MARKER ELEMENT FOR MARKING TISSUE

The invention relates to a marking body provided for implantation into soft tissue (e.g., fatty tissue, muscle tissue, tumor tissue, breast tissue, liver tissue, lymph nodes, in particular axillary lymph nodes, or the like), having an elastic, compressible and self-expanding support structure. The support structure is formed by interconnected elastic and preformed webs. The marking body has a shape that is at least approximately rotationally symmetrical about a longitudinal axis. The marking body is visually detectable or physically detectable in other ways, or machine-detectable, even in automated or semiautomated fashion. The invention furthermore relates to an implantation system and a method for implantation.

Implantable marking bodies for labeling tissue sites are well known. As a rule, such marking bodies are designed so that they can be implanted in the tissue regions to be labeled by way of a suitable apparatus, in order to remain there permanently or over a certain period of time, for example between two interventions. In this way, tissue relevant to the treatment, for example tissue containing tumors or other tissue abnormalities or else potentially healthy tissue intended to be observed, can be labeled for a relatively long period of time. The labeling effect of these marking bodies is attained as a result of the visibility thereof during examinations using methods of imaging diagnostics, in particular in the case of methods based on x-ray radiation, nuclear magnetic resonance or ultrasonic waves.

WO 2006/000568 A2 discloses a marker for marking a tissue site following the insertion of said marker using an applicator or cannula with a known structure. What is attained here is that the marker remains at the tissue site to be marked for a relatively long time and consequently clearly marks a tissue site for a subsequent diagnostic and therapeutic activity. The market consists of one or more wires which are twisted in the central marker section and which may have different shapes in the two end sections of the marker.

A surgical instrument, more particularly a marker instrument for marking body tissue sections, is furthermore described in EP 1 782 745 B1. In particular, the instrument should be suitable for marking tumor tissue prior to the surgical removal of said tissue.

From the field of surgical orthopedics for treating bone necrosis, U.S. Pat. No. 8,112,869 B2 has disclosed a manufacturing method for producing spherical cage structures consisting of nitinol. The cage structures produced in accordance with the method described therein are provided for stabilizing the femoral head by virtue of being introduced in compressed form via a channel drilled into the femur, expanding in the femoral head and cavities subsequently being filled with solidifying bone graft. In this field of application, the diameters of the cage structures range between 20 and 30 mm.

U.S. Pat. No. 9,216,069 B2 describes a marker system for breast biopsy, in which a multiplicity of marker elements are preloaded in compressed fashion in an administering tube, said marker elements containing at least one radiopaque wire segment.

For breast biopsies, U.S. Pat. No. 8,060,183 B2 discloses, in general, markers that enclose a cavity for labeling in imaging methods. In one variant, the marker consists of an outer hollow body closed at both elongate ends and a smaller permanent marker situated within the outer body. The description goes on to explain that the outer hollow body consists of a bioresorbable material and decomposes over certain period of time while the inner permanent marker continues to remain in the tissue.

It is an object of the invention to specify an improved marking body for implantation in a tissue.

A marking body as claimed in claim 1 is proposed for achieving this object. Accordingly, the marking body has an at least approximately rotationally symmetrical shape about a longitudinal axis, and is able to adopt a radially compressed and a radially expanded state. The marking body is formed by interconnected elastic and preformed webs which yield an elastic, compressible and self-expandable support structure. In its expanded state, the marking body has the greatest diameter in a central longitudinal section and tapers off in the longitudinal direction toward both longitudinal ends starting from the central longitudinal section. At least in the central longitudinal section, the marking body is formed by 5 to 100 webs in the circumferential direction, said webs extending substantially in the longitudinal direction of the marking body in the compressed state of the latter and crossing pairwise at their longitudinal ends and being interconnected in cohesive and/or interlocking fashion. Extending substantially in the longitudinal direction of the marking body means that, in the compressed state of the marking body, the webs extend at an angle of less than 10° with respect to the longitudinal axis of the marking body.

Such a marking body can advantageously fulfill two requirements: firstly, it offers good detectability on the basis of its physical parameters, for example visually in medical imaging, e.g., x-rays, or automatically by way of data analysis of ultrasound data or MRI data, for example. In this case, the data analysis can be implemented manually, visually, semiautomatically or automatically. Moreover, the marking body fulfills the requirement of staying true to its location and, as a result of its design, acts against migration, that is to say a movement of the marker in the tissue shortly after the implantation, or during the time in which the marker is implanted.

Should a biopsy, for example a vacuum biopsy, have been carried out before marking, the tissue pressure acting against the propagation direction of the marking body may be accordingly lower or nonexistent on account of an already present cavity. In such a case, the expansion of the marking body after placement prevents the marking body falling back into the biopsy cannula or being rinsed away through the puncture channel of the vacuum biopsy unit.

An implantation system having a marking body and an implantation apparatus is proposed as a further aspect of the invention.

The invention is based on the idea that the visibility of the marking bodies should be ensured even in the case of imaging methods that are based on different operational principles. Furthermore, the unique and clear visibility of marking bodies should be ensured under the largest possible range of examination conditions and application cases. In the case of ultrasound-based imaging methods, a good recognizability of the marker arises by way of the highest possible sound reflection of the support structure formed by metal or hard plastic.

