WO2004010126A1 - Method for nondestructive inspection of state of liquid flow in liquid passage device - Google Patents

Method for nondestructive inspection of state of liquid flow in liquid passage device Download PDF

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Publication number
WO2004010126A1
WO2004010126A1 PCT/JP2003/009253 JP0309253W WO2004010126A1 WO 2004010126 A1 WO2004010126 A1 WO 2004010126A1 JP 0309253 W JP0309253 W JP 0309253W WO 2004010126 A1 WO2004010126 A1 WO 2004010126A1
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Prior art keywords
liquid
contrast agent
liquid flowing
state
inspection method
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PCT/JP2003/009253
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French (fr)
Japanese (ja)
Inventor
Yoshitada Sakai
Izumi Anno
Shigehisa Wada
Hiroshi Matsumoto
Tomoko Suyama
Masahiro Kubota
Hirotsugu Takahashi
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Toray Industries, Inc.
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Publication of WO2004010126A1 publication Critical patent/WO2004010126A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/563—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution of moving material, e.g. flow contrast angiography

Definitions

  • the present invention relates to a method for non-destructively inspecting a liquid flowing state in a liquid flowing device.
  • liquid distribution equipment for example, piping as a partial element of liquid treatment equipment, or reverse osmosis equipment, filter, dialyzer, adsorption column or heat exchanger as liquid treatment equipment.
  • piping as a partial element of liquid treatment equipment
  • reverse osmosis equipment filter, dialyzer, adsorption column or heat exchanger
  • the present invention intends to apply such a computed tomography diagnostic technique to the evaluation and design of a liquid flow device, and in that case, depending on the intended use characteristics of the target liquid flow device, there are several methods. It is also necessary to observe under specific conditions by using the techniques described above.
  • the present inventors have studied diligently to overcome these problems, and are a method that can be easily carried out.More particularly, when a semipermeable membrane is targeted, it is more suitable for inspection purposes and observation purposes. It has found a way that can be adapted.
  • a first object of the present invention is to provide a non-destructive inspection method of a liquid flowing state in a liquid flowing device, which is easily performed in view of the above points.
  • a second object of the present invention is to provide a nondestructive inspection method that is more suitable for an inspection purpose when a semipermeable membrane is to be inspected.
  • the present invention has the following configurations (1) to (14) to achieve the above object.
  • liquid circulation device is a hemodialyzer having a hollow fiber membrane, and a contrast agent is trapped in the hollow fiber membrane.
  • the liquid flowing state in the liquid flowing device can be inspected without destroying the device at all. It can be used very suitably when grasping the problems related to the flow passages in the field and examining the improvement design / design change related to it.
  • FIG. 1 is a drawing showing the distribution of X-ray absorption values on the blood side in a hemodialyzer under non-perfusion conditions of the eluate in the length direction of the hemodialyzer as an example of a liquid flow device. You.
  • the blood flows from the A side to the V side, and the blood flow Qb is set to 20 Om L / min.
  • the data points are the cross sections of each part (the cross section perpendicular to the flow).
  • the average and standard deviation of the x-ray absorption values in the poxel unit within the field of view covering about 80% of the hollow fiber bundle in the image are shown.
  • FIG. 2 is a drawing showing the distribution of X-ray absorption values on the blood side in the hemodialyzer under the conditions of dialysate perfusion in the length direction of the hemodialyzer, which is also an example of the liquid flow device.
  • the blood flows from the A side to the V side
  • the blood flow Qb is set to 200 mLZ
  • the dialysate flows in the opposite direction
  • the dialysate flow is set to 50 OmLZ
  • the filtration flow Q f indicates the case of O m LZ
  • the data points are the poxel units within the field of view including about 80% of the hollow fiber bundle of the cross section (cross section perpendicular to the flow) image of each part. Shows the average and standard deviation of X-ray absorption values.
  • Fig. 3 shows a hemodialyzer, which is also an example of a liquid flow device, in which bovine blood to which about 20% of barium sulfate has been added is pulsed and injected into the hemodialyzer, and a longitudinal section (section parallel to the flow) is shown.
  • the barium sulfate-rich portion Photo It can be seen that the white part in the middle flows down, especially at the center of the hemodialyzer.
  • A shows the state of the hemodialyzer immediately after barium sulfate was injected.
  • B is the hemodialyzer 6 seconds after barium sulfate was injected.
  • C is a hemodialyzer 12 seconds after barium sulfate was injected.
  • D is the hemodialyzer 18 seconds after injecting the barium sulfate.
  • E is a hemodialyzer 24 seconds after injecting barium sulfate. "Is a hemodialyzer 30 seconds after barium sulfate was injected.
  • FIG. 4 shows an example of an X-ray computed tomography image obtained in Example 3 to be described later.
  • a vertically long image in the center is a dialyzer.
  • Fig. 5 is a model diagram of the explanatory diagram obtained by tracing the X-ray computed tomographic image of Fig. 4 in order to explain Fig. 4 clearly.
  • a computer tomography apparatus irradiates an observation target with a beam of X-rays or electromagnetic waves, detects information obtained by interaction with the observation target, and obtains a slice cross section including a part to be observed by a computer.
  • This device reconstructs and renders images (tomographic images) for inspection, diagnosis, and observation. In addition to taking and observing tomographic images, it sometimes renders a 3D image based on that information.
  • a contrast agent is in the form of particles or incorporated into a part of a polymer.
  • a liquid circulation device is a typical example of a tubular body for guiding a liquid or a device for treating a liquid, for example, a reverse osmosis device, a filter, a dialyzer, an adsorption column, a heat exchanger, and the like.
  • a reverse osmosis device for example, a filter, a dialyzer, an adsorption column, a heat exchanger, and the like.
  • Any liquid may be used as the flowing liquid, and any of solvents, solutions, suspensions, slurries, and the like can be used.
  • the liquid flowing state in the present invention refers to a state in which the liquid flows unevenly in the liquid flowing device, or a state in which the liquid is concentrated or diluted.
  • the liquid flowing state refers to the density and viscosity of the liquid. Temperature, the flow rate, the flow rate, the nature of the liquid contact surface of the liquid flow device, such as the unevenness, and the structural design of the liquid flow section.
  • an X-ray computed tomography apparatus / magnetic resonance tomography apparatus used in computer tomography diagnosis is preferably used for the purpose of observing a state in which a liquid flows in each part.
  • an X-ray computed tomography apparatus refers to an X-ray fan beam rotated and applied to an object, and the presence state of an X-ray absorption component inside the object is calculated as a tomographic image from the transmitted X-ray intensity. It refers to an apparatus having a drawing mechanism.
  • a magnetic resonance tomography device is a device that places an object in a superconducting static magnetic field, applies a gradient magnetic field, radiates radio waves as pulses, and reduces the resonance of the protons in the object by magnetic resonance. Calculates the distribution of the relaxation time of water in an object by detecting the generated electromagnetic waves. At this time, by applying various pulse sequence modes, the flow rate of the liquid can be measured. In the present invention, the flow state is observed as it is, which is a so-called online observation method. However, the obtained image information can be recorded in an electronic medium or a computer tomography apparatus. But it can be done.
  • the flowing liquid Although the inspection method according to the present invention can be carried out by using the liquid itself, if the flowing state of the flowing liquid itself cannot be observed or it is difficult to observe the flow state due to the detection principle, etc.
  • a liquid obtained by mixing an auxiliary agent and a contrast agent (sometimes referred to as a sensitizer) into the flowing liquid may be used.
  • contrast agent when an X-ray computed tomography apparatus is used, an eodo-based contrast medium or barium sulfate or bubbles are preferably used.
  • a magnetic resonance tomography apparatus When a magnetic resonance tomography apparatus is used, a gadolinium-based complex, Iron oxide-based contrast agents or air bubbles are preferably used, and it is particularly important in the present invention to use a particulate contrast agent or a high-molecular-weight contrast agent having a molecular weight of 100,000 or more.
  • the particulate contrast agent refers to a substance that does not substantially dissolve in a flowing liquid, and a conventional contrast agent such as a conventional contrast agent or a chelating agent is, in terms of such a solubility, unlikely.
  • a conventional contrast agent such as a conventional contrast agent or a chelating agent is, in terms of such a solubility, unlikely.
  • the molecular weight is larger than the conventional one (molecular weight of less than 2,000), it cannot be said to be a particulate contrast agent.
  • Barium sulphate, iron oxide agents or air bubbles correspond to particulate contrast agents.
  • the particulate contrast agent does not necessarily have to be spherical, but often becomes almost spherical due to the formation of particles.
  • Such particulate contrast agents are characterized by their average diameter (average particle size). It is necessary to select the particle size of the particulate contrast agent according to the surface roughness of the observation target site and the liquid flow conditions.
  • a particle diameter of 20 nanometers or more is required in order to prevent the membrane from penetrating, but the inner diameter of the hollow fiber (lumen diameter) ) Is usually around 200 microns, so the particle size should be less than 50 microns.
  • the air bubbles need to be stable, and gas-filled microcapsules (also called microballoons, microspheres, etc.) are preferably used.
  • a high-molecular-weight contrast agent having a molecular weight of 100,000 or more is preferably a compound in which a low-molecular-weight substance that has an imaging effect on a synthetic polymer, protein, or the like is bound by a covalent bond, an ionic bond, or a hydrophobic bond. It has a molecular weight exceeding 100,000.
  • the molecular weight of the conventional contrast agent is often 2,000 or less, and a slight amount of the contrast agent bound to albumin is seen (see “Radiol ogy) ", 198, 813, 1996), none of which has a molecular weight exceeding 100,000.
  • a high-molecular-weight contrast agent having a molecular weight of 100,000 or more cannot pass through the membrane, it is desirable for observation of a hemodialyzer or a hemofilter, and similarly, when a plasma separation membrane is observed, a contrast agent having a molecular weight of more than 200,000 is used. desirable.
  • Barium sulfate, iron oxide agent, or air bubbles are in the form of particles, and are in a state that does not conform to the concept of molecular weight (aggregate state of atomic groups or gases).
