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

Abstract

The invention provides a box for holding a small animal for an MRI of the small animal. The box contains or consists of a bottom 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 an interior space by joining the bottom wall, the at least one lateral wall and the top wall, the interior space being suitable for holding a small animal, wherein the interior space is suitable for preventing the small animal from leaving the interior space of the box and ending up in a space surrounding the box. A method for the MRI of a small animal and a control unit are also provided. The box, the method and the control unit allow for a simple, fast, inexpensive and space-saving way of performing MRI imaging of a small animal with a high signal-to-noise ratio with minimal risk to the health of the box users.

Description

[0001] Box for accommodating a small animal for an MRI of the small animal, method for MRI of a small animal, and control unit

[0002] A box is provided to accommodate a small animal for an MRI of the small animal. The box contains a bottom wall, at least one side

[0003] Wall, a ceiling wall, at least one magnetic resonance coil, a gas supply channel and a gas discharge channel or consists thereof. 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 ceiling 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. Furthermore, a method for MRI of a small animal and a control unit are provided. Using the box, the method 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 users of the box. The demand for high-resolution small animal MRI is constantly increasing.Dedicated small animal systems, which typically operate with field strengths in the range of 4 T to 7 T and often even higher, meet high demands on image quality, but have the disadvantage that a direct translation of the results to the clinical situation is not possible due to the high field strengths.

[0004] Due to this disadvantage, dedicated small animal systems are increasingly being provided that operate with low field strengths (i.e., field strengths in the range of < 4 T, e.g., 3 T). One example is the dedicated small animal system "BioSpec Maxwell" from "Bruker Biospin MR solution." Such systems are becoming increasingly relevant in preclinical research, particularly for translational questions. However, the known small animal systems have several disadvantages. For example, the known systems are very expensive to acquire (> 0.5 million euros), incur considerable operating costs (trained personnel are required for their operation, e.g., a physicist or technician), and require a large space.

[0005] It is also known that the use of MR local coils next to the main coil of a magnetic resonance imaging (MRI) scanner, i.e. MR coils placed very close to a small animal to be examined, can improve the signal-to-noise ratio during imaging and shorten measurement times (Doty, FD et al., NMR in Biomedicine, 20:304-325).

[0006] It is also known to attach MR local coils for a small animal to a small animal positioning system (see Abraham, CB et al., International Journal of Hyperthermia, 35(1):348-360). With known small animal positioning systems, a large surface of the small animal is exposed, and in the case of an MRI scan of a living small animal, the small animal is in gas exchange with the environment through its breathing. This has the disadvantage that, for example, microorganisms and / or viruses present on the surface of the small animal and / or in the exhaled air of the small animal can penetrate into the environment. If the small animal positioning system is placed in a clinical MRI machine for performing an MRI, there is a risk that the surfaces of the MRI machine will become contaminated. This can pose a health risk to small animals and / or humans who enter the MRI machine after the MRI has been performed on such a small animal.It may also pose a health risk to clinical personnel using the small animal positioning system and MRI scanner. The same applies to known small animal positioning systems that do not adequately immobilize the small animal, i.e., where there is a risk of the small animal leaving the small animal positioning system during the MRI.

[0007] Based on this, the object of the present invention was to overcome at least one disadvantage of the systems known in the prior art. In particular, a device, a method, and a control unit were to be provided that would enable an MRI scan of a small animal to be performed in a simple, rapid, cost-effective, and space-saving manner with a high signal-to-noise ratio (even at low field strengths < 4 T) while minimizing the risk to the health of a user of the box (e.g., clinical staff).

[0008] The object is achieved by the box having the features of claim 1 and the method having the features of claim 12. The dependent claims show advantageous developments of the subject matter according to the invention.

[0009] 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 imaging (MRI) of the small animal, containing or consisting of: a) a bottom wall; b) at least one side 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 accommodating a small animal and / or a bird's egg by joining the bottom wall, the at least one side 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, characterized in that the bottom wall, the at least one side wall and the top wall can be connected in such a way that an interior space is created which is suitable for preventing biological agents of group 1 (optionally of groups 2, 3 or 4) according to EC Directive 2000 / 54 / EC of September 18, 2000, as amended by EU Directive 2019 / 1833 of October 24, 2019 and EU Directive 2020 / 739 of June 3, 2020, from passing into an exterior space of the box.

[0010] The box according to the invention can be prepared quickly and easily. Furthermore, the box according to the invention allows a small animal to be easily and quickly placed inside the box by bringing its walls together. This prevents the small animal from leaving the box, thereby reducing the risk to the safety of users of the box. Together with the at least one magnetic resonance coil of the box, the box thus allows an MRI to be performed on a small animal using a magnetic resonance imaging (MRI) scanner with greater safety for the health of the user of the box.