In the case of medical ultrasound (e.g., B mode, 1 MHz-40 MHz), the support structure of the marking body causes incident ultrasound waves to strike a circular structure in cross section in the central longitudinal section of the marking body. What is obtained by matching the parameters of web diameter (or width and thickness), web number, web intensity and web material is that only some of the acoustic energy is reflected by the structure and the remaining part of the energy is transmitted. As a result, a full circle or a circular arrangement of individual points, depending on resolution and parameter settings of the ultrasound, arises as a representation in the ultrasound image. In the case of other structures of this form, the ultrasound energy is largely reflected at the first surface of the marker and a shadow arises in the image.

A further feature of this structure comes to bear within the scope of imaging at different angles of the ultrasound transmission waves (e.g., compound imaging). Within the scope of compound imaging, the sound beam is transmitted from the static ultrasonic transducer at different angles. Subsequently, the echoes of transmission waves with different angles are summated and processed. In this case, the ultrasonic waves strike the structure of the marking body from different angles but as a result of the circular cross-section the echoes will in end effect arrive at the same receivers and the representation of the marking body is amplified in comparison with nonuniform anatomical structures.

For ultrasound imaging, the marking body is preferably formed of hollow tubes, or at least some of the webs are hollow, such that a large difference in the acoustic impedance arises between the material of the webs and the hollow interior, so that there is a significant ultrasonic reflection at the site.

In the case of x-ray-based imaging methods, too, for example in mammography, an absorption of the x-ray radiation by the support structure leads to good recognizability in the x-ray image. The absorption of the x-ray radiation by the support structure can, e.g., be traced back to the metal in the support structure or is caused by additives, for example the metal wires or the metal particles embedded in plastic.

In the case of magnetic resonance imaging (MRI), the magnetic properties of the material of the marking body lead to susceptibility artifacts in the MR imaging and hence to the good recognizability thereof in MRI data and images.

Advantageous developments of the invention can be gathered from the dependent claims and, in detail, specify advantageous options of realizing the above-described concept within the scope of the problem and in respect of further advantages.

In particular, provision is made for the support structure to be woven, braided, wound or knitted. The advantage here consists in the economical producibility of a structure that is spread out over an area, which, within the scope of a subsequent production step, is brought into a hollow, approximately spherical form.

Alternatively, the support structure can be formed by a wire or tube that is slotted in the longitudinal direction and compressed such that the sections separated from one another by the slits bulge toward the outside. If the compressed state of such a support structure is its relaxed state, the support structure is self-expanding.

A further alternative for the support structure is a support structure made of a plastic, for example a basket manufactured within the scope of an injection molding method, for example made of PEEK or PLA.

The support structure of the marking body is preferably designed in such a way that it is self-expanding and can be elastically compressed under a radial force. The radial force depends on the expanded and the compressed diameter, and ranges between 1 newton and 50 newtons. If the marking body is implanted in the tissue in the elastically compressed state, the marking body independently transitions into its expanded state and keeps the latter if the tissue exerts a radial force that is less than the radial expansion force of the marker on the marking body.

For implantation purposes, the marking body is initially brought to the desired location by means of a cannula and is then pushed out of the lumen of the cannula such that it can subsequently flare in the tissue. The expansion force with which the marking body kept in a compressed state in the cannula flares immediately following the ejection from the cannula is preferably at least 1 newton.

By way of example, the support structure of the marking body can be designed in such a way that the latter has an expansion force which is more than 40 newtons in a state of the marking body where it has been compressed to less than 1 mm maximum diameter and still is more than three newtons, for example six newtons, in the case of a maximum diameter of 1.5 mm. The support structure of the marking body can be designed in such a way that its expansion force substantially corresponds to the minimum radial force that needs to be applied to elastically compress the marking body.

The energy stored in the support structure of the marking body can be set by a suitable choice of the cross-sectional dimensions (e.g., diameter) of the webs of the support structure or of the number of webs of the support structure or of the diameter of the support structure or of the treatment of the support structure (e.g., heat treatment versus electropolishing). The energy stored in the support structure of the elastically compressed marking body furthermore depends on the material that forms the webs of the support structure of the marking body (e.g., nitinol or PEEK). Accordingly, it is possible to also produce the marking body according to the invention in such a way that a radial force of more than 1.5 newtons, two newtons or even more than three newtons must be applied to compress the marking body to a maximum diameter of less than 1.5 mm. It is likewise possible to produce the marking body according to the invention in such a way that a radial force of 0.5 newtons is already sufficient to compress the marking body to a maximum diameter of less than 1.5 mm.

Since the support structure of the marking body is designed to be self-expanding, the marking body independently transitions into its expanded state as soon as the radial force drops below levels required to elastically compress the marking body. The support structure of the marking body is preferably formed by braided individual wires. Accordingly, the webs of the marking body are preferably formed by 5 to 100 wires, for example 18 to 48 wires and in particular 24 or 36 wires, which each extend from one to the other longitudinal end of the marking body and which cross over multiple times and thus form a lattice-like support structure made of a braided wire mesh with a multiplicity of crossing points. A marking body formed by 12 to 48, in particular 24 braided wires preferably consisting of a titanium alloy, in particular nitinol, is particularly preferred.

The webs of the marking body, that is to say for example the wires, are in this case interconnected, preferably pairwise interconnected, at their free longitudinal ends and are particularly preferably welded, in particular twisted and welded. To this end, the free longitudinal ends are preferably each located on a crossing point of the support structure, that is to say for example where the wires in the braided wire mesh cross, or in the direct vicinity of a crossing point.

The webs of the marking bodies may also be cohesively interconnected, in particular welded, at the crossing points as well. However, this is preferably not envisaged.