  • the contrast agent can be dissolved or suspended in the flowing liquid.
  • the contrast agent can be dissolved or suspended in the flowing liquid.
  • bubbles and particles are dispersed as uniformly as possible, and that the movement of the contrast agent itself due to gravity in the liquid does not significantly affect the observation results. It is necessary to choose a condition that is within the range that can be done.
  • V the velocity of the particles moving through the liquid
  • D p is the diameter of the particles
  • jO p is the density of the particles
  • yO is the density of the liquid
  • g the gravitational acceleration
  • viscosity of the liquid is .
  • V is positive, it means the sedimentation velocity; if it is negative, it means the ascent velocity.
  • the stationary sedimentation velocity or floating velocity in the liquid defined in this way is not more than the average linear velocity of the flowing liquid at the observation target site for the purpose of observing the liquid flow state with a contrast agent as little as possible. More preferably, the average linear velocity of the flowing liquid at the observation target site is 110 or less. The average linear velocity is calculated by dividing the liquid flow rate at the site to be observed by the cross-sectional area in the direction perpendicular to the flow at that site.
  • the speed is equal to or less than the ratio of the spatial resolution imaging time, and when it is necessary to maintain the resolution, the speed is preferably 110 or less of the ratio of the spatial resolution to the imaging time.
  • the contrast agent aggregates, adheres to and adheres to the liquid contact surface of the liquid flow device, and the characteristics of the flow liquid change significantly due to the addition of the contrast agent. It is important to examine these as well.
  • Particulate The average particle size of the contrast agent is from 300 nm or more to 10,000 nm or less from the viewpoints of semipermeable membrane permeability, sedimentation / floating speed of the contrast agent, cohesiveness, adhesiveness, etc. Those can be preferably used.
  • the blood extracorporeal circulation devices to be observed have direct functions such as plasma separators, blood perfusion adsorption tubes, plasma perfusion adsorption tubes, artificial lungs, hemodialyzers, blood filters, and heat exchangers for blood. And a blood extracorporeal circulation drive control device.
  • the observation purpose may not be achieved because the contrast agent has permeated the membrane.
  • a so-called normal filtration phenomenon occurs, in which the water is filtered from the inside of the hollow fiber to the outside of the hollow fiber on the upstream side of the dialyzer, while the hollow fiber is downstream on the dialyzer.
  • the so-called back-filtration phenomena in which filtration is performed by the flow from the outside into the hollow fiber, occurs, and the subtracted amount is considered to be the net filtration amount.
  • the liquid flowing device incorporates a membrane having a dense layer and a coarse pore layer
  • trapping a contrast agent in the membrane may be significantly significant.
  • the contrast agent tries to flow at the same time as the liquid flows through the membrane. If the surface has coarse pores larger than the size of the contrast agent particles or molecules and part of the film has a dense layer with pores smaller than the size of the contrast agent particles or molecules, the surface of the film or in the film This is because the contrast agent is deposited on the surface, and the X-ray absorption value changes depending on the amount of the deposited agent.
  • Trapping the contrast agent in the film involves flowing a liquid containing a contrast agent having a large diameter in the dense layer and a small hole in the coarse pore layer in a liquid circulation device having the film, and maintaining the flow state. This can be achieved by allowing a liquid not containing a contrast agent to flow as it is.
  • the liquid flowing device is a hemodialyzer having a hollow fiber membrane
  • a means for trapping a contrast agent in the hollow fiber membrane is preferably used.
  • Trapping the contrast agent in the hollow fiber membrane can be performed by using a blood dialyser having a hollow fiber membrane, a blood containing a contrast agent having a large pore size in a dense layer of the membrane and a small pore size in a coarse pore layer, or This can be achieved by distributing the dialysate and distributing the blood containing no contrast agent or the dialysate while maintaining the distribution state.
  • the non-destructive inspection means that inspection and observation are performed while the liquid circulation device is used, and that the structure of the liquid circulation device is not changed for observation. .
  • the fluid circulation device is not compatible with the observation means based on the method of the present invention, for example, if the flow path is made of metal and the observation is to be performed with an X-ray computer tomography apparatus, the observation apparatus is suitable for the observation means. Observation may be performed using a liquid distribution device model made of the material to be used.
  • the perfusion conditions of the hemodialyzer are as follows.
  • the average blood linear velocity in the hollow fiber is 9 mmZ seconds.
  • the observation conditions were a spatial resolution of 0.35 mm and an imaging time of 2 seconds, and the ratio of the spatial resolution and imaging time was 0.175 mmZ seconds.
  • Example 2 Analysis of blood flow in hemodialyzer by pulse injection of contrast agent (Example 2): 5% by weight of barium sulfate particles (particle size: average particle size 800 nm, range 100- Hemodialysis machine (Toray Co., Ltd., “Tresulfone”) is fed with bovine blood (hematocrit value: 30%, total protein concentration: 6.5 g / dL) to which 200 nanometers are added. About 3 ml of bovine blood spiked with barium sulfate at a high concentration (about 20% by weight) was injected into the blood circuit on the blood inlet side of (registered trademark BS-1.6 UL) in about 1 second. Scanning starts at the same timing, and X-ray computer slice images (GE Yokogawa Medical Co., Ltd., HiSpeed DX / i) are cycled for about 2 seconds.
  • X-ray computer slice images GE Yokogawa Medical Co., Ltd., HiSpeed DX / i
  • X-ray absorption values were measured by obtaining longitudinal and transverse cross-sectional images under the above two conditions. The obtained images were analyzed on a personal computer using View II software.
  • a total protein concentration of 6.5 g / d L) was flowed through the dialysate flow path at a flow rate (Qd) of 500 mI Zmin, and a saline solution was flowed for 20 minutes, followed by bovine blood flow through the blood flow path
  • the flow rate (Q d) into the dialysate flow path is 500 mI / min, and 2% by volume of barium sulfate particles (particle diameter: average particle diameter 800 nanometers, range 100 to 200 nanometers)
  • a physiological saline solution to which was added was flowed for 5 minutes, and barium sulfate particles (particle diameter: average particle diameter 800 nm, range 100 to 2000 nm) were
  • Figure 4 shows the X-ray computed tomography image.
  • the vertical image in the center is the dialyzer.
  • Fig. 5 is a model drawing of the explanatory diagram obtained by tracing the X-ray computer tomographic image of Fig. 4 in order to explain Fig. 4 clearly.
  • FIG. 5 illustrates the outline by tracing the X-ray computed tomographic image of Fig. 4, and in Fig. 4, the X-ray CT field has a black circular shape. It is.
  • the hemodialyzer at the center in FIGS. 4 and 5 has a blood inlet on the upper side and a blood outlet on the lower side as shown in FIG.
  • a dialysate outlet force blur is located near the blood inlet, and a dialysate inlet coupler is located near the blood outlet. Blood flows in the hemodialyzer from the top to the bottom as shown by the arrow, and the dialysate flows in the direction opposite to the blood flow direction, also as shown by the arrow. is there.
  • the liquid flowing state in the liquid flowing device of the present invention can be inspected and observed without breaking the device at all.
  • the apparatus can be used very suitably and efficiently when grasping problems concerning the flow passages of the apparatus and examining improvement designs and design changes related thereto.

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Abstract

A method for nondestructively inspecting the state of the flow of a liquid in a device which the liquid flows through, by means of a tomograph, characterized in that use is made of a particulate contrast medium or a high molecular weight contrast medium having a molecular weight of 100,000 or more.

Description

明 細 書 液体流通装置内の液体流動状態の非破壊検査方法 技術分野  Description Non-destructive inspection method of liquid flow state in liquid flow device
本発明は、 液体流通装置内の液体流動状態を非破壊的に検査する方法に関する ものである。  The present invention relates to a method for non-destructively inspecting a liquid flowing state in a liquid flowing device.
背景技術 Background art
これまで液体流通装置、 例えば、 液体処理装置の部分要素としての配管や、 あ るいは液体処理装置としての逆浸透装置、 濾過器、 透析器、 吸着筒もしくは熱交 換器などの機能を評価したり設計するに当たっては、 過去の経験、 理論的扱いあ るいは装置全体としての機能評価で対処することが多かった。  Up to now, we have evaluated the functions of liquid distribution equipment, for example, piping as a partial element of liquid treatment equipment, or reverse osmosis equipment, filter, dialyzer, adsorption column or heat exchanger as liquid treatment equipment. In designing or designing, we often deal with past experience, theoretical treatment, or functional evaluation of the whole equipment.
しかしながら、 従来の液体流通装置の評価■設計方法では、 被処理液の粘度、 密度あるいは固形物と液体の混合状態などにより、 流動特性、 物質交換特性およ ぴ熱交換特性などの各種特性が非線形というべき性質を伴うことが多く、 実際の 装置の機能を充分に評価 '解析することがむずかしく、 そのため、 改善すべき部 分を特定できないことも多くあった。  However, in the conventional liquid distribution device evaluation / design method, various characteristics such as flow characteristics, mass exchange characteristics, and heat exchange characteristics are non-linear depending on the viscosity and density of the liquid to be treated or the mixing state of solids and liquid. In many cases, it was difficult to fully evaluate and analyze the functions of the actual equipment, and it was often impossible to identify the areas to be improved.
ところで、 近年、 医療機関においてはコンピュータ断層診断装置の進歩が著し <、 人体内の異常部位や病変部位を断層像として得ることが可能になっている。 本発明は、 そのようなコンピュータ断層診断技術を液体流通装置の評価や設計 などに応用しょうとするものであるが、 その場合、 対象とする液体流通装置の用 途ゃ特性に応じて、 いくつかの技術を併用し、 特定の条件で観察する必要も生じ るものである。  By the way, in recent years, advances in computer tomography diagnostic equipment have been remarkable in medical institutions, and it has become possible to obtain abnormal or diseased parts in the human body as tomographic images. The present invention intends to apply such a computed tomography diagnostic technique to the evaluation and design of a liquid flow device, and in that case, depending on the intended use characteristics of the target liquid flow device, there are several methods. It is also necessary to observe under specific conditions by using the techniques described above.