[0011] Due to the fact that 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) for imaging, and a signal induced by the at least one magnetic resonance coil of the box in the main coil of the magnetic resonance tomograph is detected by means of reception paths present in the magnetic resonance tomograph, the box according to the invention can be used independently of the measurement technology used and thus universally with known clinical MRI devices. 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 the expansion stage of the MRI device.Imaging simply requires positioning the small animal in the box and then positioning the box with the small animal (e.g., using a standard patient bed) in an (existing) MRI scanner. The clinical sequences available on the MRI scanner can be used for imaging, and data acquisition and analysis can be performed according to clinical routine. This offers particular advantages regarding the translation of preclinical results into clinical practice, as well as significant cost savings through the use of existing MRI scanners for preclinical applications.

[0012] Due to the fact that the box according to the invention can be designed very compactly—that is, the interior of the box can be tailored to the dimensions of a specific small animal to be examined—the space required for the box can be very small. This is a great advantage, especially in confined spaces (e.g., in a hospital).

[0013] Due to the local proximity of the at least one magnetic resonance coil of the box to a small animal located inside the box, high signal-to-noise ratios and short measurement times are possible during MRI (effect of a local coil). The achievable signal-to-noise ratios significantly exceed the signal-to-noise ratios without using the box (i.e., simply positioning the small animal in an MRI scanner without the box). This enables excellent imaging even with magnetic resonance imaging systems with low field strengths (e.g., a field strength of < 4 T).

[0014] In summary, the box according to the invention makes it possible to perform an MRI scan of a small animal with a high signal-to-noise ratio (even at low field strengths < 4 T) in a simple, fast, cost-effective and space-saving manner, with minimal risk to the health of a user of the box.

[0015] The bottom wall can merge 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 can have a U-shape). Furthermore, the top wall can merge seamlessly into the at least one side wall, i.e., be integral with the at least one side wall (e.g., the top wall and the side wall can have the shape of an inverted U). It is also conceivable for the bottom wall, the top wall, and at least one further side wall, which is different from the at least one side wall, to merge seamlessly into one another, i.e., form a one-piece structure, e.g., a tube open at one end. In the case of the tube open at one end, a merging of the tube open at one end with the at least one side wall can form the interior space (e.g., by closing the open end of the open tube with the at least one side wall).

[0016] In a preferred embodiment of the box, the bottom wall, the at least one side wall, and the top wall of the box can be connected in such a way that an interior space is created for accommodating a small animal, wherein the small animal is preferably a small rodent, particularly preferably a mouse or a rat. Furthermore, the bottom wall, the at least one side wall, and the top wall of the box can be connected in such a way that an interior space is created for accommodating a bird's egg, wherein the bird's egg is preferably a chicken's egg. In this case, the box can have smaller dimensions than if the interior space is suitable for accommodating a small animal.

[0017] Furthermore, it is possible for the bottom wall, the at least one side wall and the top wall of the box to be connected in such a way that an interior space with a volume in the range of 0.1 dm 3 up to 200 dm 3 , preferably 0.2 dm 3up to 100 dm 3 , particularly preferably 0.5 dm 3 up to 50 dm 3 , most preferably 1.0 dm 3 up to 10 dm 3 , especially 2.0 dm 3 up to 6.0 dm 3 The smaller the interior space, the smaller the overall dimensions of the box can be, and the greater the advantage of the box allowing work in tight spaces.

[0018] In a preferred embodiment, the bottom wall, at least one side wall, and the top wall of the box can be connected in such a way that tight, preferably gas-tight, connections are created. The advantage is that it can be ensured that no biological agents as defined in EC Directive 2000 / 54 / EC of September 18, 2000, as amended by EU Directive 2019 / 1833 of October 24, 2019, and EU Directive 2020 / 739 of June 3, 2020 (i.e., no microorganisms and / or viruses) present in the small animal can leave the interior of the box and enter an external space of the box (i.e., an imaging chamber of a magnetic resonance imaging scanner). This increases the health safety of persons (e.g., patients) using the magnetic resonance imaging scanner during or after imaging the small animal.

[0019] According to the invention, the bottom wall, at least one side wall, and the ceiling wall of the box can be connected in such a way that an interior space is created that is suitable for preventing biological agents of group 1 (optionally of group 2, 3, or 4) according to EC Directive 2000 / 54 / EC of September 18, 2000, as amended by EU Directive 2019 / 1833 of October 24, 2019, and EU Directive 2020 / 739 of June 3, 2020, from passing into an exterior space of the box (i.e., the interior space is suitable for preventing the said biological agents from escaping). The higher the group of biological agents, the safer the use of the box is for the health of persons (e.g., patients) who use the magnetic resonance imaging scanner during or after imaging on small animals.

[0020] The at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, can be suitable for being coupled to a magnetic resonance tomograph by means of a cable.

