JP2017131197A - Experimental animal head fixing device and experimental animal photographing head fixing device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an experimental animal head fixing device and an experimental animal photographing head fixing device in which a large stress is hard to occur in an experimental animal when attached to an experimental animal learning device and in a living environment without becoming an obstruction of MRI imaging and PET imaging.SOLUTION: Acrylic nuts 103 positioned by using a nut fixture are made to adhere and fixed on the skull of an experimental animal 301. When the experimental animal 301 is made to learn with an experimental animal learning device and is photographed in a PET imaging apparatus, an acrylic head fixing member 105 is attached to the nut 103 bonded and fixed in the head of the experimental animal 301 with an acrylic bolt 104. This head fixing member 105 is substantially the same as a conventional head fixed frame in width and thickness, and therefore has compatibility. Consequently, it can just be installed to the experimental animal learning device.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a head fixing device for experimental animals and a head fixing device for photographing laboratory animals.

In order to elucidate the behavior of the brain, experiments are sometimes performed using small animals. After the experimental animal to be studied learns certain movements, the brain of the experimental animal is examined using MRI imaging (magnetic resonance imaging) or PET imaging (positron emission tomography). Take pictures and observe changes in the brains of experimental animals.
In such behavior experiments using small animals, in order to allow the experimental animals to learn certain movements efficiently, a fixture is often attached to the head of the experimental animal and fixed to the experimental animal learning device. . This is for restricting the movement of the head of the experimental animal and forcing the experimental animal to face the learning task of the experimental animal learning apparatus.
Patent Document 1 is shown as a prior art document considered to be related to the present invention. Patent Document 1 discloses the technical content of an animal experimental apparatus, and particularly describes that a test animal mounting bracket is mounted on the rat's head as a member for fixing the experimental animal's head.

JP 2013-5746 A

FIG. 15A is a schematic diagram showing a laboratory animal having a head fixing frame 1501 bonded and fixed to the head. FIG. 15B is a schematic diagram showing a state in which an experimental animal having a head fixing frame 1501 bonded and fixed to the head is fixed to the head fixing device 605 of the experimental animal learning apparatus. In FIG. 15A and FIG. 15B, the experimental animal is a rat 301.
As one of methods for fixing the head of the experimental animal to the head fixing device 605 in the experimental animal learning apparatus in the prior art, an aluminum head fixing frame 1501 whose surface is anodized on the head of the experimental animal. There is a method of adhering (see Patent Document 1).

  As is apparent from FIGS. 15A and 15B, the head fixing frame 1501 is a member having a width larger than the width of the experimental animal head in order to fix the experimental animal head to the experimental animal learning apparatus. Yes. For this reason, MRI imaging in which the imaging coil is narrow enough to contain only the head of the experimental animal cannot be handled because the head fixing frame 1501 itself becomes an obstacle. In addition, since the head fixing frame 1501 is made of metal, it becomes an error factor in PET imaging. Furthermore, since the head fixing frame 1501 peels off the scalp of the experimental animal and directly adheres and fixes it to the skull with the dental treatment bond 302, it is difficult to remove it once attached to the experimental animal. Therefore, the laboratory animal to which the head fixing frame 1501 is attached must always live with the head fixing frame 1501 adhered and fixed to the head thereafter. Then, in a living environment such as a breeding cage, the experimental animal becomes a factor that gives great stress to the experimental animal, for example, the head fixing frame 1501 hits the wall of the breeding cage and becomes difficult to move.

  As another method for fixing the head of the experimental animal in the experimental animal learning apparatus in the prior art, there is a method of arranging a needle-like fixing bracket in the ear hole of the experimental animal, and such an instrument is also commercially available. Has been. With this method, it is not necessary to peel off the scalp of the experimental animal and bond the metal fittings. However, when the experimental animal moves its head, the needle-like fixing bracket pierces the ear, which also gives great stress to the experimental animal, and the learning itself is likely to fail. Also, the great stress caused by laboratory equipment can shorten the life of experimental animals.

  The present invention has been made in view of such problems, and does not interfere with MRI imaging or PET imaging, and places great stress on experimental animals when they are mounted on a laboratory animal learning apparatus and in their living environment. An object of the present invention is to provide a head fixing device for laboratory animals and a head fixing device for photographing laboratory animals.

