Functional MRI bed and functional MRI bed system equipped therewith

Abstract

Provided is a bed that enables noninvasive and multipurpose functional MRI imaging.　Provided is a bed system for functional MRI, the bed system having a helmet for immobilizing the head of an animal using a U-shaped appliance.

Description

Technical Field

[0001] The present invention relates to the technical field of functional MRI, for example, the technical field of functional MRI for experimental animals.

Background Art

[0002] Magnetic resonance imaging (MRI) is widely used as a means for measuring brain activity. For conventional awake functional MRI for small animals such as marmosets, mice, and rats, there are few examples of implementation without surgery using an MRI device with a bore diameter of less than 30 cm.

[0003] In conventional awake MRI imaging for small animals, it was necessary to attach a fixing tool (head post or head bar) for fixing the head of the animal to be imaged surgically in order to fix the head of the animal. In the art, generally, among the fixtures attached to the animal's head, a fixture that extends in the vertical direction above the animal's head is called a head post, and a fixture that extends in the forward direction of the animal's head is called a head bar. For example, Non-Patent Document 1 (Yoshida et al., 2016, Journal of Neuroscience Methods, 274, 38-48) reports functional MRI in awake mice, but the head bar is a custom-made product, and the attachment of the head bar to the skull is performed surgically.

[0004] When not using a head bar or head post, it was necessary to fabricate a head fixation device according to the animal, and there was no generally applicable device. For example, Non-Patent Document 2 reports functional MRI of awake, resting marmosets, but a helmet fabricated individually according to the individual is used (Belcher et al., 2013, Journal of Neuroscience, 33(42), 16796-16804), and this is hardly a generally applicable helmet. Furthermore, in conventional MRI imaging, in order to obtain high resolution, an MRI device with a high magnetic flux density was required. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Yoshida et al., 2016, Journal of Neuroscience Methods, 274, 38-48 [Non-Patent Document 2] Belcher et al., 2013, Journal of Neuroscience, 33(42), 16796-16804 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The present invention aims to provide a compact, non-invasive, and versatile bed capable of functional MRI imaging, which at least partially solves the above-mentioned problems. Furthermore, the present invention aims to provide a coil-integrated bed that can bring out the good resolution of an MRI device. [Means for solving the problem]

[0007] The inventors of the present invention have diligently conducted research to solve the aforementioned problems, and as an example, have found that by using an adjustable U-shaped device, it is possible to fix the head in a non-invasive, highly versatile manner that does not require surgery, compared to the conventional method using a head post, and that this enables functional MRI measurement. The inventors have completed the present invention, which incorporates this as one embodiment.

[0008] Furthermore, in demonstration experiments using marmosets, the inventors encountered a situation where, when the bore diameter (inner diameter) of the MRI device was relatively small, such as 10 cm or less, it was not possible to secure sufficient space to place the receiving coil close to the imaging target in order to improve the signal-to-noise ratio of the image. Therefore, the inventors diligently continued their research and developed a mechanism that can achieve both improved image quality and fixation of the head of the imaging target animal by using the receiving coil itself as a fixation device for the imaging target. They found that by using this MRI device (also called the improved MRI device), the receiving coil can be installed even in a narrow space, and thus it is possible to measure awake MRI even in a small space. The inventors completed the present invention, which incorporates this as one embodiment.