Alternatively or in addition, the webs of the marking bodies can be twisted with one another at the crossing points or longitudinal ends.

In the expanded state of the marking body, the external diameter of the latter preferably decreases continuously in the longitudinal direction to both the longitudinal ends starting from the central longitudinal section, and so the marking body has its minimum diameter at both longitudinal ends.

The marking body is preferably side symmetrical in relation to a plane transverse to the longitudinal axis of the marking body.

Preferably, the webs of the marking body are formed from hollow tubes or wires. In the case of a marking body formed from braided webs, the external web diameter is preferably less than 0.5 mm, preferably less than or equal to 0.1 mm, for example between 0.08 mm and 0.1 mm. A small external web diameter in this case has a positive effect on the compressibility of the marking body, which is required in the case of implantation by way of a cannula with the smallest possible diameter. By contrast, a greater external web diameter has a positive influence on the set-up force of the support structure of the marking body. This leads to the marking body also being able to expand against tissue pressure prevalent in a hard tissue, for example tumor tissue.

Furthermore, it is advantageous if the diameter of the marking body in the expanded state is less than 20 mm or less than 10 mm, preferably between 2.0 mm and 6.0 mm. A marking body in this diameter range represents a compromise between visibility in the imaging methods on the one hand and the spatial requirement of a foreign body in the tissue on the other hand.

An expanded marking body with a certain minimum size offers the advantage that it can be sensed by a surgeon during the treatment.

Furthermore, it is preferable for the diameter of the marking body in the compressed state to be less than 3 mm, preferably less than 1.0 mm. A small diameter in the elastically compressed state or a significant compressibility of the marking body facilitates an implantation of the marking body using a relatively thin cannula, that is to say a cannula with a small diameter. A smaller diameter reduces the risk to the patient in relation to injury and pain, and a stab incision and/or anesthetics can be dispensed with within the scope of simplified handling. This furthermore yields advantages in respect of application duration and costs.

Preferably, the support structure, for example its webs and/or sleeves formed by wires or tubes, has been roughened, for example by sandblasting, in order to thus increase ultrasound visibility.

Preferably, the surface of the support structure has an additional coating. Pharmaceutical agents which detach from the marker during implantation (e.g., anticoagulants) can be used as a coating. Materials that improve the biocompatibility of the support structure (e.g., parylene) can also be used as a coating. Fluorescent or phosphorescent substances, which facilitate the activation by different light spectra, can also be used as a coating.

The marking body can preferably be coated with a membrane from the outside or from the inside. The membrane can be produced from silicone or polyurethane or parylene, for example. The membrane serves to fully or partly separate the interior of the marker from the surroundings. This can improve the recognizability and detectability, or this can create a space which can be filled with other substances or gases (e.g., cytostatic agents, ICG, etc.).

The webs of the marking body preferably consist of a titanium alloy, in particular nitinol. On account of the material properties of nitinol as a superelastic material, this leads to the advantage that the marking body independently transitions from an elastically compressed state to an expanded state after being driven out of the implantation apparatus, in particular transitions against the pressure which acts against the expansion direction and is developed by the tissue adjoining the marking body. The use of a further superelastic materials and/or shape-memory alloys is also possible. Similar properties can also be achieved by some polymers.

By way of example, a fast self-expansion of the marking body post-implantation, as facilitated by the use of nitinol, is decisive for preventing a migration of the marking body, especially just after the implantation.

The material of the support structure can be resorbable or non-resorbable.

The webs of the support structure need not all consist of the same material and may differ in terms of their cross-sectional shape. Rather, individual webs made of different materials may also be included in the braid in order to optimize the visibility or detectability in magnetic resonance imaging or in an ultrasound image, or else increase the x-ray visibility in computed tomography or under C-arms. By way of example, suitable materials include titanium, gold, iron-containing alloys and/or nitinol, PLA, PEEK, other polymers and composite materials.

Preferably, the marking body contains labeling features, e.g., sleeves of different shape and/or length, for example metallic or other radiopaque molded parts within the support structure, complementing or in addition to the support structure. Amongst other things, the advantage obtained thereby is that a plurality of different marking bodies implanted simultaneously in a patient can be clearly distinguished, or at least be distinguished more easily, in imaging methods. By way of example, these molded parts can be webs or spheres located within the support structure or fastened to the support structure, and can furthermore have different dimensions for improved distinguishability. By way of example, these molded parts can be formed from metal.

A further aspect relates to the detectability of the marking body following implantation. It may be possible to sense the marking body and the latter can be found as a result of sensing during a percutaneous intervention. The marking body may also be distinguished visually from the surrounding tissue in images (e.g., x-rays) or in the visualization of data (e.g., MRI, ultrasound). As a result of its properties, the marking body may also be detected automatically or semiautomatically by algorithms (e.g., by machine learning or deep learning algorithms).

A further aspect relates to an implantation system having a marking body of the type claimed here, and to an implantation apparatus.

The implantation apparatus is designed for implantation of the marking body according to the invention and comprises a cannula to this end. Consequently, by way of the implantation apparatus, the marking body can advantageously be placed at the tissue site to be labeled by puncturing the skin layers and the tissue located therebelow, with the imaging method being used in particular. Advantageously, provision is made for the external diameter of the cannula of the implantation apparatus to be less than 3 mm, preferably between 1.6 mm and 1.2 mm. This leads to the advantage that the marking body can be implanted percutaneously, in particular on account of the small cannula diameter. In particular, a small external cannula diameter facilitates the implantation of the marking body without having to resort to a stab incision of the skin at the entry site of the cannula or anesthetization of the relevant tissue.

