WO2023126546A1

WO2023126546A1 - Container for the storage and mri analysis of brains in pathology

Info

Publication number: WO2023126546A1
Application number: PCT/EP2023/050088
Authority: WO
Inventors: Wolfgang FAIGLE; Katrin FRAUENKNECHT; Michael Kummer; Thomas LUDERSDORFER
Original assignee: Zurich Universitaet Institut fuer Medizinische Virologie
Current assignee: Zurich Universitaet Institut fuer Medizinische Virologie
Priority date: 2022-01-03
Filing date: 2023-01-03
Publication date: 2023-07-06
Anticipated expiration: 2024-07-03

Abstract

The present invention relates to a container (1) for storing a human or animal brain (2), comprising: a plurality of layers, the layers (10, 20, 21, 30) being configured to be stacked on top of one another, wherein said plurality of layers comprises a bottom layer (10), a top layer (30) and optionally also intermediary layers (20, 21) configured to be arranged between the bottom and the top layer (10, 30), and wherein the layers (10, 20, 21, 30) form a cavity (3) for accommodating the brain (2) when being stacked on top of one another. Furthermore, a coordinate system is integrated into the container (1) and the container (1) can serve as a tool for correlating MRI and histology.

Description

Container for the storage and MRI analysis of brains in Pathology

Specification

The present invention relates to a container for storing a human or animal brain, particularly for MRI analysis, e.g. in pathology.

Currently, only simple containers exist for holding a brain that allow the cutting of so- called "coronal slices". For use in MRI, containers such as converted canisters or plexiglass structures are known that protect the anatomical fragility of the brain.

Based on the above, the problem to be solved by the present invention is to provide an improved container for storing a human or animal brain.

Particularly it is desirable to provide a container that improves handleability of the brain while particularly also allowing liquid storage of the brain.

This problem is solved by a container having the features of claim 1. Preferred embodiments of this aspect of the present invention are stated in the dependent claims and are describe below.

According to claim 1 , a container for storing a human or animal brain is disclosed, the container comprising:

- a plurality of layers, the layers being configured to be stacked on top of one another, wherein said plurality of layers comprises at least a bottom layer and a top layer, and

- wherein the layers delimit a cavity for accommodating the brain when being stacked on top of one another.

According to an embodiment of the present invention, the plurality of layers further comprises intermediary layers configured to be arranged between the bottom and the top layer. According to a preferred embodiment, each intermediary layer comprises a through-opening contributing to said cavity when the layers are stacked on top of one another. Further, particularly in case said plurality of layers of the container just comprises a top and a bottom layer, the bottom layer can comprise a recess contributing to said cavity when the layers are stacked on top of one another. Similarly, the top layer can comprise a recess contributing to said cavity when the layers are stacked on top of one another.

Particularly, according to a preferred embodiment of the invention, the through- openings and/or said recesse(s) are shaped such that the brain fills the cavity in a form-fitting manner when being accommodate in the cavity.

Particularly, according to an embodiment, the bottom and the top layer close the cavity in a direction extending orthogonal to the layers, wherein the top layer and/or the bottom layer can comprise a recess that contributes to the cavity.

Particularly, the through-openings of the intermediary layers (and in particular said recesses of the top and bottom layers) can be adapted to a specific brain so that an individual brain can be accommodated in the cavity in a form fitting manner. According to an embodiment, the through-openings (and in particular said recesses) can be adapted so as to correspond to an average brain, for instance an average brain obtained from a statistical shape model.

According to an embodiment, apart from merely storing a brain, the container of the present invention is also configured for transporting a brain. According to a further embodiment, the container is also configured for processing a brain, particularly by fixing the brain tissue with a chemical agent such as an aldehyde, particularly formaldehyde. Particularly the container is configured for accommodating the brain together with said chemical agent.

Advantageously, due to the multiple layers the present invention allows to easily adapt the container to the brain, so that the latter can in particular be stored by the stacked layers in a form fitting manner thus allowing optimal protection of the brain.