[0009] The present invention encompasses the following embodiments. [1] A functional magnetic resonance imaging (MRI) bed comprising a bed section, a collar section and a helmet section, The bed section is configured to hold experimental animals in a sphinx position. The helmet section is designed to fix the head of an experimental animal so that it can be subjected to functional MRI measurements, and it consists of an inner helmet with a built-in coil (receiving coil) and an outer helmet. The collar section is for restraining the neck and shoulders of experimental animals; it is a general-purpose, functional MRI bed. [2] The general-purpose functional MRI bed according to Embodiment 1, wherein the bed, helmet, and collar are made of non-magnetic material. [3] A general-purpose functional MRI bed according to any one of Embodiments 1 or 2, which is for marmosets, mice, rats, macaques, guinea pigs, or human neonates. [4] A functional magnetic resonance imaging (MRI) bed comprising a bed section, a helmet section, a collar section, and a U-shaped device, The bed section is configured to hold experimental animals in a sphinx position. The helmet portion is designed to fix the head of an experimental animal so that it can be subjected to functional MRI measurements, and has a U-shaped device attachment section for attaching a U-shaped device. The collar is for restraining the neck and shoulders of experimental animals. The U-shaped device can be adjusted according to the dimensions and shape of the head of the experimental animal being subjected to functional MRI measurement. A versatile, functional MRI bed. [5] The general-purpose functional MRI bed according to Embodiment 4, wherein the helmet portion has two or more U-shaped device mounting portions for attaching a U-shaped device. [6] The U-shaped device mounting section is configured such that the U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed section, or such that the U-shaped device is mounted diagonally to the longitudinal direction of the MRI bed section, as described in Embodiment 4, or (i) The U-shaped device mounting section is configured such that at least one U-shaped device is mounted diagonally to the longitudinal direction of the MRI bed section, and at least one other U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed section, as described in Embodiment 5. (ii) The general-purpose functional MRI bed according to Embodiment 5, wherein the U-shaped device mounting section is configured such that at least one U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed section, and at least one more U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed section, or (iii) The general-purpose functional MRI bed according to Embodiment 5, wherein the U-shaped device mounting section is configured such that at least one U-shaped device is mounted diagonally to the longitudinal direction of the MRI bed section, and at least another U-shaped device is mounted diagonally to the longitudinal direction of the MRI bed section. [7] A general-purpose functional MRI bed according to Embodiment 6, which is dependent on Embodiment 4, wherein the U-shaped device mounting section is configured such that the U-shaped device is mounted at an acute angle to the longitudinal direction of the MRI bed section, or (i) A general-purpose functional MRI bed according to Embodiment 6, which is dependent on Embodiment 5, wherein the U-shaped device mounting section is configured such that at least one U-shaped device is mounted at an acute angle to the longitudinal direction of the MRI bed section, and at least one other U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed section, (ii) A general-purpose functional MRI bed according to Embodiment 6, which is dependent on Embodiment 5, wherein the U-shaped device mounting section is configured such that at least one U-shaped device is mounted at an acute angle with respect to the longitudinal direction of the MRI bed section, and at least another U-shaped device is mounted at an obtuse angle with respect to the longitudinal direction of the MRI bed section. [8] A general-purpose functional MRI bed according to any of embodiments 4 to 7, wherein the bed, helmet, collar, U-shaped device and screws for securing the U-shaped device are made of non-magnetic material. [9] A general-purpose functional MRI bed according to any of embodiments 4 to 8, for use with marmosets.

[10] A functional MRI bed system comprising a general-purpose functional MRI bed and an MRI device as described in any of embodiments 4 to 9.

[11] A method for performing functional MRI measurements on animals using a general-purpose functional MRI bed described in any of embodiments 4 to 9 or a functional MRI bed system described in embodiment 10.

[12] The method according to embodiment 11, for measuring the brain in a resting state.

[13] The functional MRI measurement method for animals according to Embodiment 11, wherein an image capturing device is placed in front of the face of the animal to be measured, and eye tracking is performed simultaneously with the MRI measurement. This specification includes the disclosures of Japanese Patent Application No. 2021-110184, which forms the basis of the priority claim of this application. [Effects of the Invention]

[0010] This invention allows the same functional MRI bed to be used for different individuals. [Brief explanation of the drawing]

[0011] [Figure 1]It is a configuration diagram of a functional MRI bed system. [Figure 2] It is an elevation view and a plan view of a functional MRI bed (bed unit). [Figure 3] It is a functional MRI bed designed with 3D CAD. [Figure 4] It is a photo of a functional MRI bed produced by a 3D printer. [Figure 5] It is a schematic diagram (left) and a photo (right) of an animal head fixed by a U-shaped device inside a helmet. [Figure 6] A photo and an MR signal waveform of functional MRI of a marmoset using a functional MRI bed system are shown. The upper MR signal is the waveform of the prefrontal cortex, and the lower MR signal is the waveform of the auditory cortex. [Figure 7] A marmoset brain atlas is shown. [Figure 8] It is a diagram showing the amounts of vertical, horizontal, and anteroposterior displacements of the brain to be imaged by MRI. [Figure 9] It is a side view showing the mounting state of the U-shaped device in the helmet part. On the left, the first U-shaped device is mounted at an acute angle with respect to the longitudinal direction of the MRI bed unit, and the second U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed unit. On the right, the first U-shaped device is mounted at an acute angle with respect to the longitudinal direction of the MRI bed unit, and the second U-shaped device is mounted at an obtuse angle with respect to the longitudinal direction of the MRI bed unit. [Figure 10] It is a schematic diagram of an inner helmet and an outer helmet. [Figure 11] It is a photo of an inner helmet with a coil body mounted. [Figure 12] It is a photo of an inner helmet with a coil attached to an animal. [Figure 13] It is a photo of an outer helmet further attached on top of the inner helmet. There are sponges on the left and right of the inner helmet to fix the inner helmet. [Figure 14] The correspondence between a photo (left) and a schematic diagram (right) of an animal with an inner helmet with a coil body mounted and an outer helmet attached is shown. [Figure 15] The image on the left shows a functional MRI of a marmoset using a functional MRI bed system, and the image on the right shows a functional MRI of a marmoset using an improved MRI bed. [Figure 16] This figure shows the vertical, horizontal, and anterior-posterior displacement of the brain being MRI-scanned using a functional MRI bed system. [Figure 17] This figure shows the vertical, horizontal, and anterior-posterior displacement of the brain being MRI-scanned using an improved MRI bed. [Figure 18] These are functional MRI images of rats using an improved MRI bed. Image A shows the result using a coil designed for marmosets, and image B shows the result using a coil specifically designed for rat heads. [Figure 19] These are T2-weighted functional MRI images of rats using an improved MRI bed. Image A shows the result using a marmoset coil, and image B shows the result using a coil specifically designed for rat heads. [Figure 20] This is a CT image of a marmoset taken using a standard MRI bed. [Figure 21] This is an eye-tracking image captured by video recording with a separate video camera during MRI imaging using a standard MRI bed. [Modes for carrying out the invention]