As a result of the overall system, the marking body can be applied together with a suitable implantation apparatus that fits in terms of dimensions. In particular, the implantation system as overall system comprising both marking body and implantation apparatus may in the delivered state contain the marking body already in the compressed state within the cannula, and so the method step of compressing the marking body and pre-loading the implantation apparatus is dispensed with for the user and the application is further simplified in this way.

A method for producing a marking body is also proposed according to the invention. The latter comprises the following steps:

- providing a tubular braided mesh which is formed by 5 to 200 braided individual wires, and
- compressing the braided mesh in the longitudinal direction and thereby causing the braided mesh to flare radially in a central longitudinal section, and/or constricting the braided mesh at its longitudinal ends or compressing the braided mesh in the radial direction at the longitudinal ends.

Preferably, the method includes the following further method steps:

- braiding individual wires to form a tube such that the individual wires alternately cross over and under one another at crossing points, the crossing points being approximately arranged on crossing point planes which extend transversely to a longitudinal axis of the tube, and
- separating a tube section by laser cutting the wires at all crossing points in a separation plane, which is a crossing point plane, for providing the tubular braided wire mesh. The tubular braided wire mesh separated from the tube can subsequently be shaped into the marking body.

Preferably, the individual wires are welded pairwise to one another upon separation.

Preferably, the individual wires are twisted around one another at crossing point planes provided as separation planes by virtue of the respective two individual wires being wound around one another through at least 180°, preferably 360°, 540° or 720°.

Preferably, the individual wires cross over or under one another 8 to 12 times, preferably 9 to 11 times or 10 times between the longitudinal ends of the tubular braided wire mesh. Accordingly, every ninth to thirteenth, preferably each tenth, eleventh or twelfth crossing point plane of the tube braided from the individual wires represents a separation plane where the individual wires are twisted around one another, preferably pairwise.

A marking body of the type presented here serves for percutaneous marking in the soft tissue, for example breast tissue, and for marking axillary lymph nodes following a lymph node biopsy or before a subsequent lymph node resection.

The fields of application include the marking of suspicious tissue, the marking of lesions before or during chemotherapy, and the marking of a biopsy removal site. The location of a removed tumor may likewise be marked for improved orientation within the scope of radiation treatment planning.

The marking body can be used as set forth below within the scope of an intervention:

Initially, the marking body is implanted at a desired site by virtue of the distal end of a cannula of an implantation apparatus being pierced up to the desired implantation location in body tissue and a marking body being ejected from the distal end of the cannula.

Subsequently, the body tissue can be examined using an imaging ultrasound method, an ultrasound recording of the marked tissue being made. The marking body can be recognized in the ultrasound recording on account of a circular artifact.

According to a preferred application, the marking body is placed in a soft tissue without air inclusions (e.g., fatty tissue) and is insonated with ultrasonic waves ranging between 1 MHz and 40 MHz. In this case, the marking body is designed in such a way that it reflects only part of the ultrasonic power at the first side, which faces the ultrasound, and reflects a second part of the ultrasonic power at the second side, which is distant from the ultrasound, as a result of which the marking body has a circular representation in an ultrasound image within the scope of medical ultrasound imaging.

Preferably, the marking body is detected by means of an automatic or semiautomatic method, preferably by analyzing ultrasound data or by analyzing x-ray recordings or by analyzing MRI data.

Further advantages, features and details of the invention arise from the following description of the preferred embodiments and the illustrating figures, in which:

FIG. 1: shows a schematically represented marking body in a perspective view;

FIGS. 2a and 2b: show the marking body shown in FIG. 1 in an end view (FIG. 2a) and in a side view (FIG. 2b);

FIGS. 3a to 3h: show different cross-sectional shapes for webs of a marking body according to FIGS. 1 and 2;

FIGS. 4a to 4f: show different variants of how individual webs of the marking body from FIGS. 1 and 2 can be interconnected at crossing points;

FIGS. 5a to 5f: show different variants of how free ends of two webs of a marking body according to FIGS. 1 and 2 can be connected;

FIG. 6: shows a braided wire mesh as a section of the braided tube which can be used as an initial product for shaping a marking body as depicted in FIGS. 1 and 2;

FIG. 7: shows a section of a tube braided from wires, from which three braided wire meshes according to FIG. 3 can be produced by separation;

FIG. 8: shows the braided wire tube from FIG. 4, in the case of which the wires are separated at two sites by means of a laser;

FIGS. 9a to 9c: show a longitudinal section of various forms which a marking body according to FIGS. 1 and 2 can adopt;

FIG. 10: shows a perspective view of an implantation apparatus for a marking body according to FIGS. 1 and 2;

FIG. 11: shows a side view of the implantation apparatus depicted in FIG. 10;

FIG. 12A to 12C: show schematic representations of the details of the implantation apparatus depicted in FIGS. 10 and 11;

FIGS. 13a and 13b: show plan views of the implantation apparatus depicted in FIGS. 10 and 11;

FIG. 14: shows an illustration of an ultrasound recording of a marking body according to FIGS. 1 and 2, and ultrasound images resulting therefrom;

FIG. 15: illustrates how ultrasound is reflected from the webs of the marking body according to FIGS. 1 and 2;

FIG. 16: shows an ultrasound image having an artifact of the marking body, as viewed from the side;

FIG. 17: shows an ultrasound image having an artifact of the marking body in the longitudinal direction;

FIGS. 18a and 18b: show a twist of the longitudinal ends of two wires (FIG. 18a) and a twist of the free longitudinal ends of three wires (FIGS. 18b);

FIG. 19: shows a braided wire mesh similar to that illustrated in FIG. 6, with additional membranes spanned between individual wires; and

FIGS. 20a to 20d: illustrate how a marking body can look like in cross section, without a membrane (FIG. 20b), with an interior membrane (FIG. 20b) and with an exterior membrane (FIG. 20d).

