Marker, marker indwelling tool, and marker detector

Abstract

To provide a detector capable of accurately detecting the position of a marker containing fluorescent dye indwelled in a biological tissue.SOLUTION: A marker detector 60 is of a probe type, and includes: a cylindrical inner cylinder part 62 formed of light impermeable material; an excitation light emission part 63 disposed around the inner cylinder part 62; a cylindrical outer cylinder part 66 surrounding the excitation light emission part 63; an excitation light cut filter 64 disposed closer to the rear part than the tip face of the inner cylinder part 62 in the inner cylinder part 62; a light reception element 65 disposed closer to the rear part than the excitation light cut filter 64 in the inner cylinder part 62; and an output part for the intensity of the fluorescent light received by the light reception element 65. The excitation light emission part 63 is disposed closer to the rear part than the tip face of the outer cylinder part 66.SELECTED DRAWING: Figure 16A

Description

[Technical field]

[0001] The present invention relates to a marker to be placed in biological tissue, a marker placement device, and a marker detection device. [Background technology]

[0002] In surgical operations, medical clips are used as markers to pinch the affected area by attaching them to an endoscopic clipping device. For example, a clip (Patent Document 1) is used that consists of a clip body made of a metal leaf spring such as stainless steel bent into an approximate ">" shape, and a crimping ring that fits over the clip body to close it.

[0003] However, when a clip consisting of a metal leaf spring and a crimping ring is used as a marker for an affected area during surgery, if the clip is bitten by an automatic suturing device called a stapler when the affected area is cut off, the clip will not break because it is made of metal, causing a problem in that the stapler will not move.

[0004] In response to this, the present inventor has proposed a clip made of resin containing a fluorescent dye (Patent Document 2). This clip solves the problem that the stapler cannot move even if it bites into the clip because it is made of resin. Furthermore, there is an advantage that the position of the clip can be clearly confirmed from the serosal side by irradiating excitation light from the serosal side after clamping the mucous membrane of a hollow organ with the clip to cause the fluorescent dye to emit light. However, this clip has a weaker force for clamping biological tissue than conventional clips made of metal.

[0005] Meanwhile, in gastrointestinal polyp surgery, endoscopic mucosal resection (EMR) is performed in which a bulge is formed by injecting physiological saline into the submucosa of the lesion using an endoscopic injection needle, and the bulge is used as a marker to squeeze and resect with a snare (Patent Document 3). However, even when an endoscopic injection needle is used to pierce the lesion, the angle of the needle's entry into the mucosal surface is not constant because the direction of the needle changes depending on the puncture position. Therefore, there are cases where the needle tip penetrates the gastrointestinal tract and a bulge cannot be formed. In addition, the bulge disappears when the injected physiological saline is absorbed in the body. There is also a demand for the lesion to be more clearly identified, as in the case of marking the lesion with a clip containing a fluorescent dye described in Patent Document 2.

[0006] Also, as a marker for non-palpable cancer, an embedded marker with a diameter of about 1 to 2 mm and a length of about 5 to 15 mm is used. That is, the position of non-palpable cancer is identified by MRI examination, mammography, ultrasound examination, etc. Non-palpable cancer includes cancers that are non-palpable at the time of diagnosis and cancers that were palpable at the time of diagnosis but became non-palpable due to chemotherapy. However, non-palpable cancer cannot be surgically excised while identifying the position with MRI, etc. Therefore, in order to determine the resection range including non-palpable cancer with a means that is easy to use during surgery, a method is adopted in which an embedded marker is embedded in the biological tissue surrounding the non-palpable cancer while observing the position of the non-palpable cancer with MRI, etc., and the position of the marker is identified by a marker detection means during surgery. This method is useful for minimizing the resection range, and the marker embedded in the biological tissue is also useful for accurately knowing the area to be monitored after surgery.

[0007] Known types of implantable markers and methods for identifying their positions include, for example, a system that uses a coil made of magnetic wire with an inner diameter of less than 2 mm as the marker, excites the marker with an alternating magnetic field, and uses a probe to detect the marker from changes in magnetic flux density (Patent Document 4), a method that uses nanoparticles of ferromagnetic material such as iron oxide dispersed in a bioabsorbable gel as the marker and identifies the marker's position with a handheld magnetometer (Patent Document 5), a system that uses a passive tag equipped with a photosensitive diode as the marker and uses an ultra-wideband radar as the probe (Patent Document 6), and a system that uses a passive RFID (Radio Frequency Identification) tag as the marker (LOCalizer (registered trademark), Hologic).

[0008] However, these implantable markers contain metal, which becomes a source of noise in MRI and CT scans. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Patent No. 6572229 [Patent Document 2] Patent No. 6675674 [Patent Document 3] Patent No. 6382444 [Patent Document 4] Special Publication No. 2021-523751 [Patent Document 5] Special Publication No. 2015-524689 [Patent Document 6] Special Publication No. 2018-524059 Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention provides a marker of a new configuration that is to be placed in the lesion or near the lesion, and that uses a marking method that differs from conventional clips, bulges created by injection fluid, and embedded metal markers, is free of risk of falling off, does not become a source of noise in MRI or CT, and can be simply and reliably placed in the lesion, as well as a placement device for the marker, and also provides a marker detection device that can accurately detect a marker placed in the lesion or near the lesion and can be easily used during surgical procedures. [Means for solving the problem]

[0011] The present inventors have discovered that making the implantable marker a molded article containing a fluorescent dye is preferable in that it allows the marker to be detected without becoming a source of noise in MRI or CT, and that providing a fluid flow path on the surface or inside of the article is preferable in that it makes it easier to place the marker. Furthermore, the present inventors have discovered that the method of detecting a marker containing a fluorescent dye is preferably to identify the embedded position by fluorescence intensity using a probe-type device that can be pressed against biological tissue, rather than identifying the embedded position by creating a fluorescent image, and have completed the present invention.

