Box for holding a small animal for an MRI of the small animal, method for MRI of a small animal, and control unit

Abstract

A box for accommodating a small animal for an MRI of the small animal is provided. The box contains or consists of a bottom wall, at least one side wall, a top wall, at least one magnetic resonance coil, a gas supply channel, and a gas discharge channel. The box is suitable for forming an interior space suitable for accommodating a small animal by merging the bottom wall, the at least one side wall, and the top wall, wherein the interior space is suitable for preventing the small animal from leaving the interior of the box and entering an exterior space of the box. A method for MRI of a small animal and a control unit are also provided.Using the box, the procedure and the control unit, it is possible to perform an MRI scan of a small animal with a high signal-to-noise ratio in a simple, fast, cost-effective and space-saving manner with minimal risk to the health of the box users.

Description

A box for holding a small animal is provided for an MRT of the small animal. The box contains or consists of a base wall, at least one lateral wall, a top wall, at least one magnetic resonance coil, a gas supply channel and a gas discharge channel. The box is suitable for forming, by bringing the bottom wall, the at least one lateral wall and the top wall together, an interior suitable for receiving a small animal, wherein the interior is suitable for preventing the small animal from leaving the interior of the box and entering an exterior of the box. A method for MRI a small animal and a control unit are also provided. With the box, the method and the control unit, it is possible to perform an MRI recording of a small animal at a high signal-to-noise ratio in a simple, fast, cost-effective and space-saving manner with a minimum risk for the health of users of the box.The demand for high resolution small animal MRI is constantly increasing. Dedicated small animal systems which operate with field strengths usually in the range of 4 T to 7 T and often also above, meet high demands on the image quality, but have the disadvantage that a direct translation of the results to the clinical situation is not possible on account of the high field strengths.Due to this drawback, dedicated little animal systems are increasingly being provided that operate with a low field strength (i.e. field strengths in the range of <4 T, e.g. 3 T). An example is the dedicated small animal system "BioSpec Maxwell" from "Bruker Biospin MR" solution. Such systems are becoming increasingly relevant in the context of preclinical research, in particular for translational questions. However, the known small animal systems have some disadvantages. For example, the known systems with small animal inserts are very cost-intensive (>0.5 million Euros) in their purchase, cause considerable operating costs (trained personnel are necessary for their operation, e.g. a physicist or technician) and require a large space.It is also known that by using MR local coils next to the main coil of a magnetic resonance tomography (MRI apparatus), i.e. MR coils which are placed very close to a small animal to be examined, the signal-to-noise ratio during imaging can be improved and the measurement times can be shortened (Doty, F. D. et al., NMR in Biomedicine, 20:304-325).It is also known to attach MR local coils for a small animal to a small animal positioning system (see Abraham, C.B. et al., International Journal of Hyperthermia, 35(1):348-360). In known small animal positioning systems, a large surface area of the small animal is exposed and, in the case of MRI recording of living small animals, the small animal is in gas exchange with the environment as a result of its breathing. This has the disadvantage that, for example, microorganisms and / or viruses which are present on the surface of the small animal and / or in the exhalation air of the small animals can penetrate into the environment. If the small animal positioning system for performing an MRI is now placed in a clinical MRI apparatus, there is a risk that surfaces of the MRI apparatus will be contaminated. This can represent a health risk for small animals and / or humans who are going into the MRT device after the execution of the MRT in such a small animal. It may also be a health risk for clinical personnel using the small animal positioning system and MRI apparatus. The same applies to known small animal positioning systems which do not immobilize the small animal sufficiently, i.e. in which there is a risk that the small animal leaves the small animal positioning system during the MRI.Proceeding from this, it was the object of the present invention to overcome at least one disadvantage of the systems known in the prior art. In particular, a device, a method and a control unit should be provided with which it is possible to perform an MRI recording of a small animal at a high signal-to-noise ratio (even at low field strengths <4 T) in a simple, fast, cost-effective and space-saving manner with a minimum risk for the health of a user of the box (e.g. clinic personnel).The object is achieved by the box having the features of claim 1, the method having the features of claim 12 and the control unit having the features of claim 17.According to the invention, a box for accommodating a small animal and / or a bird's egg is provided, which box is suitable for magnetic resonance tomography (MRI) of the small animal, containing or consisting of: a) a base wall; b) at least one lateral wall; c) a top wall; d) at least one magnetic resonance coil; e) a gas supply channel; and f) a gas discharge channel; wherein the box is suitable for forming an interior space, which is suitable for accommodating a small animal and / or a bird's egg, via a merging of the base wall, the at least one lateral wall and the top wall, wherein the interior space is furthermore suitable for preventing the small animal from leaving the interior space of the box and entering an exterior space of the box.The box according to the invention can be provided easily and quickly. Furthermore, the box according to the invention makes it possible, by bringing together its walls, to arrange a small animal in a simple and quick manner in