FIG. 1 shows a perspective view of a schematically illustrated marking body 100 in the expanded state.

FIG. 2a shows an end view of the marking body 100 in the expanded state and FIG. 2b shows a side view of the marking body 100 in the expanded state.

The marking body 100 comprises a support structure formed by a braided wire mesh 101. The wires 108 extend from one longitudinal end of the marking body 100 to its other longitudinal end. On the path from one longitudinal end to the other longitudinal end, the wires 108 cross other wires 108 and are braided in particular, that is to say each wire 108 is alternately guided first below and then above another wire 108 of the braided wire mesh 101. As a result, a lattice-like support structure with a multiplicity of crossing points 110 arises. In relation to the depicted representation in FIGS. 1 and 2, it should be observed that these crossing points 110, at which two wires 108 in each case cross over one another and are in lateral contact, are not reproduced with accurate detail. The braided structure of the marking body 100 is better depicted in FIGS. 6 to 8, which show the initial product. The crossing points 110 at which two wires 108 are in contact in each case may for example be designed like in the braided wire mesh 101, formed by crossing wires, in FIG. 6.

The free ends 112 of the wires 108 located at the respective longitudinal ends 114, 116 of the marking body 100 are each twisted around and welded to one or more free ends of the further wires 108. Preferably, two wires 108 are always interconnected with the respective longitudinal ends 114, 116 by twisting and welding at a crossing point at the respective longitudinal end of the marking body 100.

At its longitudinal ends, the marking body 100 has two longitudinal sections 102, 104, from where the marking body 100 flares to a central longitudinal section 106. Consequently, the external diameter of the marking body 100 has a maximum in the central longitudinal section 106.

In the illustrated example, the braided wire mesh 101 comprises 24 wires which consist of nitinol and have a diameter of approximately 0.1 mm. In alternative embodiments of the marking body not shown here, the braided wire mesh comprises between 8 and 200 wires, for example 48 or 96 wires. In the embodiments not shown here, the marking bodies comprise braided wire meshes which are formed by wires with diameters ranging between 0.05 mm and 0.15 mm. Wires that consist of other metals, for example other titanium alloys other than nitinol can also be used. “Wires” made of plastic, for example PEEK or PLA, may also be provided in alternative embodiments of the marking body.

The individual webs may have different diameters and also different cross-sectional shapes. FIGS. 3a to 3h show different cross-sectional shapes. By way of example, the webs can be formed as a round solid wire and have a cross section as depicted in FIG. 3a. Preferably, the webs consist of a hollow wire—that is to say a type of tube—which may have a cross section as depicted in FIG. 3b. Such a hollow wire is advantageous in that it reflects sound particularly well on account of the acoustic impedance differences between the material of the wire wall and the hollow interior. FIGS. 3c and 3d illustrate that the cross-sectional form can also be a square, in particular quadrilateral. FIGS. 3e and 3f show a triangular cross-sectional form for webs, in the form of solid material (FIG. 3i) or as hollow webs (FIG. 30. FIGS. 3g and 3h illustrate that the webs in principle can each have an arbitrary, prismatic cross-sectional shape, and hence also a hexagonal shape as shown in FIGS. 3g and 3h.

Since the marking body 100 is preferably formed from a braided wire mesh, the wires typically contact each other once the crossing points. Then, a crossing point can have an appearance as depicted in exemplary fashion in FIG. 4a. A secure connection between the two crossing wires can be produced by welding at such a crossing point. FIG. 4b illustrates this on the basis of a weld spot 118 on the crossing point. Should the webs not be braided but simply contact one another laterally in an arc, as depicted in FIG. 4c, a stable marking body can also be produced by virtue of the fact that the contacting webs are connected by welding, as depicted in FIG. 4d. A weld spot 118 is also shown here. Finally, the webs can also be twisted at the crossing points. FIG. 4e shows a twist, within the scope of which the webs are wrapped around one another by 360° and are subsequently interconnected by means of a weld spot 118; see also FIG. 4f. Instead of a 360° twist, a 180° twist is also sufficient. The arising image then is similar to FIG. 4c, with the exception that the webs are then hooked in one another.

FIGS. 5a to 5f illustrate that the webs can be connected by welding (FIG. 5b), by twisting (FIGS. 5c and 5e), or by twisting and welding (FIGS. 5d and 50 not only at the crossing points but also at the free longitudinal ends 112. Weld beads 120 that typically have a larger diameter than an individual web 103 or a wire that forms a web 103 then arise as a result of welding the webs 103 at their free longitudinal ends 112.

The marking body 100 has a length LM of 6 mm; in alternative embodiments not shown here, this length may also range between 4 mm and 8 mm, however.

The maximum external diameter DMA of the marking body in the central longitudinal section 106 is 4 mm and can be between 3.5 mm and 10 mm in alternative embodiments not shown here.

