Patent Application
20220313108
The present invention relates to an implantable array, in particular to an implantable electrode array, with a reference structure, and to a method of manufacturing an implantable array, in particular an implantable electrode array, with a reference structure which is visible in magnetic resonance images (MRI) when implanted for example in a human or animal body.
Such an array is implanted on the surface of the brain e.g., for pre-surgical assessment of cortical electrical activity in patients with epilepsy.
Hereby, MM is used to localize the electrode contacts of the implanted array with respect to the anatomy of the patient. However, metal components or other good electric current conductive materials like carbon and electric conductive polymers may cause MRI artifacts that compromise the results especially in the direct vicinity of the implants. Thin-film implants which may feature 100× less metal thickness may mitigate these artifacts, but thin-film implants produce inconspicuous MM signal voids in many clinical MRI sequences, and are therefore not suitable for localizing the electrode with MM.
On the other hand, implants having very small metal contacts, very thin metal layers, or no metal at all may not become visible in clinical MRI at all.
But imperatively, physicians need to know the implant position, and the value of intracranial EEG increases with the precision of electrode localization.
The present disclosure is directed towards the problem to provide an implantable array for MRI-based localization of its standard or micro-sized planar electrode contacts, and a method of manufacturing such electrode arrays which can be precisely localized in MRI.
This problem may be solved by the implantable array, in particular by an implantable electrode array, and the method of manufacturing an implantable array, in particular an implantable electrode array, according to the claims.
Accordingly provided is an implantable array, in particular an electrode array, suitable for being placed in anatomic tissue of a human or animal body, comprising
a structure for referencing predefined distinct points of the implantable electrode array in magnetic resonance images, the structure being arranged in a predefined portion of the implantable array, the structure comprising:
a plurality of patterns, each pattern having a predefined form and comprising a material having a magnetic susceptibility which is different from the magnetic susceptibility of the anatomic tissue surrounding the electrode array when placed in the human or animal body,
each pattern being in a predefined spatial relationship with one of the predefined distinct points.
Advantageous embodiments of the invention may comprise the following features. The material may comprise particles with a material selected from the group comprising iron, iron oxide, oxides of rare earths, and pyrolytic carbon material.
The patterns may comprise a material having a magnetic susceptibility which is higher than the magnetic susceptibility of the anatomic tissue surrounding the electrode array when placed in the human or animal body.
Each pattern may be isolated and spaced apart from each other pattern.
The structure may form a grid over the predefined portion of the electrode array.
The predefined points may be at least one of:
The predefined form may be a cross-like form.
The predefined portion may comprise at least one of/;
At least three patterns may be aligned along a straight first line, and at least three patterns may be aligned along a straight second line, the second line being perpendicular to the first line.
The material may be polymer, in particular selected from the group comprising silicone rubber, polyurethane, polyimide, epoxy, liquid crystal polymer, and parylene.
The implantable electrode array may comprise at least one layer of a polymer, in particular selected from the group comprising silicone rubber, polyurethane, polyimide, epoxy, liquid crystal polymer, and parylene.
The contacts may form a first grid with a first grid constant, and the patterns may form a second grid with the same grid constant as the metal contacts.
The invention further comprises a method of manufacturing an implantable array suitable for being placed in anatomic tissue of a human or animal body, in particular the electrode array as discussed above, comprising the following steps:
The polymer may be selected from the group comprising silicone rubber, polyurethane, polyimide, epoxy, liquid crystal polymer, and parylene.
The material may be selected from the group comprising iron, iron oxide, oxides of rare earths, and pyrolytic carbon.
The conductive layer may be selected from the group comprising metal, conductive polymer, carbon.
The material may have a magnetic susceptibility which is higher than the magnetic susceptibility of the anatomic tissue surrounding the electrode array when placed in the human or animal body.
As mentioned above, the implantable array may be an implantable electrode array.
The invention and embodiments thereof will be described below in further detail in connection with the drawing.
The implantable electrode array is flexible such that it can adapt its form to the form of the location in the cortex of a human or animal where it is placed. The electrode array comprises sensor contacts 2 of diameter c on its surface 8. The electrode contacts 2 may be located in apertures 6 in the polymer 1 of a diameter smaller than diameter c.
The electrode array further comprises a structure 5 for referencing predefined distinct points 2, e.g., the contacts 2, of the implantable electrode array in MRI. The structure 5 is arranged on the implantable electrode array, i.e., on the surface 8 or under the surface 8, and comprises single patterns 51, 52, 53.