一方、 医療機関における画像診断技術としては、 生体への侵襲が少ないことが 必要条件であるが、 一般に、 液体流通装置を対象にする場合には、 そのような条 件は必要ではなく課されない。  On the other hand, as a diagnostic imaging technique in medical institutions, it is a necessary condition that there is little invasion to the living body. However, such a condition is generally not required and imposed when targeting a liquid distribution device.
よって、 たとえ、 既存の診断装置を用いる場合であっても、 特殊な条件や対象 で観察することが必要となり、 医療現場で用いられる条件とは全く異なる固有の 条件を採用することが重要になるものである。 ところで、 既に、 液体流通装置を対象に、 コンピュータ断層撮影装置による観 察は試みられてきており、 いくつかの報告もされてし'、る。 Therefore, even when using existing diagnostic equipment, it is necessary to observe under special conditions and targets, and it is important to adopt unique conditions that are completely different from those used in medical settings Things. By the way, observations with a computer tomography apparatus have already been attempted for liquid distribution devices, and some reports have been made.
例えば、 竹沢らは、 血液透析器の透析液側の流動状況をアジピオドン （分子量 1， 1 40) や硝酸鉛 （分子量 33 1 ) を造影剤として用いて、 X線コンビュ一 タ断層撮影装置で観察し（ 「トランスアクション ォブ ザ アメリカン ソサェ ティ一 フォア アーティフィシャル インタ一ナル オーガンズ （Trans. Am. S oc. Artif. Intern. Organs) 」 ，24:794, 1988·、 あるいは、 「血液透析スタッフのた めのハイパフォーマンスメンブレン」 ， pp.66 - 78, 1990、 東京医学社） 、 あるいは、 C. Roncoらは、 中空糸型血液透析器内での中空糸内側から外側への濾過 外側から 内側への濾過を放射化ラベルアルブミン （分子量約 7 0, 000) を指標として シンチグラフィ一で観察をし （ 「キドニ一 インタ一ナショナル （Kidney Inter national) J ,41, 1383, 1992、 同， 54， 979, 1998、 同， 58, 809, 2000) 、 あるいは、 ま た、 血液灌流吸着筒内での流れを造影剤 conray 60 (分子量 809) を用いてヘリ カルスキャン X線コンピュータ断層撮影装置で観察をしている （ 「ザ インター ナショナル ジャーナル ォブ アーティフイツシャル オーガンズ （Intern.丄 Artif. Organs) J , 24， 167, 2001) 。  For example, Takezawa et al. Observed the flow state of the dialysate side of a hemodialyzer with an X-ray computer tomograph using adipiodone (molecular weight 1, 140) and lead nitrate (molecular weight 331) as a contrast agent. (Trans. Am. Soc. Artif. Intern. Organs), 24: 794, 1988 ·, or “Transactions of the American Society” High Performance Membrane ”, pp.66-78, 1990, Tokyo Medical Co.) or C. Ronco et al., Filtration from inside to outside of hollow fiber in hollow fiber hemodialyzer Filtration from outside to inside Was observed by scintigraphy using activated label albumin (molecular weight of about 70,000) as an index (see “Kidney International J, 41, 1383, 1992, 54, 979, 1998”). , Same 58, 809, 2000) Alternatively, the flow in the blood perfusion adsorption tube is observed with a helical scan X-ray computed tomography apparatus using a contrast agent, conray 60 (molecular weight: 809). International Journal of Artif. Organs J, 24, 167, 2001).
発明の開示 Disclosure of the invention
しかし、 これらの報告例では、 濾過器や透析器などの半透膜を組み込んだ装置 を対象とした場合には造影剤の分子量が小さく、 半透膜を通り抜けてしまう可能 性があり、 また、 予め放射化ラベルした指標物質を作らねばならない、 等の問題 があり、 このようなことが、 検査目的や観察目的に、 より適合した簡便な検査や 観察を行なうことに対しての問題となっていた。  However, in these reports, when a device incorporating a semipermeable membrane, such as a filter or a dialyzer, is targeted, the molecular weight of the contrast agent is small and may pass through the semipermeable membrane. There is a problem such as the need to make an indicator material that has been previously activated and labeled.This is a problem for performing simple inspections and observations that are more suitable for the purpose of inspection and observation. Was.
本発明者らは、 これらの問題を克服するために鋭意検討し、 簡便に行ないうる 方法であって、 かつまた、 特に半透膜を対象とする場合には、 より検査目的 '観 察目的に適合させることができる方法を見い出したものである。  The present inventors have studied diligently to overcome these problems, and are a method that can be easily carried out.More particularly, when a semipermeable membrane is targeted, it is more suitable for inspection purposes and observation purposes. It has found a way that can be adapted.
すなわち、 本発明の第一の目的は、 上述したような点に鑑み、 簡便に行ないう る、 液体流通装置内の液体流動状態の非破壊検査方法を提供することにある。 また、 本発明の第二の目的は、 半透膜を被検査対象とする場合には、 検査目的 に、 より適合した非破壊検査方法を提供することにある。 本発明は、 上記課題を達成するため、 以下の （ 1 ) 〜 （1 4) の構成を有する。That is, a first object of the present invention is to provide a non-destructive inspection method of a liquid flowing state in a liquid flowing device, which is easily performed in view of the above points. Further, a second object of the present invention is to provide a nondestructive inspection method that is more suitable for an inspection purpose when a semipermeable membrane is to be inspected. The present invention has the following configurations (1) to (14) to achieve the above object.
( 1 ) コンピュータ断層撮影装置により液体流通装置内の液体流動状態を検査す る方法であって、 造影剤として、 粒子状造影剤または分子量 1 0万以上の高分子 量化造影剤を用いることを特徴とする液体流通装置内の液体流動状態の非破壊検 査方法。 (1) A method for examining the flow state of a liquid in a liquid flow device using a computer tomography apparatus, wherein a particulate contrast agent or a high-molecular-weight contrast agent having a molecular weight of 100,000 or more is used as a contrast agent. Non-destructive inspection method of liquid flow state in liquid flow device.
(2) 前記粒子状造影剤または前記分子量 1 0万以上の高分子量化造影剤が、 液 体流通装置内を流動する液体に含まれることを特徴とする上記（1 )に記載の液体 流通装置内の液体流動状態の非破壊検査方法。  (2) The liquid distribution device according to (1), wherein the particulate contrast agent or the high-molecular-weight contrast agent having a molecular weight of 100,000 or more is contained in the liquid flowing in the liquid distribution device. Method for non-destructive inspection of the fluid flow state in the interior.
(3) 該コンピュータ断層撮影装置が、 X線コンピュータ断層撮影装置であるこ .とを特徴とする上記 （ 1 ) または （2) に記載の液体流通装置内の液体流動状態 の非破壊検査方法。  (3) The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to the above (1) or (2), wherein the computed tomography apparatus is an X-ray computed tomography apparatus.
(4) 該コンピュータ断層撮影装置が、 磁気共鳴断層撮影装置であることを特徴 とする上記 （ 1 ) または （2) に記載の液体流通装置内の液体流動状態の非破壊 検査方法。  (4) The nondestructive inspection method for a liquid flowing state in a liquid flowing device according to (1) or (2), wherein the computed tomography apparatus is a magnetic resonance tomography apparatus.
(5) 前記粒子状造影剤が、 気泡であることを特徴とする上記 （ 1 ) ~ (4) の いずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  (5) The nondestructive inspection method for a liquid flowing state in a liquid flowing device according to any one of the above (1) to (4), wherein the particulate contrast agent is a bubble.
(6) 前記粒子状造影剤が、 硫酸バリウム粒子であることを特徴とする上記 (1 ) 〜 （4) のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査 方法。  (6) The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to any one of the above (1) to (4), wherein the particulate contrast agent is barium sulfate particles.
(7) 前記粒子状造影剤の平均粒子径が、 300ナノメータ一以上、 1万ナノメ —ター以下であることを特徴とする上記 （5) または （6) に記載の液体流通装 置内の液体流動状態の非破壊検査方法。  (7) The liquid in the liquid distribution device according to the above (5) or (6), wherein the average particle diameter of the particulate contrast agent is not less than 300 nanometers and not more than 10,000 nanometers. Non-destructive inspection method of fluid state.
(8) 前記粒子状造影剤の液体中の沈降速度または浮上速度が、 該液体の被観察 部位における平均線速度以下であることを特徴とする上記 （5) 〜 （7) のいず れかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  (8) The method according to any one of (5) to (7) above, wherein the sedimentation speed or the floating speed of the particulate contrast agent in the liquid is equal to or lower than the average linear velocity of the liquid at the observation site. The non-destructive inspection method of a liquid flowing state in the liquid flowing device according to claim 1.
(9) 前記粒子状造影剤の該液体中の沈降速度または浮上速度が、 コンピュータ 断層撮影装置の観察条件である空間分解能 撮像時間の比以下であることを特徴 とする上記 （5) 〜 （8) のいずれかに記載の液体流通装置内の液体流動状態の 非破壊検査方法。 (10) 前記粒子状造影剤の液体中の沈降速度または浮上速度が、 該液体の被観察 部位における平均線速度以下であり、 かつコンピュータ断層撮影装置の観察条件 である空間分解能 撮像時間の比以下であることを特徴とする上記 （5) 〜 (9) のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。 (9) The above-mentioned (5) to (8), wherein the sedimentation speed or the floating speed of the particulate contrast agent in the liquid is equal to or less than a ratio of a spatial resolution imaging time which is an observation condition of a computer tomography apparatus. The non-destructive inspection method of a liquid flowing state in the liquid flowing device according to any one of the above. (10) The sedimentation speed or the floating speed of the particulate contrast agent in the liquid is equal to or less than the average linear velocity of the liquid at the observation site, and is equal to or less than the ratio of the spatial resolution and the imaging time, which is the observation condition of the computed tomography apparatus. The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to any one of the above (5) to (9), characterized in that:
(11) 該液体流通装置が血液体外循環用装置であることを特徴とする上記 （1 ) 〜 （10) のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  (11) The nondestructive inspection method for a liquid flowing state in a liquid circulation device according to any one of (1) to (10), wherein the liquid circulation device is a device for extracorporeal blood circulation.