To bring the marking body 100 into an elastically compressed state from the expanded state, a radial force of at least one newton must be exerted on the marking body 100.

In alternative embodiments not shown here, the self-expanding marking body 100 may have more wires and accordingly more crossing points, and so said marking body is comparatively stiffer. Accordingly, a comparatively greater radial force then is required to bring the marking body into an elastically compressed state. Likewise, the number of wires can be lower in alternative embodiments not shown here, in order to realize a marking body which already transitions into its elastically compressed state when a radial force of less than one newton is exerted.

FIGS. 3, 4 and 5 illustrate various phases of a production method for producing a marking body which has a support structure formed by a braided wire mesh. By way of example, a marking body as described in relation to FIGS. 1 and 2 can be produced in accordance with the method described below.

Initially, a tubular braided wire mesh is provided, the latter for example being able to comprise between 8 and 200 individual wires which are braided with one another and, as a consequence, cross at crossing points. These are 24 individual wires in the depicted example.

As may be gathered from FIG. 2b, the marking body 100 preferably has a length LM ranging between 5 mm and 8 mm. The external diameter DMA in the fully expanded state is between 4 mm and 6 mm. The diameter of the individual wires 108 is preferably slightly less than 0.1 mm. The weld beads 120 at the free ends 112 of the wires have a diameter of greater than 0.1 mm, the latter preferably being at least 0.12 mm Hence, the marking body 100 is suitable for use with an implantation apparatus 1004 in which the difference between an internal cannula diameter DKI and a driving-out element external diameter DA is no more than 0.1 mm—even when the manufacturing tolerances are taken into account. Incidentally, the internal cannula diameter DKI is not necessarily greater than the external diameter d of the compressed marking body 100.

As can already be gathered from FIG. 3, the webs of the support structure can either be solid (wires) or hollow (tubes). The profiles may have a circular or ellipsoidal cross section. They may also be triangular, quadrilateral or in the form of an n-gon. The profiles can also change along a web. By way of example, a web could have a rectangular profile in the center and a circular profile at the longitudinal ends.

FIG. 4, which is explained in more detail above, shows examples of possible interlocking connections as a result of crossing, contacting or twisting at the crossing points. FIG. 4 likewise illustrates that the connection of the crossing points can additionally be cohesive, for example as a result of adhesive bonding, welding or soldering.

FIG. 5, likewise explained in more detail above, shows examples of possible forms of interlocking and cohesive connections at the free longitudinal ends 112 of the wires 108. The ends can be interconnected in pairs or in groups; see also FIG. 18.

What can likewise be gathered from FIG. 6 is that the free longitudinal ends 218 of the wires 202 are not only welded to one another but also twisted around one another. In combination, this ensures that the interconnected longitudinal ends of the wires do not separate from one another.

Unlike what is depicted in idealized fashion in the FIGS. 3 to 5, the longitudinal ends of the individual wires 202 are not all exactly in one (separation) plane 212 (see FIGS. 4 and 5), but are alternately slightly offset in relation to such an idealized plane, preferably in the longitudinal direction. This has the advantageous effect that the marking body 200 can be better compressed at its longitudinal ends 218 because the weld beads 220 are not all located next to one another but are at least slightly offset from one another in the longitudinal direction of the marking body 200.

The marking body 100 is preferably formed from a braided wire mesh 200, as depicted in FIG. 6 in exemplary fashion. FIG. 6 shows a braided wire mesh 200 as a section of a braided wire tube 202 (see FIG. 7), which is braided from 24 individual wires in the depicted example. The braided wire mesh 200 that will form the marking body 100 is formed from 24 individual wires 108 which cross under or over one another nine times between their longitudinal ends 112 and which are twisted around one another and welded to one another at their longitudinal ends 112 in pairs such that the braided wire mesh 200 has respective weld beads 120 at the longitudinal ends 112 of the wires 108. As can be gathered from FIG. 6, the longitudinal ends 112 of the interconnected wires 108 are not only welded to one another but also twisted around one another.

To produce a braided wire mesh 200 as depicted in FIG. 3, a wire tube 202 as depicted in FIG. 4 is produced first. To produce the tube 202, 24 individual wires 108, for example, are braided with one another such that they alternately cross over and under one another at the crossing points 210. Crossing point planes 214 that extend transversely to a longitudinal direction of the tube 202 arise in this way. Once the individual wires 108 have each crossed one another in pairs nine times, two individual wires are twisted around one another in each case such that twists 216 arise. The wire tube 202 thus forms crossing point planes 214 that alternate with separating planes 212 at which a respective braided wire mesh 200 should be separated from the wire tube 202. In the example illustrated, nine crossing point planes 214 are followed in each case by a respective separation plane 212. In the separation planes, the wires 108 are in each case fully wrapped about one another twice in pairs such that a wrap-around angle of 720° arises. In other exemplary embodiments not shown, the wrap-around angle can also be only 360° or else 540°.

FIG. 7 shows the tube 202 formed by the wires 108, the tube 206 having been separated at two separation sites 208 by means of a laser beam. The separation sites 208 are situated in precisely one separation plane 212, that is to say where the twists 216 are situated. The weld beads 120 arise from the laser cutting such that the then free, pairwise interconnected longitudinal ends 112 of the wires 108 are interconnected both by twisting and by a laser welding. As a result of the twisting 216, the connected longitudinal ends 112 of in each case two wires 108 arise as depicted in FIGS. 5d and 5f following the laser cutting.