Furthermore, the container according to the present invention allows for easier, timesaving processing and archiving of the post-mortem brain, but also allows for direct use as a container for liquid storage and imaging with MRI equipment.

According to an embodiment of the container according to the present invention, each intermediary layer comprises a first side having a plurality of grooves formed therein, each groove being configured to guide a blade for cutting a portion of the brain accommodated in the through-opening of the respective intermediary layer along the respective groove. Particularly, in an embodiment, also the bottom layer and/or the top layer can comprise a first side having a plurality of grooves formed therein, each groove being configured to guide a blade for cutting a portion of the brain accommodated in the recess of the respective bottom or top layer.

Particularly, according to an embodiment of the container, the plurality of grooves comprises parallel first grooves extending in a first direction and parallel second grooves extending in a second direction, the first and the second direction being orthogonal with respect to one another. Thus, with help of these grooves precise cutting of the brain is supported, particularly into cuboidal shapes (e.g. cubes). Particularly, such cuts correspond to vertical cuts into the brain (e.g. parallel to the coronal or sagittal plane).

Furthermore, according to an embodiment of the container, the plurality of intermediary layers comprises first intermediary layers configured to be stacked on top of one another on top of the bottom layer, and second intermediary layers being configured to be stacked on top of one another on top of the first intermediary layers (so as to be arranged adjacent the final top layer).

Furthermore, according to an embodiment of the invention, the container comprises an annular member, the annular member being configured to be arranged between the top layer and the bottom layer of the container, particularly between the first intermediary layers and the second intermediary layers. Particularly, the annular member is configured to prevent that neighbouring first and second intermediary layers (or the top and bottom layers) at an interface between the first and second intermediary layers (or at an interface between the top and bottom layers)_move laterally with respect to one another. For this, the annular member can be configured to engage with each adjacent first and second intermediary layer (or with the top and bottom layers). In particularly, said annular member serves to divide the first intermediary layers arranged adjacent the bottom layer and the second intermediary layers being arranged adjacent the top layer. Particularly, the layers can be taken apart at said annular member, a part of the container formed by the bottom layer and the first intermediary layers from a part of the container formed by the second intermediary layers and the top layer. Particularly, each part can be arranged on a surface with the top and bottom layers resting on the surface, respectively, so that the first sides (see also below) comprising said grooves face upwards. This allows one to process two portions (e.g. halves) of the brain separately.

Further, according to an embodiment of the container, when the intermediary layers are stacked on top of one another as intended, the first side of the respective first intermediary layer faces towards the second intermediary layers and the fist side of the respective second intermediary layer faces towards the first intermediary layers.

Furthermore, according to an embodiment of the container, each layer of said plurality of layers is configured to engage with at least one adjacent layer for preventing a lateral movement of the respective layer when the layers are stacked on top of one another. In particular, as indicated above, the annular member prevents such a movement at the interface between the first and second intermediary layers.

Furthermore, according to an embodiment of the container according to the present invention, each layer of said plurality of layers comprises a plurality of markings to allow identification of the respective layer in an image and/or localizing a position of a tissue portion of the of interest, particularly in a medical image, particularly in form of an MRI image or an image using another suitable imaging technique. Particularly said (medical) image is a 3D image.

Particularly, a first marking of the respective layer labels the respective layer and thus can indicate a position of the respective layer along the vertical z axis.

Further second markings of the respective layer that are formed into the layer along a first edge of the respective layer as well as third markings that are formed into the layer along a second edge can indicate a position of a certain region of interest of the brain in the respective layer (and may thus correspond to positions along an x-axis and a y- axis forming a coordinate system together with said z-axis).

According to a preferred embodiment, the respective marking comprises a plurality of blind holes and/or slits. These blind holes or slits can be filled with a fluid in which the brain is stored in the container and may thus generate a visible contrast in a medical image.

Furthermore, as already indicated above, in an embodiment of the invention, the respective layer of said plurality of layers forms a guide configured to guide a blade for cutting a portion of the brain accommodated in the through-opening or recess of the respective layer along the respective layer. Thus, particularly horizontal cuts through the brain (i.e. parallel to the transverse plane) can be achieved in a guided fashion by cutting along the respective layer.

