Method for detecting air leak present in luminal organ, and agent for detecting air leak

Abstract

The main problem to be addressed by the present invention is to provide: a method for detecting an air leak present in a luminal organ with high reliability; and an agent for detecting an air leak.　As a means for solving the problem, provided are: a method for detecting an air leak present in a luminal organ, the method including a step for detecting the air leak by using CT to detect leakage, from the luminal organ, of at least one type of gas selected from the group consisting of xenon, krypton, and argon; and an agent for detecting an air leak present in a luminal organ, the agent containing at least one type of gas selected from the group consisting of xenon, krypton, and argon.

Description

Method for detecting air leakage in a luminal organ and air leakage detection agent

[0001] The present invention relates to a method for detecting air leakage in a luminal organ and an air leakage detection agent.

[0002] Air leakage is a pathological condition in which air or the like in the lumen leaks out due to the formation of a hole in the luminal organ for some reason. Air leakage mainly occurs in the digestive and respiratory organs. For example, when air leakage occurs in the trachea or bronchus, it can cause diseases such as pneumothorax.

[0003] Currently, as treatment methods for pneumothorax, drainage of air in the thoracic cavity by thoracic drainage and lung resection by thoracoscopic surgery are performed. Furthermore, in recent years, methods such as closing the bronchus with a filler such as EWS (Endobronchial Watanabe Spigot) to improve air leakage downstream (Non-Patent Document 1) and injecting a paste-like substance using a biomolecule such as fibrin around the air leakage to close the air leakage have been devised (Non-Patent Document 2).

[0004] In treatment methods using bronchial fillers or paste-like substances, the detection of the position of air leakage affects the success or failure of the treatment method. However, air leakage is difficult to detect by simple CT (Computed Tomography) examination. Currently, mainly the identification of the position of air leakage by balloon test is being tried, but in the balloon test, only the bronchus on the central side of the air leakage can be identified, and it is very difficult to identify the air leakage itself. Therefore, a method for accurately detecting the position of air leakage has been demanded.

[0005] Xenon is used as a contrast agent in CT examinations and is mainly used for evaluating cerebral blood flow. Also, it has been reported that xenon can be used for evaluating the ventilation state of the lungs (Non-Patent Document 3). However, the usefulness of xenon for detecting air leakage was unknown.

[0006] Watanabe Y, et al., "Bronchial occlusion with endobronchial Watanabe spigot." J Bronchol, 10 (2003). "SY4-1. Challenges in developing medical devices aimed at fistula closure near air leak-responsible lesions." Bronchology, 46 Suppl (2024). Xiang K, et al., "Xenon-enhanced dual-energy CT lung ventilation imaging: techniques and clinical applications." AJR Am J Roentgenol, 202 (2014).

[0007] The present invention aims to provide a method for detecting air leaks present in tubular organs with high reliability, and an air leak detection agent.

[0008] In order to solve the above problems, the inventors conducted diligent research and discovered that air leaks present in tubular organs can be detected with high reliability by using a gas containing at least one selected from the group consisting of xenon, krypton, and argon, thus completing the present invention.

[0009] That is, the present invention includes the following embodiments: 1. A method for detecting an air leak in a tubular organ, comprising the step of detecting the air leak by detecting the leakage of at least one gas selected from the group consisting of xenon, krypton, and argon from within the tubular organ using CT. 2. The method according to 1, wherein the gas is xenon. 3. The method according to 1 or 2, further comprising the step of introducing the gas into the tubular organ using a delivery conduit. 4. Use of at least one gas selected from the group consisting of xenon, krypton, and argon for detecting an air leak in a tubular organ. 5. A detection agent for air leaks in tubular organs comprising at least one gas selected from the group consisting of xenon, krypton, and argon. 6. The detection agent according to 5, wherein the gas is xenon.

[0010] The present invention provides a method for detecting air leaks present in tubular organs with high reliability, and an air leak detection agent.

[0011] This figure shows images of xenon detected using CT scans at various concentrations. This figure shows the correlation between xenon concentration and detection intensity. This figure shows images of ejected xenon detected using CT scans. This figure shows images of xenon leaking from pig lungs detected using CT scans. This figure shows images of ejected xenon and krypton mixture detected using CT scans.

[0012] <Definition of Terms> In this invention, the term "tubular organ" refers to an organ having a tubular or sac-like shape. Examples of tubular organs include the respiratory system, digestive system, and urinary system. In the respiratory system, the air passage from the upper respiratory tract (nasal cavity, paranasal sinuses, pharynx, larynx) to the lower respiratory tract (trachea, bronchi, alveoli) can be called a tubular organ.