Following the separation of the braided wire mesh 200 from the wire tube 202, the former can be shaped into the marking body 100 by virtue of being compressed in the longitudinal direction. As a result, the braided wire mesh 200 bulges outward in a central longitudinal section while the longitudinal ends are constricted if the compression is for example implemented by means of two tools, each formed by a hollow hemisphere, moving toward one another. Depending on the tool shape, the marking body 100 can adopt shapes as depicted in longitudinal sections in FIGS. 9a to 9c.

FIGS. 10, 11, 12 and 13 show an implantation apparatus 1004 for implanting a marking body 100. The implantation apparatus 1004 comprises a handle 1010 and an implantation part 1008. The cannula 1006, in which the marking body 100 is initially situated, is part of the implantation part 1008.

A cannula tip 1012 at the distal end of the cannula 1006 has been whetted in such a way that it facilitates a percutaneous implantation of the marking body 100 by piercing the cannula 1006 into body tissue. The cannula 1006 preferably consists of stainless steel.

To eject the marking body 100 from the cannula 1006, provision is made of a displaceable driving-out element 1018, which can be actuated from the handle 1010 by means of the sliding element 1016.

FIG. 12A shows an implantation system 1000 having a marking body 100 of an implantation apparatus 1004. In this case, the marking body 100 in the pre-loaded state, that is to say with a compressed support structure, is situated within the cannula 1006 of the implantation apparatus 1004. This state of the implantation system 1000 represents a typical delivery state, in which the implantation system 1000 is made available in a ready-to-use state for the user, for example a surgeon.

The implantation part 1008 of the implantation apparatus 1004 substantially consists of a cannula 1006 which has a cannula tip 1012 at its distal end, that is to say the end distant from the handle 1010. As a rule, the marking body 100 in the preloaded state is situated in this region within the cannula 1006, just inside the outlet at the cannula tip 1012. In particular, the cannula 1006 can be formed from a suitable metal.

The cannula 1006 has a length LKA which for example can adopt a value ranging between 25 mm and 200 mm, preferably between 50 mm and 150 mm. The length LKA of the cannula 1006 has an influence on the range of the implantation apparatus 1004 in respect of the reachability of tissue sites in the body of a patient to be labeled. The longer cannulas are used when adjustment aids are used, for example stereotaxis.

The implantation apparatus 1004 comprises a handle 1010 and an implantation part 1008. The handle 1010 comprises a handle housing 1014 and a sliding element 1016, which for example could be produced from a suitable plastic.

The sliding element 1016 is connected to the handle housing 1014 but is movable relative to the handle housing 1014 in the axial direction of the cannula 1006. Consequently, the sliding element 1016 can be moved along a straight, guided sliding path between a pre-loaded position 1020 and a driving-out position 1022.

This movement is transferred from the sliding element 1016 via a driving-out element 1018, which is connected to the sliding element 1016 and which can be formed for example by way of a wire or a sufficiently stable plastics fiber, to the distal region at a distance from the handle 1010. Consequently, when the sliding element 1016 is moved to the driving-out position 1022, the pre-loaded marking body 100 can be driven out of the cannula 1006 to the tissue site to be labeled at the distal end of the cannula 1006 by way of a sliding movement of the driving-out element 1018.

This is achieved by virtue of the driving-out element 1018 that is aligned coaxially with respect to the cannula 1006 being moved in the direction of the cannula tip 1012 and hence pushing the pre-loaded marking body 100 out of the cannula 1006 past the cannula tip 1012.

FIG. 12B depicts detail B of FIG. 12A, specifically a detailed view in the region of the cannula tip 1012 of the implantation system 1000 in the pre-loaded state. In this view, the marking body 100, in particular, can be seen in the compressed state, said marking body being situated within the cannula 1006 behind the driving-out element 1018 and in front of the cannula tip 1012 from the view of the handle 1010. On account of its prestress, the marking body maintains the position in the cannula 1006 and cannot fall out on its own. On account of this property, additional features or apparatuses for fixing the marking body 100 within the cannula 1006 can be dispensed with.

FIG. 12C shows a further detailed, schematic view of the cannula 1006, this time as detail C from FIG. 12B. In this view, the distal end of the driving-out element 1018 is visible within the cannula 1006. Furthermore, the external diameter DKA and the internal diameter DKI of the cannula 1006 are labeled.

Together with the cannula length LKA, the internal diameter DKI of the cannula 1006 describes the size of the internal cavity formed by the cannula 1006 and at the same time restricts the maximum possible diameter DM of the marking body 100 in the compressed state or, optionally, the maximum possible diameter DK of a clamp (should the marking body comprise the latter), in order to ensure an ability of the marking body 100 to pass through or move in the cannula 1006 during pre-loading and driving out. An internal diameter DKI of less than 1.1 mm, particularly preferably of 1.0 mm was found to be preferable.

The external diameter DKA of the cannula 1006 describes the diameter of the external cannula wall. Under the assumption of a constant cannula wall thickness that is as small as possible, the internal diameter DKI of the cannula 1006 simultaneously increases with increasing external diameter DKA, and hence there also is an increase in the maximum possible external diameter of a marking body 100 to be implanted. However, at the same time, an increasing external diameter DKA leads to a greater degree of invasiveness or injury to skin and tissue when carrying out the implantation.

A sufficiently small external diameter DKA ensures the option of a percutaneous implantation of the marking body 100 without having to resort to a stab incision of the skin at the entry site of the cannula 1006 or anesthetization of the relevant tissue. An external diameter DKA of between 1 mm and 1.5 mm, particularly preferably of 1.2 mm was found to be preferable.