[0012] In one embodiment, the present invention provides a functional MRI bed. In another embodiment, the present invention provides a functional MRI bed system equipped with a functional MRI bed. In one embodiment, the functional MRI bed system according to the present invention has an awake functional MRI system. The functional MRI system has an MRI bed. The functional MRI system may further include a camera and a sensory stimulation device. If audiovisual stimulation is provided by the sensory stimulation device, a screen, projector and / or earphones may be provided. The camera may be connected to a computer so that data from the camera can be taken into the computer. The sensory stimulation device may also provide olfactory stimulation or tactile stimulation. The computer may also control the sensory stimulation device. However, the camera, sensory stimulation device and computer are not essential components and may be connected to external devices. MRI measurements are performed by inserting the functional MRI system into an MRI apparatus and controlling it with a computer as needed. In the present invention, the MRI apparatus has an MRI apparatus body and coils unless otherwise specified. The functional MRI bed system according to the present invention can also be used with computed tomography apparatuses.

[0013] In one embodiment, the functional MRI bed comprises a bed section, a helmet section, a collar section, and a U-shaped restraint. The collar section is for restraining the animal's neck and shoulders. The U-shaped restraint is for restraining the animal's head.

[0014] To perform an MRI measurement, the functional MRI system is inserted into the MRI machine. The coil is positioned to allow MRI measurements of a stationary animal. In one embodiment, the coil is cylindrical and has dimensions that allow the entire functional MRI bed (e.g., the functional MRI bed shown in Figure 3) to be inserted inside the coil. In another embodiment, the receiving coil can be built into an inner helmet. The MRI machine is controlled by a computer, and measurement data from the MRI machine is sent to the computer.

[0015] In this specification, the term "functional MRI bed system" refers not only to the functional MRI bed included in the system, but to the entire functional MRI bed system comprising the functional MRI bed and the MRI apparatus itself. In this specification, the term "functional MRI bed" refers not only to the bed portion included in the functional MRI bed, but to a functional MRI bed comprising the bed portion, helmet portion, collar portion, and U-shaped device. In this specification, a functional MRI bed may simply be referred to as a restraint device. In this specification, a functional MRI bed equipped with a U-shaped device may be referred to as a standard functional MRI bed.

[0016] In one embodiment, the size of the restraint device (functional MRI bed) used for small-diameter MRI with a bore diameter of less than 30 cm is preferably 10 cm in diameter or less. This can be used, for example, for marmosets. The MRI bed section has a collar section for fixing the animal's shoulders and neck, a tunnel section for fixing the waist, and a helmet section for fixing the head. The helmet section is for accommodating the animal's head. Corresponding to the helmet section, the bed section may have a chin rest. The helmet side of the tunnel section may have a collar attachment section for attaching the collar. The opposite side of the tunnel section from the helmet side may have a corset. The corset may be made of a flexible material such as sponge. The corset may also have a cable tie attachment section so that the animal's lower body or hind limbs can be restrained with cable ties. In the case of the corset, adhesive tape may be used instead of cable ties for fastening. The MRI bed section may also have a pocket section for the forelimbs when the animal is in a sphinx position.