[0012] That is, the present invention provides a marker containing a fluorescent dye, which is loaded into the inner cavity of a catheter or an injection needle, pushed out by a pusher, inserted into biological tissue, and left in place, a molded product having at least one of surface irregularities and through holes as a fluid flow path on the surface or inside of the marker so that the marker loaded in the cavity is not directly pressed by a pusher and the marker is held in the cavity when the fluid filled in the cavity is subjected to an extrusion force, To provide a marker which is pushed out from an injection needle when the marker loaded in the inner cavity is directly pressed by a pusher.

[0013] The present invention also provides a first marker placement device for inserting and placing the marker in biological tissue, comprising: syringe needle, a tube having the injection needle attached to one end; a cylinder in communication with the other end of the tube; A piston sliding inside a cylinder, a pusher having one end inserted into a tube and the other end connected to a piston within a cylinder; and a liquid supplying section for supplying an injection liquid to the cylinder; The tube or needle falls under the following items (a1) and (a2): (a1) When the marker is loaded into a tube or an injection needle and the cylinder is filled with an injection liquid from a liquid supply unit, even if the pusher is pushed in by a piston, the marker is held in the tube or the injection needle before the pusher directly presses the marker. (a2) in a state where the marker is loaded in a tube or an injection needle, a pusher directly presses the marker to push the marker out of the injection needle; The present invention provides a marker placement device having an inner diameter or shape that enables the above.

[0014] In addition, as a second marker placement device, Hypodermic needles, and A pusher that slides within the injection needle is provided, The injection needle is as follows: (b1) and (b2) (b1) Even if the pusher is pushed into the injection needle with the marker loaded in the injection needle, the marker is held in the injection needle before the pusher directly presses the marker. (b2) a pusher directly presses the marker while the marker is loaded into the injection needle, thereby pushing the marker out of the injection needle; The present invention provides a marker placement device having an inner diameter or shape that enables the above.

[0015] Furthermore, the present invention provides a probe-type marker detection device for detecting a marker containing a fluorescent dye placed in a biological tissue, comprising: A cylindrical inner cylinder portion formed of a light-impermeable material; an excitation light emitting portion disposed around the inner cylindrical portion; an excitation light cut filter provided within the inner cylindrical portion and closer to the rear than the tip surface of the inner cylindrical portion; a light receiving element provided in the inner cylindrical portion closer to the rear than the excitation light cut filter; and Output section for the intensity of the fluorescent light received by the light receiving element The present invention provides a marker detection device having a Effect of the Invention

[0016] When the marker of the present invention and the first marker retaining device are used endoscopically on biological tissue such as the mucosa of a hollow organ, an injection needle is inserted into the lesion and an injection solution is injected. If a bulge is formed there, the marker can be pushed out on the spot, and the marker can be retained at the lesion. On the other hand, if a bulge is not formed at a lesion in the biological tissue even when an injection needle is inserted into the lesion and an injection solution is injected, it is possible to know that the injection needle has penetrated the biological tissue, and the insertion of the injection needle can be redone. Therefore, the marker can be reliably retained at the lesion.

[0017] Furthermore, the marker of the present invention can be inserted and placed in biological tissues such as the breast, lungs, and bronchi by using the second marker placement device of the present invention.

[0018] There is no risk of the markers being dropped off once placed in the biological tissue. In addition, since there is no need to use metals, which are a source of noise in MRI and CT scans, in the material used to make the markers, the markers do not cause artifacts in MRI or CT scans. In addition, since the markers contain fluorescent dyes, the markers emit fluorescence when irradiated with excitation light, and the embedded position of the marker can be identified by searching for areas with strong fluorescence intensity.

[0019] There are no particular limitations on the fluorescence detection device for detecting the marker of the present invention embedded in biological tissue, but according to the marker detection device of the present invention, a light receiving element rather than an imaging element is used as the light receiving sensor, and the light receiving element is located rearward of the tip surface of the cylindrical inner tube portion, thereby improving the directionality when detecting the marker and increasing the accuracy of the detection position of the marker.

[0020] In addition, because the marker detection device of the present invention is of the probe type, it can be pressed against biological tissue during surgery and moved up and down and left and right, or pushed in, and the embedded position of the marker can be identified by the intensity of the received fluorescent light at that time. In particular, if a sound whose volume or pitch changes according to the intensity of the received light is made to be emitted when the probe is moved to find the embedded position, the detector can know the position where the intensity of the received light is strong without taking his / her eyes off the biological tissue where the probe is being moved, and therefore the embedded position of the marker can be easily identified. [Brief description of the drawings]