(12) 該液体流通装置が血液透析器であることを特徴とする上記 （ 1 ) 〜 （10) のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  (12) The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to any one of the above (1) to (10), wherein the liquid flowing device is a hemodialyzer.
(13) 該液体流通装置が膜を有するものであり、 該膜中に造影剤を卜ラップさせ ることを特徴とする上記 （1 ) ~ (10) のいずれかに記載の液体流通装置内の液 体流動状態の非破壊検査方法。  (13) The liquid circulation device according to any one of (1) to (10), wherein the liquid circulation device has a film, and a contrast agent is trapped in the film. Non-destructive inspection method for liquid flow state.
(14) 該液体流通装置が中空糸膜を有する血液透析器であり、 該中空糸膜中に造 影剤をトラップさせることを特徴とする上記 （ 1 ) 〜 （10) のいずれかに記載の 液体流通装置内の液体流動状態の非破壊検査方法。  (14) The method according to any one of the above (1) to (10), wherein the liquid circulation device is a hemodialyzer having a hollow fiber membrane, and a contrast agent is trapped in the hollow fiber membrane. Non-destructive inspection method of liquid flow state in liquid circulation device.
上述した本発明の液体流通装置内の液体流動状態の非破壊検査方法によれば、 該装置を何ら破壊することなしに、 該液体流通装置内の液体流動状態を検査する ことができ、 該装置の流通路に関する問題点の把握やそれに関する改善設計ゃ設 計変更などの検討を行うに際して極めて好適に使用できるものである。  According to the non-destructive inspection method of the liquid flowing state in the liquid flowing device of the present invention described above, the liquid flowing state in the liquid flowing device can be inspected without destroying the device at all. It can be used very suitably when grasping the problems related to the flow passages in the field and examining the improvement design / design change related to it.
図面の簡単な説明 BRIEF DESCRIPTION OF THE FIGURES
図 1は、 液体流通装置の一例としての、 血液透析器の長さ方向における、 該透 析液の非灌流条件下での血液透析器内の血液側 X線吸収値の分布を示す図面であ る。  FIG. 1 is a drawing showing the distribution of X-ray absorption values on the blood side in a hemodialyzer under non-perfusion conditions of the eluate in the length direction of the hemodialyzer as an example of a liquid flow device. You.
同図において、 血液は A面から V面方向に流れ、 血液流量 Q bを 20 Om L/ 分とした場合を示したものであり、 データ点は各部位の横断面 （流れに垂直な断 面） 像の中空糸束の約 80%を包含する視野内のポクセル単位 X線吸収値の平均 と標準偏差を示す。  In the figure, the blood flows from the A side to the V side, and the blood flow Qb is set to 20 Om L / min. The data points are the cross sections of each part (the cross section perpendicular to the flow). The average and standard deviation of the x-ray absorption values in the poxel unit within the field of view covering about 80% of the hollow fiber bundle in the image are shown.
図 2は、 同じく液体流通装置の一例としての、 血液透析器の長さ方向における, 透析液の灌流条件下での血液透析器内の血液側 X線吸収値の分布を示す図面であ る。 同図において、 血液は A面から V面方向に流れ、 血液流量 Q bを 2 0 0 m L Z 分とし、 透析液は反対方向に流れ、 透析液流量 5 0 O m L Z分とし、 濾過流量 Q f は O m L Z分とした場合を示したものであり、 データ点は各部位の横断面 （流 れに垂直な断面） 像の中空糸束の約 8 0 %を包含する視野内のポクセル単位 X線 吸収値の平均と標準偏差を示す。 FIG. 2 is a drawing showing the distribution of X-ray absorption values on the blood side in the hemodialyzer under the conditions of dialysate perfusion in the length direction of the hemodialyzer, which is also an example of the liquid flow device. In the figure, the blood flows from the A side to the V side, the blood flow Qb is set to 200 mLZ, the dialysate flows in the opposite direction, the dialysate flow is set to 50 OmLZ, and the filtration flow Q f indicates the case of O m LZ, and the data points are the poxel units within the field of view including about 80% of the hollow fiber bundle of the cross section (cross section perpendicular to the flow) image of each part. Shows the average and standard deviation of X-ray absorption values.
図 3は、 同じく液体流通装置の一例としての血液透析器に、 約 2 0 %の硫酸バ リウムを添加した牛血液を血液透析器にパルス的に注入し、 縦断面 （流れに平行 な断面） を、 X線コンピューター断層撮影装置で 2秒間隔で連続的に撮影した像 から 3枚目ごとに計 6回ピックアップした連続撮影写真であり、 時間の経過につ れて硫酸バリウムの濃い部分 （写真中の白い部分） が流れて行き、 特に血液透析 器の中心部で先行していることがわかる。  Fig. 3 shows a hemodialyzer, which is also an example of a liquid flow device, in which bovine blood to which about 20% of barium sulfate has been added is pulsed and injected into the hemodialyzer, and a longitudinal section (section parallel to the flow) is shown. A series of photographs taken three times every 3 seconds from images taken consecutively at 2-second intervals with an X-ray computed tomography apparatus. The barium sulfate-rich portion (Photo It can be seen that the white part in the middle flows down, especially at the center of the hemodialyzer.
同図 3において、 Aは、 硫酸バリウムを注入した直後の血液透析器の状態を例 示したものである。 Bは、 硫酸バリウムを注入した 6秒後の血液透析器である。  In FIG. 3, A shows the state of the hemodialyzer immediately after barium sulfate was injected. B is the hemodialyzer 6 seconds after barium sulfate was injected.
Cは、 硫酸バリウムを注入した 1 2秒後の血液透析器である。 Dは、 硫酸バリゥ ムを注入した 1 8秒後の血液透析器である。 Eは、 硫酸バリウムを注入した 2 4 秒後の血液透析器である。 「は、 硫酸バリウムを注入した 3 0秒後の血液透析器 である。 C is a hemodialyzer 12 seconds after barium sulfate was injected. D is the hemodialyzer 18 seconds after injecting the barium sulfate. E is a hemodialyzer 24 seconds after injecting barium sulfate. "Is a hemodialyzer 30 seconds after barium sulfate was injected.
図 4は、 後述する実施例 3で得られた X線コンピュータ断層撮影像の一例を示 したものであり、 中央にある縦長の像が透析器である。  FIG. 4 shows an example of an X-ray computed tomography image obtained in Example 3 to be described later. A vertically long image in the center is a dialyzer.
図 5は、 図 4をわかりやすく説明するために、 同図 4の X線コンピュータ断層 像をトレースして、 解説図をモデル的に示したものである。  Fig. 5 is a model diagram of the explanatory diagram obtained by tracing the X-ray computed tomographic image of Fig. 4 in order to explain Fig. 4 clearly.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
以下、 本発明にかかる液体流通装置内の液体流動状態の非破壊検査方法につい て説明をする。  Hereinafter, a non-destructive inspection method of a liquid flowing state in a liquid flowing device according to the present invention will be described.
本発明において、 コンピュータ断層撮影装置とは、 観察対象に X線や電磁波の ビームを照射し、 観察対象との相互作用により得られる情報を検出し、 コンビュ —タにより観察したい部位を含むスライス断面の画像 （断層像） を再構成■描出 し、 検査、 診断、 観察に供する装置である。 断層像の撮影や観察だけでなく、' そ の情報を基に立体像として描出することもある。 コンピュータ断層撮影装置により液体流通装置内の液体流動状態を検査するに は、 何らかの造影効果 （観察像にコントラストを付ける効果） を示す成分が、 液 体に含まれていることが必要である。 In the present invention, a computer tomography apparatus irradiates an observation target with a beam of X-rays or electromagnetic waves, detects information obtained by interaction with the observation target, and obtains a slice cross section including a part to be observed by a computer. This device reconstructs and renders images (tomographic images) for inspection, diagnosis, and observation. In addition to taking and observing tomographic images, it sometimes renders a 3D image based on that information. In order to inspect the liquid flow state in the liquid flow device using a computer tomography apparatus, it is necessary for the liquid to contain a component that exhibits some contrast effect (effect of giving a contrast to the observed image).
そのような造影効果を示す成分として、 造影剤が粒子状になっていたり、 高分 子の一部に取り込まれたものがある。  As a component exhibiting such a contrast effect, there are those in which a contrast agent is in the form of particles or incorporated into a part of a polymer.
本発明において液体流通装置とは、 液体を導くための管状体や液体を処理する ための装置、 例えば、 逆浸透装置、 濾過器、 透析器、 吸着筒、 熱交換器などが代 表的な例であるが、 これらに限るものではない。 流通液体としては液体状のもの であれば良く、 溶媒、 溶液、 懸濁液、 スラリーなどのいずれもが対象となる。 本発明における液体流動状態とは、 液体流通装置内で該液が偏りを持って流れ ていたり、 液体が濃縮，希釈されたりしている状態を指しており、 液体流動状態 は液体の密度、 粘度、 温度、 流通速度など、 および液体流通装置の液接触面の凹 凸などの性状や液体流通部の構造設計などにより異なってくる。  In the present invention, a liquid circulation device is a typical example of a tubular body for guiding a liquid or a device for treating a liquid, for example, a reverse osmosis device, a filter, a dialyzer, an adsorption column, a heat exchanger, and the like. However, it is not limited to these. Any liquid may be used as the flowing liquid, and any of solvents, solutions, suspensions, slurries, and the like can be used. The liquid flowing state in the present invention refers to a state in which the liquid flows unevenly in the liquid flowing device, or a state in which the liquid is concentrated or diluted. The liquid flowing state refers to the density and viscosity of the liquid. Temperature, the flow rate, the flow rate, the nature of the liquid contact surface of the liquid flow device, such as the unevenness, and the structural design of the liquid flow section.