[0013] In this invention, the term "air leak" refers to the leakage of air or other substances from within a lumen of a living organism due to the formation of an anatomically non-existent opening in the lumen of the organ, as well as the location of such leakage. Depending on the location where it occurs, air leaks are classified into tracheobronchial fistulas, esophagobronchial fistulas, pleuroporhelic fistulas, etc.

[0014] In this invention, the term "CT (Computed Tomography)" refers to a technique or equipment for performing an image of an object's internal structure by scanning the object using X-rays and processing the image using a computer. Furthermore, it is not limited to the general method of obtaining a tomographic image by rotating an X-ray tube and detector by 180 degrees or more using X-rays, but also includes X-ray tomosynthesis, which obtains a tomographic image of a limited range by rotating or translating an X-ray tube and detector in sync with each other by less than 180 degrees. It also includes positron emission tomography (PET) and single-photon emission computed tomography (SPECT), which obtain a tomographic image based on gamma rays emitted from within the body after administering a radioactive isotope.

[0015] 1. Method for detecting air leaks in a tubular organ The present invention includes a method for detecting air leaks in a tubular organ, comprising the step of detecting the air leak by detecting the leakage of at least one gas selected from the group consisting of xenon, krypton, and argon from within the tubular organ using CT.

[0016] Xenon, krypton, or argon may be introduced into a tubular organ either alone or as a mixture thereof.

[0017] Xenon, krypton, or argon are detected by X-rays because they have the property of preventing the transmission of high-energy electromagnetic waves such as X-rays. The detection intensity is strongest in the order of xenon, krypton, and argon, so it is preferable to use xenon and / or krypton, and it is particularly preferable to use xenon. Argon has a weak detection intensity, and it is not easy to visually detect air leaks from processed images by CT, but it has the advantage of being inexpensive.

[0018] The test animals are not particularly limited to those with tubular organs and can be any animal. Specific examples of test animals include humans and non-human mammals. Examples of non-human mammals include laboratory animals (rodents such as mice, rats, hamsters, and guinea pigs, and rabbits), livestock (pigs, cattle, goats, horses, sheep, etc.), pets (dogs, cats, etc.), and primates (monkeys, orangutans, chimpanzees, etc.). Primates are preferred as test animals, and humans are more preferred.

[0019] The method of the present invention is not particularly limited to any tubular organ, and examples include the respiratory system, digestive system, urinary system, etc. From the viewpoint of the background art, the method of the present invention is particularly advantageous when applied to the respiratory system.

[0020] The method of the present invention may further include the step of introducing at least one gas selected from the group consisting of xenon, krypton, and argon into a tubular organ. The means of introduction are not particularly limited and include, for example, means using a face mask or a delivery conduit. Known devices such as bronchoscopes, cannulas, catheters, tubes, and lung isolation ventilators can be used as delivery conduits. When using a delivery conduit, the gas can be introduced locally to a location where an air leak is suspected.

[0021] The method of the present invention is advantageous in that it can be used with existing CT equipment. The CT equipment used in the present invention is not particularly limited, and existing methods such as the Translate / Rotate method, Rotate / Rotate method, Stationary / Rotate method, and Nutate / Rotate method can be applied to the present invention. Furthermore, if the gas introduced into the tubular organ contains radioactive isotopes, equipment capable of performing PET or SPECT may also be used. In addition, equipment capable of performing dual-energy CT or photon-counting CT may be used for image processing.

[0022] For example, when detecting xenon, since existing CT equipment is used, it is preferable that xenon be present at a concentration of 10% by volume or more relative to the air at the detection site, more preferably 20% by volume or more, even more preferably 40% by volume or more, and particularly preferably 80% by volume or more. On the other hand, the inventors have found that the concentration of the gas used in this invention correlates with the detection intensity, and known technologies such as dual-energy CT and photon-counting CT can enable detection even at lower concentrations of xenon, or when krypton or argon are used. Therefore, the lower limit of the gas concentration used in this invention is not particularly limited as long as it is detectable depending on the equipment used.