[0017] The helmet portion of a standard functional MRI bed may have U-shaped device mounting sections for attaching 1 to 4 U-shaped devices. In one embodiment, the helmet portion has one U-shaped device mounting section. In another embodiment, the helmet portion has two U-shaped device mounting sections. In yet another embodiment, the helmet portion has three U-shaped device mounting sections. In yet another embodiment, the helmet portion has four U-shaped device mounting sections. The U-shaped device mounting sections may be configured so that the U-shaped devices are mounted perpendicular to the longitudinal direction of the MRI bed portion, or so that the U-shaped devices are mounted diagonally to the longitudinal direction of the MRI bed portion. In one embodiment, the helmet portion has two U-shaped device mounting sections, one of which is configured so that the U-shaped device is mounted diagonally to the longitudinal direction of the MRI bed portion, and the other U-shaped device mounting section is configured so that the U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed portion. In yet another embodiment, both U-shaped device mounting sections are configured so that the U-shaped devices are mounted diagonally to the longitudinal direction of the MRI bed. In another embodiment, the two U-shaped device mounting sections are configured such that the U-shaped device is mounted perpendicular to the longitudinal direction of the MRI bed.

[0018] When a U-shaped device is attached diagonally to the longitudinal direction of a standard MRI bed, the angle may be, for example, the angle shown in Figure 2, but is not limited to this. In one embodiment, when a U-shaped device is attached diagonally to the longitudinal direction of an MRI bed, the angle may be, but is not limited to, 45-85 degrees, 50-80 degrees, 55-75 degrees, 60-74 degrees, 65-73 degrees, for example 66-72 degrees, 67-71 degrees, 68-70 degrees, or for example 70 degrees, when the direction perpendicular to the longitudinal direction of the MRI bed is 90 degrees, the longitudinal direction on the animal's nose side is 0 degrees, and the longitudinal direction on the animal's tail side is 180 degrees. When a U-shaped device is attached diagonally to the longitudinal direction of an MRI bed at an angle of less than 90 degrees, for convenience, this specification refers to the U-shaped device being attached at an acute angle to the longitudinal direction of the MRI bed. In another embodiment, when the U-shaped device is attached diagonally to the longitudinal direction of the MRI bed, the angle can be 95-135 degrees, 100-130 degrees, 105-125 degrees, 106-120 degrees, 107-115 degrees, for example 108-114 degrees, 111-113 degrees, 110-112 degrees, for example 110 degrees, when the direction perpendicular to the longitudinal direction of the MRI bed is 90 degrees, the longitudinal direction on the animal's nose side is 0 degrees, and the longitudinal direction on the animal's tail side is 180 degrees, but is not limited to these. When the U-shaped device is attached diagonally to the longitudinal direction of the MRI bed at a large angle exceeding 90 degrees, for convenience, in this specification, the U-shaped device is attached at an obtuse angle to the longitudinal direction of the MRI bed.

[0019] In a standard functional MRI bed, with respect to a helmet section having at least two U-shaped device mounting sections, if at least one U-shaped device mounting section (first U-shaped device) is mounted diagonally to the longitudinal direction of the MRI bed and at least one U-shaped device mounting section (second U-shaped device) is mounted perpendicular to the longitudinal direction of the MRI bed, the first U-shaped device may be mounted at an acute angle to the longitudinal direction of the MRI bed. If at least two U-shaped device mounting sections are configured so that the U-shaped devices are mounted diagonally to the longitudinal direction of the MRI bed, in one embodiment, at least one U-shaped device (first U-shaped device) may be mounted at an acute angle and at least one U-shaped device (second U-shaped device) may be mounted at an obtuse angle. In this case, the dimensions of the helmet may be appropriately designed so that the first U-shaped device restrains the frontal part of the animal's head from the top of the head, and the second U-shaped device restrains the occipital part from the top of the head. In one embodiment, the dimensions of the helmet may be designed based on the average head size of the animal being measured. In another embodiment, the dimensions of the helmet are designed to be larger than the average head size of the animal being measured, and the U-shaped device can be adjusted according to the actual animal being measured.

[0020] The standard functional MRI bed according to the present invention positions the animal to be measured in a sphinx position, and then fixes its head with a U-shaped device. The height of the U-shaped device can be adjusted by, for example, two, four, six, or eight adjustment screws. In one embodiment, the functional MRI bed according to the present invention is preferably adjusted so that the head of a marmoset does not move by more than 0.5 mm (up and down, left and right, and front and back).