検査■観察装置としては、 液体が流れている状態を各部位で見る目的から、 コ ンピュ一タ断層診断で用いられている X線コンピュータ断層撮影装置ゃ磁気共鳴 断層撮影装置が好ましく用いられる。  As an inspection / observation apparatus, an X-ray computed tomography apparatus / magnetic resonance tomography apparatus used in computer tomography diagnosis is preferably used for the purpose of observing a state in which a liquid flows in each part.
本発明において、 X線コンピュータ断層撮影装置とは、 対象物に X線扇形ビ一 ムを回転させて当て、 透過 X線強度から対象物内部の X線吸収成分の存在状態を 断層像として算出■描画する機構を有する装置をいうものである。  In the present invention, an X-ray computed tomography apparatus refers to an X-ray fan beam rotated and applied to an object, and the presence state of an X-ray absorption component inside the object is calculated as a tomographic image from the transmitted X-ray intensity. It refers to an apparatus having a drawing mechanism.
また、 磁気共鳴断層撮影装置とは、 対象物を超伝導静磁場内に置き、 さらに傾 斜磁場を付加し、 ラジオ波をパルスとして照射し、 対象物内のプロ トンの磁気共 鳴緩和現象により生じる電磁波を検出することにより、 対象物内の水の緩和時間 の分布を算出 '描画する装置をいうものである。 このときに、 各種のパルスシ一 ケンスモードを適用することによリ、 液体の流通速度を測定することもできる。 本発明では、 流動状態をそのまま観察するので、 いわばオンライン観察という べき観察方法であるが、 得られた画像情報は電子媒体あるいはコンピュータ断層 撮影装置内に記録することができるので、 解析自体は後からでも行ない得るもの である。  A magnetic resonance tomography device is a device that places an object in a superconducting static magnetic field, applies a gradient magnetic field, radiates radio waves as pulses, and reduces the resonance of the protons in the object by magnetic resonance. Calculates the distribution of the relaxation time of water in an object by detecting the generated electromagnetic waves. At this time, by applying various pulse sequence modes, the flow rate of the liquid can be measured. In the present invention, the flow state is observed as it is, which is a so-called online observation method. However, the obtained image information can be recorded in an electronic medium or a computer tomography apparatus. But it can be done.
流通液体の特性と検査■観察装置の検出原理との組合せによっては、 流通液体 そのものを用いることで本発明にかかる検査方法を実施することもできるが、 も し、 流通液体そのものでは検出原理から流動状態を観察できないか、 もしくは観 察がしにくいという場合などにおいては、 検出のための助剤、 造影剤 （増感剤と いうこともある） を流通液体に混入した液を用いることもできる。 Depending on the combination of the characteristics of the flowing liquid and the detection principle of the inspection / observation device, the flowing liquid Although the inspection method according to the present invention can be carried out by using the liquid itself, if the flowing state of the flowing liquid itself cannot be observed or it is difficult to observe the flow state due to the detection principle, etc. A liquid obtained by mixing an auxiliary agent and a contrast agent (sometimes referred to as a sensitizer) into the flowing liquid may be used.
造影剤としては、 X線コンピュータ断層撮影装置を使用する場合には、 ョード 系造影剤、 あるいは硫酸バリウムや気泡などが好ましく用いられ、 磁気共鳴断層 撮影装置を使用する場合には、 ガドリニウム系錯体、 酸化鉄系造影剤、 あるいは 気泡などが好ましく用いられ、 特に、 粒子状造影剤または分子量 1 0万以上の高 分子量化造影剤を用いることが本発明において重要な点である。  As the contrast agent, when an X-ray computed tomography apparatus is used, an eodo-based contrast medium or barium sulfate or bubbles are preferably used.When a magnetic resonance tomography apparatus is used, a gadolinium-based complex, Iron oxide-based contrast agents or air bubbles are preferably used, and it is particularly important in the present invention to use a particulate contrast agent or a high-molecular-weight contrast agent having a molecular weight of 100,000 or more.
本発明において、 粒子状造影剤とは、 流通液体中で実質的に溶解しないものを いい、 従来のョ一ド系造影剤ゃキレート剤などは、 このような溶解性の点では、た とえ、 その分子量が従来 （分子量 2, 000以下） よりも大きいものが作られたとして も粒子状の造影剤とは言えないものである。  In the present invention, the particulate contrast agent refers to a substance that does not substantially dissolve in a flowing liquid, and a conventional contrast agent such as a conventional contrast agent or a chelating agent is, in terms of such a solubility, unlikely. However, even if the molecular weight is larger than the conventional one (molecular weight of less than 2,000), it cannot be said to be a particulate contrast agent.
硫酸バリウムや酸化鉄剤あるいは気泡は、 粒子状造影剤に該当する。 ここで、 粒子状造影剤は、 必ずしも球状である必要はないが、 粒子化によりほぼ球状にな ることが多い。 このような粒子状造影剤は、 その直径の平均値 （平均粒径） によ つて特徴付けられる。 観察対象部位の表面粗度や液体流通条件に応じた粒子状造 影剤の粒子径の選択が必要となる。  Barium sulphate, iron oxide agents or air bubbles correspond to particulate contrast agents. Here, the particulate contrast agent does not necessarily have to be spherical, but often becomes almost spherical due to the formation of particles. Such particulate contrast agents are characterized by their average diameter (average particle size). It is necessary to select the particle size of the particulate contrast agent according to the surface roughness of the observation target site and the liquid flow conditions.
例えば、 中空糸型血液透析器や中空糸型濾過器を対象とした場合には、 膜を透 過しないために、 粒子径 2 0ナノメータ以上が必要であるが、 中空糸の内径 （内 腔直径） は、 通常は 2 0 0ミクロン前後であるので、 5 0ミクロン以下の粒子サ ィズとすべきである。 粒子状造影剤として気泡を用いる場合には、 気泡が安定し ている必要があり、 ガス封入マイクロカプセリレ (マイクロバルーン、 マイクロス フィァなどともいう） などが好ましく用いられる。  For example, in the case of a hollow fiber hemodialyzer or a hollow fiber filter, a particle diameter of 20 nanometers or more is required in order to prevent the membrane from penetrating, but the inner diameter of the hollow fiber (lumen diameter) ) Is usually around 200 microns, so the particle size should be less than 50 microns. When air bubbles are used as the particulate contrast agent, the air bubbles need to be stable, and gas-filled microcapsules (also called microballoons, microspheres, etc.) are preferably used.
また、 分子量 1 0万以上の高分子量化造影剤とは、 合成高分子、 蛋白などに造 影効果をます低分子量物質を共有結合、 イオン結合、 疎水結合などで結合したも のが好ましく用いられ、 その分子量が 1 0万を越えるものをいう。  In addition, a high-molecular-weight contrast agent having a molecular weight of 100,000 or more is preferably a compound in which a low-molecular-weight substance that has an imaging effect on a synthetic polymer, protein, or the like is bound by a covalent bond, an ionic bond, or a hydrophobic bond. It has a molecular weight exceeding 100,000.
ここで、 従来使用されている造影剤の分子量は 2， 000以下のものが多く、 わずか にアルブミンに造影剤が結合されたものが見られるが （ 「ラジオロジー （Rad i o l ogy) 」 ， 198, 813, 1996) 、 分子量 1 0万を越えるものはみられない。 Here, the molecular weight of the conventional contrast agent is often 2,000 or less, and a slight amount of the contrast agent bound to albumin is seen (see “Radiol ogy) ", 198, 813, 1996), none of which has a molecular weight exceeding 100,000.
分子量 1 0万以上の高分子量化造影剤は、 膜を通過できないので、 血液透析器 や血液濾過器の観察において望ましく、 同様に、 血漿分離膜の観察では分子量 2 0 0万を越える造影剤が望ましい。 硫酸バリウムや酸化鉄剤あるいは気泡は粒子 状であり、 分子量という概念にはそぐわない状態 （原子団あるいはガスの集合状 態） にある。  Since a high-molecular-weight contrast agent having a molecular weight of 100,000 or more cannot pass through the membrane, it is desirable for observation of a hemodialyzer or a hemofilter, and similarly, when a plasma separation membrane is observed, a contrast agent having a molecular weight of more than 200,000 is used. desirable. Barium sulfate, iron oxide agent, or air bubbles are in the form of particles, and are in a state that does not conform to the concept of molecular weight (aggregate state of atomic groups or gases).
観察に当たっては、 流通液体の特性、 観察目的、 観察部位などにより、 適切な 造影剤を選択する必要がある。  In the observation, it is necessary to select an appropriate contrast agent depending on the characteristics of the flowing liquid, the purpose of the observation, the observation site, and the like.
まず、 造影剤が流通液体に溶解または懸濁できるものが好ましい。 気泡、 硫酸 バリウム粒子、 あるいは酸化鉄粒子などを造影剤として併用する場合には、 その 粒径を選択することが肝要である。  First, it is preferable that the contrast agent can be dissolved or suspended in the flowing liquid. When using air bubbles, barium sulfate particles, or iron oxide particles as a contrast agent, it is important to select the particle size.
すなわち、 極力、 均一に気泡や粒子が分散していて、 更に造影剤自身の該液体 中での重力による移動が観察結果に大きな影響を及ぼさないことが望ましいので、 観察中に沈降や浮上が無視できる範囲内にある条件を選ぶ必要がある。  In other words, it is desirable that bubbles and particles are dispersed as uniformly as possible, and that the movement of the contrast agent itself due to gravity in the liquid does not significantly affect the observation results. It is necessary to choose a condition that is within the range that can be done.