an interior space of the box. It can thus be prevented that the small animal can leave the interior of the box, whereby a risk for the safety of users of the box is reduced. Together with the at least one magnetic resonance coil of the box, the box thus allows an MRT to be carried out on a small animal with greater certainty for the health of a user of the box using a magnetic resonance tomography (MRT device).Due to the fact that for imaging the at least one magnetic resonance coil of the box can be coupled (e.g. inductively coupled) to a main coil of the magnetic resonance tomograph (e.g. to a built-in whole body coil QBC of the magnetic resonance tomograph) and in the process a signal induced by the at least one magnetic resonance coil of the box in the main coil of the magnetic resonance tomograph is acquired by means of reception paths present in the magnetic resonance tomograph, the box according to the invention can be used independently of the measurement technique used and thus universally in known clinical MRI apparatuses. The box can be used independently of the manufacturer of the MRI device, independently of the software installed on the MRI device (e.g. installed sequences, reconstruction and data analysis tools) and independently of a design stage of the MRI device. To carry out the imaging, it is only necessary to position the small animal in the box and then position the box with the small animal (for example by means of a normal patient bed) in an MRI apparatus (already present). For imaging, the clinical sequences present on the MRI apparatus can be used and the data acquisition and evaluation can take place according to a clinical routine. This results in particular in advantages with respect to the translation of preclinical results into the clinic, but also in great cost advantages through the use of existing MRI devices for preclinical applications.Due to the fact that the box according to the invention can be designed to be very small, i.e. the interior space of the box can be matched to the dimensions of a specific small animal to be examined, the space requirement of the box can be very small. This is a great advantage especially in the case of narrow premises (e.g. in a clinic).Due to the local proximity that the at least one magnetic resonance coil of the box has to a small animal, which is arranged in an interior of the box, high signal-to-noise ratios and short measurement times are possible in the MRI (effect of a local coil). The attainable signal-to-noise ratios exceed the signal-to-noise ratios by a multiple without using the box (i.e., with simple positioning of the small animal in an MRI apparatus without the box). Excellent imaging is thus also possible with magnetic resonance tomography systems which have only a low field strength (e.g. a field strength of <4 T).In summary, it is therefore possible with the box according to the invention to perform an MRT recording of a small animal at a high signal-to-noise ratio (even at low field strengths<4 T) in a simple, fast, cost-effective and space-saving manner with a minimum risk for the health of a user of the box.The bottom wall may transition seamlessly into the at least one side wall, i.e. be integral with the at least one side wall (e.g. the bottom wall and the side wall may have a U-shape). Further, the ceiling wall may transition seamlessly into the at least one sidewall, i.e., be integral with the at least one sidewall (e.g., the ceiling wall and the sidewall may have the shape of an inverted U). It is also conceivable that the bottom wall, the top wall and at least one further side wall, which is different from the at least one side wall, merge seamlessly into one another, i.e. form a one-piece construct, e.g. a tube open at one end. In the one-end open tube, a merging of the one-end open tube with the at least one sidewall may form the interior (e.g., by closing the open end of the open tube with the at least one sidewall).In a preferred embodiment of the box, the bottom wall, the at least one lateral wall and the top wall of the box can be connected in such a way that an interior for receiving a small animal is formed, wherein the small animal is preferably a small rodent, particularly preferably a mouse or a rat. Furthermore, the bottom wall, the at least one lateral wall and the top wall of the box can be connected in such a way that an interior space for accommodating a bird egg is formed, wherein the bird egg is preferably a chicken egg. In this case, the box can have smaller dimensions than when the interior space is suitable for receiving a small animal.It is also possible for the bottom wall, the at least one lateral wall and the top wall of the box to be connectable in such a way that an interior space having a volume in the range from 0.1 dm 3 to 200 dm 3, preferably 0.2 dm 3 to 100 dm 3, particularly preferably 0.5 dm 3 to 50 dm 3, very particularly preferably 1.0 dm 3 to 10 dm 3, in particular 2.0 dm 3 to 6.0 dm 3, is formed. The smaller the interior space, the smaller the overall dimensions of the box, and the greater the advantage that the box enables operation in a confined space.In a preferred embodiment, the bottom wall, the at least one lateral wall and the top wall of the box can be connected in such a way that tight, preferably gas-tight, connection points are produced. The advantage is that it can be ensured that no biological working substances according to EC Directive 2000 / 54 / EC of 18.09.2000, changed by EU Directive 2019 / 1833 of 24.10.2019 and EU Directive 2020 / 739 of 03.06.2020 (i.e. no microorganisms and / or viruses) which the small animal has can leave the interior of the box and can enter an exterior of the box (i.e. e. g. an accommodation space of a magnetic resonance tomography system). This increases the health safety of persons (e.g. patients) who use the magnetic resonance tomography system during or after imaging on the small animal.The bottom wall, the at least one lateral wall and the top wall of the box can be connected in such a way that an interior space is formed which is suitable for not allowing biological working substances of group 1, 2, 3 or 4 to pass into an exterior space of the box according to the EC Directive 2000 / 54 / EC of 18.09.2000, changed by the EU Directive 