[0021] Improved functional MRI bed Standard functional MRI beds are equipped with a U-shaped device. After fixing the animal's head with the U-shaped device, the entire functional MRI bed, as shown in Figure 3, is inserted inside the coil to perform MRI measurements. In contrast, improved functional MRI beds do not use a U-shaped device. Improved functional MRI beds are equipped with a helmet section having an inner helmet and an outer helmet. Examples of the inner and outer helmets are shown in Figure 10, and an example of how they are worn is shown in Figure 13. A coil can be attached to the inner helmet. An inner helmet with a coil attached is sometimes called a coil-integrated inner helmet. The dimensions and shape of the inner helmet can be designed according to the dimensions and shape of the head of the experimental animal of interest (for example, Figures 11 and 12). In one embodiment, the dimensions and shape of the inner helmet are general-purpose. General-purpose means that it is not limited to a specific individual, can be attached to multiple individuals, and functional MRI measurements can be performed on multiple individuals. By using a helmet section having an inner and outer helmet, body movement in the Z-axis direction, i.e., the longitudinal direction, can be suppressed. Furthermore, in a specific embodiment, the inner helmet can be further fixed with sponge or the like. This allows for movement in the X-axis and Y-axis directions, i.e., left to right and up to the animal. under This can reduce body movement.

[0022] The functional MRI bed according to the present invention uses non-magnetic materials unless otherwise specified. For example, in one embodiment, the material of the functional MRI bed according to the present invention may be plastic, acrylic, or resin. Also, in one embodiment, the screws for fixing the U-shaped device are preferably made of a non-magnetic material, including resin. In one embodiment, the screws may be pan head screws, where the head has a larger diameter than the threaded portion. In another embodiment, the screws may be grub screws, where the head has a diameter equal to or smaller than the threaded portion. For example, in one embodiment, by using grub screws, the functional MRI bed can be easily inserted into the MRI device. In one embodiment, the inner helmet may be made of ultraviolet-curing resin. For example, the main frame of the inner helmet can be manufactured by 3D printing, the coil can be fitted to it, and then the ultraviolet-curing resin can be layered on top. In one embodiment, the coil is placed on the inside (animal side) of the inner helmet. In another embodiment, the coil is placed on the outside of the inner helmet.

[0023] In one embodiment, the functional MRI bed according to the present invention is equipped with means for securing the animal's shoulders, neck, and waist. In another embodiment, the functional MRI bed according to the present invention is equipped with a configuration, i.e., pockets, for inserting the forelimbs. This allows the animal to assume a sphinx position, reducing physical strain.

[0024] In one embodiment, the functional MRI bed according to the present invention may be manufactured in whole or in part by 3D printing or injection molding. In another embodiment, the inner helmet may be manufactured by 3D printing or injection molding.

[0025] The functional MRI bed according to the present invention can be used for both small and large animals. In one embodiment, the functional MRI bed according to the present invention is for marmosets. In another embodiment, the functional MRI bed according to the present invention may be for laboratory animals or pets, including mice, rats, guinea pigs, and macaques. In yet another embodiment, the functional MRI bed according to the present invention may be for human neonates.

[0026] In one embodiment, a method for performing functional MRI measurements on an animal using a functional MRI bed according to the present invention is provided. For example, first, the animal is placed on the functional MRI bed. The animal is placed in the tunnel section, with its forelimbs in the pockets to assume a sphinx position. Next, a collar is fitted to secure the neck. Then, the animal's chin is placed on the chin rest, and a helmet is fitted in that position. When using a standard functional MRI bed, a U-shaped device is inserted into the U-shaped device mounting section, and then the U-shaped device is adjusted. At this time, the height of the U-shaped device is adjusted so that the animal's head hardly moves, for example, not more than 0.5 mm in the up / down, left / right, and front / back directions, and then the U-shaped device is secured with screws. When using an improved MRI bed, first, an inner helmet with a coil is fitted to the animal. Depending on the case, the left and right sides of the inner helmet may be stabilized with sponge to prevent the animal from moving. Next, an outer helmet is fitted. The hind limbs and lower body can be secured with cable ties or tape. Then, the functional MRI bed, along with the animal, is set in the MRI device, and a functional MRI measurement is performed.