Furthermore, according to an embodiment of the container, the container comprises an outer container, the outer container defining an internal space, wherein the internal space is configured to accommodate said plurality of layers, particularly when said layers are stacked on top of one another as intended, and the brain arranged therein. Thus, particularly, said layers form an inner part of the container being configured to be placed into the internal space of the outer container.

Furthermore, according to an embodiment of the container, the internal space of the outer container is configured to hold a liquid for immersing the brain arranged in the cavity formed by the intermediary layers in said liquid.

Furthermore, according to an embodiment of the invention, the outer container comprises a sealing member for providing a liquid-tight seal of the outer container.

Furthermore, according to yet another embodiment of the invention, the sealing member forms a plate configured to be arranged on top of the top layer, when said plurality of layers is arranged in the internal space with the brain therein.

Furthermore, according to an embodiment of the container, the outer container comprises a lid for closing the outer container, wherein the lid is configured to be releasably connected to a flange of the outer container.

Furthermore, according to an embodiment of the container according to the present invention, the outer container comprises a discharge opening for discharging liquid contained in the internal space out of the outer container, and a closure for closing the discharge opening.

According to a further aspect of the present invention, a method for producing a container is disclosed, particularly a container according to one of the preceding claims, the method comprising the steps of:

- forming a plurality of layers, the layers being configured to be stacked on top of one another, wherein said plurality of layers comprises at least a bottom layer and a top layer, and

- wherein the layers are formed such that the layers form a cavity for accommodating the brain when being stacked on top of one another.

Furthermore, according to an embodiment of the method, forming the plurality of layers further comprises forming intermediary layers configured to be arranged between the bottom and the top layer.

Further, in an embodiment of the method according to the present invention, each intermediary layer comprises a through-opening contributing to said cavity when the layers are stacked on top of one another.

According to yet another embodiment of the method, the bottom layer comprises a recess contributing to said cavity when the layers are stacked on top of one another and/or wherein the top layer comprises a recess contributing to said cavity when the layers are stacked on top of one another.

According to a preferred embodiment of the method, the recesses of the top and bottom layers and/or the through-openings of the intermediary layers are adapted in size to a given brain shape and volume such that said brain fills the cavity in a formfitting manner when being accommodate in the cavity.

Particularly, in further steps, the features of the container as described above, and particularly as claimed in one of the claims 1 to 18, can be provided in embodiments of the method according to the present invention.

According to yet another aspect of the present invention, a method for processing a human or animal brain is disclosed, the method comprising the steps of:

- Accommodating the brain in the cavity of a container according to the present invention or in a container produced with the method according to the present invention,

Immersing the brain in a chemical agent filled into the container and/or cutting the brain with a blade using at least one of the layers as a guide for the blade.

The chemical agent can be any suitable chemical agent used for storing/immersing the brain therein. Particularly, the chemical agent can comprise an aldehyde or a similar substance for fixing tissue of the brain.

Particularly, according to an embodiment, the respective groove formed into the at least one layer (particularly intermediary layer) as described above, can be used as said guide for making a cut into the brain orthogonal to the at least one layer, and/or the at least one layer can be used as said guide for making a cut into the brain with the blade parallel to the at least one layer.

Particularly, all methods described herein for processing an animal or human brain are ex-vivo processes involving non-living animal or human brains.

Further features and advantages of the present inventions as well as embodiments of the present invention shall be described in the following with reference to the Figures, wherein

Fig. 1 shows two sections of MRI scans. These are frames of MRI scans of a formalin-fixed brain from pathology,

Fig. 2 shows (A) placement of the fixed brain in multiple stacked layers of a container according to an embodiment of the invention, and (B) a cut surface of the brain cut in the container along a layer acting as horizontal cutting guide,

Fig. 3 shows an illustration of the cutting process with a knife using a groove of the layer shown in Fig. 3, wherein particularly the grooves allow to cut blocks from a slice of the brain (cf. Fig. 4),