[0021] [Figure 1A] FIG. 1A is a side view of a marker 1A according to an embodiment. [Figure 1B] FIG. 1B is a view of the marker 1A of the embodiment as seen from the arrow A. [Figure 1C] FIG. 1C is a cross-sectional view taken along line BB of the marker 1A of the embodiment. [Figure 2A] FIG. 2A is a side view of the marker 1B of the embodiment. [Figure 2B] FIG. 2B is a view taken along the arrow C of the marker 1B of the embodiment. [Figure 2C] FIG. 2C is a DD cross-sectional view of the marker 1B of the embodiment. [Figure 3A] FIG. 3A is a side view of a marker 1C according to an embodiment. [Figure 3B] FIG. 3B is a view of the marker 1C of the embodiment as seen from the arrow E. [Figure 3C] FIG. 3C is an FF cross-sectional view of a marker 1C according to an embodiment. [Figure 4] FIG. 4 is a diagram showing the overall configuration of a first embodiment of the marker placement device. [Diagram 5] FIG. 5 is an explanatory diagram of the operation of the liquid supply unit. [Figure 6] FIG. 6 is an explanatory diagram of the function of the first marker placement device. [Figure 7] FIG. 7 is an explanatory diagram of the function of the first marker placement device. [Figure 8A]FIG. 8A is a side view of an injection needle having a reduced diameter portion as a movement resistance adjusting portion. [Figure 8B] FIG. 8B is a perspective view of an injection needle having a portion of the needle tip curved inward as a movement resistance adjusting portion. [Figure 9A] FIG. 9A is an explanatory diagram of a method of using the first marker placement device. [Figure 9B] FIG. 9B is an explanatory diagram of a method of using the first marker placement device. [Figure 9C] FIG. 9C is an explanatory diagram of a method of using the first marker placement device. [Figure 9D] FIG. 9D is an explanatory diagram of a method of using the first marker placement device. [Figure 9E] FIG. 9E is an explanatory diagram of a method of using the first marker placement device. [Figure 10] FIG. 10 is an explanatory diagram of a method of using the first marker placement device. [Figure 11] FIG. 11 is an explanatory diagram of a method of using the first marker placement device. [Figure 12] FIG. 12 is an explanatory diagram of a method of using the first marker placement device. [Figure 13A] FIG. 13A is a cross-sectional view of the second marker placement device. [Figure 13B] FIG. 13B is a cross-sectional view of the second marker placement device. [Figure 13C] FIG. 13C is a cross-sectional view of the second marker placement device. [Figure 14A] FIG. 14A is an explanatory diagram of a method of using the second marker placement device. [Figure 14B] FIG. 14B is an explanatory diagram of how to use the marker. [Figure 15] FIG. 15 is a perspective view of an embodiment of a marker detection device. [Figure 16A] FIG. 16A is a cross-sectional view of a marker detection device. [Figure 16B] FIG. 16B is an enlarged cross-sectional view and a front view of the tip of the probe of the marker detection device. [Figure 17]FIG. 17 is an explanatory diagram of a method for using the marker detection device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the drawings, the same reference numerals denote the same or equivalent components.

[0023] [marker] Fig. 1A is a side view of a marker 1A according to an embodiment of the present invention, Fig. 1B is a view taken along the line A, and Fig. 1C is a cross-sectional view taken along the line B-B. The marker 1A contains a fluorescent dye. The marker 1A is a molded product formed into a specific shape so that it is loaded into the inner cavity of a catheter or injection needle 11, pushed out by a pusher, inserted into biological tissue, and retained therein.

[0024] That is, even if the marker 1 of the present invention including the above-mentioned marker 1A is loaded into the inner cavity of the first marker holder 10A shown in FIG. 4 or the second marker holder 10B shown in FIG. 13A and the pusher 23 starts to push in the direction of the injection needle 11, the marker 1 is not directly mechanically pressed by the pusher 23, and when the injection solution, air, or other fluid filled in the inner cavity receives a pushing force, the fluid is pushed out from the injection needle 11 of the marker holder, but the marker 1 is held in the inner cavity by the movement resistance such as surface friction. On the other hand, when the marker 1 is directly pressed by the pusher 23, the marker 1 is also pushed out from the injection needle of the marker holder. In order to have the mobility in the inner cavity of being held in the inner cavity or pushed out from the inner cavity, the marker of the present invention has a shape that adjusts the movement resistance in the inner cavity, and also has surface irregularities or through holes that become a flow path for the fluid. The details of the shape of the marker will be described later.

[0025] (Marker forming material) The marker 1 of the present invention can be made of various materials such as resin, ceramics, cellulose molded products, and metals such as titanium that are not a noise source in MRI or CT, as long as the marker 1 can contain a fluorescent dye. It is preferably molded from a flexible resin that can deform its external shape. If the marker 1 is made of a hard material, there is a risk that when the marker is placed in the stomach, intestines, etc., the marker may move from its initial placement position due to peristalsis.

[0026] The hardness of the marker 1 is preferably in the range of A10 to A90 as Shore A (JIS K 6253) or D40 to D70 as Shore D (JIS K 6253) measured with a durometer.

[0027] Examples of such flexible resins include resins used in medical devices, such as soft polyvinyl chloride, thermoplastic polyurethane, silicone, and ethylene-vinyl acetate copolymer.

[0028] The marker 1 contains a fluorescent dye. This allows the location of the lesion to be identified as a location where the fluorescence intensity emitted by the marker is strong during surgery, and also makes it possible to visually confirm the location using a fluorescent camera. The marker 1 may contain a radiopaque contrast agent such as barium sulfate. This allows the location of the lesion to be confirmed by X-ray photography.