[0027] The MRI device can be a known or commercially available one. In one embodiment, the MRI device may have a magnetic flux density of 7-14, 7-11.7, or 7-9.4 Tesla, for example, 7.0, 9.4, 11.7, or 14 Tesla, but is not limited to these. In one embodiment, the MRI device may have a bore diameter of 15 cm or less, 14 cm or less, 13 cm or less, 12 cm or less, 11 cm or less, 10 cm or less, 9 cm or less, or 8 cm or less, for example, 7-15 cm, 7.2 cm-14 cm, or 7.2 cm-10 cm. The inner diameter refers to the diameter inside the bore. The functional MRI bed according to the present invention can be designed to fit the dimensions of the MRI device. The design can be done using CAD or 3D CAD, etc. By using the functional MRI bed according to this disclosure, high-resolution functional MRI measurements can be performed even when using an MRI device with standard magnetic force performance (e.g., 7 Tesla, 6 Tesla, 5 Tesla, etc.). For example, in one embodiment, by using the functional MRI bed according to this disclosure, functional MRI measurements can be performed with a resolution comparable to that of conventional methods using an MRI device with high-performance magnetic fields (e.g., 10 Tesla, 11 Tesla, 11.9 Tesla). In one embodiment, the functional MRI bed according to this disclosure may have a resolution per unit magnetic flux density of 0.6 microns / 7 Tesla or higher, i.e., 0.086 microns / Tesla or higher, in the case of marmosets. This represents a higher resolution per unit magnetic flux density than conventional methods that achieve the same resolution at, for example, 11.9 Tesla.

[0028] The functional MRI bed according to the present invention is non-invasive because it does not use a head post. Non-invasive means that no surgical procedure or surgery is required. Furthermore, the functional MRI bed according to the present invention can be used with small-diameter to large-diameter MRI machines. The standard functional MRI bed according to the present invention has a U-shaped device that can be adjusted according to the dimensions and shape of the head of the individual being measured for functional MRI, so there is no need to design a helmet for each individual animal being measured, and it can be used universally for different individuals. Furthermore, the improved functional MRI bed of this disclosure can be used universally for different individuals or different animal species without requiring any surgical procedure or surgery. In this specification, universal means that the same helmet or the same bed can be used for different individuals or different animal species. That is, conventional MRI beds were custom-made, such as designing a first helmet for one individual and a second helmet for another individual, but the functional MRI bed of the present invention can be used universally for different individuals. Furthermore, since the present invention does not require invasive procedures on the head of the target animal, it is possible to analyze and examine the same individual over long periods, such as months or years. In addition, the standard functional MRI bed and the improved functional MRI bed of this disclosure enable functional MRI measurements without anesthesia. This can be used, for example, to measure the brain at rest while the subject is awake. Furthermore, it is possible to extract the default mode network from the measured resting brain activity through analysis. Moreover, brain activity can be measured while stimulating the subject, such as by showing them images. [Examples]

[0029] The present invention will be described in more detail in the following examples, but the present invention is not limited to these.

[0030] Example 1 - Standard functional MRI bed The functional MRI bed shown in Figure 3 was designed using 3D CAD and fabricated using a 3D printer. The material used for the functional MRI bed was resin. Commercially available nylon cable ties were used to secure the animal's lower body. Polycarbonate screws were used to secure the U-shaped device. A photograph of the fabricated functional MRI bed is shown in Figure 4.

[0031] In this embodiment, a 5-year-old male marmoset was placed inside the tunnel section, with its forelimbs in a pocket to assume a sphinx-like posture. Next, a collar was fitted to secure its neck. Then, the marmoset's chin was placed on a chin rest, and a helmet was fitted. Next, a U-shaped device was inserted into the U-shaped device mounting section, and the U-shaped device was secured with screws to fix the marmoset's head in place. In this embodiment, of the two U-shaped devices, the one on the animal's face side was positioned diagonally to the longitudinal direction of the bed, and the one on the back of the animal's head side was positioned relative to the longitudinal direction of the bed. vertical The device was attached to the patient. The lower body was also secured with cable ties. A schematic diagram and photograph of the head being secured are shown in Figure 5. Next, the functional MRI bed was set on the functional MRI device, and functional MRI measurements were performed. The MRI device used was a Bruker PharmaScan 70 / 16, and the measurement conditions were: repetition / echo time; 1500 / 15ms, field of view; 38.4×38.4 mm, image matrix; 96×96, slice thickness; 1 mm, 21 slices, repetitions; 200.

[0032] Brain activity was measured in marmosets when they listened to a phee call, or contact call. The results are shown in Figure 6. The results show a negative correlation between auditory cortex activity and prefrontal cortex activity, indicating connectivity between the two regions. Since it is known that there is a pathway from the auditory cortex to the prefrontal cortex when hearing sounds in both humans and marmosets (Figure 7), this may be a reasonable indication of inter-regional activity.