[0021] Alternatively, the at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, can be suitable for wirelessly inductively coupling to a magnetic resonance tomograph. It is possible for the at least one magnetic resonance coil of the box, preferably all magnetic resonance coils of the box, to not have a cable that can be coupled to a magnetic resonance tomograph. The advantage is that the box can be designed more compactly and its use is simplified. Of particular note here is that the box can be operated independently of the manufacturer's proprietary coil connections and does not need to be galvanically connected to the MRI device.

[0022] The box can be equipped with an anesthesia mask. This allows an anesthetic gas to be introduced into the interior of the box. Using this anesthetic gas, a small animal can be sedated or anesthetized within the box. The advantage is that the quality and sharpness of the images are improved, as a sedated or anesthetized small animal moves little to no inside the box during imaging using an MRI system.

[0023] The anesthesia mask is preferably attached to the bottom wall, to the at least one side wall, or to the ceiling wall of the box, particularly preferably to the bottom of the box. Attaching it to the bottom wall has the advantage that the anesthesia mask is very stably positioned within the interior of the box and can remain in place in the event of a separation of the bottom wall, the at least one side wall, and the ceiling wall and / or the ceiling wall.

[0024] The anesthesia mask can be fluidically connected to a gas line, which is arranged at least partially in the gas supply channel of the box. The advantage of at least partially arranging 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 from external mechanical influences and the box can be designed more compactly. The gas line can be connected to a source of anesthetic gas, wherein the source of anesthetic gas is optionally communicatively connected to a control unit of the box. The connection to the source of anesthetic gas allows the introduction of anesthetic gas from the source of anesthetic gas 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 fed into the interior of the box.If the box contains a suitable gas sensor in the interior, which is also communicatively connected to the control unit, it is even possible to regulate the amount of anesthetic gas that is introduced into the interior of the box.

[0025] Furthermore, the box can have a temperature sensor. The temperature sensor can be configured to detect 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 side wall, on the ceiling wall, in the gas supply channel or in the gas discharge channel of the box. An arrangement in the gas supply channel has the disadvantage that only the temperature of a gas supplied 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 designed more compactly, since no space is lost for the temperature sensor in the interior of the box.An arrangement in the gas discharge duct has the advantage that the temperature in the interior can be measured indirectly but more accurately than with an arrangement in the gas supply duct, and the box can also be designed very compactly. Although an arrangement on the floor wall, at least one side wall, or on the ceiling wall results in a certain loss of space in the interior of the box, it allows for a direct (i.e., more accurate) measurement of the temperature of the small animal's environment inside the box.

[0026] The temperature sensor can be designed to be attached to or inside an animal, preferably rectally. The resulting proximity to the small animal allows for a very accurate and reliable measurement of the small animal's body temperature.

[0027] Furthermore, the temperature sensor can be communicatively connected to a control unit of the box. The advantage of this is that the control unit receives information about the small animal's body temperature or the temperature inside the box and can use this information to control or regulate a heating element in the box.

[0028] Furthermore, the temperature sensor can be connected to a cable suitable for connection to a magnetic resonance imaging scanner. The advantage of this is that the magnetic resonance imaging scanner is provided with direct information about the small animal's body temperature or the temperature inside the box, which can be incorporated into the imaging. The box can have at least two electrodes. The advantage of this is that an electrocardiogram of the small animal can be recorded and also incorporated into the imaging.

[0029] The at least two electrodes can be arranged on the bottom wall of the box, preferably in a central area of ​​the bottom wall. The advantage is that the two electrodes can be easily positioned underneath a small animal, and the small animal can reliably establish electrically conductive contact with the at least two electrodes using its body weight.

[0030] Furthermore, the at least two electrodes can be communicatively connected to a control unit of the box. The advantage is that information (i.e., electrical signals) from the at least two electrodes is made available to the control unit of the box, and the control unit can use this information for control or regulation. The electrical signals from the at least two electrodes can, for example, be taken into account during imaging using an MR device (i.e., a magnetic resonance imaging scanner), which can further improve the signal-to-noise ratio.

[0031] The at least two electrodes can each be connected by a cable, wherein the cables are suitable for connection to an electrocardiogram device. The advantage of this is that the information (i.e., electrical signals) is made available directly to an electrocardiogram device, allowing an electrocardiogram of a small animal located inside the box to be recorded. Furthermore, the box can 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 by a cable, wherein the cables are suitable for connection to an electrocardiogram device.

[0032] In addition, the box can be equipped with a respiration sensor for detecting respiratory activity. The advantage is that the respiration of a small animal located inside the box can be detected and monitored. The respiration sensor can be located on the bottom wall of the box, preferably in a central area. This arrangement has the advantage that the body weight of the small animal establishes a stable connection between the sensor and the small animal, thus providing reliable results.