2019 / 1833 of 24.10.2019, and the EU Directive 2020 / 739 of 03.06.2020 (i.e. the interior space is suitable for preventing the egress of said biological working substances). The higher the group of biological working substances is situated, the more reliable a use of the box for the health of persons (e.g. patients) who use the magnetic resonance tomography system during or after imaging on the small animal.The at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, can / can be suitable for being coupled to a magnetic resonance tomograph by cable.Alternatively, the at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, can be suitable for being inductively coupled wirelessly to a magnetic resonance tomography system. It is possible here for the at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, to (in each case) not have / have a cable which can be coupled to a magnetic resonance tomography system. The advantage is that the box can be made structurally more compact and its use is simplified. It should be mentioned here in particular that the box can be operated independently of the proprietary coil connections of the manufacturers and does not have to be galvanically connected to the MRT device.The box may have an anesthetic mask. The advantage is that an anesthetic gas can be directed into the interior of the box. Using the anesthetic gas, a small animal in the interior of the box can be sedated or anesthetized. The advantage is that the quality or sharpness of the imaging is improved, since a sedated or anesthetized small animal moves only slightly, if at all, in the interior of the box during the imaging with the aid of an MR system.The anesthetic mask is preferably fastened to the bottom wall, to the at least one lateral wall, or to the top wall of the box, particularly preferably to the bottom of the box. A fastening to the base wall has the advantage that the anesthetic mask is arranged very stably in the interior of the box and, in the event of the base wall being moved apart from the at least one lateral wall and the top wall and / or from the top wall, can remain on this part of the box.The anesthetic mask can be fluidically connected to a gas line which is arranged at least in regions in the gas supply channel of the box. The advantage of the at least regional arrangement of the gas line or anesthetic gas line within the gas supply channel of the box has the advantage that the anesthetic gas line is protected against external mechanical influences and the box can be made more compact. The gas conduit may be connected to a source of anesthetic gas, optionally wherein the source of anesthetic gas is communicatively connected to a controller of the box. The connection to the source of anesthetic gas allows anesthetic gas from the source of anesthetic gas to be introduced into the interior of the box. The connection of the source of anesthetic gas to a control unit of the box allows control of the amount of anesthetic gas that is directed into the interior of the box. If the box in the interior contains a suitable gas sensor, which is also communicatively connected to the control unit, even a regulation of the amount of anesthetic gas introduced into the interior of the box is possible.Furthermore, the box may have a temperature sensor. The temperature sensor may be configured to sense a temperature in the interior of the box and / or a body temperature of a small animal in the interior of the box. The advantage is that a body temperature of a small animal located in the interior of the box can be detected directly or indirectly and can also be monitored.The temperature sensor is preferably arranged on the bottom wall, on the at least one lateral wall, on the top wall, in the gas feed channel or in the gas discharge channel of the box. An arrangement in the gas feed channel has the disadvantage that only a temperature of a gas fed to the interior of the box can be detected and monitored, which only allows an indirect conclusion to be drawn about the temperature in the interior of the box. The advantage, however, is that the box can be made more compact, since no space for the temperature sensor is lost in the interior of the box. An arrangement in the gas discharge channel has the advantage that although the temperature in the interior can be detected indirectly, it can be detected more correctly than in the arrangement in the gas feed channel and the box can likewise be designed to be very compact. Although an arrangement on the bottom wall, the at least one lateral wall or on the top wall is connected with a certain loss of space in the interior of the box, it allows a direct (i.e. more accurate) measurement of the temperature of the environment of the small animal in the interior of the box.The temperature sensor may be suitable for being attached to or in an animal, preferably rectally attached to or in an animal. The proximity to the small animal produced thereby permits a very accurate and reliable measurement of the body temperature of the small animal.Further, the temperature sensor may be communicatively connected to a control unit of the box. The advantage here is that the control unit receives information about a body temperature of the small animal or a temperature in the interior of the box and can use this for controlling or regulating a heating element of the box.In addition, the temperature sensor can be connected to a cable, wherein the cable is suitable for being connected to a magnetic resonance tomography system. The advantage here is that the magnetic resonance tomography apparatus is provided directly with information about a body temperature of the small animal or about a temperature in the interior of the box and this can be taken into account during the imaging.The box may have at least two electrodes. The advantage here is that an electrocardiogram of the small animal can be recorded and can also be taken into account during the imaging.The at least two electrodes can be arranged on the bottom wall of the box, preferably arranged in a region in the middle of the bottom wall. The advantage is that the two electrodes can be arranged in a simple manner beneath a small animal and the small animal can establish an electrically conductive contact with the at least two electrodes in