  In order to solve the above-mentioned problem, a head fixing device for a laboratory animal of the present invention has a plurality of nuts bonded and fixed to the head of the laboratory animal, and a length exceeding the width of the head of the laboratory animal, A head fixing member having two holes at the same position as the hole of the nut at the center and a plurality of bolts for fixing the head fixing member to the plurality of nuts are provided. The plurality of nuts, bolts, and head fixing members are all made of non-metal. Here, “plurality” means that at least two or more are required.

According to the present invention, there is provided a head fixing device for a laboratory animal that does not interfere with MRI imaging or PET imaging, and is less likely to cause great stress on the laboratory animal when the laboratory animal is attached to the laboratory animal learning apparatus and in its living environment. A head fixing device for photographing laboratory animals can be provided.
Problems, configurations, and effects other than those described above will be clarified by the following description of embodiments.

FIG. 1 is an external perspective view of a head fixing device for a laboratory animal and a head fixing device for photographing a laboratory animal, which is an example of an embodiment of the present invention, and a side view of the head fixing device for photographing and the head fixing device viewed from the side. FIG. It is the external appearance perspective view of the head fixing member, the top view, and the side view which looked at the head fixing member from the horizontal direction. It is the schematic which shows the relationship between the head fixing member, the volt | bolt, and the rat by which the nut was adhere | attached on the head. It is the schematic which shows the state with which the rat to which the head fixing member was attached is mounted | worn with the imaging | photography head fixing device. It is the schematic which shows the state with which the rat with which the head fixing member was attached was mounted | worn with the imaging | photography head fixing device. It is an external view of the learning apparatus for experimental animals. It is an external view of the operation | movement detection instrument which comprises a part of learning apparatus for experimental animals. It is a photograph which shows the state with which the rat was mounted | worn with the learning apparatus for laboratory animals. It is the external appearance perspective view of a nut fixture, a top view, and the side view which looked at the nut fixture from the horizontal direction. It is the schematic which shows the state which adhere | attaches and fixes a nut to the skull of a rat using a nut fixture. It is a conceptual diagram which shows the state which adhered and fixed the nut to the skull of a rat. It is the photograph which shows the head of the rat to which the nut was attached, and the photograph which shows the state which fixed the head fixing member to the rat's head to which the nut was attached. It is the photograph which shows the mode in the breeding cage of the rat to which the nut was attached. It is the graph which shows the result of the comparative experiment of the head fixing member and head fixing frame in PET imaging, and the photograph which shows the mode of the comparative experiment of the head fixing member and head fixing frame in PET imaging. Schematic diagram showing a laboratory animal with a head-fixing frame bonded and fixed to the head, and a state in which the experimental animal with the head-fixing frame bonded and fixed to the head is fixed to the head fixing device of the experimental animal learning device FIG.

First, an outline of an embodiment of the present invention will be described.
In the experimental animal head fixing device described in the embodiment of the present invention, an acrylic nut is bonded and fixed to the skull of the experimental animal instead of a conventional metal fitting. Then, the acrylic head fixing member is attached to an acrylic nut bonded to the skull of the experimental animal with an acrylic bolt.
This acrylic head fixing member has almost the same size as a conventional metal fitting, and can be mounted on an existing laboratory animal learning apparatus as it is. Further, if the head fixing member is removed, only a nut made of acrylic is attached to the skull of the experimental animal, so that narrow MRI imaging can be handled.
Furthermore, in the embodiment of the present invention, an acrylic imaging fixture is provided that fixes an acrylic head fixing member during PET imaging. Since these members are all made of non-metallic acrylic, they do not hinder imaging during PET imaging.

[Overall Configuration of Head Fixing Device 101 and Shooting Head Fixing Device 102]
FIG. 1A is an example of an embodiment of the present invention, a laboratory animal head fixing device (hereinafter abbreviated as “head fixing device”) 101 and a laboratory animal imaging head fixing device (hereinafter “imaging head”). It is abbreviated as “fixing device”.) FIG. FIG. 1B is a side view of the imaging head fixing device 102 and the head fixing device 101 as seen from the lateral direction (arrow X direction). In FIG. 1, illustration of experimental animals is omitted. FIG. 2A is an external perspective view of the head fixing member. FIG. 2B is a top view of the head fixing member. FIG. 2C is a diagram of the head fixing member viewed from the lateral direction. In FIG. 2C, an acrylic nut and bolt are attached.