Fig. 4 shows square blocks cut from the brain slice (A) using the grooves. The "lacuna" in block HR5 is shown in (B). Block HR5 was snap frozen in isopenthane and subsequently sectioned using a cryotome. (C) shows immunohistochemical staining, of the same block,

Fig. 5 shows a perspective view of an embodiment of the container according to the present invention, particularly showing an outer container of the container, the outer container comprising a lid and an openable discharge opening,

Fig. 6 shows a lateral view of an inner part of the container shown in Fig. 1 , the inner part being configured to be placed into an internal space of the outer container shown in Fig. 5, wherein the inner part comprises a plurality of layers that are configured to be stacked on top of one another,

Fig. 7 shows the inner part of the container being placed in the internal space of the outer container according to an embodiment of the container of the present invention,

Fig. 8 shows a top view onto a sealing member for sealing the internal space of the outer container shown in Figs. 5 to 7,

Fig. 9 shows a detail of the stacked layers of the inner part of the container according to an embodiment of the invention,

Fig. 10 shows a top view onto a top layer of the inner part of the container according to an embodiment of the container according to the invention,

Fig. 11 shows a top view onto a first side of a top layer opposite the outside of the top layer shown in Fig. 10, the first side comprising grooves forming a guide for a blade,

Fig. 12 shows the first side of the top layer and a first side of an adjacent intermediary layer of the inner part of the container according to an embodiment of the container according to the invention, Fig. 13 shows two further intermediary layers of the inner part of the container according to an embodiment of the container according to the invention,

Fig. 14 shows an annular member of the inner part of the container configured to be arranged a first portion (particularly half) of the inner part and a second portion (particularly half) of the inner part according to an embodiment of the container of the present invention,

Fig. 15 shows a top view onto an outside of a bottom layer of the inner part of the container according to an embodiment of the container of the present invention,

Fig. 16 shows an exploded view of the inner part of the container showing the top layer as well as adjacent intermediary layers and the annular member,

Fig. 17 shows an exploded view of an alternative inner part of a container according to the present invention, wherein here the inner part comprises a top layer and a bottom layer comprising recesses for forming the cavity for accommodating a brain,

Fig. 18 shows a lateral view of the inner part shown in Fig. 17, and

Fig. 19 shows a perspective view of an inner part of a further embodiment of a container according to the present invention, the inner part being preferably configured to be placed into an internal space of an outer container (e.g. as shown in Fig. 5), wherein the inner part comprises a plurality of layers that are configured to be stacked on top of one another,

Fig. 20 shows a perspective view of said layers shown in Fig. 19 with some of the layers being removed to show the through-openings of the layers forming a cavity for receiving a brain,

Fig. 21 shows a lateral view of the stacked layers shown in Fig. 19,

Fig. 22 shows a further lateral view of the stacked layers shown in Fig. 19,

Fig. 23 shows a top view onto a top layer of the inner part of the container shown in Fig. 19, Fig. 24 shows a top view onto a first side of the top layer opposite the outside of the top layer shown in Fig. 23, the first side comprising grooves forming a guide for a blade,

Fig. 25 shows a top view onto an intermediary layer adjacent the top layer of Figs. 23 and 24,

Fig. 26 shows a top view onto a first side of the intermediary layer of Fig. 25, the first side comprising grooves forming a guide for a blade,

Fig. 27 shows a top view onto a bottom layer of the inner part of the container shown in Fig. 19, and

Fig. 28 shows a top view onto a first side of the bottom layer opposite the outside of the bottom layer shown in Fig. 27, the first side comprising grooves forming a guide for a blade.

Fig. 5 shows in conjunction with Figs. 2, 12, 13 and 16 an embodiment of a container 1 according to the present invention for storing, particularly transporting, and also processing a human or animal brain 2.