[0033] The respiration sensor can be communicatively connected to a control unit in the box. The advantage is that the control unit can use information about respiration activity for control or regulation. For example, respiration activity can also be taken into account during imaging using an MRI scanner, which can improve the signal-to-noise ratio.

[0034] The respiration sensor can be connected to a cable, which is suitable for connection to a magnetic resonance imaging device, preferably to a scanner of an MRI device. This measure provides information about the respiratory activity of a small animal located inside the box directly to the MRI device (i.e., a magnetic resonance imaging scanner). The information can thus be used directly during imaging to improve the signal-to-noise ratio.

[0035] The box can have a control unit. The advantage is that this makes it suitable for controlling or regulating certain processes.

[0036] The control unit can be configured to control or regulate the amount of anesthetic gas supplied to an anesthesia mask of the box. The box preferably has a sensor for detecting anesthetic gas concentration, which is communicatively connected to the control unit of the box. The advantage is that an under- or over-dosage of anesthetic gas can be avoided, thus allowing a small animal located inside the box to be anesthetized in a safer and more reliable manner.

[0037] Furthermore, the control unit can 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 can be supplied air and / or a supplied anesthetic gas, i.e., a temperature of air and / or a supplied anesthetic gas can be regulated by the control unit.

[0038] The control unit is preferably communicatively connected to a heating element of the box. One advantage is that the heating element of the box can be controlled by the control unit, allowing, for example, the temperature of the air and / or an anesthetic gas to be regulated by the control unit. A further advantage is that an excessively low or excessively high temperature in the interior of the box or the body temperature of a small animal in the interior of the box can be avoided, thus allowing a small animal inside the box to be kept at a specific temperature in a safer and more reliable manner. This can ensure that ethical criteria are reliably adhered to.

[0039] Furthermore, the control unit can be configured to detect signals from at least two electrodes of the box. The control unit is preferably configured to provide the signals via an electronic data transmission interface of the box, in particular to an electrocardiogram device and / or a magnetic resonance imaging device that is communicatively connected, preferably wirelessly, to the electronic data transmission interface. The advantage is that cardiac activity of a small animal located inside the box can be detected and monitored, and said cardiac activity can be taken into account during imaging. This can improve imaging.

[0040] Furthermore, the control unit can be configured to detect signals from a respiration sensor of the box. The control unit can be configured to use the signals from the respiration sensor to control the amount of anesthetic gas delivered to an anesthesia mask of the box. This provides the advantage that anesthesia of a small animal can be controlled based on the small animal's respiratory rate. Furthermore, the control unit can be configured to provide the signals from the respiration sensor via an electronic data transmission interface of the box. Furthermore, the control unit can be configured to provide the signals from the respiration sensor to a device for detecting respiratory activity and / or a magnetic resonance imaging scanner, which is communicatively connected, preferably wirelessly, to the electronic data transmission interface.The advantage is that the respiratory activity of a small animal inside the box can be recorded and monitored, and this respiratory activity can be taken into account during imaging. This can improve imaging. Furthermore, the recorded respiratory activity can be used to regulate the flow of an oxygen-containing gas through the gas supply channel into the box to ensure the desired respiratory activity in the small animal.

[0041] 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 tomograph. The advantage is that the signal-to-noise ratio can be significantly increased by said adaptation, since the energy transfer between the two coils is particularly efficient and, with the aid of the resonance condition (i.e., since the at least one magnetic resonance coil is resonant at the Larmor frequency), a signal amplification of the signal induced into the coil by the object is achieved. This enables a significant increase in the signal-to-noise ratio compared to a lack of adaptation of the resonance frequencies of the two coils. Improving the signal-to-noise ratio can 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).In this case, the control unit of the box is particularly preferably configured to carry out the following steps: i) measuring an existing resonance frequency of the at least one magnetic resonance coil of the box and determining a difference between the measured, existing resonance frequency of the at least one coil and a resonance frequency of a main coil of a magnetic resonance tomograph; ii) adjusting a tuning capacitance of a resonant circuit based on the difference determined in step i), preferably by means of a varactor; and iii) repeating steps i) and ii) until a desired accuracy is achieved, wherein the desired accuracy preferably means a match between the resonance frequency measured in i) and the resonance frequency of the main coil of the magnetic resonance tomograph, wherein the match means an identity of the two resonance frequencies with an error that is within half the maximum of the full width.: "full width half maximum" or "FWHM") of a resonance curve of the main coil of the magnetic resonance tomograph.

[0042] The gas supply channel can be connected to a gas source containing oxygen, with the gas supply channel optionally being connected to an air source. The advantage is that the interior of the box can be supplied with oxygen, thus ensuring the survival of a small animal inside the box even if the box has gas-tight connections between the floor wall, at least one side wall, and the ceiling wall.

