mixed gas consists of 1-4% of xenon, 10-15% of nitrogen and 80-88% of helium (volume ratio). According to the invention, research on reasonable composition of the mixed gas which can be used as a nuclear magnetic resonance contrast agent is focused for the first time to improve the detection effect of nuclear magnetic resonance; on the basis of physicochemical properties, hyperpolarization efficiency, safety and imaging requirements of all gases and in combination with clinical experiment effects, the mixed gas with the optimal proportion for human body gas magnetic resonance imaging is developed, and multi-dimensional balance of hyperpolarization efficiency, physiological safety and imaging performance can be achieved; and the nuclear magnetic signal can be maximally enhanced, so that the nuclear magnetic resonance imaging effect, especially the imaging effect during lung detection, is optimal.

Description

Technical Field

[0001] The present invention relates to the field of nuclear magnetic resonance technology, in particular to a mixed gas for nuclear magnetic resonance and applications thereof. Background Art

[0002] For a long time, chest X-ray, CT, and PET have been the main clinical screening methods for early lung cancer lesions. However, due to the high cost of the equipment and the high radiation damage, and the inability of most lung imaging instruments to perform functional examinations of the lung's ventilation, microstructure, and blood exchange, clinically accurate screening cannot be achieved in the field of early cancer screening and early lung lesions. With the development of technology, MRI, as a detection method without radiation damage, has gradually entered the field of early cancer screening. However, although traditional magnetic resonance imaging technology used to detect other tissues of the human body does not cause radiation damage, it can only image water (hydrogen nuclei). Lung tissue is filled with alveoli, which is a special cavity structure with an extremely low content of hydrogen nuclei in the tissue. Therefore, there is a visual "blind spot" when testing the lungs, making it difficult to detect early lung lesions.

[0003] With continuous technological advancements, a gas magnetic resonance imaging (MRI) instrument for human lungs has been developed. The images obtained not only display the complete lung structure, including the trachea, bronchi, and lung lobes, but also enable quantitative assessment of pulmonary ventilation function and the physiological functions of gas-blood exchange. After post-processing, the instrument can also display a three-dimensional reconstruction of the lungs. Specifically, for lung structural imaging, this instrument can detect early-stage pulmonary ventilation lesions that are not visible on clinical CT. It can non-invasively, quantitatively, and visually measure changes in the gas diffusion capacity within the lungs, effectively reflecting changes in the lung microstructure in patients with chronic obstructive pulmonary disease. For functional lung imaging, it can non-invasively obtain a series of important physiological parameters of lung structure and function, including lung gas-blood barrier thickness, lung gas-blood exchange time, and alveolar enlargement and damage. This instrument can thus detect functional changes that precede structural changes in the lung, enabling early detection and diagnosis of lung diseases. Furthermore, this instrument is also suitable for functional imaging of highly perfused tissues such as the brain and heart.

[0004] In the application of gas magnetic resonance imaging (MRI) instruments for human lungs, a gas mixture containing xenon is required as a contrast agent. Due to its excellent biochemical inertness, lipid solubility, and chemical shift sensitivity, xenon can dissolve in lung blood and tissue, generating distinct magnetic resonance signals. This can enhance the nuclear magnetic resonance (NMR) signal by more than 50,000 times, resolving the problem of gas magnetic resonance (MRI) signals being too low to be able to image lungs. However, the xenon concentration in the NMR imaging agent and its combination with other gases significantly impacts the imaging and detection results. Currently, there is little research focused on gas mixtures for NMR imaging to enhance NMR detection. Summary of the Invention

[0005] Therefore, based on the above background, the present invention provides a mixed gas for nuclear magnetic resonance and applications thereof.

[0006] The technical solution provided by the present invention is:

[0007] A mixed gas for nuclear magnetic resonance, which is composed of the following gases in volume ratio:

[0008] Xenon 1-4%, nitrogen 10-15%, helium 80-88%.

[0009] Preferably, the xenon gas is xenon-129 gas, and the gas abundance is greater than or equal to 85%.

[0010] Preferably, the purity of the nitrogen is 99.999%.

[0011] Preferably, the purity of the helium is 99.999%.

[0012] Preferably, it is a mixture of the following gases in volume ratio:

[0013] Xenon 2%, nitrogen 10%, helium 88%.

[0014] Based on the same inventive concept, the present invention also provides the use of the above-mentioned mixed gas for nuclear magnetic resonance as a contrast agent in xenon hyperpolarized magnetic resonance imaging.

[0015] Preferably, the xenon hyperpolarized magnetic resonance imaging is for lung gas imaging.

[0016] Preferably, the mixed gas for nuclear magnetic resonance is used in conjunction with a medical xenon gas generator.