  FIG. 3 is a schematic view showing the relationship between a head fixing member, a bolt, and a rat 301 having a nut bonded to the head. In the following description, it is assumed that the experimental animal to which the head fixing device 101 as an example of the embodiment of the present invention is attached is the rat 301. FIG. 4 is a schematic diagram showing a state in which the rat 301 to which the head fixing member is attached is attached to the imaging head fixing device 102. FIG. 5 is a schematic view showing a state in which a rat 301 having a head fixing member attached thereto is attached to the imaging head fixing device 102.

  As can be seen from FIGS. 1A and 1B, the head fixing device 101 is fixed by being inserted into the grip portions 114 and 115 of the imaging head fixing device 102. Referring to FIGS. 1B, 2A, 2B, and 2C, the head fixing device 101 is configured by fixing a rectangular head fixing member 105 with an acrylic nut 103 and an acrylic bolt 104. Is done. As shown in FIGS. 2C and 3, the acrylic nut 103 is bonded and fixed to the skull of the rat 301 with a bond 302 for dental treatment. The method for fixing the nut 103 to the skull of the experimental animal will be described in detail with reference to FIG.

  1A, 1B, 2A, 2B, 3, 4 and 5, the head fixing member 105 has a total of 2 holes 105a and 105b through which the bolt 104 passes. Individually opened. The positions of the holes 105 a and 105 b coincide with the positions of the holes of the nut 103 that is bonded and fixed to the skull of the rat 301. Further, the head fixing member 105 is provided with tongues 105c and 105d and steps 105e and 105f on its short side, and can be attached to the acrylic imaging head fixing device 102, and will be described later in FIG. It can also be attached to a laboratory animal learning device.

  As shown in FIGS. 2A, 2B, and 2C, the length of the head fixing member 105 in the longitudinal direction is equal to the length of the head fixing frame 1501 of the related art (see FIGS. 15A and 15B). The thickness of the head fixing member 105 is substantially the same as the thickness of both ends of the head fixing frame 1501 in the longitudinal direction. That is, the shape of the head fixing member 105 is compatible with the head fixing frame 1501 of the prior art.

  As shown in FIGS. 1A, 1B, 4 and 5, the imaging head fixing device 102 includes a rectangular substrate 111, columns 112 and 113 provided at both ends of one short side of the substrate 111, columns It has the holding parts 114 and 115 provided on the top of 112 and 113. The substrate 111 carries the body of the rat 301 and plays a role of stabilizing the entire imaging head fixing device 102 by the weight of the rat 301. The pillars 112 and 113 fix the grips 114 and 115 to an appropriate height. The gripping part 114 has a groove 114a into which the head fixing member 105 is inserted. Similarly, the grip 115 has a groove 115a into which the head fixing member 105 is inserted.

  Further, the groove 114 a provided in the grip portion 114 and the groove 115 a provided in the grip portion 115 are slightly smaller than the thickness of the head fixing member 105 so that the head fixing member 105 can be smoothly inserted. Widely formed. The columns 112 and 113 are screwed to the substrate 111 using acrylic screws 116 and 117. Similarly, the grips 114 and 115 are screwed to the columns 112 and 113 using acrylic screws 118 and 119, respectively.

  As a method for fixing the pillars 112 and 113 and the substrate 111, an adhesive such as acrylic or epoxy or an ultraviolet curable resin may be used. An adhesive may be used as a method of fixing the grip portions 114 and 115 and the pillars 112 and 113, but an appropriate gap is formed between the grip portions 114 and 115 and the steps 105e and 105f of the head fixing member 105. In order to achieve this, screwing that can adjust the fixing position is preferable.

As described above, all of the substrate 111, the pillars 112 and 113, and the gripping portions 114 and 115 constituting the imaging head fixing device 102 are made of acrylic. The nut 103 that is bonded and fixed to the skull of the rat 301, the head fixing member 105 that is attached to the nut 103, and the bolt 104 that fixes the head fixing member 105 to the nut 103 are all made of acrylic.