[0043] Furthermore, the gas supply channel can be connected to a heating element suitable for heating an oxygen-containing gas in the gas supply channel and / or an anesthetic gas in an anesthetic gas line within the gas supply channel to a predetermined temperature. 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 warmed up (e.g., to 37°C) before they enter the interior of the box, thus creating a desired climate for a small animal located inside the box.

[0044] In addition, the gas supply channel can be arranged in the floor wall, in at least one side wall or in the ceiling wall, preferably in the floor wall. An arrangement in the floor wall has the advantage that the gas supply channel is arranged very securely in the interior of the box and, if the anesthesia mask is also attached to the floor wall, only short transport paths for the anesthetic gas are created, whereby the box can take up less installation space and more space is available inside the box for accommodating a small animal. The gas discharge channel can have a filter that is suitable for filtering the gas in the gas discharge channel. The advantage is that contamination of the exhaust air in the interior of the box (e.g. with microorganisms and / or viruses that a small animal may have in the interior of the box) can be avoided. This increases the health safety for a user of the box.

[0045] The filter can be a filter suitable for preventing the passage of biological agents of Group 1 (optionally Group 2, 3, or 4) according to EC Directive 2000 / 54 / EC of September 18, 2000, as amended by EU Directive 2019 / 1833 of October 24, 2019, and EU Directive 2020 / 739 of June 3, 2020. The higher the group, the more stringent the filter requirements and the safer the user of the box.

[0046] The gas discharge channel can be arranged in the floor wall, in at least one side wall, or in the ceiling wall, preferably in the floor wall. The advantage of arranging it in the floor wall is its high stability.

[0047] The box can have (in total) at least two, preferably at least ten, more preferably at least 20, most preferably at least 50, especially 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 area with a high signal-to-noise ratio (FOV) can be.

[0048] 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 subsequently using the same MRI system.

[0049] Furthermore, the magnetic resonance coils can be present in an array, in particular in an array of multi-core coils.

[0050] Furthermore, the magnetic resonance coils can be designed to acquire signals from different magnetic resonance imaging nuclei either simultaneously or sequentially. In this case, the different nuclei of the coils can be measured simultaneously or subsequently using the same MRI system.

[0051] According to the invention, a method for magnetic resonance imaging (MRI) of a small animal is further provided, comprising or consisting of the following steps: a) receiving a small animal in the box according to the invention; b) moving the box into a magnetic resonance imaging scanner; c) coupling (e.g. inductively or by cable) the at least one magnetic resonance coil of the box to a magnetic resonance imaging scanner; d) recording magnetic resonance imaging images by the magnetic resonance imaging scanner, wherein a signal recorded by the at least one magnetic resonance coil of the box is recorded inductively or by cable connection by the magnetic resonance imaging scanner.

[0052] The method has the advantages mentioned above in connection with the box according to the invention.

[0053] Before step c) of the method, a resonance frequency of the at least one magnetic resonance coil of the box can be adjusted to a resonance frequency of a main coil of the magnetic resonance tomograph, with a control unit of the box preferably being configured to perform the adjustment. The advantage of this adjustment is that the signal-to-noise ratio is increased, allowing higher-resolution images of the small animal to be generated using the method, or lower-resolution images to be generated more quickly using the method.In this case, the control unit of the box is particularly preferably configured to carry out the following steps: i) measuring an existing resonance frequency of the at least one magnetic resonance coil of the box and determining a difference between the measured, existing resonance frequency of the at least one coil and a resonance frequency of a main coil of a magnetic resonance tomograph; ii) adjusting a tuning capacitance of a resonant circuit based on the difference determined in step i), preferably by means of a varactor; and iii) repeating steps i) and ii) until a desired accuracy is achieved, wherein the desired accuracy preferably means a match between the resonance frequency measured in i) and the resonance frequency of the main coil of the magnetic resonance tomograph, wherein the match means an identity of the two resonance frequencies with an error that is within half the maximum of the full width.: "full width half maximum" or "FWHM") of a resonance curve of the main coil of the magnetic resonance tomograph.

[0054] The resonant frequency of the main coil of the magnetic resonance imaging scanner is determined by the Larmor frequency. This frequency depends on the field strength of the magnetic resonance imaging scanner and the desired nuclei (e.g., in a conventional examination, with the most common field strengths for human systems today: 1H at 3T -> 127.73 MHz, but 1H at 1.5T -> 63.87 MHz). The at least one magnetic resonance coil in the box can be adjusted for different nuclei as well as for different field strengths. Therefore, the information (field strength, nuclei) must be provided to the control unit or preset. The difference between the measured frequency and the target frequency creates an error, which the control unit automatically minimizes. Since the inductance of the at least one magnetic resonance coil in the box is fixed, the capacitance that causes the at least one magnetic resonance coil in the box to resonate is changed.This can be achieved, for example, by connecting and / or disconnecting capacitances via a switch or via a capacitance diode. Other possibilities are conceivable. The box's control unit thus operates similarly to a binary search algorithm for an n-bit adjustable capacitance, i.e., the individual bits are set one after the other from MSB to LSB ("most significant bit" to "least significant bit"). This sets the capacitance value to half the setting range, determines the resonant frequency in this state, and then either switches the next bit on or off, depending on whether the frequency is too high or too low.