すなわち、 該液体中の定常的な沈降速度あるいは浮上速度を、 特に特定の範囲 に定める必要がある。 定常的な沈降速度あるいは浮上速度は、 ストークス域での 式 V = D ( p - ) g / 1 8 i ( 「微粒子工学大系第一巻基本技術」 、 p . 2 0 6、 柳田博明監修、 2 0 0 1年） により算出される。 ここに、 Vは粒子の液 体中の移動速度、 D pは粒子の直径、 jO p は粒子の密度、 yOは液体の密度、 gは 重力加速度、 ま液体の粘度である。 . That is, it is necessary to set the steady sedimentation speed or the ascent speed in the liquid in a specific range. Steady sedimentation or ascent rate is calculated by the formula V = D (p-) g / 18i in the Stokes region ("Particle Engineering Large Volume 1 Basic Technology", p. 206, supervised by Yanagida Hiroaki, 2 001). Where V is the velocity of the particles moving through the liquid, D p is the diameter of the particles, jO p is the density of the particles, yO is the density of the liquid, g is the gravitational acceleration, and the viscosity of the liquid. .
Vが正の場合には沈降速度を意味し、 負の場合には浮上速度を意味する。 この ように定義される該液体中の定常的な沈降速度あるいは浮上速度は、 液体流動状 態を造影剤により極力乱さずに観察する目的から、 観察対象部位における流通液 の平均線速度以下であることが好ましく、 さらには、 観察対象部位における流通 液の平均線速度の 1 1 0以下であることがより好ましい。 平均線速度は、 観察 しょうとする部位での液流量を、 その部位での流れに対して垂直方向での断面積 で除することで算出されるものである。  If V is positive, it means the sedimentation velocity; if it is negative, it means the ascent velocity. The stationary sedimentation velocity or floating velocity in the liquid defined in this way is not more than the average linear velocity of the flowing liquid at the observation target site for the purpose of observing the liquid flow state with a contrast agent as little as possible. More preferably, the average linear velocity of the flowing liquid at the observation target site is 110 or less. The average linear velocity is calculated by dividing the liquid flow rate at the site to be observed by the cross-sectional area in the direction perpendicular to the flow at that site.
また、 該液体中の定常的な沈降速度あるいは浮上速度は、 分解能をある程度犠 性にしても観察目的にかなう場合は、 コンピュータ断層撮影装置の観察条件であ る、 空間分解能 撮像時間の比以下であることが好ましく、 分解能を維持する必 要がある場合には、 空間分解能ノ撮像時間の比の 1 1 0以下の速度であること が好ましい。 In addition, if the steady sedimentation velocity or the ascent velocity in the liquid is sufficient for the observation purpose even if the resolution is sacrificed to some extent, it is the observation condition of the computer tomography apparatus. Preferably, the speed is equal to or less than the ratio of the spatial resolution imaging time, and when it is necessary to maintain the resolution, the speed is preferably 110 or less of the ratio of the spatial resolution to the imaging time.
この他に、 造影剤が凝集したり、 液体流通装置の液体接触面に吸着■粘着した リ、 造影剤添加により流通液の特性が大幅に変わる、 なども目的に反するので、 造影剤の選択においては、 これらについても吟味することが重要である。 粒子状 造影剤の平均粒子径は、 半透膜の透過性、 造影剤の沈降 ·浮上速度や凝集性、 粘 着性などの観点から、 粒子径は 3 0 0ナノメータ以上、 1万ナノメータ以下のも のが好ましく用いられ得る。  In addition to this, the contrast agent aggregates, adheres to and adheres to the liquid contact surface of the liquid flow device, and the characteristics of the flow liquid change significantly due to the addition of the contrast agent. It is important to examine these as well. Particulate The average particle size of the contrast agent is from 300 nm or more to 10,000 nm or less from the viewpoints of semipermeable membrane permeability, sedimentation / floating speed of the contrast agent, cohesiveness, adhesiveness, etc. Those can be preferably used.
観察対象となる血液体外循環用装置には、 血漿分離器、 血液灌流吸着筒、 血漿 灌流吸着筒、 人工肺、 血液透析器、 血液濾過器、 血液用熱交換器などの直接的に 機能を発揮する装置、 及び血液体外循環駆動制御装置などが含まれる。  The blood extracorporeal circulation devices to be observed have direct functions such as plasma separators, blood perfusion adsorption tubes, plasma perfusion adsorption tubes, artificial lungs, hemodialyzers, blood filters, and heat exchangers for blood. And a blood extracorporeal circulation drive control device.
中空糸型透析器を対象とする場合には、 造影剤が膜を透過したのでは観察目的 が達成されない場合がある。  In the case of a hollow fiber dialyzer, the observation purpose may not be achieved because the contrast agent has permeated the membrane.
中空糸型血液透析器では、 透析器内での上流側では中空糸内から中空糸外への 流れで濾過する、 いわゆる正濾過現象が生じ、 一方、 透析器内での下流側では中 空糸外から中空糸内への流れで濾過する、 いわゆる逆濾過現象が生じ、 その差し 引き量が、 正味の濾過量であるとされている （ 「血液透析スタッフのための新し いハイパフォーマンスダイライザ一」 、 p p . 2 3 0— 2 4 6、 東京医学社、 1 9 9 8 ) o  In a hollow-fiber hemodialyzer, a so-called normal filtration phenomenon occurs, in which the water is filtered from the inside of the hollow fiber to the outside of the hollow fiber on the upstream side of the dialyzer, while the hollow fiber is downstream on the dialyzer. The so-called back-filtration phenomena, in which filtration is performed by the flow from the outside into the hollow fiber, occurs, and the subtracted amount is considered to be the net filtration amount. Pp. 23 0—2 46, Tokyo Medical, 1998) o
この場合に、 透析器内の血液濃縮ノ希釈状態を観察し、 透析効率や圧力損失等 について、 最適な設計とする必要があるが、 造影剤が膜を透過したのでは目的は 達成されない。 よって、 この場合には粒子状造影剤、 高分子量化造影剤、 あるい は気泡を選ぶ必要がある。 また、 透析液側の流れを観察し、 透析効率を極大化す る設計を目的とする場合にも同様である。  In this case, it is necessary to observe the state of dilution of the blood concentration in the dialyzer and optimize the dialysis efficiency and pressure loss, etc., but the objective cannot be achieved if the contrast agent has permeated the membrane. Therefore, in this case, it is necessary to select a particulate contrast agent, a high molecular weight contrast agent, or bubbles. The same applies to the case of observing the flow on the dialysate side and designing to maximize dialysis efficiency.
本発明において、 液体流通装置が緻密層ノ粗大孔層を有する膜を組み込まれた ものである場合には、 該膜中に造影剤をトラップさせることに著しく意義がある 場合がある。  In the present invention, when the liquid flowing device incorporates a membrane having a dense layer and a coarse pore layer, trapping a contrast agent in the membrane may be significantly significant.
すなわち、 膜を液体が流通するとき同時に造影剤も流通しょうとするが、 膜表 面に造影剤の粒子または分子の大きさより大きい粗大孔があり、 かつ、 膜の一部 に造影剤の粒子または分子の大きさより小さい孔を持つ緻密層がある場合に、 膜 の表面あるいは膜中に造影剤が沈積し、 その沈積量によって、 X線吸収値が変化 するからである。 In other words, the contrast agent tries to flow at the same time as the liquid flows through the membrane. If the surface has coarse pores larger than the size of the contrast agent particles or molecules and part of the film has a dense layer with pores smaller than the size of the contrast agent particles or molecules, the surface of the film or in the film This is because the contrast agent is deposited on the surface, and the X-ray absorption value changes depending on the amount of the deposited agent.
該膜中に造影剤をトラップさせることは、 膜を有する液体流通装置内に緻密層 の孔径ょリ大きく粗大孔層の孔ょリ小さい造影剤を含む液体を流通させ、 その流 通状態を保持したまま造影剤を含まない液体を流通させることにより達成できる。 また、 液体流通装置が中空糸膜を有する血液透析器である場合には該中空糸膜 中に造影剤を卜ラップさせる手段が好適に用いられる。  Trapping the contrast agent in the film involves flowing a liquid containing a contrast agent having a large diameter in the dense layer and a small hole in the coarse pore layer in a liquid circulation device having the film, and maintaining the flow state. This can be achieved by allowing a liquid not containing a contrast agent to flow as it is. When the liquid flowing device is a hemodialyzer having a hollow fiber membrane, a means for trapping a contrast agent in the hollow fiber membrane is preferably used.
その理由は、 中空糸膜を血液、 あるいは、 透析液が流通するとき同時に造影剤 も流通しょうとするが、 緻密層 粗大孔層を有する中空糸膜が多く、 中空糸膜の 表面あるいは中空糸膜中に造影剤が沈積し、 その沈積量によって X線吸収値が変 化するからである。  The reason is that when a blood or dialysate flows through the hollow fiber membrane, a contrast agent will also flow simultaneously.However, many hollow fiber membranes have a dense layer and a coarse pore layer, and the surface of the hollow fiber membrane or the hollow fiber membrane This is because the contrast agent is deposited inside, and the X-ray absorption value changes depending on the amount of deposition.
該中空糸膜中に造影剤をトラップさせることは、 中空糸膜を有する血液透析器 内に膜の緻密層の孔径ょリ大きく粗大孔層の孔ょり小さい造影剤を含む血液、 あ るいは、 透析液を流通させ、 その流通状態を保持したまま造影剤を含まない血液、 あるいは、 透析液を流通させることによリ達成できる。  Trapping the contrast agent in the hollow fiber membrane can be performed by using a blood dialyser having a hollow fiber membrane, a blood containing a contrast agent having a large pore size in a dense layer of the membrane and a small pore size in a coarse pore layer, or This can be achieved by distributing the dialysate and distributing the blood containing no contrast agent or the dialysate while maintaining the distribution state.
本発明において、 非破壊検査とは、 液体流通装置が使用される状態のままで検 査■観察するということであり、 観察のために液体流通装置の構造を変えること はしない、 ということである。  In the present invention, the non-destructive inspection means that inspection and observation are performed while the liquid circulation device is used, and that the structure of the liquid circulation device is not changed for observation. .