[0017] The beneficial effects achieved by the present invention are:

[0018] The present invention is the first to focus on the study of the reasonable composition of mixed gases that can be used as nuclear magnetic resonance contrast agents to improve the detection effect of nuclear magnetic resonance. Based on the physicochemical properties, hyperpolarization efficiency, safety, imaging requirements of each gas and combined with the results of clinical experiments, the present invention has developed an optimally proportioned mixed gas for lung gas imaging. It can achieve a multi-dimensional balance of "hyperpolarization efficiency-physiological safety-imaging performance", can maximize the enhancement of nuclear magnetic signals, and make the nuclear magnetic resonance imaging effect, especially the imaging effect when detecting the lungs, the best. DETAILED DESCRIPTION

[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0020] Example 1: A mixed gas for nuclear magnetic resonance, which is composed of the following gases in volume ratio:

[0021] Xenon-129 gas 2%, nitrogen 10%, helium 88%.

[0022] The abundance of the xenon-129 gas is greater than or equal to 85%.

[0023] The purity of the nitrogen is 99.999%.

[0024] The purity of the helium is 99.999%.

[0025] The composition of the mixed gas in this embodiment is the result of comprehensive optimization based on multiple factors including the physicochemical properties of each gas, hyperpolarization efficiency, safety, imaging requirements, and clinical experimental results.

[0026] 1) The 2% xenon-129 gas contained in this embodiment is the source of the hyperpolarized signal in xenon hyperpolarized magnetic resonance imaging, which is

[0027] Xenon-129( 129 Xe is the only xenon isotope (natural abundance approximately 26.4%) with nuclear magnetic resonance (NMR) activity (for example, xenon-131 hyperpolarization efficiency is too low to significantly enhance the MRI signal). Its nuclear spin (I = 1 / 2) enables it to generate a detectable signal in a magnetic field. Hyperpolarization techniques (such as spin-exchange optical pumping, SEOP) can increase the nuclear spin polarization of 129Xe by millions of times (far beyond thermal equilibrium), thereby enhancing the MRI signal by more than 50,000 times, enabling functional imaging of lung ventilation, blood flow, and microstructure.

[0028] However, in actual application, if the xenon concentration in the mixed gas is too high (for example, above 3%), the viscosity of the mixed gas will increase and the diffusion coefficient will decrease, affecting the distribution uniformity during lung ventilation and may even have a potential impact on respiratory function (xenon has an anesthetic effect).

[0029] While higher xenon concentrations theoretically provide more polarization, collisions between xenon molecules during the SEOP process can lead to polarization relaxation (spin-spin interactions). Excessively high concentrations can shorten the polarization lifetime, affecting the trade-off between hyperpolarization efficiency and signal strength. This reduces the actual usable signal intensity, while too low a concentration can result in insufficient magnetic resonance information. Experimental verification has shown that a concentration of 2% is the optimal value for balancing polarization efficiency and signal stability.

[0030] 2) The 88% helium in this embodiment is the primary carrier of the mixed gas and plays multiple roles in the hyperpolarization and imaging process. The first is to enhance the spin exchange efficiency: during the SEOP process, helium, as an inert gas, can transfer the angular momentum generated by optical pumping to the xenon nuclei through collisions with xenon molecules, significantly improving the polarization efficiency of 129Xe (this process is called the "buffer gas effect"). The high diffusion coefficient and low molecular weight of helium make it an ideal "energy transfer medium"; secondly, the low density and low viscosity of helium can reduce the respiratory resistance of the mixed gas, making it closer to the fluid mechanics of air, facilitating inhalation and exhalation by the subject, and is particularly suitable for the physiological compatibility requirements of lung ventilation imaging; thirdly, helium is non-toxic, does not participate in chemical reactions, and does not produce anesthetic or toxic effects on the human body at high concentrations, which can effectively dilute the potential physiological effects of xenon.

[0031] Sufficient helium concentration in the gas mixture ensures that the spin exchange process proceeds fully while maintaining the low viscosity and physiological safety of the gas. Experiments show that when the helium concentration is lower than 80%, the polarization efficiency and gas fluidity will drop significantly. However, in actual application, when the helium concentration in the gas mixture is lower than 80%, the polarization efficiency and gas fluidity will drop significantly. When the helium concentration increases from 80% to 90%, the polarization rate of 129Xe increases by about 15%, but too high a concentration (greater than 90%) will cause the gas density to be too low, which may affect the subject's breathing rhythm (needing to inhale more forcefully).