[0029] The fluorescent dye is preferably one that emits fluorescence in the wavelength range of red light to near infrared light of 600 to 1400 nm, preferably in the wavelength range of red light to near infrared light of 700 to 1100 nm. Light in such a wavelength range has high permeability to human tissues such as skin, fat, and muscle, and can easily reach, for example, the mucous membrane to the serosal surface of tubular human tissues such as the rectum.

[0030] Examples of fluorescent dyes that emit fluorescence in the above-mentioned wavelength ranges include riboflavin, thiamine, NADH (nicotinamide adenine dinucleotide), indocyanine green (ICG), an azo-boron complex compound described in JP 2011-162445 A, a dye having a condensed ring structure described in WO 2016 / 132596 A, a dye having a boron dipyrromethene skeleton described in JP 5177427 A, a dye that chemically bonds to silica particles described in JP 2020-74905 A, and a phthalocyanine dye described in JP 2020-105170 A.

[0031] A specific embodiment of incorporating a fluorescent dye into the marker 1 involves, for example, kneading the fluorescent dye into a resin using a twin-screw kneader, and then injection molding the resin to form the marker 1. In this case, a preferred concentration of the fluorescent dye in the resin can be set depending on the type of the fluorescent dye and resin, and is usually preferably 0.001 to 1% by mass.

[0032] Moreover, a coating film containing a fluorescent dye may be formed on the surface of the marker 1 made of a flexible resin or the like.

[0033] (Marker shape) In the present invention, the shape of the marker 1 can be roughly cylindrical, rectangular, or other columnar or tubular, bullet-shaped, spiral, or coil-shaped. However, as described above, it is preferable to provide the marker with a movement resistance adjustment part so that after the marker 1 is loaded into the inner cavity of the first marker holder 10A shown in FIG. 4 or the second marker holder 10B shown in FIG. 13A, the marker 1 is not directly mechanically pressed by the pusher 23 and is not pushed out of the injection needle 11 only by the hydraulic or pneumatic pressure of the fluid such as the injection solution or air filled in the inner cavity.

[0034] In the marker of the present invention, the movement resistance adjusting portion may be, for example, a plurality of hemispherical protrusions 5 that slide against the inner surface of the injection needle 11 or tube, provided on the circumferential surface of the bullet-shaped marker 1A, as in the marker 1A of the embodiment shown in Figs. 1A and 1B. The protrusions 5 increase the movement resistance of the marker 1A by friction with the inner surface of the injection needle 11 or tube. In addition, as the movement resistance adjusting portion, a flare shape 6a that slides against the inner surface of the injection needle 11 or tube may be provided at the end of the marker 1A. In this marker 1A, the flare shapes 6a are provided radially.

[0035] On the other hand, in this marker 1A, the peripheral surface of the marker 1A where the protrusion 5 is not formed becomes the flow path 7a for the fluid such as the injection liquid. Therefore, when the marker 1 is loaded into the first marker indwelling device 10A shown in Fig. 4 and the piston 21 is pushed in, it becomes possible to eject only the injection liquid A from the injection needle 11 through the flow path 7a, and this ejection can release the fluid pressure applied to the marker 1. Also, when the marker 1 is loaded into the second marker indwelling device 10B shown in Fig. 13A and the pusher 23 is pushed in, it becomes possible to eject only air from the injection needle 11 through the flow path 7a (Fig. 1A) when the pusher 23 does not reach the marker 1.

[0036] The marker 1B shown in Figures 2A, 2B, and 2C also has a roughly bullet-shaped outer shape, and has a flare shape 6b at the end of the bullet shape as a movement resistance adjustment part, which comes into sliding contact with the inner surface of the injection needle 11 or tube. The flare shape 6b of this marker 1B is formed in a semicircular arc shape with a central angle θ of about 180°, so it is less likely to deform than the radial flare shape 6a of the marker 1A shown in Figures 1A and 1B, and the movement resistance of the marker can be increased.

[0037] Furthermore, the marker 1B has a groove 7b formed in the circumferential surface of the marker in the longitudinal direction as a flow path.

[0038] The marker 1C shown in Figures 3A, 3B, and 3C also has a roughly bullet-shaped outer shape, and has a flare shape 6c formed around the entire circumference of the end of the bullet shape as a movement resistance adjustment part. This flare shape 6c can further increase the movement resistance compared to the semicircular arc-shaped flare shape 6b described above.

[0039] Furthermore, the marker 1C has a through hole 7c formed in the axial direction passing through the center of the marker as a flow path.

[0040] From the viewpoint of ease of production, the marker 1A shown in FIG. 1A is preferred as the marker. [Marker placement device] (First marker placement device) 4 is an overall configuration diagram of one embodiment of the first marker retaining device of the present invention, showing a state in which a marker 1 is loaded. The first marker retaining device 10A can be used by being inserted through the forceps hole of an endoscope, and includes the marker 1 of the present invention which is inserted into and retained in biological tissue such as a hollow organ, an injection needle 11 of a tube diameter through which the marker 1 can be passed, a tube (also called an inner tube) 12 to which the injection needle 11 is attached at one end, a cylinder 20 which communicates with the other end of the tube 12, and a piston 21 which slides within the cylinder 20. A rubber piston head 22 is attached to the end of the piston 21 on the cylinder side.