[0055] The coupling of the at least one magnetic resonance coil of the box to the main coil of the magnetic resonance tomograph in step c) of the method can be an inductive coupling, wherein the inductive coupling is preferably i) a continuous resonant coupling during excitation and reception of signals; or ii) a non-resonant coupling during excitation.

[0056] With continuous resonant coupling (T / R) during excitation (T) and reception (R) of signals, a local Bl enhancement occurs due to the coupling, even during excitation. This allows for a high excitation angle locally with a low excitation angle globally. The advantage is that very broadband excitation pulses can be realized, as the power limitation (Bl) of the whole-body systems can be circumvented, meaning more power is available locally while the required power is lower. (This is limited by SAR limits in the MRI system.)

[0057] Non-resonant coupling during excitation, i.e., coupling only during reception (R), can easily be achieved passively by integrating crossed diodes, which limit the maximum current during excitation and thus limit the local BL peak. When the diodes are switched on, the magnetic resonance coil is no longer tuned to the Larmor frequency, e.g., when the diodes short-circuit the capacitance that generates the resonance. At the low currents during reception, the diodes have no effect. The advantage is that the signal-to-noise ratio (in the reception case) is increased.

[0058] Furthermore, the coupling of the at least one magnetic resonance coil of the box to the magnetic resonance tomograph in step c) of the method can be a wired coupling, wherein the wired coupling is preferably i) a continuous resonant coupling during excitation and reception of signals; or ii) a non-resonant coupling during excitation.

[0059] The acquisition of magnetic resonance tomography images by the magnetic resonance tomograph in step d) of the method can be carried out depending on a heart rate and / or respiratory activity of the small animal, wherein preferably a signal from an electrocardiogram device and / or a respiratory signal from a respiratory sensor of the box is transmitted to the magnetic resonance tomograph.

[0060] A control unit is further provided which is configured to adapt a resonant frequency of at least one magnetic resonance coil to a resonant frequency of a main coil of a magnetic resonance tomograph, wherein the control unit is configured to perform the following steps for this purpose: i) measuring an existing resonant frequency of the at least one magnetic resonance coil of the box and determining a difference between the measured, existing resonant frequency of the at least one coil and a resonant frequency of a main coil of a magnetic resonance tomograph; ii) adapting a tuning capacitance of a resonant circuit based on the difference determined in step i), preferably by means of a varactor;and iii) repeating steps i) and ii) until a desired accuracy is achieved, wherein the desired accuracy preferably means a match between the resonance frequency measured in i) and the resonance frequency of the main coil of the magnetic resonance tomograph, wherein the match means an identity of the two resonance frequencies with an error that lies within half the full width half maximum (FWHM) of a resonance curve of the main coil of the magnetic resonance tomograph.

[0061] The advantage of the control unit is that it can improve the signal-to-noise ratio, thus enabling higher-resolution MR images of a small animal to be obtained. The box according to the invention can comprise the control unit according to the invention.

[0062] The subject matter of the invention will be explained in more detail with reference to the following figures, without wishing to restrict it to the specific embodiments shown here.

[0063] Figure 1 schematically shows the structure of a box according to the invention for accommodating a small animal for magnetic resonance imaging of the small animal. The box contains a bottom wall 1, at least one side 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 designed to form an interior space suitable for accommodating a small animal by merging the bottom wall 1, the at least one side wall 2, and the top wall 3. The interior space is further designed to prevent the small animal from leaving the interior of the box and entering an exterior space of the box. In the exemplary embodiment shown here, the box further contains an anesthesia mask 7 connected to a gas line 8. Furthermore, the box contains a temperature sensor 10, two electrodes 11, and a respiration sensor 12. Furthermore, the box contains a control unit 13.

[0064] Figure 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 Figure 1 and additionally has a gas source 14 containing oxygen and a source 9 for anesthetic gas. The gas source 14 is fluidically connected to the gas supply channel 5 of the box, with a heating element 15 arranged in the gas supply channel to heat the gas from the gas source. The source 9 for 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.

[0065] Figure 3 shows phantom measurements for quantifying the signal-to-noise ratio gain, which were performed using a box according to the invention and the MRI device "Philips dStream 3.0 T". All data were acquired with a resolution of 150 pm using 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 local B1 enhancement were achieved by using the box according to the invention compared to the main coil (QBC coil) installed in the MRI device, so 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 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.