  In addition, the magnitude | size of the head fixing member 105 and the imaging | photography head fixing device 102 is suitably changed according to the physique of a laboratory animal. In this embodiment, the experimental animal is described as the rat 301. However, when the experimental animal is a monkey, for example, the longitudinal width and the short direction of the head fixing member 105 according to the size of the head of the monkey. The width of is also changed. In addition, since the monkey has a larger physique and stronger muscle strength than the rat 301, it is considered necessary to increase the number of bolts 104 used for the head fixing member 105 to three or four.

  The material of the head fixing device 102 for imaging, the head fixing member 105, the nut 103, and the bolt 104 is the first condition. In MRI imaging, the magnetic substance is an artifact on the image (MRI imaging by an artifact). It is not possible to use it because it causes undesired virtual images), and in PET imaging, it is necessary to use a non-metallic substance with low adsorption of RI substance because of the use of RI (radioisotope) substance is there. As a second condition, it is required that the nut 103 and the bolt 104 have a hardness that is high enough to constitute the nut 103 and the bolt 104 and that there is little elastic deformation. Therefore, for example, a PET resin that is easily elastically deformed is not suitable. Further, as the third condition, since the nut 103 is in contact with the experimental animal, the nut 103 does not generate an endocrine disrupting substance (environmental hormone) or the like, and the chemical resistance is at a level necessary to protect the experimental animal. It is required to have reached. Since acrylic satisfies these conditions and is more transparent, it can be said that at the time of filing the present application, it is optimal as a material that can easily visually check the state of an experimental animal. Moreover, although it is inferior to acrylic in that it is not transparent, it is a non-magnetic material and may be a material having no adsorptivity such as RI, for example, a carbon-based, ceramic-based, or hard plastic-based material. In particular, since the substrate 111 of the imaging head fixing device 102 does not have to be transparent at all, the degree of freedom of material selection is higher than that of other components.

  Next, a procedure for fixing the rat 301 to the imaging head fixing device 102 will be described. First, as shown in FIG. 3, a head fixing member 105 is screwed to a rat 301 having an acrylic nut 103 bonded and fixed to a skull with an acrylic bolt 104. Then, the head fixing member 105 is inserted into the grooves provided in the gripping portions 114 and 115 of the imaging head fixing device 102 (see FIG. 4). Then, the head of the rat 301 is completely fixed by the imaging head fixing device 102 and the head fixing member 105, and the head cannot be moved (see FIG. 5). In the state shown in FIG. 5, the rat 301 is subjected to imaging processing by PET imaging.

[Rat 301 equipped with experimental animal learning device 601 and head fixing member 105]
FIG. 6 is an external view of the experimental animal learning apparatus 601, and FIG. 7 is an external view of the motion detection instrument 701 constituting a part of the experimental animal learning apparatus 601. FIG. 8 is a photograph showing a state in which the rat 301 is mounted on the experimental animal learning apparatus 601.

  Referring to FIGS. 6 to 8, the stainless steel cylinder 602 shown in FIG. 6 is a cylinder provided for receiving the body of the rat 301. Further, a head fixing device 605 is fixed to the tip portion of the equipment fixing bar 604 that is provided from the base 603. The head fixing device 605 is provided with a grip portion 606, and the head fixing member 105 is fixed to the grip portion 606.

  The motion detection instrument 701 will be described with reference to FIGS. The motion detection instrument 701 is provided with a manipulator 702 that interlocks with the mouth of the rat 301. The rat 301 holds the manipulator 702 and bites the manipulator 702 as a result of predetermined learning. Then, a switch (not shown) performs an on / off operation in response to the operation of the manipulator 702. As shown in FIG. 8, the body of the rat 301 to which the head fixing member 105 is attached is housed in a stainless steel cylinder 602. Then, the head fixing member 105 is fixed to the head fixing device 605. The rat 301 holds the manipulator 702 and undergoes a predetermined learning experiment.

[Procedure for attaching the nut 103 to the skull of the rat 301]
FIG. 9A is an external perspective view of the nut fixture 901. FIG. 9B is a top view of the nut fixture 901. FIG. 9C is a view of the nut fixture 901 viewed from the lateral direction (arrow direction). In FIG. 9C, an acrylic nut 103, a metal bolt 902, and a nut 903 are attached.