[0041] In the first marker retaining device 10A, the marker 1 can be inserted into the tube 12 from the open end of the tube 12 on the cylinder 20 side, and is loaded near the end of the tube 12 closer to the injection needle 11 or into the inner cavity of the injection needle 11. Alternatively, the injection needle 11 may be attached to the tube 12 after the marker 1 is loaded into the needle tube of the injection needle 11.

[0042] In addition, although the marker 1 is loaded in the injection needle 11 in FIG. 4, the marker 1 may be loaded in the tube 12 in the present invention.

[0043] The size of the injection needle 11 can be the same as that of a typical endoscopic injection needle, and for example, a 19 gauge (inner diameter 0.70 mm, outer diameter 1.06 mm), length 3 to 10 mm, or a 20 gauge (inner diameter 0.58 mm, outer diameter 0.88 mm), length 3 to 10 mm can be used.

[0044] However, as described above, when the marker 1 is pressed only by the liquid pressure of the injection solution, the marker 1 is not pushed out from the injection needle 11, and the inner diameter or shape of the injection needle 11 is determined so that the marker 1 generates a movement resistance to be held in the injection needle 11. The same applies to the tube 12. For example, the size or shape of the inner diameter of the injection needle 11 or the tube 12 is determined so that the marker 1 slides in contact with the inside of the injection needle 11 or the tube 12. Also, as shown in FIG. 8A, the movement resistance adjustment part may be formed by one or more reduced diameter parts 11a formed on the injection needle 11. The reduced diameter parts 11a can be formed by, for example, concaving the injection needle 11 with a punch or the like. In addition, as the movement resistance adjustment part, a part curved inwardly at the needle tip 11b of the injection needle 11 may be provided as shown in FIG. 8B.

[0045] An outer cylinder tube 13 is provided on the outside of the tube 12, and the tube 12 can be extended from the outer cylinder tube 13 or retracted into the outer cylinder tube 13 by an operating unit (not shown). The tube 12 and the outer cylinder tube 13 are also referred to as a catheter.

[0046] The injection needle 11, the tube 12, the marker 1 loaded in the injection needle 11 or the tube 12, the outer tube 13, the cylinder 20, the pusher 23 and the piston 21 can constitute a disposable product.

[0047] The tube 12, the outer tube 13 and the pusher 23 may be flexible or rigid depending on the part of the biological tissue in which the first marker retaining device 10A is used. For example, they can be rigid when used in a cystoscope, and are preferably flexible when used in a gastrointestinal endoscope.

[0048] An end of a pusher 23 is connected to the piston 21 via a piston head 22. The pusher 23 is inserted into the tube 12, and the end of the pusher 23 reaches the vicinity of the injection needle 11. Therefore, the piston 21 is pushed into the cylinder 20, and the pusher 23 directly and mechanically presses the marker 1, so that the marker 1 is pushed out of the injection needle 11. The piston 21 and the pusher 23 may be formed integrally or separately.

[0049] The cylinder 20 is provided with a liquid supply unit 30 that supplies an injection liquid A. As the injection liquid A, for example, physiological saline, hyaluronic acid liquid, etc. can be used.

[0050] The liquid supply unit 30 has a syringe 31 and a plunger 32, and communicates with the cylinder 20 via a valve 33 such as a two-way valve. As shown in Fig. 5, by opening the valve 33 and pushing the injection liquid A in the syringe 31 with the plunger 32, it is possible to inject an amount of the injection liquid A suitable for forming a bulge (usually 1 to 2 mL) into the cylinder 20. Note that in the present invention, the liquid supply unit 30 is not limited to being composed of a syringe and a plunger, and a fixed amount of the injection liquid may be discharged using a trigger mechanism.

[0051] According to this first marker retaining device 10A, as shown in Fig. 6, when the marker 1 is loaded into the inner cavity of the injection needle 11 or the tube 12 and the cylinder 20 and the tube 12 are filled with the injection fluid A, and the piston 21 is pushed into the cylinder 20 with the valve 33 closed, if the pusher 23 does not reach the marker 1 due to the amount of pushing (i.e., the marker is not directly pressed by the pusher), the injection fluid A is discharged from the injection needle 11, but the marker 1 is held in the inner cavity of the tube 12 or the injection needle 11. In other words, the marker 1 is not pushed out from the injection needle 11 only by the liquid pressure when the injection fluid A is pushed in by the piston 21. On the other hand, when the piston 21 is further pushed into the cylinder 20 and the pusher 23 mechanically directly presses the marker 1 as shown in Fig. 7, the marker 1 is pushed out from the injection needle 11.

[0052] (Method of using the first marker placement device) (How to use 1) The first marker retaining device 10A is preferably used when retaining a marker in the biological tissue of a hollow organ. In this case, the marker retaining device 10A is first inserted into the forceps hole of the endoscope and set. The injection liquid A is supplied from the liquid supply unit 30 to the cylinder 20, and the injection needle 11, the tube 12, and the cylinder 20 are filled with the injection liquid A. The valve 33 is closed, the piston 21 is slightly pushed into the cylinder 20, and it is confirmed that the injection liquid is discharged from the injection needle 11.