[0033] To image marmoset brain activity using functional MRI, a spatial resolution of 0.5 mm or less is required. If the experimental animal being scanned moves by more than 0.5 mm, image processing becomes impossible, resulting in unsuitable images. Therefore, it is necessary that the marmoset's head does not move by more than 0.5 mm in the vertical, horizontal, and anterior-posterior directions. Figure 8 shows the results of analyzing the positional displacement of the animal's head in the plane perpendicular to the longitudinal direction of the bed (x-axis, y-axis) and in the longitudinal direction of the bed (z-axis) from the MRI imaging data when the animals were exposed to the aforementioned fee call. The maximum displacement in each axis was 0.23 mm, and the displacement in other axes when this displacement occurred... teeth The measurement was within 0.05 mm. In addition, since we were able to effectively measure the brain activity of marmosets using the fabricated functional MRI bed, it was demonstrated that the functional MRI bed of the present invention can be used for general purposes.

[0034] Figure 9 shows another embodiment of the present invention. In this embodiment, the two U-shaped devices installed inside the helmet are configured such that the animal's face side (forehead side) is at an acute angle to the longitudinal direction of the bed, and the animal's back head side is at an obtuse angle to the longitudinal direction of the bed (Figure 9 right).

[0035] Since the MRI bed according to the present invention is made of an X-ray transparent material, it can also be used for CT scanning.

[0036] As described above, brain activity in marmosets could be measured without surgically attaching a cranial head bar or head post to the animal's head. The functional MRI bed according to the present invention can be used for multiple individuals by adjusting the U-shaped device, and is therefore versatile.

[0037] Example 2 - Improved Functional MRI Bed When the bore diameter of an MRI device is relatively small, such as 10 cm or less, it can be difficult to secure sufficient space to install the receiving coil, which improves the signal-to-noise ratio of the image, near the subject being imaged. Therefore, the inventors have provided a mechanism that allows for both improved image quality and fixation of the animal's head by using the receiving coil itself as a fixation device for the subject being imaged. Using this MRI device (also called the improved MRI device), the receiving coil can be installed even in a narrow space. Furthermore, it is possible to perform awake MRI measurements. This mechanism allows for observation of changes in the brain and organs before and after the administration of specific drugs.

[0038] Improved MRI device The experimental animal's head was secured using a double-layered structure consisting of an inner helmet and an outer helmet. This configuration allows for the incorporation of a coil inside the inner helmet. The inner helmet with the coil is shown in Figures 11 and 12. First, the animal was fitted with the inner helmet, and then the outer helmet was placed on top to further secure the head. The configuration with the outer helmet also attached is shown in Figures 10 and 13. In this configuration, the inner helmet can be further secured with sponge or similar material to reduce the animal's body movement (Figures 13 and 14).

[0039] Next, MRI measurements were performed on animals wearing the improved helmet. The equipment used was as follows: 1) Magnetic Resonance Imaging (MRI) 7.0T MRI system for small animals (Biospec 70 / 16; manufactured by Bruker) (same as Example 1) 2) MRI coil Receiving coil (inner helmet): 4-channel phased array coil (manufactured by Takashima Seisakusho) Transmitter coil: 72mm volume coil (Bruker)

[0040] The information from the MRI scan images is as follows: Imaging area: 38.4 × 38.4 × 21 (mm) Resolution: 0.6 × 0.6 × 1 (mm)

[0041] The results are shown in Figures 15, 16, and 17. The left side of Figure 15 shows the result using the MRI bed from Example 1, while the right side shows the result using the improved MRI bed from Example 2. Similarly, Figure 16 shows the result using the MRI bed from Example 1, and Figure 17 shows the result using the improved MRI bed from Example 2. It was confirmed that the improved MRI bed could suppress animal movement to the same extent as the MRI bed from Example 1. Furthermore, the signal-to-noise ratio improved by approximately twofold when imaging was performed using the improved MRI bed compared to before use (Figure 15).

[0042] First, an inner helmet is fitted, the animal is placed on the MRI bed, and an outer helmet is placed over it to secure the head. This method allows for the acquisition of clearer images compared to conventional methods and the MRI bed used in Example 1. Furthermore, because the entire head is secured, a U-shaped device is unnecessary, reducing the level of discomfort to the animal.

[0043] Furthermore, when the improved MRI helmet was fitted to six different marmosets, functional MRI measurements could be performed on all six. Conventional methods required the use of expensive coils depending on the animal species and individual animal, limiting imaging due to cost. Alternatively, reusing a single coil for multiple animals resulted in inconsistent resolution due to differences in size and shape of the imaging targets. For example, the helmet described in Non-Patent Literature 2 was individually manufactured to fit each animal. The method described in Non-Patent Literature 1 also lacked versatility because the head bar required surgical attachment to the skull, inflicting pain on the animals being imaged. Applying the configuration of this disclosure allows imaging of multiple animal species or multiple individual animals with a single coil without increasing costs. Furthermore, applying the configuration of this disclosure eliminates the need for surgery, thus eliminating the risk factor of surgery and the pain inflicted on the animals.