  FIG. 10 is a schematic view showing a state in which the nut 103 is bonded and fixed to the skull of the rat 301 using the nut fixture 901. FIG. 11 is a conceptual diagram showing a state where the nut 103 is bonded and fixed to the skull 1101 of the rat 301. In FIG. 11, the skull 1101 itself of the rat 301 is illustrated for explanation.

  Hereinafter, a description will be given with reference to FIGS. 9A, 9B, and 9C. The nut attachment 901 is made of a metal such as aluminum. 2A, 2B, and 2C, the nut fixture 901 is formed with the same length, the same width, and the same thickness as the head fixing member 105, except that it has a hollow shape. . Further, holes 901 a and 901 b are provided at the same positions as the holes 105 a and 105 b of the head fixing member 105. Further, tongue portions 901c, 901d and steps 901e, 901f are provided at the same positions as the tongue portions 105c, 105d and steps 105e, 105f of the head fixing member 105.

  In order for the head fixing member 105 to be correctly attached to the head of the rat 301, the nut 103 of the head of the rat 301 is disposed at the same position as the hole provided in the head fixing member 105. Need to be done. Therefore, a nut fixture 901 having holes 901a and 901b at the same positions as the holes 105a and 105b provided in the head fixing member 105 is required.

  9A and 9B, a nut 103 to be bonded and fixed to the head of the rat 301 is fixed in advance with bolts 902 and nuts 903, as shown in FIG. 9C. Then, as shown in FIGS. 10 and 11, the nut fixture 901 is fixed to the head fixing device 605 of the experimental animal learning device 601. Then, after the scalp is peeled and the skull 1101 is exposed, the dental treatment bond 302 is thickly applied to the head of the rat 301. Then, the head of the rat 301 is placed directly below the nut fitting 901, The nut 103 fixed to the nut fitting 901 is bonded to the dental treatment bond 302 applied to the head. When the dental treatment bond 302 applied to the head of the rat 301 is solidified, the bolt 902 is loosened and the nut fitting 901 is removed from the nut 103.

  In this way, by attaching the nut 103 whose position is fixed in advance by the nut fitting 901 to the head of the rat 301, as shown in FIG. 11, the nut 103 is in a horizontal state on the skull 1101 of the rat 301. And it arrange | positions in the position completely corresponded with the hole of the head fixing member 105. FIG. The parietal portion of the skull 1101 of the rat 301 has irregularities, but the positioning of the nut 103 on the skull 1101 can be achieved without any problems by providing the dental treatment bond 302 between the nut 103 and the skull 1101.

  FIG. 12A is a photograph showing the head of the rat 301 to which the nut 103 is attached. FIG. 12B is a photograph showing a state in which the head fixing member 105 is fixed to the head of the rat 301 to which the nut 103 is attached. FIG. 13 is a photograph showing the state of the rat 301 attached with the nut 103 in the breeding cage.

  12A, the nut 103 bonded to the skull 1101 of the rat 301 by the nut attachment 901 is accurately positioned and attached by the nut attachment 901, so that the head fixing member 105 is attached as shown in FIG. 12B. It can be fixed securely. For this reason, when the head fixing member 105 is fixed, even if the bolt 104 is tightened, the skull 1101 of the rat 301 is not distorted. Furthermore, compared with the prior art, the nut 103 attached to the head of the rat 301 is extremely small and light in weight, so that the rat 301 can move freely in the breeding cage (see FIG. 13).

[Comparison of Head Fixing Member 105 with Conventional Technology]
A comparative experiment of the head fixing member 105, which is an example of the embodiment of the present invention, with the head fixing frame 1501, which is a conventional technique, was performed and will be described below.
FIG. 14A is a photograph showing a comparison experiment between the head fixing member 105 and the head fixing frame 1501 in PET imaging. FIG. 14B is a graph showing the results of a comparison experiment between the head fixing member 105 and the head fixing frame 1501 in PET imaging. The horizontal axis represents the distance in the longitudinal direction of the imaging head fixing device 102, and the vertical axis represents the quantitative error calculated from the captured PET image.