[0053] Next, the injection needle 11 is inserted into the hollow organ through a natural opening such as the mouth, nose, or anus, an incision, or other opening, and the injection needle 11 is inserted near the lesion 42 of the mucosa 41 of the hollow organ under endoscopic observation as shown in Fig. 9A. Then, the piston 21 is pushed to inject the injection solution A into the mucosa 41 as shown in Fig. 9B, and it is confirmed that a bulge 43 is formed. The formation of the bulge 43 indicates that the injection needle 11 has not penetrated the wall of the hollow organ, and after this confirmation, the piston 21 is further pushed to push the marker 1 with the pusher 23 as shown in Fig. 9C, thereby forcing the marker 1 into the mucosa 41 and leaving it there.

[0054] On the other hand, if no bulge is formed even after injection of the injection solution A, it is considered that the injection needle 11 penetrates the wall of the hollow organ and the injection solution A is injected outside the serosal surface 44, as shown in Fig. 9D. In this case, the injection needle 11 is inserted again.

[0055] The bulge formed in the mucosa 41 by the injection of the injection solution A generally disappears about one hour after the injection.

[0056] After placing the marker 1 in the mucosa 41, as shown in Fig. 9E, excitation light L1 is irradiated from the serosal surface 44 side by a near-infrared fluorescence endoscope 50, and the position of the marker 1 can be accurately visually confirmed by the fluorescence L2 emitted by the marker 1. This makes it easy to accurately identify the position of the affected area during surgery.

[0057] (How to use 2) As a method of using the first marker retaining device 10A of the present invention, a plurality of markers 1a, 1b may be loaded into an injection needle 11 or a tube 12 as shown in FIG.

[0058] In this case, after the first marker 1a on the needle tip side is placed on the mucosa 41 as described above, the injection needle 11 is pulled out from the mucosa, the piston 21 is pulled back, and the pusher 23 is separated from the second marker 1b inside the injection needle 11. Next, the valve 33 of the liquid supply unit 30 is opened to supply the injection liquid A into the cylinder 20. Thereafter, as in the above, the valve 33 is closed and the injection needle 11 is inserted into the mucosa 41, the piston 21 is pushed to inject the injection liquid A into the mucosa 41, and after the bulging portion is confirmed, the piston 21 is further pushed to push the second marker 1b into the mucosa 41.

[0059] In this way, if a plurality of markers 1a and 1b are stored in the injection needle 11 or tube 12 of the first marker retaining device 10A, the markers 1a and 1b can be shot continuously by setting the marker retaining device 10A once in the forceps hole of the endoscope. Therefore, for example, when identifying the location of a cancer in the digestive tract, as shown in Fig. 11, the first marker 1a can be placed on the oral side of a lesion 42, and the second marker 1b can be placed on the anal side, and as shown in Fig. 12, by irradiating excitation light L1 from the serosal surface 44 of the digestive tract using a near-infrared fluorescence endoscope 50, the location of the cancer in the digestive tract can be accurately identified by the fluorescence L2 emitted by the first marker 1a and the second marker 1b.

[0060] Furthermore, by storing multiple markers 1a, 1b in the first marker holder 10A, markers can be placed in multiple locations in biological tissue with one marker holder, which reduces the burden on the doctor and cuts the cost of the marker holder. Therefore, the present invention also includes holder 10A in which multiple markers are stored.

[0061] (Second marker placement device) 13A is a cross-sectional view of one embodiment of the second marker indwelling device of the present invention, showing a state in which a marker 1 is loaded into an injection needle. The second marker indwelling device 10B comprises an injection needle 11 and a pusher 23 that slides inside the injection needle 11. The end of the pusher 23 opposite to the injection needle 11 forms a large-diameter pressing part 23a.

[0062] It is preferable to provide a finger hook 24 at the end of the outer circumferential surface of the injection needle 11. In addition, a temporary plug 25 made of bleached beeswax or the like is provided inside the injection needle 11 near the needle tip to prevent the marker 1 from accidentally coming out of the injection needle 11.

[0063] When placing a marker within the wall of a hollow organ, there is a risk that the injection needle loaded with the marker will penetrate the wall of the hollow organ, so as mentioned above, a bulge is formed in the injection fluid to check whether the position of the needle tip is appropriate (Figures 9A to 9E). However, if the site where the marker is to be placed is the breast, etc., where there is no such risk, or if the site is the lungs, bronchi, etc., where it is not desirable to inject the injection fluid, it is preferable to use the second marker placement device 10B, which pushes out the marker without injecting the injection fluid.

[0064] The injection needle 11 of the second marker retaining device 10B has an inner diameter that generates a movement resistance to the marker 1 of the present invention, similar to the injection needle 11 of the first marker retaining device 10A. In addition, the marker 1 of the present invention has surface irregularities or through holes that serve as a flow path for air, as described above. Therefore, as shown in FIG. 13A, when the pusher 23 is pushed into the injection needle 11 in which the marker 1 is loaded, the marker 1 does not pop out at the same time as the pusher 23 is pushed. Even if the pusher 23 is pushed, the pusher 23 does not reach the marker 1, and in the state before the marker 1 is directly pressed, a fluid such as air is pushed out of the injection needle 11 through the flow path of the marker 1, and the marker 1 is held in the injection needle 11. Next, as shown in FIG. 13B, when the pusher 23 starts to directly press the marker 1, the marker 1 moves together with the pusher 23, and is pushed out of the injection needle 11 as shown in FIG. 13C.