[0066] Figure 4 shows an ex vivo image of a mouse brain positioned in a box according to the invention and of which an MRI was performed using the MRI device "Philips dStream 3.0 T". In Figure 4A, the acquisition time was 14 h 38 min and the resolution was 60x60x100 pm 3 In Figure 4B, the acquisition time was only 1 min 37s and the resolution was only 170x180x500 pm 3 .

[0067] Figure 5 shows in vivo images of a mouse positioned in a box according to the invention and subjected to an MRI using the Philips dStream 3.0 T MRI scanner. In Figure 5A, the images were obtained with a 20-MP TSE sequence at an acquisition time of 7 min. In Figure 5B, the images were obtained with a 30-MP RAGE sequence at an acquisition time of 10 min. The resolution in both cases was 150x150x500 pm 3 .

[0068] 1: Bottom wall of the box;

[0069] 2: at least one side wall of the box;

[0070] 3: Ceiling wall of the box;

[0071] 4: at least one magnetic resonance coil of the box;

[0072] 5: Gas supply channel of the box;

[0073] 6: Gas discharge channel of the box;

[0074] 7: anesthesia mask;

[0075] 8: Gas line of the anesthesia mask;

[0076] 9: Source of anesthetic gas;

[0077] 10: Temperature sensor;

[0078] 11: two electrodes;

[0079] 12: Respiration sensor;

[0080] 13: control unit;

[0081] 14: Gas source containing oxygen;

[0082] 15: Heating element in / on the gas supply channel;

[0083] 16: Filter in the gas discharge duct.

Claims

Patent claims 1. A box for accommodating a small animal for magnetic resonance imaging of the small animal, containing or consisting of: a) a bottom wall; b) at least one side wall; c) a ceiling 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 accommodating a small animal by bringing together the bottom wall, the at least one side wall and the top wall, the interior space being further suitable for preventing the small animal from leaving the interior space of the box and entering an exterior space of the box, characterized in that the bottom wall, the at least one side wall and the top wall can be connected in such a way that an interior space is created which is suitable for accommodating biological agents of group 1 in accordance with EC Directive 2000 / 54 / EC of September 18, 2000, as amended by EU Directive 2019 / 1833 of October 24.2019 and EU Directive 2020 / 739 of 03.06.2020, not to allow it to pass into an external space of the box.

2. Box according to the preceding claim, characterized in that the bottom wall, the at least one side wall and the top wall can be connected in such a way that i) an interior space for accommodating a small animal and / or a bird's egg is created, 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 space with a volume in the range of 0.1 dm 3 up to 200 dm 3 , preferably 0.2 dm 3 up to 100 dm 3 , particularly preferably 0.5 dm 3 up to 50 dm 3 , most preferably 1.0 dm 3 up to 10 dm 3 , especially 2.0 dm 3 up to 6.0 dm 3, is created; and / or iii) tight, preferably gas-tight, connection points are created; and / or iv) an interior space is created which is suitable for preventing biological agents of group 2, 3 or 4 according to EC Directive 2000 / 54 / EC of 18 September 2000, as amended by EU Directive 2019 / 1833 of 24 October 2019 and EU Directive 2020 / 739 of 3 June 2020, from passing into an external space of the box.

3. 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 i) cable-coupled to a magnetic resonance tomograph; or ii) wirelessly inductively coupled, wherein the at least one magnetic resonance coil, preferably all magnetic resonance coils of the box, do not have a cable that can be coupled to a magnetic resonance tomograph.

4. Box according to one of the preceding claims, characterized in that the box has an anesthetic mask, wherein the anesthetic mask is preferably i) attached to the bottom wall, to the at least one lateral wall, or to the top wall of the box, particularly preferably attached to the bottom of the box; and / or ii) fluidically connected to a gas line which is arranged at least partially in the gas supply channel of the box, wherein the gas line is particularly preferably connected to a source for Anesthetic gas is connected, whereby the source of anesthetic gas is optionally communicatively connected to a control unit of the box.

5. Box according to one of the preceding claims, characterized in that the box has a temperature sensor, wherein the temperature sensor is preferably i) arranged on the bottom wall, on the at least one lateral wall, on the ceiling wall, in the gas supply channel or in the gas discharge channel of the box; and / or ii) is suitable for being attached to or in an animal, preferably rectally attached to or in an animal; and / or iii) is communicatively connected to a control unit of the box; and / or iv) is connected to a cable, wherein the cable is suitable for being connected to a magnetic resonance tomograph.

6. Box according to one of the preceding claims, characterized in that the box has at least two electrodes, wherein the at least two electrodes are preferably i) arranged on the bottom wall of the box, preferably in a region in the middle of the bottom wall; and / or ii) communicatively connected to a control unit of the box; and / or iii) each connected to a cable, wherein the cables are suitable for connection to an electrocardiogram device.