  In FIG. 14A, a polyethylene container is used as a phantom instead of the rat 301. 18F-FDG (fluorodeoxy glucose) using a fluorine radioisotope fluorine 18 as a tracer was enclosed in this phantom, and continuous imaging processing was performed with a PET imaging device. Then, the quantitative error was calculated from the data obtained by the continuous imaging process. A graph in which quantitative error data in a state where a head fixing frame 1501 of the prior art is attached to a phantom and quantitative error data in a state where the head fixing member 105 according to the embodiment of the present invention is attached is drawn on a graph. It is FIG. 14B. As can be seen from FIG. 14B, the quantitative error of the acrylic head fixing member 105 of this embodiment is reduced by about 30 to 60% compared to the quantitative error of the conventional aluminum head fixing frame 1501. You can see that Further, since the nut 103 is made of a non-magnetic acrylic material, it can cope with MRI imaging without causing an obstacle such as an artifact.

  In the present embodiment, the head fixing device 101 and the nut fixture 901 are disclosed. That is, instead of the head fixing frame 1501 of the prior art, the acrylic nut 103 positioned by using the nut attachment 901 is bonded and fixed to the skull 1101 of the experimental animal. When the experimental animal is learned by the experimental animal learning device 601 or photographed by the PET imaging device, an acrylic head fixing member 105 is attached to the nut 103 bonded and fixed to the head of the experimental animal. Install with bolts 104. The head fixing member 105 is compatible with the head fixing frame 1501 of the prior art because the width and thickness are substantially the same. Therefore, it can be mounted on the experimental animal learning apparatus 601 as it is. Further, if the head fixing member 105 is removed from the head of the laboratory animal, the acrylic nut 103 is only attached to the skull 1101 of the laboratory animal.

  In addition, an acrylic imaging head fixing device 102 was provided for imaging an experimental animal with a PET imaging apparatus. In this embodiment, since all the members are made of non-metallic acrylic, PET imaging errors are reduced. Further, when the experiment or photographing is not performed, by removing the head fixing member 105 from the experimental animal, the experimental animal can realize a life style with little stress, which is substantially the same as before the nut 103 is attached.

  The embodiments of the present invention have been described above. However, the present invention is not limited to the above-described embodiments, and other modifications and application examples are provided without departing from the gist of the present invention described in the claims. including.

DESCRIPTION OF SYMBOLS 101 ... Head fixing instrument, 102 ... Imaging | photography head fixing device, 103 ... Nut, 104 ... Bolt, 105 ... Head fixing member, 111 ... Board | substrate, 112 ... Pillar, 114, 115 ... Gripping part, 116, 118 ... Screw, 301 ... Rat, 302 ... Dental treatment bond, 601 ... Laboratory animal learning device, 602 ... Tube, 603 ... Base, 604 ... Equipment fixing bar, 605 ... Head fixing device, 606 ... Grasping part, 701 ... Operation Detecting instrument, 702 ... manipulator, 901 ... nut fitting, 902 ... bolt, 903 ... nut, 1101 ... skull, 1501 ... head fixing frame

Claims (4)

A plurality of nuts made of non-metal and bonded and fixed to the head of a laboratory animal;
A head fixing member made of a non-metal, having a length exceeding the width of the head of the experimental animal, and having two holes at the same position as the hole of the nut in the center;
A laboratory animal head fixing instrument comprising a plurality of bolts configured of a non-metal and fixing the head fixing member to the plurality of nuts.   The laboratory animal head fixing instrument according to claim 1, wherein the nonmetal constituting the nut, the head fixing member, and the bolt is acrylic. A substrate made of non-metal;
Columns made of non-metal and provided at both ends of one short side of the substrate,
Comprising a non-metal, and a grip portion provided on the top of the pillar,
The gripping part is
A plurality of nuts made of non-metal and bonded and fixed to the head of a laboratory animal;
A head fixing member made of a non-metal, having a length exceeding the width of the head of the experimental animal, and having a plurality of holes at the same position as the hole of the nut in the center;
The end part which exists in the both ends of the longitudinal direction of the said head fixing member of the head fixing instrument for laboratory animals which comprises a plurality of volt | bolts comprised with a non-metal and fixing the said head fixing member to these nuts A head fixing device for photographing a laboratory animal, having a groove into which is inserted. The head fixing device for photographing a laboratory animal according to claim 3, wherein the non-metal constituting the pillar and the grip portion is acrylic.