The container comprises a plurality of layers, the layers being configured to be stacked on top of one another, particularly so as top form an inner part of the container 1, wherein said plurality of layers comprises (cf. Fig. 2) a bottom layer 10, a top layer 30, and intermediary layers 20, 21 configured to be arranged between the bottom and the top layer 10, 30, and wherein each intermediary layer 20, 21 comprises a through- opening 20a, 21a, so that the layers 10, 20, 21 , 30 form a cavity 3 for accommodating the brain 2 when being stacked on top of one another, cf. also Figs. 12, 13 and 16. The bottom layer 10 and the top layer 30 can each comprise a recess (see e.g. recess 30a of top layer 30 as shown in Fig. 12) that contributes to the cavity 3.

Particularly, the through-openings 20a, 21a (and in particular said recesses) are shaped such that the brain 2 to be stored, transported and/or processed fills the cavity 3 in a form-fitting manner when being accommodated in the cavity 3 which is e.g. indicated in Figs. 2A and 2B.

Particularly, the layers 10, 20, 21 , 30 holding the brain 2 are also adapted for cutting the brain 2. Particularly, Fig. 2B shows the brain being cut in half using an intermediary layer 21 as guide for a cutting blade, which will be described in more detail below.

Particularly, the container 1 can be used for holding the brain 2 during acquisition of MRI scans as shown in Fig. 1 showing two sections of MRI scans. These are frames of MRI scans of a formalin-fixed brain from pathology. The images were selected in order to later histologically characterize the regions of interest R.

In order to be able to locate such regions R, each layer 10, 20, 21 , 30 of the inner part of the container 1 comprises a plurality of markings M1 , M2, M3 which are e.g. shown in Figs. 1 , 4, 7, 9 to 13, 15, and 16. Particularly, the marking M1 indicates the layer (e.g. position along a vertical z-axis). According to an embodiment, the markings M1 label the layers from the bottom layer 10 to the top layer alphabetically as indicated in Fig. 9. Furthermore, particularly, the markings M2, M3 indicate the position of said region within the respective layer, e.g., in the corresponding horizontal plane (e.g. along horizontal x- and y-axes). Particularly, all markings M1 , M2, M3 are formed as recesses. Particularly, the markings M2, M3 are comprised of blind holes and/or slits. Thus, when the brain 2 is stored in the container 1 in a liquid, these blind holes or slits fill with the liquid which preferably generates a visible contrast in a medical image such as an MRI.

In order to be able to cut the brain 2 in precise manner, the layers 10, 20, 21 , 30 preferably each comprise a first side (e.g. first side 20b of intermediary layer 20 shown in Fig. 12) having a plurality of grooves formed therein, namely first grooves 22 extending in a first direction and second grooves 23 extending in a second direction, the first and the second direction being orthogonal with respect to one another. Each of these grooves is configured to guide a blade 5 as indicated in Fig. 4 to allow precise vertical cutting of a portion of the brain 2 that is accommodated in the through-opening of the respective layer comprising the guiding grooves 22, 23 being used.

Furthermore, the respective layer 10, 20, 21 , 30 forms a guide for a blade for cutting a portion of the brain 2 along the respective layer, i.e., horizontally, generating a horizontal cut as shown in Figs. 2B and 4. Particularly, Fig. 4 shows square blocks cut from the brain slice (A) using the grooves. The "lacuna" in block HR5 is shown in (B). Block HR5 was snap frozen in isopenthane and subsequently sectioned using a cryotome. Further, (C) shows immunohistochemical staining of the same block,

In order to be able to organize and process portions of the brain held by the layers of the inner part of the container efficiently, the intermediary layers 20, 21 are comprised of first intermediary layers 20 configured to be stacked on top of one another on top of the bottom layer 10, and second intermediary layers 21 being configured to be stacked on top of one another on top of the first intermediary layers 20 (cf. Fig. 6). Particularly, after suitably cutting the brain horizontally, the first and second intermediary layers 20, 21 can be separated from one another and thereby allow arranging the respective half of the brain 2 as shown e.g. for one half of the brain in Fig, 2B.