By means the implantation apparatus, a marking body of the type presented here for percutaneous marking can be implanted into soft tissue, such as breast tissue or axillary lymph nodes following a lymph node biopsy.

By way of example, within the scope of an intervention, the marking body 100 is used as follows:

Initially, the marking body is implanted at a desired site by virtue of the distal end 1012 of the cannula 1006 of the implantation apparatus 1004 being pierced up to the desired implantation location in body tissue and a marking body 100 being ejected from the distal end 1012 of the cannula 1006.

Subsequently, the body tissue can be examined using an imaging ultrasound method for example, an ultrasound recording of the marked tissue being made. This is depicted in FIGS. 14 and 15. The marking body can be recognized in the ultrasound recording on account of a circular artifact 310 or X-shaped artifact 312; see FIGS. 16 and 17.

In the case of sonography using medical ultrasound (1 MHz to 40 MHz, for example in the B mode [brightness modulation]; the mode in which two-dimensional brightness images are generated), the support structure of the marking body 100 causes incident ultrasound waves in the central longitudinal section of the marking body to strike a structure that is circular in cross section. What is obtained by matching the parameters of web diameter (or width and thickness), web number, web intensity and web material is that only some of the acoustic energy is reflected by the structure and the remaining part of the energy is transmitted, as depicted in exemplary fashion in FIG. 15. As a result, a full circle or a circular arrangement of individual points, depending on resolution and parameter settings of the ultrasound, arises as a representation in the ultrasound image; see FIG. 16. In the case of other structures of this form, the ultrasound energy would be largely reflected at the first surface of the marker and a shadow would arise in the image. A marking body 100 of the type described here can consequently be distinguished from other markers with a similar shape.

To make ultrasound recordings by means of sonography, use is made of a probe 300 which can transmit ultrasound 302 and can receive reflected ultrasound. By way of example, if the transmitted ultrasound strikes an object with a different acoustic impedance to the surrounding body tissue, the ultrasound is scattered and partly 304 reflected back to the probe 300; see FIG. 15. The wires of a marking body can be ultrasound-reflecting objects. A marking body of the type described here is then represented in ultrasound recordings (sonography recordings) as is indicated in FIG. 14 and as is visible in FIGS. 16 and 17.

The characteristic circular shape of the image representation of the marking body in the ultrasound image allows the marking body to be automatically recognized and hence detected in an ultrasound recording, for example by means of an appropriately trained convolutional neural network (CNN).

The marking body 100 can be placed in a soft tissue without air inclusions (e.g., fatty tissue) and can be insonated with ultrasonic waves ranging between 1 MHz and 40 MHz. It then reflects only part of the ultrasonic power at the first side, which faces the ultrasound, and reflects a second part of the ultrasonic power at the second side, which is distant from the ultrasound, as a result of which the marking body has a circular representation in an ultrasound image within the scope of medical ultrasound imaging; see FIGS. 14 and 15.

Then, the marking body is detectable by means of an automatic or semiautomatic method, preferably by analyzing ultrasound data or by analyzing x-ray recordings or by analyzing MRI data.

To improve the visibility in the ultrasound image, or for other purposes, the marking body can be provided with a membrane 400. This can be realized in various ways; see FIGS. 19 and 20. By way of example, the marking body 100 can be coated with a membrane 400 from the outside or from the inside; see FIGS. 20b and 20d. The membrane 400 can be produced from silicone or polyurethane or parylene, for example. The membrane serves to fully or partly separate the interior of the marking body from the surroundings. This can improve the recognizability and detectability, or this can create a space which can be filled with other substances or gases (e.g., cytostatic agents, ICG, etc.). As shown in FIG. 19, the membrane may also only be spanned between the relevant wires in individual fields of the lattice-like support structure formed by the wires 108.

LIST OF REFERENCE SIGNS

100 Marking body

101 Braided wire mesh

102, 104 Constricted longitudinal sections

103 Webs

105 Crossing points

106 Central longitudinal section

108 Wires

110 Crossing points

112 Free ends of the wires

114, 116 Longitudinal ends of the marking body

118 Weld spot

120 Weld beads

200 Braided wire mesh

202 Wire tube

208 Separation point

212 (Separation) plane

214 Crossing point plane

216 Twist

300 Ultrasound probe

302 Transmitted ultrasound

304 Reflected ultrasound

310, 312 Image representation of a marking body in the ultrasound image

400 Membrane

LM Length of the marking body

DMA Maximum external diameter of the marking body in the flared state

DKI Internal cannula diameter

DKA External cannula diameter

LKA Cannula length

1000 Implantation system

1004 Implantation apparatus

1005 Clamp

1006 Cannula

1008 Implantation part

1010 Handle

1012 Cannula tip

1014 Handle housing

1016 Sliding element

1018 Driving-out element

1020 Pre-loaded position

1022 Driving-out position

1102 Wires

1104 Braided wire mesh

1106, 1108 Longitudinal ends of the marking body

1110 Crossing points

1112 Central longitudinal section

1118 Free ends

1120 Weld beads

1122 Sleeve

1124 Weld spot

1200 Braided wire mesh

1202 Wire tube

1206 Twist

1210 Crossing point planes

1212 Separation plane

1214 Separation points

1300 Circular artifact

1302 X-shaped artifact

MARKER ELEMENT FOR MARKING TISSUE

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