a reliable manner via its body weight.Further, the at least two electrodes may be communicatively connected to a control unit of the box. The advantage is that the control unit of the box is provided with information (i.e. electrical signals) of the at least two electrodes and the control unit can use these for open-loop or closed-loop control. The electrical signals of the at least two electrodes can be taken into account, for example, during imaging with the aid of an MR device (i.e. a magnetic resonance tomography system), which can further improve the signal-to-noise ratio.The at least two electrodes may each be connected to a cable, the cables being adapted to be connected to an electrocardiogram device. The advantage here is that the information (i.e. electrical signals) is made available directly to an electrocardiogram device and therefore an electrocardiogram of a small animal located in the interior of the box can be recorded. Further, the box may have at least three electrodes or at least four electrodes. In this case, the at least three electrodes or at least four electrodes can each be connected to a cable, wherein the cables are suitable for being connected to an electrocardiogram device.Apart from this, the box may comprise a respiration sensor for detecting a respiration activity. The advantage is that a breathing of a small animal located in the interior of the box can be detected and monitored.The respiration sensor can be arranged on the bottom wall of the box, preferably in a region in the middle of the bottom wall. This arrangement has the advantage that the body weight of the small animal establishes a stable connection of the sensor to the small animal, which provides reliable results.The respiration sensor may be communicatively connected to a control unit of the box. The advantage is that information about the breathability can be used by the control unit for control or regulation. For example, respiratory activity can also be taken into account in imaging using an MR device, which can improve the signal-to-noise ratio.The respiration sensor can be connected to a cable, wherein the cable is suitable for being connected to a magnetic resonance device, preferably to a scanner of an MR device. By means of this measure, information about a breathability of a small animal located in the interior of the box is made available directly to the MR device (i.e., a magnetic resonance tomography system). The information can thus be used directly during the imaging to improve the signal-to-noise ratio.The box may comprise a control unit. The advantage is that the box is thereby suitable for controlling or regulating certain operations.The control unit may be configured to control or regulate an amount of anesthetic gas supplied to an anesthetic mask of the box, wherein the box preferably comprises a sensor for detecting a concentration of anesthetic gas communicatively connected to the control unit of the box. The advantage is that an excessively low or excessively high dosage of anesthetic gas can be avoided and a small animal located in the interior of the box can thus be put under anesthetic in a more secure and reliable manner.Further, the control unit may be configured to detect a temperature from a temperature sensor of the box, wherein the control unit is preferably configured to regulate a temperature of at least one gas supplied to the box via the gas supply channel based on the detected temperature. The supplied gas may be supplied air and / or a supplied anesthetic gas, i.e. a temperature of air and / or a supplied anesthetic gas may be controlled by the control unit.The control unit is preferably communicatively connected to a heating element of the box. An advantage is that the heating element of the box can be controlled by the control unit of the box and thus, for example, a temperature of air and / or a supplied anesthetic gas can be controlled by the control unit. A further advantage is that too low a temperature or too high a temperature in the interior of the box or body temperature of a small animal in the interior of the box can be avoided and thus a small animal located in the interior of the box can be held at a specific temperature in a more secure and reliable manner. This can ensure that ethics criteria are met securely.In addition, the control unit can be configured to acquire signals from at least two electrodes of the box, wherein the control unit is preferably configured to provide the signals via an electronic data transmission interface of the box, in particular to provide an electrocardiogram device and / or a magnetic resonance tomography device which is / are communicatively connected, preferably in a wireless manner, to the electronic data transmission interface. The advantage is that a heart activity of a small animal located in the interior of the box can be detected and monitored and said heart activity can be taken into account in the imaging. This can improve imaging.Apart from this, the control unit may be configured to detect signals from a respiration sensor of the box. The controller may be configured to use the signals of the respiration sensor to control an amount of anesthetic gas directed into an anesthetic mask of the box. This results in the advantage that anaesthesia of a small animal can be controlled on the basis of the breathing frequency of the small animal. Further, the controller may be configured to provide the signals of the breathing sensor via an electronic communication interface of the box. Apart from this, the control unit can be configured to provide the signals of the respiration sensor to a device for detecting a respiration activity and / or a magnetic resonance tomography device which is / are communicatively connected, preferably in a wireless manner, to the electronic data transmission interface. The advantage is that a breathability of a small animal located in the interior of the box can be detected and monitored and said breathability can be taken into account in the imaging. This can improve imaging. Apart from this, a detected breathability can be used to regulate a flow of an oxygen-containing gas via the gas supply channel into the interior of the box in order to ensure a desired breathability in the small animal.Furthermore, the