[0023] The upper limit of the gas concentration used in the method of the present invention is not particularly limited and can be, for example, 100% by volume or less, 99% by volume or less, 95% by volume or less, or 90% by volume or less relative to the air at the detection site. Xenon is known to have an anesthetic effect and is used at a concentration of about 70% by volume when used as an anesthetic. Anesthetics are inhaled continuously for a certain period of time, such as during surgery, and this concentration is set to ensure safety even under such usage conditions. In the method of the present invention, detection is possible if the gas is introduced into a tubular organ in a short time, such as a few seconds to tens of seconds. Thus, even when xenon is used in the present invention, the time it takes for xenon to be introduced into the body is shorter than when it is used as an anesthetic, so it is considered that xenon at a concentration exceeding that normally used as an anesthetic can be introduced into a tubular organ.

[0024] Therefore, the concentration of at least one gas selected from the group consisting of xenon, krypton, and argon used in the method of the present invention is not particularly limited as long as it is detectable, and can be set to, for example, 10% to 100% by volume, 20% to 99% by volume, 40% to 95% by volume, 50% to 90% by volume, etc., relative to the air at the detection site, depending on the equipment used.

[0025] In the method of the present invention, when a mixture of xenon and krypton is used, it is significant that the concentration can be set so that the anesthetic effect of xenon does not manifest, while maintaining good detection sensitivity. In such cases, for example, the air at the detection site can be set to contain xenon and krypton, and the volume ratio of xenon to krypton can be set to 1:0.5 to 1:2, 1:0.8 to 1:1.8, 1:1 to 1:1.5, etc.

[0026] In the method of the present invention, image processing in CT can obtain cross-sectional views and stereoscopic views by reconstructing images from the obtained projection data, and known image processing techniques can be used for these. Here, the method of the present invention may include an image processing step that emphasizes the region where gas introduced into a tubular organ is present. The image processing techniques may include, for example, dual-energy CT or photon-counting CT, and the various parameters related to these image processing techniques are not particularly limited as long as the conditions for carrying out the present invention are met, and can be appropriately changed without changing the essence of the invention.

[0027] The method of the present invention makes it possible to visually detect air leaks from processed images obtained by CT. Specifically, the method of the present invention determines that an air leak exists at a location where an image is obtained showing gas being introduced into a tubular organ and leaking out of the tubular organ.

[0028] As described above, air leaks can be detected by using at least one gas selected from the group consisting of xenon, krypton, and argon. The use of such at least one gas selected from the group consisting of xenon, krypton, and argon to detect air leaks present in tubular organs is also included in the present invention.

[0029] 2. Air leak detection agent for tubular organs The present invention encompasses an air leak detection agent for tubular organs comprising at least one gas selected from the group consisting of xenon, krypton, and argon. In the air leak detection agent of the present invention, xenon, krypton, or argon may be included individually or as a mixture.

[0030] From the viewpoint of detection intensity, the air leak detection agent preferably contains xenon and / or krypton, and is particularly preferably xenon.

[0031] For example, when using xenon as an air leak detection agent, existing equipment can be reused, so the xenon content is preferably 10% by volume or more, more preferably 20% by volume or more, even more preferably 40% by volume or more, and particularly preferably 80% by volume or more relative to the air leak detection agent. On the other hand, since the concentration of the gas used in the present invention correlates with the detection intensity, known technologies such as dual-energy CT and photon-counting CT can enable detection of the air leak detection agent even at lower xenon concentrations, or when krypton or argon are used. Therefore, the lower limit of the gas concentration used in the present invention is not particularly limited as long as it is detectable depending on the equipment used.

[0032] In the air leak detection agent of the present invention, the upper limit of the content of xenon, krypton, or argon is not particularly limited and can be, for example, 100% by volume or less, 99% by volume or less, 95% by volume or less, or 90% by volume or less relative to the air leak detection agent.

[0033] Accordingly, the content of at least one gas selected from the group consisting of xenon, krypton, and argon in the air leak detection agent of the present invention is not particularly limited as long as it is detectable, and can be set to, for example, 10% to 100% by volume, 20% to 99% by volume, 40% to 95% by volume, 50% to 90% by volume, etc., relative to the air leak detection agent, depending on the equipment used.

[0034] When the air leak detection agent of the present invention contains xenon and krypton, the volume ratio of xenon to krypton can be set to 1:0.5 to 1:2, 1:0.8 to 1:1.8, 1:1 to 1:1.5, etc., in order to avoid the anesthetic effect of xenon and to obtain good detection sensitivity.