Each pattern 51, 52, 53 comprises particles (i.e., nanoparticles, NPs) with a material producing a large magnetic susceptibility difference with respect to the surroundings, that is the tissue of the patient where the electrode array is to be placed.
This difference in magnetic susceptibility is linked with a difference in the respective effective transverse relaxation times (T2*), e.g., a very short T2* for the material with a high magnetic susceptibility, and a longer T2* for the surrounding human tissue, having a smaller magnetic susceptibility, such that the MRI signal in and near the pattern is lost, and thus a contrast to the surrounding material is established with the result that the pattern becomes visible in a magnetic resonance image of the electrode array.
The material having a very short T2* for the patterns can be selected from the group comprising, e.g., iron, iron oxide and oxides of rare earths.
The reference structure 5 forms a grid over a predefined portion of the electrode array; each pattern 51, 52, 53, 54, 55 is in a predefined spatial relationship, e.g., distance d, to one of the metal contacts 2 to be referenced.
As can be seen from the figure, each pattern 51, 52, 53, 54, 55 is isolated and spaced apart from each other pattern. The patterns may have cross-like form.
The patterns 51, 52, 53, 54, 55 may be equidistant to each other. At least two patterns 51, 52, 53, 54, 55 may be aligned along a straight first line 7. Moreover, at least two patterns 52, 54, 55 may be aligned along a straight second line 9, the second line 9 being perpendicular to the first line 7. In this example, the patterns form a regular 2-dimensional grid over the surface 8 of the electrode array, as indicated in
However, other forms for the structure 5 are also possible.
As can be seen, the metal contacts form a first grid with a first grid constant, and the patterns form a second grid with the same grid constant as the metal contacts.
In sectional view of the implantable electrode array according to
Typical diameters c of the electrode contacts 2 are 4 mm. The apertures 6 may have a diameter of 2.3 mm. Typical electrode arrays may comprise e.g. 3×3 electrode contacts or 3×6 electrode contacts, depending on the intended application. A typical spacing between two electrode contacts 2 (interelectrode spacing) may be 10 mm. Microelectrode arrays, according to a further embodiment of the invention as illustrated in
According to a particular variant, the patterns 51, 52, 53, 54, 55 of reference structure 5 may comprise silicone rubber doped with iron oxide (e.g. Fe2O3) particles. Herein, iron oxide is selected for its good ferromagnetic properties and its very good biocompatibility.
The predefined points 2 which are referenced by the patterns 51, 52, 53, 54, 55 may be
As mentioned above, the structure 5 may form a grid over a predefined portion of the electrode array. The predefined portion may comprise or be at least one of the top surface 8 (i.e., the side where the contacts are), the rear surface (i.e., the side where no contact is), an edge, and a corner of the electrode array, or be in the interior of the electrode array.
Table 1 gives typical, non-limiting dimensions of the implantable electrode arrays with reference structures 5.
In the following, a manufacturing process of an implantable electrode array with a reference structure 5 is described.
The manufacturing is based on a layer-by-layer deposition method, starting with a mechanical carrier, typically a ceramic substrate: The method comprises the following steps:
Instead of silicone rubber, any flexible polymer can be used, in particular one from the group comprising silicone rubber, polyurethane, polyimide, epoxy, liquid crystal polymer, and parylene.
The electrode array as described above is particularly well suited for being imaged with MM.
Advantageously, the reference structures as described above can be freely shaped in all dimensions, and the NP concentration can be varied. As a result, the implant thickness could be as little as 50 μm and thus feature high flexibility. Since these reference structures do not alter the outside silicone slab shape, the handling of these implants is identical to that of conventional implants. Due to their distinct contrast to the surroundings, the reference structures may be especially useful for electrode contact placement in sulci. Since the patterns of the reference structure can be placed +on the complete surface of the electrode array like a grid, they can reference the electrode contacts in situ even if the electrode is strongly bent or curved.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19218170.9 | Dec 2019 | EP | regional |
This application is a continuation of International Application No. PCT/EP2020/086881, filed Dec. 17, 2020, which claims priority to European Patent Application No. 19218170.9, filed Dec. 19, 2019, the contents of each of which are incorporated by reference herein.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/EP2020/086881 | Dec 2020 | US |
| Child | 17844324 | US |