[0044] Figure 15 shows an awake MRI head image acquired with an improved MRI bed (bore diameter 72 mm, left) and an anesthetized MRI head image acquired with a coil of a diameter suitable for rat imaging (bore diameter 38 mm, right). Even when using an MRI bed with a larger bore diameter, no grainy noise was observed in either the fMRI or T2-weighted images. left and right We were able to obtain a signal-to-noise ratio of a similar magnitude.

[0045] Example 3 - Functional MRI measurement in rats The improved MRI helmet from Example 2 was used on rats as is. The rat's head, fitted with an inner helmet, was secured with sponge and then fixed with the outer helmet. Figure 18A shows images of an awake rat wearing the helmet of the present invention, and Figure 18B shows the results using a conventional fixing device with a coil specifically designed for rat heads; both showed comparable resolution. Figure 19 shows T2-weighted images, which are commonly used in MRI imaging. Figure 19A shows the results of imaging an awake rat using the helmet of the present invention, and Figure 19B shows the results of imaging an anesthetized rat using the same rat-carrying coil as in Figure 18B. The present invention provides comparable resolution to conventional products used on anesthetized rats, even when the rat is awake. Resolution We were able to obtain this result. The helmet of the present invention also enabled the measurement of functional MRI in rats. The configuration of this disclosure allows for imaging of multiple animal species with a single coil.

[0046] Example 4 - CT scan of a marmoset while awake A CT scan of a marmoset was performed using a standard functional MRI bed. Similar to the MRI scan, the marmoset's head was secured with a helmet and U-shaped pins, allowing the CT scan to be performed while the marmoset was awake, as shown in Figure 20.

[0047] Example 5 - Eye Tracking Standard functional MRI beds allow for frontal observation of the face because the head remains still. During MRI scanning of a marmoset in a sphinx posture, video recording was performed from the front of the face, and the iris was detected, enabling simultaneous eye tracking during the MRI scan. Figure 21 shows an image of eye tracking being performed by detecting the iris. [Industrial applicability]

[0048] The functional MRI bed of the present invention can be used for MRI measurements and CT scans of experimental animals.

[0049] This specification references numerous documents, including manufacturer manuals. While the disclosures of these documents are not considered relevant to the patentability of the present invention, their entirety is incorporated herein by reference. More specifically, all referenced documents are incorporated herein by reference in the same manner as each individual document is specifically and individually indicated as being incorporated by reference. [Explanation of Symbols]

[0050] 1: Functional MRI bed 2: Helmet 3: U-shaped fixture 4: Color 5: Tunnel section 6: Corset 7: Sponge 8: Chin rest 9: Pocket 10: Animal heads 11: Screws 20: Outer helmet 21: Inner helmet 22: Improved MRI bed (bed frame) 23: Coil All publications, patents, and patent applications cited herein shall be incorporated herein by direct reference.

Claims

1. A general-purpose functional magnetic resonance imaging (MRI) bed comprising a bed section, a collar section, and a helmet section, The bed section is configured to hold experimental animals in a sphinx position. The helmet section is designed to secure the head of an experimental animal so that it can be subjected to functional MRI measurements, and it consists of an inner helmet with a built-in coil and an outer helmet. The collar is for restraining the neck and shoulders of experimental animals. The bed, helmet, and collar are made of non-magnetic material. The aforementioned general-purpose functional MRI bed, wherein the inner helmet is general-purpose.

2. A general-purpose functional MRI bed according to claim 1, for use with marmosets, mice, rats, macaques, or guinea pigs.

3. The general-purpose functional MRI bed according to Claim 1, wherein the inner helmet is secured by a sponge.

4. A general-purpose functional MRI bed according to claim 1, and a functional MRI bed system equipped with an MRI device.

5. A method for performing functional MRI measurements on an animal, using a general-purpose functional MRI bed according to claim 1, 2, or 3, or a functional MRI bed system according to claim 4.

6. The method according to claim 5, for measuring the brain while at rest.

7. The method for performing functional MRI on an animal according to claim 5, wherein an image acquisition device is placed in front of the face of the animal to be imaged, and eye tracking is performed simultaneously with the functional MRI measurement.

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