control unit can be configured to adapt a resonance frequency of the at least one magnetic resonance coil of the box to a resonance frequency of a main coil of a magnetic resonance tomography system. The advantage is that the signal-to-noise ratio can be significantly increased by said adaptation, since the energy transmission between the two coils is particularly efficient and, with the aid of the resonance condition (i.e. in that the at least one magnetic resonance coil is resonant at the Larmor frequency), a signal increase of the signal induced by the object into the coil is achieved. This enables a marked increase in the signal-to-noise ratio compared to a lack of matching of the resonant frequencies of the two coils. Improving the signal-to-noise ratio may shorten the measurement time and / or improve the resolution of the generated MRI images. The control unit may have the configuration of a control unit according to the invention (see below for details).The gas supply channel may be connected to a gas source containing oxygen, optionally wherein the gas supply channel is connected to an air source. The advantage is that the interior of the box can be supplied with oxygen and thus survival of a small animal located in the interior of the box can be ensured even if the box has gas-tight connection points between the bottom wall, at least one lateral wall and the top wall.Furthermore, the gas feed channel can be connected to a heating element which is suitable for heating an oxygen-containing gas in the gas feed channel and / or an anesthetic gas in an anesthetic gas line within the gas feed channel to a predefined temperature, wherein the heating element optionally contains or consists of a heating wire. The advantage is that the oxygen-containing gas and / or the anesthetic gas can be heated (e.g. to 37° C.) even before it enters the interior of the box, and thus a desired climate for a small animal located in the interior of the box can be created.In addition, the gas feed channel can be arranged in the bottom conversion, in the at least one lateral wall or in the top wall, preferably in the bottom wall. An arrangement in the base wall has the advantage that the gas supply channel is arranged very stably in the interior of the box and, if the anesthetic mask is also fastened to the base wall, only short transport paths for the anesthetic gas are formed, as a result of which the box can take up less installation space or more space is available in the interior of the box for receiving a small animal.The gas discharge channel may include a filter adapted to filter the gas in the gas discharge channel. The advantage is that contamination of the exhaust air of the interior of the box (e.g. with microorganisms and / or viruses which a small animal has in the interior of the box) can be avoided. This increases the health safety for a user of the box.The filter may be a filter suitable for not passing biological working substances of group 1, 2, 3 or 4 according to EC Directive 2000 / 54 / EC of 18.09.2000, changed by EU Directive 2019 / 1833 of 24.10.2019 and EU Directive 2020 / 739 of 03.06.2020. The higher the group, the more stringent the requirements on the filter and the safer a user of the box.The gas discharge channel can be arranged in the bottom conversion, in the at least one lateral wall or in the top wall, preferably in the bottom wall. The advantage of an arrangement in the base wall is a high stability.The box can have (in total) at least two, preferably at least ten, particularly preferably at least 20, very particularly preferably at least 50, in particular at least 100, optionally at least 128, magnetic resonance coils. The more magnetic resonance coils the box has, the higher the local signal-to-noise ratio can be, or the larger the high signal-to-noise ratio range can be (FOV).The magnetic resonance coils can each be multi-core magnetic resonance coils. In this case, the different cores of the coils can be measured simultaneously or subsequeously using the same MRI system.Furthermore, the magnetic resonance coils can be present in an array, in particular in an array of multi-core coils.In addition, the magnetic resonance coils can be suitable for capturing signals of different magnetic resonance-representable nuclei either simultaneously or sequentially. In this case, the different cores of the coils can be measured simultaneously or subsequeously using the same MRI system.According to the invention, a method for magnetic resonance tomography (MRI) of a small animal is also provided, comprising or consisting of the following steps: a) recording a small animal into the box according to the invention; b) moving the box into a magnetic resonance tomograph; c) coupling (e.g. inductively or by cable) the at least one magnetic resonance coil of the box with a magnetic resonance tomograph; d) recording magnetic resonance tomography images by the magnetic resonance tomograph, wherein a signal, which is recorded by the at least one magnetic resonance coil of the box, is recorded by the magnetic resonance tomograph inductively or by cable connection.The method has the advantages mentioned above in connection with the box according to the invention.Before step c) of the method, an adaptation of a resonant frequency of the at least one magnetic resonance coil of the box to a resonant frequency of a main coil of the magnetic resonance tomography system can take place, wherein a control unit of the box is preferably configured to carry out the adaptation. The advantage of this adaptation is that the signal-to-noise ratio increases and thus higher-resolution images of the small animal can be generated with the method or lower-resolution images can be generated with the method in a more rapid manner.The coupling of the at least one magnetic resonance coil of the box to the main coil of the magnetic resonance tomography apparatus in step c) of the method can be an inductive coupling, wherein the inductive coupling is preferably an i) continuous resonant coupling during an excitation and a reception of signals; or ii) in the case of an excitation is non-resonant coupling.In the case of continuous resonant coupling (T / R) during excitation (T) and reception (R) of signals, a local B1 increase takes place due to