[0032] 3) The 10% nitrogen in this embodiment can, on the one hand, extend the polarization lifespan. During the SEOP process, the polarization state of xenon gas is easily affected by external factors (such as magnetic field inhomogeneity and molecular collisions) and attenuated. The introduction of nitrogen molecules can optimize the relaxation time (T1) of the xenon nucleus through the "spin-lattice relaxation" regulation mechanism, thereby extending the maintenance time of the polarization signal and improving the availability of the imaging window; on the other hand, it simulates the physiological gas environment. Nitrogen accounts for about 78% in the air. Adding 10% nitrogen can make the composition of the mixed gas closer to the natural environment of human breathing, reduce irritation to the respiratory mucosa, and avoid physiological discomfort such as changes in voice frequency caused by high helium concentrations (helium will change the vibration frequency of the vocal cords, and nitrogen can alleviate this phenomenon).

[0033] However, in practical application, the nitrogen concentration of 10% is the result of balancing the polarization stability and physiological compatibility. When the nitrogen concentration exceeds 15%, the ventilation efficiency may be affected due to the increase in gas density; when the nitrogen concentration is less than 5%, the optimization effect on the polarization life is not significant.

[0034] The mixed gas of the application is used in a medical xenon gas generator (an existing product, mainly composed of a laser system, a vacuum system, a magnetic field system, a pressure flow control system, a central power unit, a gas storage system, and gas path monitoring software (release version R01)). The mixed gas is superpolarized by using the medical xenon gas generator.

[0035] The SEOP technology of the medical xenon gas generator is the key to realizing 129Xe superpolarization. The principle is to use circularly polarized light to excite alkali metal (such as rubidium) atoms, and through the collision between the atoms and xenon gas molecules, the electron spin polarization is transferred to the xenon nucleus. In this process, the ratio of the mixed gas directly affects the following key links:

[0036] ① Light pumping efficiency: Helium as a buffer gas can reduce the collision de-excitation of alkali metal atoms, making them more efficiently absorb photon energy, and thus improving the polarization transfer efficiency to the xenon nucleus.

[0037] ② Spin relaxation regulation: The interaction between nitrogen molecules and xenon nuclei can adjust the T1 relaxation time (i.e., the longitudinal relaxation time) of xenon, so that the polarization signal remains stable during imaging (T1 extension means slower polarization decay).

[0038] ③ Gas dynamics: The mixing of helium and nitrogen ensures that the diffusion coefficient of the gas in the lungs is close to that of air (0.2 cm 2 / s), so that xenon can be uniformly distributed in the alveolar cavity to realize precise imaging of ventilation function.

[0039] The mixed gas of the embodiment has high safety, and the concentration of 2% xenon is much lower than the clinical anesthetic dose (usually more than 70% xenon concentration is required to produce anesthetic effect), and the reasonable ratio of helium and nitrogen can ensure that the oxygen partial pressure of the mixed gas is not lower than the safety threshold (if the ratio does not contain nitrogen, additional oxygen needs to be supplemented, but this will introduce the quenching effect of oxygen molecules on polarization, so 10% nitrogen can avoid this problem).

[0040] And the imaging effect is optimal. In lung ventilation MRI, the 129Xe signal intensity of the mixed gas of the embodiment is about 3-5 times higher than that of pure xenon or other ratios, and the signal uniformity is improved by more than 20%, significantly improving the diagnostic accuracy of lung dysfunction (such as asthma and chronic obstructive pulmonary disease).

[0041] The present invention and its embodiments are described above. Such description is not restrictive. The embodiment shown in the embodiment is only one embodiment of the present invention, and the actual structure is not limited thereto. In short, if a person skilled in the art is inspired by the above, and does not deviate from the purpose of the invention, without creatively designing a structure and embodiment similar to the technical solution, they shall fall within the scope of protection of the present invention.

Claims

1. A mixed gas for nuclear magnetic resonance, characterized in that: It is a mixture of the following gases in volume ratio; Xenon 1-4%, nitrogen 10-15%, helium 80-88%.

2. The mixed gas for nuclear magnetic resonance according to claim 1, characterized in that: The xenon gas is xenon-129 gas.

3. The mixed gas for nuclear magnetic resonance according to claim 1, characterized in that: The purity of the nitrogen is 99.999%.

4. The mixed gas for nuclear magnetic resonance according to claim 1, characterized in that: The purity of the helium is 99.999%.

5. A mixed gas for nuclear magnetic resonance according to any one of claims 1 to 4, characterized in that It is a mixture of the following gases in volume ratio; Xenon 2%, nitrogen 10%, helium 88%.

6. Use of the mixed gas for nuclear magnetic resonance according to any one of claims 1 to 5 as a contrast agent in xenon hyperpolarized magnetic resonance imaging.

7. The use according to claim 6, characterized in that The xenon hyperpolarized magnetic resonance imaging is aimed at gas magnetic resonance imaging of the human body.

8. The use according to claim 7, characterized in that The mixed gas for nuclear magnetic resonance is used in conjunction with a medical xenon gas generator.