Particularly, the inner part of the container 1 comprises an annular member 24 as shown in Fig. 14 that is configured to be arranged between the first intermediary layers

20 and the second intermediary layers 21 (cf. Figs. 6, 9, and 16) thereby preventing lateral movement of the first and second intermediary layers 20, 21 with respect to one another and allowing to divide the first intermediary layers 20 arranged adjacent the bottom layer 10 from the second intermediary layers 21 being arranged adjacent the top layer 30. Further, when the intermediary layers 20, 21 are stacked on top of one another as shown in Fig. 6, for instance, the first side 20b of the respective first intermediary layer 20 faces towards the second intermediary layers 21 and the fist side

21 b of the respective second intermediary layer 21 faces towards the first intermediary layers 20.

Further, each layer 10, 20, 21 , 30 of said plurality of layers of the inner part of the container 1 is configured to engage with at least one adjacent layer for preventing a lateral movement of the respective layer when the layers are stacked on top of one another as e.g. shown in Figs. 6, 9 and 16.

While the inner part that comprises the above-described layers 10, 20, 21 , 30 is predominantly configured for holding and supporting the brain 2, the container further preferably comprises an outer container 4 as shown in Figs. 5, 7, and 8, wherein the outer container 4 encloses an internal space 40, wherein the internal space 40 is configured to accommodate said inner part comprising said plurality of layers 10, 21 , 22, 30, when the latter are stacked on top of one another as intended and the brain 2 is arranged in the cavity 3 therein.

For storing and/or processing the brain 2, the internal space 40 of the outer container is configured to hold a liquid such as a chemical agent for immersing the brain 2 arranged in the cavity 3 in said liquid. The liquid can be adapted just for liquid storage of the brain 2, but may also be a chemical agent such as an aldehyde for fixing, e.g. crosslinking, tissue of the brain.

In order to be able to avoid leakage of the liquid, the outer container 4 preferably comprises a lid 42 having a sealing member 41 as shown in Fig. 8 for providing a liquid- tight seal of the internal space 40 of the outer container 4. Further, Fig. 5 shows the lid 42 releasably connected to a flange 43 of the outer container 4. Particularly, the sealing member 41 seals the outer container 4, when the latter is secured (e.g. by threaded bolts and nuts) to the flange 43.

In order to discharge liquid residing in the internal space 40 of the outer container 4, the outer container 4 comprises a discharge opening 44 as shown in Fig. 4 that can be closed by means of a closure 45, e.g. in form of a cap that can be screwed on an outer thread formed on the outer housing 4.

Fig. 17 shows in conjunction with Fig. 18 a further embodiment of a container 1 according to the present invention comprising an inner part 24, 10, 30 that is configured to accommodate a brain 2 and can also be arranged in an outer container 4 as shown in Fig. 5. Here, said plurality of layers merely comprises a top layer 30 and a bottom layer 30, each of these layers comprising a recess 10a, 30a that forms a cavity 3 when the layers 10, 30 are arranged on top of one another and the recesses 10a, 30a are aligned with one another. Furthermore, the inner part can comprise an annular member 24 to be arranged between the two layers 10, 30, which annular member 24 prevents lateral movement between the top and bottom layers 30, 10.

As before, the cavity 3 is adapted such that the brain 2 can be accommodated in the cavity in a form-fitting manner.

Fig. 19 shows in conjunction with Figs. 20 to 28 a further embodiment of a container 1 according to the present invention for storing, particularly transporting, and also processing a human or animal brain 2, which container is particularly optimized for easy manufacturing of the container.

As described before, the container comprises a plurality of layers, the layers being configured to be stacked on top of one another, particularly so as top form an inner part of the container 1 shown in Fig. 19, wherein said plurality of layers comprises a bottom layer 10 (cf. e.g. Figs. 27 and 28), a top layer 30 (cf. e.g. Figs. 23 and 24), and intermediary layers 20, 21 configured to be arranged between the bottom and the top layer 10, 30, and wherein each intermediary layer 20, 21 comprises a through-opening 20a, 21a, so that the layers 10, 20, 21 , 30 form a cavity 3 for accommodating the brain

2 when being stacked on top of one another, cf. also Fig. 20. The bottom and top layers 10, 30 may each comprise a recess 10a, 30a that can contribute to said cavity 3.