the coupling even in the case of excitation. This allows a high excitation angle locally at a globally low excitation angle. The advantage is that very broadband excitation pulses can be realized since power limitation (B 1) of the whole body systems can be bypassed, i.e. more power is locally available at low power which is required. (This is limited on the MRT system by SAR limit values).A coupling that is non-resonant in the case of excitation, i.e. a coupling only in the case of reception (R), can easily be achieved passively by integration of crossed diodes, which limit the maximum current in the case of excitation and thus limit the local B1 overshoot. When the diodes turn on, the magnetic resonance coil is no longer tuned to the Larmor frequency, for example, when the diodes short-circuit the capacitance that produces the resonance. At the low currents in the reception case, the diodes have no influence. The advantage is that an increase in the signal-to-noise ratio results (in the case of reception).Furthermore, the coupling of the at least one magnetic resonance coil of the box to the magnetic resonance tomography apparatus in step c) of the method can be a wired coupling, wherein the wired coupling is preferably an i) continuous resonant coupling during excitation and reception of signals; or ii) is non-resonant coupling during excitation.The acquisition of magnetic resonance tomography images by the magnetic resonance tomography apparatus in step d) of the method can take place as a function of a heart rate and / or a respiratory activity of the small animal, wherein preferably a signal of an electrocardiogram device and / or a respiratory signal of a respiratory sensor of the box is transmitted to the magnetic resonance tomography apparatus.According to the invention, a control unit is also provided which is configured to adapt a resonant frequency of at least one magnetic resonance coil to a desired resonant frequency of a main coil of a magnetic resonance tomography system, wherein the control unit is configured to carry out the following steps for this: a) measurement of an existing resonant frequency of the at least one magnetic resonance coil of the box; b) adaptation of a tuning capacitance of an resonant circuit on the basis of the difference determined in step a), preferably by means of a varactor; and c) repeating steps a) and b) until a desired accuracy is achieved, wherein the desired accuracy preferably means a correspondence of the resonant frequency measured in a) with a resonant frequency of the magnetic resonance tomograph, wherein the correspondence means an identity of the two resonant frequencies with an error which lies within half the maximum of the full width ("full width half maximum" or "FWHM") of a resonant curve of the main coil of the magnetic resonance tomograph.The advantage of the control unit is that it can improve the signal-to-noise ratio and thus higher-resolution MR images of a small animal can be obtained. The box according to the invention can have the control unit according to the invention.The object according to the invention is intended to be explained in more detail on the basis of the following figures, without wishing to restrict it to the specific embodiments shown here. FIG. 1 schematically shows a structure of a box according to the invention for recording a small animal for magnetic resonance tomography of the small animal. The box comprises a bottom wall 1, at least one lateral wall 2, a top wall 3, at least one magnetic resonance coil 4, a gas supply channel 5 and a gas discharge channel 6. The box is suitable for forming an interior space suitable for receiving a small animal via a merging of the bottom wall 1, the at least one lateral wall 2 and the top wall 3, wherein the interior space is further suitable for preventing the small animal from leaving the interior space of the box and entering an exterior space of the box. In the embodiment shown here, the box further contains an anesthetic mask 7 which is connected to a gas line 8. Moreover, the box includes a temperature sensor 10, two electrodes 11 and a respiration sensor 12, except that the box includes a control unit 13. FIG. 2 schematically shows a structure of the further box according to the invention. The further box according to the invention has the features of the box shown in Fig. 1 and also has a gas source 14 containing oxygen and a source 9 of anesthetic gas. The gas source 14 is fluidically connected to the gas supply channel 5 of the box, wherein a heating element 15 is arranged in the gas supply channel in order to heat gas of the gas source. The source 9 of anesthetic gas is fluidically connected to the anesthetic mask 7 of the box. In this further box according to the invention, a filter 16 is arranged in the gas discharge channel 6. FIG. 3 shows phantom measurements for quantifying the signal-to-noise ratio gain, which were carried out using a box according to the invention and the MRT device "Philips dStream 3.0 T". All data were acquired with a resolution of 150 μm by means of a FLASH sequence. For the various approaches (receive-only (R) and transmit-receive (T / R) with 15° and 1° excitation angles, an excellent fill factor and a local B1 superelevation could be achieved by using the box according to the invention in comparison with the main coil (QBC coil) installed in the MRT device, such that signal-to-noise ratio gains between 6 and 17 were achieved. A further advantage is that the signal-to-noise ratio increases quadratically with respect to the measurement time and the improvements correspond to a measurement time reduction by a factor of 36 to 289, i.e. the measurement times can be significantly shorter. Figure 4 shows an ex vivoimage of a mouse brain positioned in a box according to the invention and from which MRT was performed with the MRT device "Philips dStream 3.0 T". In Figure 4A, the acquisition time 14 hours was 38 min and the resolution 60x60x100μm 3. In Figure 4B, the acquisition time was only 1 min 37s and the resolution was only 170x180x500μm 3. Figure 5 shows in vivoimages of a mouse positioned in a box according to the invention and from which MRT was performed using the MRT device "Philips dStream 3.0 T". In Figure 5A, the images were obtained with a 20-TSE