7. Box according to one of the preceding claims, characterized in that the box has a respiration sensor for detecting respiratory activity, wherein the respiration sensor is preferably i) arranged on the bottom wall of the box, preferably in a region in the middle of the bottom wall; and / or ii) is communicatively connected to a control unit of the box; and / or iii) is connected to a cable, wherein the cable is suitable for connection to a magnetic resonance device, preferably to a scanner of a magnetic resonance device.

8. Box according to one of the preceding claims, characterized in that the box has a control unit, wherein the control unit is preferably configured to i) control or regulate an amount of anesthetic gas supplied to an anesthetic mask of the box, wherein the box preferably has a sensor for detecting a concentration of anesthetic gas, which is communicatively connected to the control unit of the box; and / or ii) 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 detect 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 an electrocardiogram device and / or a magnetic resonance tomograph, which is communicatively connected, preferably in a wireless manner, to the electronic data transmission interface; and / or iv) to detect signals from a respiration sensor of the box, wherein the control unit is preferably configured to use the signals from the respiration sensor to control an amount of anesthetic gas that is fed into an anesthetic mask of the box, and / or the; To provide signals from the respiration sensor via an electronic data transmission interface of the box, in particular to a device for detecting respiratory activity and / or a magnetic resonance tomograph, which is communicatively connected, preferably wirelessly, 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 tomograph.

9. Box according to one of the preceding claims, characterized in that the gas supply channel i) is connected to a gas source containing oxygen, wherein the gas supply channel is optionally connected to an air source; and / or ii) is connected to a heating element which is suitable for heating an oxygen-containing gas in the gas supply channel and / or an anesthetic gas in an anesthetic gas line within the gas supply channel to a predetermined temperature, wherein the heating element optionally contains or consists of a heating wire; and / or iii) is arranged in the bottom wall, in the at least one lateral wall or in the top wall, preferably in the bottom wall.

10. Box according to one of the preceding claims, characterized in that the gas discharge channel i) has a filter suitable for filtering the gas in the gas discharge channel, wherein the filter is preferably a filter suitable for preventing the passage of biological agents of group 1, optionally of group 2, 3 or 4, according to EC Directive 2000 / 54 / EC of 18.09.2000, amended by EU Directive 2019 / 1833 of 24.10.2019 and EU Directive 2020 / 739 of 03.06.2020; and / or ii) in the floor wall, in which at least one side wall or in the ceiling wall is arranged, preferably in the floor wall.

11. 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) each 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 acquiring signals from different magnetic resonance-imageable nuclei either simultaneously or sequentially.

12. A method for magnetic resonance imaging of a small animal, comprising or consisting of the following steps: a) receiving a small animal in the box according to one of the preceding claims; b) moving the box into a magnetic resonance tomograph; c) coupling the at least one magnetic resonance coil of the box to a magnetic resonance tomograph; d) recording magnetic resonance tomography images by the magnetic resonance tomograph, wherein a signal detected by the at least one magnetic resonance coil of the box is detected inductively or via a cable connection by the magnetic resonance tomograph.

13. Method according to claim 12, characterized 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 tomograph, wherein preferably a control unit of the box is configured to carry out the adaptation, wherein the control unit of the box is particularly preferably configured to carry out the following steps: i) measuring an existing resonance frequency of the at least one magnetic resonance coil of the box and determining a difference between the measured, existing resonance frequency and a resonance frequency of a main coil of a magnetic resonance tomograph; ii) adjusting a tuning capacitance of an oscillating circuit based on the difference determined in step i), preferably by means of a varactor;and iii) repeating steps i) and ii) until a desired accuracy is achieved, wherein the desired accuracy preferably means a match between the resonance frequency of the at least one coil measured in i) and the resonance frequency of the main coil of the magnetic resonance tomograph, wherein the match means an identity of the two resonance frequencies with an error that lies within half the maximum of the full width of a resonance curve of the main coil of the magnetic resonance tomograph.; 14. The method according to claim 12 or 13, characterized in that the coupling of the at least one magnetic resonance coil of the box to the main coil of the magnetic resonance tomograph in step c) is an inductive coupling, wherein the inductive coupling is preferably i) continuous resonant coupling during excitation and reception of signals; or ii) non-resonant coupling during excitation.

15. 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 magnetic resonance tomograph in step c) is a wired coupling, wherein the wired coupling is preferably i) continuous resonant coupling during excitation and reception of signals; or ii) non-resonant coupling during excitation.

16. The method according to any one of claims 12 to 15, characterized in that the recording of magnetic resonance tomography images by the magnetic resonance tomograph in step d) is carried out as a function of a heart rate and / or a respiratory activity of the small animal, wherein preferably a signal from an electrocardiogram device and / or a respiratory signal from a respiratory sensor of the box is transmitted to the magnetic resonance tomograph.

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