[0035] The air leak detection agent of the present invention may contain commonly used base materials and / or additives. Examples of such base materials and / or additives include medical gases (oxygen, nitrogen, carbon dioxide, therapeutic air, etc.), inhalation anesthetics (nitrous oxide, ether, halothane, isoflurane, sevoflurane, etc.), and radioactive isotopes of various gases. These may be included in the air leak detection agent alone or as a mixture. Furthermore, the air leak detection agent of the present invention may be diluted and mixed with base materials and / or additives at the time of use.

[0036] The air leak detection agent of the present invention is not particularly limited in its form when stored, and may be stored in liquid or solid state. In that case, it is used after being vaporized as appropriate. The means of liquefaction or solidification are not particularly limited, and examples include pressurization and cooling.

[0037] The present invention will be described in more detail below with reference to examples, but the present invention is not limited in any way to these examples.

[0038] 1. The specimen for the pneumothorax model was prepared by purchasing pig lungs (Tokyo Shibaura Organ Co., Ltd., hybrid breed, 6 months old) and making slit-like holes of about 1 mm using a scalpel, and used for the study.

[0039] The chest cavity model mannequin used was the Chest Phantom N-1 (Kyoto Science Co., Ltd.).

[0040] 2. Preparation of air leak detection agent Xenon (Air Liquide) at a concentration of 99.995% or more by volume and krypton (Air Liquide) at a concentration of approximately 99.995% by volume were purchased and diluted with air or oxygen as needed, and used as an air leak detection agent.

[0041] 3. CT scanning of the CT imaging detection agent was performed using Neo-Tom Alpha (SIEMENS Healthineers, 304AIBZX00004000) and was carried out according to the protocol provided with the device.

[0042] Example 1 Xenon at 90% by volume, 45% by volume, 23% by volume, 11% by volume, 6% by volume, 3% by volume, 1% by volume, 0.7% by volume, and 0.3% by volume was prepared, filled into a 20 mL syringe (TERUMO, SS-20ESZ), and CT imaging was performed. The results are shown in Figure 1. Under the conditions of this example, it can be seen that if the concentration is 11% by volume or more, the presence of xenon can be confirmed by visually observing the image.

[0043] Example 2 Xenon at various concentrations was prepared and filled into a 20 mL syringe. The syringe was further placed inside a thoracic model mannequin, and CT imaging was performed to examine the relationship between the concentration of xenon and the detection intensity. The results are shown in Figure 2. It can be seen that the concentration of xenon and the detection intensity show a strong positive correlation.

[0044] Example 3 In pneumothorax, the clinically problematic gas leakage volume is generally considered to be 60 mL / min (i.e., 1.0 mL / s). Therefore, using Dual Shot GX7 (K根本杏林堂社, 223ABBZX00051000), 69% by volume xenon was ejected at 1.0 mL / s, and CT imaging was performed. The results are shown in Figure 3. Under the conditions of this example, it can be seen that xenon can be detected even at a low flow rate of 1.0 mL / s, and clinically problematic air leaks can be detected.

[0045] Example 4 A specimen of a pneumothorax model using a porcine lung was filled with xenon, and CT imaging was performed. Also, using Interactive Spectral Imaging (SIEMENS Healthineers, syngo CT VA50SP1), image processing was performed to emphasize the region where xenon is present. The results are shown in Figure 4. Under these conditions, it can be seen that leakage of xenon from the pneumothorax model specimen was confirmed, and air leaks can be detected.

[0046] Example 5 Xenon and / or krypton were mixed with oxygen to prepare mixtures of the following compositions: 69 vol% xenon; 69 vol% krypton; 33 vol% xenon; and 33 vol% xenon + 45 vol% krypton. These mixtures were ejected inside a chest cavity model using a Dual Shot GX7, and CT scans were performed. The results are shown in Figure 5. It can be seen that the mixture of 33 vol% xenon + 45 vol% krypton was detected more strongly than 33 vol% xenon.

Claims

1. A method for detecting an air leak in a tubular organ, comprising the step of detecting the air leak by detecting the leakage of at least one gas selected from the group consisting of xenon, krypton, and argon from within the tubular organ using CT.

2. The method according to claim 1, wherein the gas is xenon.

3. The method according to claim 1 or 2, further comprising the step of introducing the gas into the tubular organ using a delivery conduit.

4. Use of at least one gas selected from the group consisting of xenon, krypton, and argon to detect air leaks present in tubular organs.

5. A detection agent for air leaks present in tubular organs, comprising at least one gas selected from the group consisting of xenon, krypton, and argon.

6. The detection agent according to claim 5, wherein the gas is xenon.

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