sequence at an acquisition time of 7 min. In Figure 5B, the images were recorded with a 30-MP RAGE sequence at an acquisition time of 10 min. The resolution was 150x150x500 μm 3. in both cases.List of reference characters1 Bottom wall of the box; 2 at least one lateral wall of the box; 3 top wall of the box; 4 at least one magnetic resonance coil of the box; 5 gas supply channel of the box; 6 gas discharge channel of the box; 7 anesthetic mask; 8 gas line of the anesthetic mask; 9 source of anesthetic gas; 10 temperature sensor; 11 two electrodes; 12 respiration sensor; 13 control unit; 14 gas source containing oxygen; 15 heating element in / at the gas supply channel; 16 filter in the gas discharge channel.References included in the specificationThis list of documents cited by the applicant has been produced in an automated manner and is only included for the better information of the reader. The list is not part of the German patent application or utility model application. The DPMA does not take any adhesion for any faults or omissions.Cited Non-Patent LiteratureDoty, F. D. et al., NMR in Biomedicine, 20:304-325

[0004] Abraham, C.B. et al., International Journal of Hyperthermia, 35(1):348-360

[0005]

Claims

A box for receiving a small animal for magnetic resonance tomography of the small animal, containing or consisting of: a) a base wall; b) at least one lateral wall; c) a top wall; d) at least one magnetic resonance coil; e) a gas supply channel; and f) a gas discharge channel; wherein the box is suitable for forming an interior space suitable for receiving a small animal via a merging of the base wall, the at least one lateral wall and the top wall, wherein the interior space is further suitable for preventing the small animal from leaving the interior space of the box and entering an exterior space of the box.Box according to the preceding claim, characterized in that the bottom wall, the at least one lateral wall and the top wall can be connected in such a way that i) an interior space for receiving a small animal and / or a bird egg is formed, wherein the small animal is preferably a small rodent, particularly preferably a mouse or a rat, and / or wherein the bird egg is preferably a chicken egg; and / or ii) an interior having a volume in the range from 0.1 dm 3 to 200 dm 3, preferably 0.2 dm 3 to 100 dm 3, particularly preferably 0.5 dm 3 to 50 dm 3, very particularly preferably 1.0 dm 3 to 10 dm 3, in particular 2.0 dm 3 to 6.0 dm 3, is formed; and / or iii) dense, preferably gas-tight, connection sites are formed; and / or iv) an interior space is formed which is suitable for not allowing biological working substances of group 1, 2, 3 or 4 to pass into an exterior space of the box according to the EC Directive 2000 / 54 / EC of 18.09.2000, changed by the EU Directive 2019 / 1833 of 24.10.2019 and the EU Directive 2020 / 739 of 03.06.2020.Box according to one of the preceding claims, characterized in that the at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, is / are suitable for being coupled to a magnetic resonance tomography system i) by cable; or ii) to be inductively coupled wirelessly, wherein the at least one magnetic resonance coil, preferably all magnetic resonance coils of the box, do not have a cable which can be coupled to a magnetic resonance tomography system.Box according to one of the preceding claims, characterized in that the box has an anesthetic mask, wherein the anesthetic mask is preferably i) fastened to the bottom wall, to the at least one lateral wall, or to the ceiling wall of the box, particularly preferably fastened to the bottom of the box; and / or ii) fluidically connected to a gas line which is arranged at least in regions in the gas feed channel of the box, wherein the gas line is particularly preferably connected to a source of anesthetic gas, wherein the source of anesthetic gas is optionally communicatively connected to a control unit of the box.Box according to any of the preceding claims, characterized in that the box comprises a temperature sensor, wherein the temperature sensor is preferably i) arranged on the bottom wall, on the at least one lateral wall, on the top wall, in the gas supply channel or in the gas discharge channel of the box; and / or ii) suitable for being attached to or in an animal, preferably rectally attached to or in an animal; and / or iii) communicatively connected to a control unit of the box; and / or iv) a cable, wherein the cable is suitable for being connected to a magnetic resonance tomography apparatus.Box according to any one of the preceding claims, characterized in that the box comprises at least two electrodes, the at least two electrodes preferably being arranged i) on the bottom wall of the box, preferably in a region in the middle of the bottom wall; and / or ii) being communicatively connected to a control unit of the box; and / or iii) being each connected to a cable, the cables being suitable for being connected to an electrocardiogram device.Box according to any of the preceding claims, characterized in that the box comprises a respiration sensor for detecting a respiration activity, wherein the respiration sensor is preferably arranged i) on the bottom wall of the box, preferably in an area in the middle of the bottom wall; and / or ii) communicatively connected to a control unit of the box; and / or iii) connected to a cable, wherein the cable is suitable for being connected to a magnetic resonance device, preferably to a scanner of a magnetic resonance device.Box according to any of the preceding claims, characterized in that the box comprises a control unit, wherein the control unit is preferably configured to control or regulate an amount of anesthetic gas supplied to an anesthetic mask of the box, wherein the box preferably comprises a sensor for detecting a concentration of anesthetic gas communicatively connected to the control unit of the box; and / or ii) to detect a temperature from a temperature sensor of the box, wherein the control unit is preferably configured to regulate a temperature of at least one gas supplied to the box via the gas supply channel based on the temperature of the temperature sensor, wherein the control unit is preferably communicatively connected to a heating element of the