なお、 流体流通装置が、 本発明方法に基づく観察手段になじまない場合、 例え ば、 流路が金属製で X線コンピュ一タ断層撮影装置で観察しょうとする場合など には、 観察手段に適合する材質で作成した液体流通装置モデルを用いて観察を行 なえばよい。  If the fluid circulation device is not compatible with the observation means based on the method of the present invention, for example, if the flow path is made of metal and the observation is to be performed with an X-ray computer tomography apparatus, the observation apparatus is suitable for the observation means. Observation may be performed using a liquid distribution device model made of the material to be used.
実施例 Example
次に、 実施例に基づき本発明を説明するが、 本発明は、 これらの例によって限 定されるものではない。  Next, the present invention will be described based on examples, but the present invention is not limited to these examples.
なお、 ここで用いた検査方法と条件は、 以下の通りである。  The inspection method and conditions used here are as follows.
( 1 ) 血液透析器内牛血液の濾過ノ逆濾過現象の観察■解析 （実施例 1 ) ： 臨床用の X線コンピュータ断層撮影装置 （G E横河メディカル （株） 、 HiSpee d DX/i) を用い、 5重量 容量％ の硫酸バリウム粒子 （粒径：平均粒径 8 0 0 ナノメータ、 範囲 1 0 0〜 2 0 0 0ナノメータ） を添加した牛血液 （へマトクリ ッ ト値： 3 0%、 総蛋白濃度： 6. 5 g/ d L) を流し、 定常状態にある血液透 析器 （東レ （株） 製" トレスルホン" （登録商標） B S— 1 . 6 U L) を観察し、 血液透析器内の牛血液の濾過 逆濾過現象の観察■解析を行なった。 (1) Observation and analysis of back-filtration phenomenon of bovine blood in hemodialyzer (Example 1): Using a clinical X-ray computed tomography apparatus (GE Yokogawa Medical Corp., HiSpee d DX / i), 5% by volume barium sulfate particles (particle size: average particle size 800 nm, range 10 0 to 2000 nanometers of bovine blood (hematocrit: 30%, total protein concentration: 6.5 g / dL) is allowed to flow, and a steady state blood analyzer (Toray ( Co., Ltd. "Tresulfone" (registered trademark) BS-1.6 UL) was observed, and the observation and analysis of the back filtration phenomenon of bovine blood in a hemodialyzer were performed.
血液透析器の灌流条件は、 以下のとおりである。  The perfusion conditions of the hemodialyzer are as follows.
( a ) 透析液の非灌流条件：  (a) Non-perfusion conditions of dialysate:
血液流量 （Q b ) = 20 Om I /m i n、 透析液流量 （Q d ) = 0  Blood flow (Q b) = 20 Om I / min, dialysate flow (Q d) = 0
( b ) 透析液灌流条件：血液流量 （Q b) = 2 0 Om I /m i n、 透析液流量 (Q d ) = 5 0 0 m l Zm i n、 濾過流量 (Q f ) = 0 m I Zm i n  (b) Dialysate perfusion conditions: blood flow (Q b) = 20 Om I / min, dialysate flow (Q d) = 500 ml Zmin, filtration flow (Qf) = 0 m I Zmin
このときの硫酸バリウムの沈降速度はスト一クス域での式 v = D P 2 (p P ) gZ I 8 に、 硫酸バリウム粒子密度 4. 5 g/ c m3 (理化学辞典 第 5 版： 1 9 9 8年、 p. 1 46 3) 、 血液密度 1 . 0 5 gZ c m3 、 J¾液粘度 0. 0 0 3 7 P a ' s、 硫酸バリウム粒子平均直径 8 0 0ナノメータを代入し、 3. 2 X 1 0一4 mmZ秒と算出される。 The sedimentation velocity of barium sulfate at this time is calculated by the equation v = D P 2 (p P) gZ I 8 in the stoichiometric region, and the barium sulfate particle density 4.5 g / cm 3 (physical and chemical dictionary 5th edition: 1 9 1998, p. 146 3), blood density 1.05 gZ cm 3 , viscosity of liquid J 0.03 0 7 Pas, average diameter of barium sulfate particles 800 nm, substituting 3. It is calculated as 2 X 1 0 one 4 mmZ seconds.
—方、 中空糸内の平均血液線速度は 9 mmZ秒である。 また観察条件は、 空間 分解能 0. 3 5 mm、 撮像時間 2秒であり、 空間分解能 撮像時間の比は 0. 1 7 5 mmZ秒であった。  — On the other hand, the average blood linear velocity in the hollow fiber is 9 mmZ seconds. The observation conditions were a spatial resolution of 0.35 mm and an imaging time of 2 seconds, and the ratio of the spatial resolution and imaging time was 0.175 mmZ seconds.
( 2 ) 造影剤のパルス注入による、 血液透析器内血液流れの解析 （実施例 2) ： 5重量ノ容量％の硫酸バリウム粒子 （粒径： 平均粒径 8 0 0ナノメータ、 範囲 1 0 0〜 2 00 0ナノメータ） を添加した牛血液 （へマトクリツト値： 3 0%、 総蛋白濃度： 6. 5 g/d L) を流し、 定常状態にある血液透析器 （東レ （株） 製" トレスルホン" （登録商標） B S— 1 . 6 U L) の血液入口側の血液回路に 高濃度 （約 2 0重量ノ容量％) の硫酸バリウムを添加した牛血約 3 m I を約 1秒 でパルス注入し、 同じタイミングでスキャニングを開始し、 X線コンピュータ断 層像 （G E横河メディカル （株） 、 HiSpeed DX/i) を約 2秒のサイクルタイム (2) Analysis of blood flow in hemodialyzer by pulse injection of contrast agent (Example 2): 5% by weight of barium sulfate particles (particle size: average particle size 800 nm, range 100- Hemodialysis machine (Toray Co., Ltd., “Tresulfone”) is fed with bovine blood (hematocrit value: 30%, total protein concentration: 6.5 g / dL) to which 200 nanometers are added. About 3 ml of bovine blood spiked with barium sulfate at a high concentration (about 20% by weight) was injected into the blood circuit on the blood inlet side of (registered trademark BS-1.6 UL) in about 1 second. Scanning starts at the same timing, and X-ray computer slice images (GE Yokogawa Medical Co., Ltd., HiSpeed DX / i) are cycled for about 2 seconds.
(スキャン時間 1秒、 待ち時間 1秒） で連続撮影し、 血液透析器内における血液 流れの解析を行なった。 以上の 2つの条件における縦断面画像と横断面画像を得て、 X線吸収値 （ハン スフィ一ルド値） を測定した。 なお、 得られた画像はビューヮソフトによりパソ コン上で解析した。 (Scan time 1 second, wait time 1 second), and analyzed the blood flow in the hemodialyzer. X-ray absorption values (Hansfield values) were measured by obtaining longitudinal and transverse cross-sectional images under the above two conditions. The obtained images were analyzed on a personal computer using View II software.
(1 ) の観察で得られた画像は、 （a) (図 1 ) 、 （b) (図 2) 両方の条件におい て血液が透析器に入った直後に急激に濃縮され、 その後出口側に近づくにつれ徐 々に希釈されるという結果を示した。 また、 （a)と（b)で血液が最も濃縮される位 置にほとんど差はないが、 濃縮の度合いは（b)の方が大きいことが観察できた。 次に、 （b)の透析液灌流条件で定常状態にある血液透析器を用いて、 （b) の条 件で （2) の観察を行なった。  The images obtained by the observation in (1) show that, under both conditions (a) (Fig. 1) and (b) (Fig. 2), the blood is rapidly concentrated immediately after entering the dialyzer, and then the blood exits to the outlet side. The results showed that it was gradually diluted as approached. In addition, although there was almost no difference in the position where blood was concentrated most in (a) and (b), it was observed that the degree of concentration was larger in (b). Next, the observation of (2) was performed under the conditions of (b) using a hemodialyzer in a steady state under the dialysate perfusion conditions of (b).
パルス注入後の硫酸バリウム濃度の過渡的変化が経時的に観察した像において 見られ、 血液は血液透析器の外周部に比べて中心部で早く流れることが図 3に見 られるように観察できた。  Transient changes in barium sulfate concentration after pulse injection were observed in the images observed over time, and it was observed that blood flows faster at the center of the hemodialyzer than at the periphery, as shown in Figure 3. .
(3) 血液透析器内牛血液の逆濾過領域の観察■解析 （実施例 3) ：  (3) Observation and analysis of the reverse filtration area of bovine blood in a hemodialyzer (Example 3):
血液透析器 （東レ （株） 製" トレスルホン" （登録商標） BS— 1. 6 U L) の血液流路に流量 （Q b) = 20 Om I /m i nで牛血液 （へマトクリツト値： 30%、 総蛋白濃度： 6. 5 g/d L) を、 透析液流路に流量 （Qd) = 500 m I Zm i nで生理食塩水液を 20分間流した後、 血液流路に牛血液を流した 状態で、 透析液流路に流量 （Q d ) = 500 m I /m i nで、 2重量ノ容量％の 硫酸バリウム粒子 （粒径：平均粒径 800ナノメータ、 範囲 1 00〜2ひ 00ナ ノメータ） を添加した生理食塩液を 5分間流し、 中空糸膜の膜中に硫酸バリウム 粒子 （粒径：平均粒径 800ナノメータ、 範囲 1 00〜2000ナノメータ） を トラップさせた。 流動状態を維持したまま、 透析液流路を生理食塩液で洗浄後、 血液透析器の X線コンピュータ断層像を撮影した。  Bovine blood (hematocrit value: 30%, flow rate (Qb) = 20 Om I / min) in the blood flow path of a hemodialyzer (“Toray Sulfone” (registered trademark) BS—1.6 UL manufactured by Toray Industries, Inc.) A total protein concentration of 6.5 g / d L) was flowed through the dialysate flow path at a flow rate (Qd) of 500 mI Zmin, and a saline solution was flowed for 20 minutes, followed by bovine blood flow through the blood flow path In the state, the flow rate (Q d) into the dialysate flow path is 500 mI / min, and 2% by volume of barium sulfate particles (particle diameter: average particle diameter 800 nanometers, range 100 to 200 nanometers) A physiological saline solution to which was added was flowed for 5 minutes, and barium sulfate particles (particle diameter: average particle diameter 800 nm, range 100 to 2000 nm) were trapped in the hollow fiber membrane. After maintaining the fluid state, the dialysate channel was washed with physiological saline, and an X-ray computed tomogram of a hemodialyzer was taken.