Particularly, the through-openings 21a (and in particular said recesses 10a, 30a) are shaped such that the brain 2 to be stored, transported and/or processed fills the cavity

3 in a form-fitting manner when being accommodated in the cavity 3. In order to be able to locate interesting regions of the stores brain, each layer 10, 20, 21 , 30 of the inner part of the container 1 can have a plurality of markings. Particularly, the marking M1 may indicates the respective layer (e.g. position along a vertical z- axis). According to an embodiment, the markings M1 label the layers from the top layer 30 to the bottom layer 30 alphabetically as indicated in Fig. 20. Furthermore, other markings may be employed to indicate positions of interesting regions within the respective layer, e.g., in the corresponding horizontal plane (e.g. along horizontal x- and y-axes). Such markings may be formed as recesses, particularly slits. Such recesses/slits can be arranged on each layer, in particular.

Particularly, the layers 10, 20, 21 , 30 holding the brain 2 are also adapted for cutting the brain 2, e.g. as described above. In order to be able to cut the brain 2 in precise manner, the layers 10, 20, 21 , 30 preferably each comprise a first side (e.g. first side 21b of intermediary layer 21 shown in Figs. 25 and 26) having a plurality of grooves formed therein, namely first grooves 22 extending in a first direction and second grooves 23 extending in a second direction, the first and the second direction being orthogonal with respect to one another. Each of these grooves is configured to guide a blade 5 as described above to allow precise vertical cutting of a portion of the brain 2 that is accommodated in the through-opening of the respective layer comprising the guiding grooves 22, 23 being used.

Furthermore, the respective layer 10, 20, 21 , 30 forms a guide for a blade for cutting a portion of the brain 2 along the respective layer, i.e., horizontally, generating a horizontal cut.

Preferably, as before, In order to be able to organize and process portions of the brain held by the layers of the inner part of the container efficiently, the intermediary layers 20, 21 are comprised of first intermediary layers 20 configured to be stacked on top of one another on top of the bottom layer 10, and second intermediary layers 21 being configured to be stacked on top of one another on top of the first intermediary layers 20 (cf. Fig. 19).

Claims

1. A container (1) for storing a human or animal brain (2), comprising:

- a plurality of layers, the layers being configured to be stacked on top of one another, wherein said plurality of layers comprises at least a bottom layer (10) and a top layer (30), and

- wherein the layers (10, 20, 21 , 30) form a cavity (3) for accommodating the brain (2) when being stacked on top of one another.

2. The container according to claim 1 , wherein the plurality of layers further comprises intermediary layers (20, 21) configured to be arranged between the bottom and the top layer (10, 30).

3. The container according to claim 2, wherein each intermediary layer (20, 21) comprises a through-opening (20a, 21a) contributing to said cavity (3) when the layers are stacked on top of one another.

4. The container according to one of the preceding claims, wherein the bottom layer (10) comprises a recess (10a) contributing to said cavity (3) when the layers are stacked on top of one another and/or wherein the top layer (30) comprises a recess (30a) contributing to said cavity (3) when the layers are stacked on top of one another.

5. The container according to one of the preceding claims, wherein the through- openings (20a, 21a) and/or said recesses (10a, 30a) are shaped such that the brain (2) fills the cavity (3) in a form-fitting manner when being accommodated in the cavity (3).

6. The container according to claim 2 or according to one of the claims 3 to 5 in so far referring to claim 2, wherein each intermediary layer (20, 21) comprises a first side (20b) having a plurality of grooves (22, 23) formed therein, each groove (22, 23) being configured to guide a blade (5) for cutting a portion of the brain (2) accommodated in the through-opening (20a, 21a) of the respective intermediary layer (20, 21) along the respective groove (22, 23).

7. The container according to claim 6, wherein the plurality of grooves (22, 23) comprises first grooves (22) extending in a first direction and second grooves (23) extending in a second direction, the first and the second direction being orthogonal with respect to one another.

8. The container according to one of the preceding claims, wherein the intermediary layers (20, 21) comprise first intermediary layers (20) configured to be stacked on top of one another on top of the bottom layer (10), and second intermediary layers (21) being configured to be stacked on top of one another on top of the first intermediary layers (20).