box; and / or iii) to acquire signals from at least two electrodes of the box, wherein the control unit is preferably configured to provide the signals via an electronic data transmission interface of the box, in particular to provide an electrocardiogram device and / or a magnetic resonance tomography device which is / are communicatively connected, preferably in a wireless manner, to the electronic data transmission interface; and / or iv) to acquire signals from a respiration sensor of the box, wherein the control unit is preferably configured to use the signals of the respiration sensor for controlling an amount of anesthetic gas that is conducted into an anesthetic mask of the box and / or to provide the signals of the respiration sensor via an electronic data transmission interface of the box, in particular to a device for acquiring a respiration activity and / or a magnetic resonance tomography device, which is / are communicatively connected, preferably in a wireless manner, to the electronic data transmission interface; and / or v) to adapt a resonance frequency of the at least one magnetic resonance coil of the box to a resonance frequency of a main coil of a magnetic resonance tomography device.Box according to any of the preceding claims, characterized in that the gas supply duct i) is connected to a gas source containing oxygen, optionally the gas supply duct being connected to an air source; and / or ii) is connected to a heating element suitable for heating an oxygen-containing gas in the gas supply duct and / or an anesthetic gas in an anesthetic gas line within the gas supply duct to a predetermined temperature, optionally the heating element containing or consisting of a heating wire; and / or iii) is preferably arranged in the bottom wall in the bottom conversion in which at least one lateral wall or in the top wall.Box according to any one of the preceding claims, characterized in that the gas discharge duct i) comprises a filter suitable for filtering the gas in the gas discharge duct, the filter preferably being a filter suitable for not allowing biological working substances of group 1, 2, 3 or 4 to pass according to the EC guideline 2000 / 54 / EC of 18.09.2000, changed by the EU guideline 2019 / 1833 of 24.10.2019 and the EU guideline 2020 / 739 of 03.06.2020; and / or ii) is preferably arranged in the bottom wall in the bottom wall in which at least one lateral wall or in the top wall are arranged.Box according to one of the preceding claims, characterized in that the box has a total of at least two, preferably at least ten, particularly preferably at least 20, very particularly preferably at least 50, in particular at least 100, optionally at least 128, magnetic resonance coils, wherein the magnetic resonance coils are preferably i) in each case multi-core magnetic resonance coils; and / or ii) are present in an array, in particular in an array of multi-core coils; and / or iii) are suitable for capturing signals of different magnetic resonance-representable cores either simultaneously or sequentially.Method for magnetic resonance tomography of a small animal, comprising or consisting of the following steps: a) recording a small animal into the box according to one of the preceding claims; b) moving the box into a magnetic resonance tomography apparatus; c) coupling the at least one magnetic resonance coil of the box with a magnetic resonance tomography apparatus; d) recording magnetic resonance tomography images by the magnetic resonance tomography apparatus, wherein a signal which is recorded by the at least one magnetic resonance coil of the box is recorded by the magnetic resonance tomography apparatus inductively or by cable connection.Method according to claim 12, characterised in that before step c) an adaptation of a resonance frequency of the at least one magnetic resonance coil of the box to a resonance frequency of a main coil of the magnetic resonance tomography apparatus takes place, wherein preferably a control unit of the box is configured to carry out the adaptation.Method according to one of claims 12 or 13, characterized in that the coupling of the at least one magnetic resonance coil of the box with the main coil of the magnetic resonance tomography apparatus in step c) is an inductive coupling, wherein the inductive coupling is preferably an i) continuous resonant coupling during an excitation and a reception of signals; or ii) in an excitation is non-resonant coupling.Method according to one of claims 12 or 13, characterized in that the coupling of the at least one magnetic resonance coil of the box to the magnetic resonance tomography apparatus in step c) is a wired coupling, wherein the wired coupling is preferably an i) continuous resonant coupling during excitation and reception of signals; or ii) is non-resonant coupling during excitation.Method according to one of Claims 12 to 15, characterized in that the magnetic resonance tomography images are recorded by the magnetic resonance tomography system in step d) as a function of a heart rate and / or a breathability of the small animal, wherein preferably a signal of an electrocardiogram device and / or a breathing signal of a breathing sensor of the box is transmitted to the magnetic resonance tomography system.Control unit configured to adapt a resonance frequency of at least one magnetic resonance coil to a desired resonance frequency of a main coil of a magnetic resonance tomography system, wherein the control unit is configured to carry out the following steps for this: a) measurement of an existing resonance frequency of the at least one magnetic resonance coil of the box; b) adaptation of a tuning capacitance of an oscillator circuit based on the difference determined in step a), preferably by means of a varactor; and c) repeating steps a) and b) until a desired accuracy is achieved, wherein the desired accuracy preferably means a correspondence of the resonant frequency measured in a) with a resonant frequency of the magnetic resonance tomograph, wherein the correspondence means an identity of the two resonant frequencies with an error which lies within half the maximum of the full width of a resonant curve of the main coil of the magnetic resonance tomograph.

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