[0065] (How to use the second marker placement device) When the marker 1 of the present invention is placed in a lesion of a breast, for example, using the second marker placement device 10B, as shown in Fig. 14A, the pusher 23 is pushed in to move the marker 1 to the tip of the injection needle 11, and then the skin is punctured and the marker 1 is placed in the lesion or in its vicinity while the lesion and the injection needle 11 are confirmed on an image by ultrasound examination or mammography. During surgery to remove the lesion, the fluorescence emitted from the marker 1 by irradiation with excitation light L1 is observed with a fluorescence camera (not shown). It is preferable that the fluorescence camera not only displays a fluorescent image of red or infrared fluorescence L2, but also displays a visible light image superimposed on the fluorescent image.

[0066] It is also possible to load a plurality of markers into the injection needle 11 of the second marker placement device 10B, and therefore a plurality of markers 1 can be easily placed around the affected area.

[0067] When marker 1 is placed in biological tissue in this manner, even if the original lesion becomes non-palpable due to chemotherapy, radiation therapy, etc., marker 1 emits fluorescence when irradiated with excitation light, as shown in Figure 14B, so the location of the original lesion can be easily determined.Furthermore, by using the position of the marker as a guide during surgery, the area of ​​resection can be kept to the minimum necessary.

[0068] [Marker detection device] (Configuration of the marker detection device) Figure 15 is an oblique view of one embodiment of a probe-type marker detection device 60 of the present invention, Figure 16A is a cross-sectional view of the marker detection device 60, and Figure 16B is an enlarged cross-sectional view and a front view (viewed from the direction of arrow G) of the tip of the probe of the marker detection device 60.

[0069] This marker detection device 60 is a probe-type device that detects a marker containing a fluorescent dye placed in biological tissue, and is suitable for detecting the above-mentioned marker 1 of the present invention. The marker detected by this marker detection device 60 may be any material that contains a fluorescent dye, and may be made of resin, ceramic, or metal, or may be a liquid containing a fluorescent dye. It is not limited to the marker of the present invention in which the movement resistance is adjusted as described above.

[0070] A probe 61 of a marker detection device 60 has a cylindrical inner tube portion 62 made of a light-impermeable material such as metal, an excitation light emitting portion 63 arranged around the inner tube portion 62, an excitation light cut filter 64 (64a, 64b) provided within the inner tube portion 62 closer to the rear than the tip surface of the inner tube portion 62, and a light receiving element 65 provided within the inner tube portion 62 closer to the rear than the excitation light cut filter 64. The outermost surface of the probe 61 is formed of a cylindrical outer tube portion 66, which surrounds the excitation light emitting portion 63.

[0071] A transparent glass member 67 is provided inside the outer cylinder 66 and in front of the excitation light emission part 63. The transparent glass member 67 fills the space between the outer cylinder 66 and the inner cylinder 62. The light receiving element 65 and the excitation light emission part 63 are connected to a substrate 68.

[0072] Meanwhile, a gripping part 70 is formed at the rear end of the probe 61, and a battery box 71 and a speaker 72 are provided inside the gripping part 70. The speaker 72 emits a sound whose volume or pitch corresponds to the intensity of the fluorescence received by the light-receiving element 65. A board 73 is provided on the rear side of the battery box 71. In addition, a main switch 74 of the marker detection device 60 is provided on the rear end surface of the gripping part 70.

[0073] Here, it is preferable to provide an LED as the excitation light emitting section 63, which emits light of a wavelength in the red to near infrared range that excites the fluorescent dye contained in the marker 1. A plurality of LEDs 63 can be provided around the inner tube section 62. It is also preferable to provide the LEDs 63 closer to the rear than the tip surface of the outer tube section 66. This can improve the directionality of the excitation light. For example, when the excitation light emitting section 63 is formed of a bullet-shaped LED and the inner diameter D1 of the outer tube section 66 is 10 to 16 mm, it is preferable that the distance K1 between the excitation light emitting section 63 and the tip surface of the outer tube section 66 is 2 to 4 mm.

[0074] In contrast, guiding light from a light source outside the probe to the excitation light emitting section 63 through an optical fiber is not preferable because it complicates the configuration of the marker detection device and also causes light loss.

[0075] As the light receiving element 65, it is preferable to provide a photodiode, phototransistor, or the like having sensitivity to light of a wavelength from red to near infrared. It is not necessary to provide an imaging element such as a CCD in which light receiving elements are arranged in an array. By providing a light receiving element such as a photodiode alone, it is possible to increase the intensity of received fluorescent light. Furthermore, by not providing an imaging element, there is no need for an optical system such as a lens system for focusing or an aperture for adjusting the amount of light, which simplifies the configuration of the marker detection device and enables it to be manufactured at low cost.

[0076] Furthermore, by providing the light receiving element 65 closer to the rear than the tip surface of the inner cylinder 62, the directivity of the fluorescence received by the light receiving element 65 can be improved, and the positional accuracy when detecting the marker placed in the biological tissue can be improved. For example, when the inner diameter D2 of the inner cylinder 62 is 3 to 6 mm and the light receiving element 65 is a bullet-shaped photodiode, the distance K2 between the tip surface of the inner cylinder 62 and the light receiving element 65 is preferably 5 to 9 mm, and the distance K3 between the tip surface of the outer cylinder 66 and the light receiving element 65 is preferably 8 to 15 mm.

[0077] The excitation light cutoff filter 64 disposed in front of the light receiving element 65 may be provided with overlapping filters 64a and 64b with different cutoff wavelengths, if necessary.