図 4は、 その X線コンピュータ断層撮影像であり、 中央にある縦長の像が透析 器である。 図 5は、 図 4をわかりやすく説明するために、 同図 4の X線コンビュ —タ断層像を卜レースして、 解説図をモデル的に示したものである。  Figure 4 shows the X-ray computed tomography image. The vertical image in the center is the dialyzer. Fig. 5 is a model drawing of the explanatory diagram obtained by tracing the X-ray computer tomographic image of Fig. 4 in order to explain Fig. 4 clearly.
すなわち、 図 5は、 図 4の X線コンピュータ断層像を卜レースして、 概略をモ デル的に説明するものであり、 図 4において、 X線 CT視野は、 黒い円形状にな つているものである。 図 4、 図 5において中央にある血液透析器は、 図 5にて解説を示しているよう に、 上方に血液入口を有し、 下方に血液出口を有するものである。 In other words, Fig. 5 illustrates the outline by tracing the X-ray computed tomographic image of Fig. 4, and in Fig. 4, the X-ray CT field has a black circular shape. It is. The hemodialyzer at the center in FIGS. 4 and 5 has a blood inlet on the upper side and a blood outlet on the lower side as shown in FIG.
血液入口の横付近には透析液の出口力ブラーが配置されてあリ、 血液出口の横 付近には透析液の入口カプラーが配置されてある。 血液は、 矢印で示したように 血液透析器内を方向的には上方から下方に向かって流れ、 透析液はこれも矢印で 示したように血液の流れ方向とは反対の方向に流れるものである。  A dialysate outlet force blur is located near the blood inlet, and a dialysate inlet coupler is located near the blood outlet. Blood flows in the hemodialyzer from the top to the bottom as shown by the arrow, and the dialysate flows in the direction opposite to the blood flow direction, also as shown by the arrow. is there.
図 4に示したように、 得られた画像を解析したところ、 血液透析器の中心部を 境に透析液上流側で X線の吸収が見られ、 逆濾過領域を可視化して確認すること ができた。 これは、 図 4では、 正濾過領域が黒っぽく見え、 逆濾過領域では白つ ぽく見えているので、 確認できたものである。  As shown in Fig. 4, when the obtained image was analyzed, X-ray absorption was observed upstream of the dialysate from the center of the hemodialyzer, and the reverse filtration region was visualized and confirmed. did it. This can be confirmed in FIG. 4 because the normal filtration area looks black and the reverse filtration area looks white.
すなわち、 正濾過領域と逆濾過領域の、 両者間の境界は、 図 4に写真、 図 5に て概略モデル図を示しているように、 相互に入り組んでいることが良くわかり、 実際の両濾過領域の状況を正確に知ることができたものである。  In other words, the boundary between the normal filtration region and the reverse filtration region is clearly intertwined with each other as shown in the photograph in Fig. 4 and the schematic model diagram in Fig. 5. The situation of the area could be accurately known.
産業上の利用可能性 Industrial applicability
本発明の液体流通装置内の液体流動状態の非破壊検査方法によれば、 該装置を 何ら破壊することなしに、 該液体流通装置内の液体流動状態を検査することや観 察することができ、 ひいては、 該装置の流通路に関する問題点の把握やそれに関 する改善設計や設計変更などの検討を行なうに際して、 極めて好適かつ効率的に 使用できるものである。  According to the non-destructive inspection method of the liquid flowing state in the liquid flowing device of the present invention, the liquid flowing state in the liquid flowing device can be inspected and observed without breaking the device at all. As a result, the apparatus can be used very suitably and efficiently when grasping problems concerning the flow passages of the apparatus and examining improvement designs and design changes related thereto.

Claims

請求の範囲 The scope of the claims
1 . コンピュータ断層撮影装置によリ液体流通装置内の液体流動状態を検査する 方法であって、 造影剤として、 粒子状造影剤または分子量 1 0万以上の高分子量 化造影剤を用いることを特徴とする液体流通装置内の液体流動状態の非破壊検査 方法。  1. A method for inspecting a liquid flowing state in a liquid flowing device by a computer tomography apparatus, wherein a particulate contrast agent or a high-molecular-weight contrast agent having a molecular weight of 100,000 or more is used as a contrast agent. Non-destructive inspection method of liquid flow state in liquid flow device.
2 . 前記粒子状造影剤または前記分子量 1 0万以上の高分子量化造影剤が、 液体 流通装置内を流動する液体に含まれることを特徴とする請求項 1に記載の液体流 通装置内の液体流動状態の非破壊検査方法。  2. The liquid flowing device according to claim 1, wherein the particulate contrast agent or the high molecular weight contrast agent having a molecular weight of 100,000 or more is contained in a liquid flowing in a liquid flowing device. Non-destructive inspection method for liquid flowing state.
3 . 該コンピュータ断層撮影装置が、 X線コンピュータ断層撮影装置であること を特徴とする請求項 1または 2に記載の液体流通装置内の液体流動状態の非破壊 検査方法。  3. The method according to claim 1, wherein the computed tomography apparatus is an X-ray computed tomography apparatus.
4 . 該コンピュータ断層撮影装置が、 磁気共鳴断層撮影装置であることを特徴と する請求項 1または 2に記載の液体流通装置内の液体流動状態の非破壊検査方法。 4. The method according to claim 1, wherein the computed tomography apparatus is a magnetic resonance tomography apparatus.
5 . 前記粒子状造影剤が、 気泡であることを特徴とする請求項 1 〜 4のいずれか に記載の液体流通装置内の液体流動状態の非破壊検査方法。 5. The nondestructive inspection method for a liquid flowing state in a liquid flowing device according to any one of claims 1 to 4, wherein the particulate contrast agent is a bubble.
6 . 前記粒子状造影剤が、 硫酸バリウム粒子であることを特徴とする請求項 1 〜 4のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  6. The nondestructive inspection method for a liquid flowing state in a liquid flowing device according to any one of claims 1 to 4, wherein the particulate contrast agent is barium sulfate particles.
7 . 前記粒子状造影剤の平均粒径が、 3 0 0ナノメータ一以上、 1万ナノメータ 以下であることを特徴とする請求項 5または 6に記載の液体流通装置内の液体流 動状態の非破壊検査方法。  7. The liquid flowing state in the liquid flow device according to claim 5 or 6, wherein the average particle diameter of the particulate contrast agent is not less than 300 nanometers and not more than 10,000 nanometers. Destructive inspection method.
8 . 前記粒子状造影剤の液体中の沈降速度または浮上速度が、 該液体の被観察部 位における平均線速度以下であることを特徴とする請求項 5〜 7のいずれかに記 載の液体流通装置内の液体流動状態の非破壊検査方法。  8. The liquid according to any one of claims 5 to 7, wherein a sedimentation velocity or a floating velocity of the particulate contrast agent in the liquid is equal to or lower than an average linear velocity of the liquid at a position to be observed. Non-destructive inspection method of liquid flow state in distribution device.
9 . 前記粒子状造影剤の該液体中の沈降速度、 または浮上速度が、 コンピュータ 断層撮影装置の観察条件である空間分解能ノ撮像時間の比以下であることを特徴 とする請求項 5〜 8のいずれかに記載の液体流通装置内の液体流動状態の非破壊 検査方法。  9. The sedimentation speed or the floating speed of the particulate contrast agent in the liquid is not more than the ratio of the imaging time of the spatial resolution, which is the observation condition of the computer tomography apparatus. The nondestructive inspection method of a liquid flowing state in the liquid flowing device according to any one of the above.
1 0 . 前記粒子状造影剤の液体中の沈降速度または浮上速度が、 該液体の被観察 部位における平均線速度以下であり、 かつコンピュータ断層撮影装置の観察条件 である空間分解能 撮像時間の比以下の速度であることを特徴とする請求項 5〜 9のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。 10. The sedimentation velocity or the floating velocity of the particulate contrast agent in the liquid is equal to or less than the average linear velocity of the liquid at the observation site, and the observation conditions of the computed tomography apparatus 10. The non-destructive inspection method of a liquid flowing state in a liquid flowing device according to claim 5, wherein the speed is equal to or less than a ratio of an imaging time.
1 1 . 該液体流通装置が、 血液体外循環用装置であることを特徴とする請求項 1 〜 1 0のいずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  11. The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to any one of claims 1 to 10, wherein the liquid flowing device is a device for extracorporeal blood circulation.
1 2 . 該液体流通装置が、 血液透析器であることを特徴とする請求項 1 〜 1 0の いずれかに記載の液体流通装置内の液体流動状態の非破壊検査方法。  12. The non-destructive inspection method for a liquid flowing state in a liquid flowing device according to any one of claims 1 to 10, wherein the liquid flowing device is a hemodialyzer.
1 3 . 該液体流通装置が、 膜を有するものであり、 該膜中に造影剤を卜ラップさ せることを特徴とする請求項 1 〜 1 0のいずれかに記載の液体流通装置内の液体 流動状態の非破壊検査方法。  13. The liquid in the liquid flow device according to any one of claims 1 to 10, wherein the liquid flow device has a film, and a contrast agent is trapped in the film. Non-destructive inspection method of fluid state.
1 4 . 該液体流通装置が、 中空糸膜を有する血液透析器であり、 該中空糸膜中に 造影剤をトラップさせることを特徴とする請求項 1 〜 1 0のいずれかに記載の液 体流通装置内の液体流動状態の非破壊検査方法。  14. The liquid according to any one of claims 1 to 10, wherein the liquid circulation device is a hemodialyzer having a hollow fiber membrane, and a contrast agent is trapped in the hollow fiber membrane. Non-destructive inspection method of liquid flow state in distribution device.
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