9. The container according to one of the preceding claims, wherein the container (1) comprises an annular member (24), the annular member (24) being configured to be arranged between the top layer (30) and the bottom layer (10) and/or between the first intermediary layers (20) and the second intermediary layers (21).

10. The container according to claim 6 and according to claim 8 or 9, wherein, when the intermediary layers (20, 21) are stacked on top of one another, the first side (20b) of the respective first intermediary layer (20) faces towards the second intermediary layers (21) and the fist side (21b) of the respective second intermediary layer (21) faces towards the first intermediary layers (20).

11. The container according to one of the preceding claims, wherein each layer (10, 20, 21 , 30) of said plurality of layers is configured to engage with at least one adjacent layer for preventing a lateral movement of the respective layer when the layers are stacked on top of one another.

12. The container according to one of the preceding claims, wherein each layer (10, 20, 21 , 30) of said plurality of layers comprises a plurality of markings (M1 , M2, M3) to allow identification of the respective layer in an image and/or localizing a position of a tissue portion of the brain in an image when the brain (2) is arranged in the container (1).

13. The container according to one of the preceding claims, wherein the respective layer (10, 20, 21 , 30) of said plurality of layers forms a guide for a blade (5) for cutting a portion of the brain (2) along the respective layer.

14. The container according to one of the preceding claims, wherein the container (1) comprises an outer container (4), the outer container (4) defining an internal space (40), wherein the internal space (40) is configured to accommodate said plurality of layers (10, 21 , 22, 30) and the brain arranged therein.

15. The container according to claim 14, wherein the internal space (40) is configured to hold a liquid for immersing the brain (2) arranged in the cavity (3) formed by the layers in said liquid. 16

16. The container according to one of the claims 14 to 15, wherein the outer container (4) comprises a lid (42) for closing the outer container (4), wherein the lid (42) is configured to be releasably connected to a flange (43) of the outer container (4).

17. The container according to one of the claims 14 to 16, wherein the outer container (4) comprises a sealing member (41) for providing a liquid-tight seal of the outer container (4), wherein particularly the sealing member (41) is arranged on the lid (42).

18. The container according to one of the claims 14 to 17, wherein the outer container (4) comprises a discharge opening (44) for discharging liquid contained in the internal space (40) out of the outer container (4), and a closure (45) for closing the discharge opening (44).

19. A method for producing a container (1), particularly a container (1) according to one of the preceding claims, the method comprising the steps of:

- forming a plurality of layers (10, 20, 21 , 30), the layers being configured to be stacked on top of one another, wherein said plurality of layers comprises at least a bottom layer (10) and a top layer (30), and

- wherein the layers (10, 20, 21 , 30) are formed such that the layers form a cavity (3) for accommodating the brain (2) when being stacked on top of one another.

20. The method according to claim 19, wherein forming the plurality of layers further comprises forming intermediary layers (20, 21) configured to be arranged between the bottom and the top layer (10, 30).

21. The method according to claim 20, wherein each intermediary layer (20, 21) comprises a through-opening (20a, 21a) contributing to said cavity (3) when the layers are stacked on top of one another.

22. The container according to one of the claims 19 to 21 , wherein the bottom layer (10) comprises a recess (10a) contributing to said cavity (3) when the layers are stacked on top of one another and/or wherein the top layer (30) comprises a recess (30a) contributing to said cavity (3) when the layers are stacked on top of one another.

23. The method according to one of the claims 19 to 22, wherein the recesses (10a, 30a) and/or the through-openings (20a, 21a) are adapted in size to a given brain shape and volume such that said brain (2) fills the cavity (3) in a form-fitting manner when being accommodate in the cavity (3). 17 Method for processing a human or animal brain, the method comprising the steps of:

- Accommodating the brain (2) in the cavity (3) of a container (1) according to one of the claims 1 to 18, and - Immersing the brain (3) in a chemical agent filled into the container (1) and/or cutting the brain (2) with a blade (5) using at least one of the layers (10, 20, 21 , 30) as guide for the blade (5).