[0078] As an output section for the intensity of the fluorescent light detected by the light receiving element 65, a Bluetooth or Wi-Fi transmitter may be provided instead of the speaker 72 or together with the speaker 72, or a display may be provided.

[0079] (How to use the marker detection device) As a method of using the marker detection device, for example, when detecting a marker that has been placed in advance at or near a breast lesion when surgically removing the lesion, it is preferable to press the tip of a probe 61 against the milk and move it back and forth, left and right, or up and down to find a location where the detection intensity of the fluorescence emitted by the marker 1 is strong, as shown in Fig. 17. By pressing the tip of the probe 61 against the milk and moving it, the distance to the probe 61 is shortened even for a marker 1 embedded deep under the skin, and the light receiving intensity at the light receiving element 65 is increased, making detection easier. In addition, by pressing the probe 61, blood between the marker 1 and the probe 61 can be removed, so that scattering or absorption of the excitation light and fluorescence by blood can be suppressed, and this also increases the light receiving intensity at the light receiving element 65.

[0080] If the marker detection device 60 is equipped with a speaker 72, the surgeon can easily find the location where the marker is placed by the pitch or intensity of the sound. Also, if the marker detection device 60 is equipped with a Bluetooth or Wi-Fi transmitter, the output waveform of the fluorescence intensity can be displayed on a display 81 of a receiving device 80 such as a personal computer, tablet, or smartphone that receives radio waves from the transmitter.

[0081] According to this marker detection device 60, the fluorescence emitted by the marker is detected by a light receiving element such as a single photodiode without being detected by an imaging element, and further, the directionality during detection is improved, and further, since the probe 61 can be moved back and forth, left and right, or up and down while being pressed against the biological tissue, the marker 1 placed in the biological tissue can be detected with high positional accuracy and high sensitivity. Therefore, for example, a marker placed at a depth of up to 4 cm from the surface of the biological tissue can be reliably detected.

[0082] Generally, when a marker placed in biological tissue is photographed with a fluorescent camera, markers located at a depth of up to about 2 cm can be detected, but markers located deeper than 2 cm cannot be detected, indicating that the detection sensitivity of the marker detection device of the present invention is superior to that of a fluorescent camera.

[0083] In addition, after the location where the marker is placed in the biological tissue is detected by the marker detection device 60 and the vicinity of the detection location is incised so that the marker can be detected by the fluorescent camera, the lesion may be excised while confirming the position of the marker with the fluorescent camera. In this case, the fluorescent camera is preferably one that can simultaneously display the fluorescent image emitted by the marker and the visible light image from the biological tissue, and for example, the HyperEye Medical System (Mizuho Corporation) can be used. [Explanation of symbols]

[0084] 1, 1a, 1b, 1A, 1B, 1C markers 5 Protrusion 6a, 6b, 6c Flare shape 7a, 7b Channel, groove 7c Channel, through hole 10A First marker placement device 10B Second marker placement device 11 Syringe needle 11a Reduction part 11b Needle tip 12 Tube (inner tube) 13 External tube 20 Cylinders 21 Piston 22 Piston head 23 Pusher 23a Pressing part 24 Finger rest 25 Temporary stopper 30 Liquid supply section 31 Syringe 32 Plunger 33 Valve 41 Mucous membrane of hollow organs 42 Lesion 43 Bulge 44 Serous Surface of Hollow Organs 45 Breasts 50 Near-infrared fluorescence endoscope 60 Marker detection device 61 Probe 62 Inner cylinder 63 Excitation light emitter, LED 64, 64a, 64b Excitation light cut filter 65 Photodetector 66 External cylinder 67 Transparent glass parts 68 Substrate 70 Gripping part 71 Battery box 72 speakers 73 Substrate 74 Main Switch 80 Receiving device 81 Display A injection solution D1 Inner diameter of outer cylinder D2 Inner diameter of the inner cylinder K1: Distance between the excitation light output part and the tip of the outer tube K2 Distance between the tip of the inner cylinder and the light receiving element K3 Distance between the tip of the outer cylinder and the light receiving element L1 excitation light L2 fluorescence

Claims

1. A probe-type marker detection device for detecting a marker containing a fluorescent dye placed in a biological tissue, comprising: A cylindrical inner cylinder portion formed of a light-impermeable material; an excitation light emitting portion disposed around the inner cylindrical portion; a cylindrical outer cylinder portion surrounding the excitation light emission portion; an excitation light cut filter provided within the inner cylindrical portion and closer to the rear than the tip surface of the inner cylindrical portion; a light receiving element provided in the inner cylindrical portion closer to the rear than the excitation light cut filter; and Output section for the intensity of the fluorescent light received by the light receiving element and an excitation light emitting portion is provided rearward from the tip surface of the outer tube portion.

2. 2. A marker detection device as described in claim 1, wherein no optical fiber is interposed between the excitation light exit end face of the marker detection device and the excitation light exit portion, and no optical fiber is interposed between the fluorescence receiving side tip face of the marker detection device and the light receiving element.

3. 3. The marker detection device according to claim 2, wherein an LED is provided as the excitation light emitting section.

4. 4. The marker detection device according to claim 1, further comprising a speaker as an output section, the volume or pitch of the sound being changed according to the intensity of the fluorescent light.

5. 4. The marker detection device according to claim 1, further comprising a display as an output section, the display displaying the fluorescence intensity.

Images