Implantable medical device with acoustic lens

Abstract

The present invention relates to an implantable device comprising a transducer (11) for generating ultrasonic waves and an acoustic lens (13) for adjusting the phase of the wavefront of the ultrasonic waves generated by the transducer (11), wherein the acoustic lens (13) comprises a proximal layer (133) consisting of a polymer matrix and hollow microspheres, and a distal layer (134) consisting of a retarder material.

Description

TECHNICAL FIELD

[0001] The present invention relates to the general technical field of ultrasound devices for the treatment of brain tissue - human or animal brain tissue - by ultrasound, for assisting a practitioner in the treatment of a medical condition.

BACKGROUND ART

[0002] Several techniques for treating brain tissue are known.

[0003] In particular, a known technique developed by the present applicant involves using a therapeutic apparatus comprising an implantable intracranial device.

[0004] Such an implantable intracranial device is described in document WO2021 / 105179. This intracranial device is intended to be placed in a burr hole created in the patient's skull. This device is - a support, - one (or more) transducers mounted on the support, for generating ultrasonic therapeutic waves, - one (or more) electrical connection terminals intended to cooperate with connection means .

[0005] Once the intracranial device is implanted in the patient's skull, a series of treatment sessions can be performed to treat the underlying condition, such as cancer. In each session, a microbubble solution may be injected into the patient to enhance the effectiveness of the ultrasound therapy. In fact, the vibration of microbubbles under the influence of ultrasound modulates the permeability of the blood-brain barrier.

[0006] However, to improve the effectiveness of brain tissue treatment, the shape of the wavefront generated by the transducer of the intracranial device may be adjusted, for example to: - focus the ultrasound beam generated by the transducer, so as to better target a region of interest in the brain tissue, or - To increase the volume of brain tissue being treated, diffuse this / these ultrasound beams, or - In particular, adjusting the direction and / or orientation of the propagation of these ultrasonic beams to compensate for the curvature and / or orientation of the transducer, etc. This may be necessary.

[0007] One object of the present invention is to propose a solution for modulating the wavefront phase of an acoustic beam emitted by an intracranial device comprising one (or more) transducers, such as those described in reference WO2021 / 105179. [Overview of the project]

[0008] For this purpose, the present invention provides a device that can be implanted in an opening created in the skull of a patient, wherein the implantable device is - A transducer for generating ultrasound, wherein the transducer includes a front surface intended to be positioned opposite to the tissue to be treated, and a rear surface opposite to the front surface. - At least one acoustic lens for adjusting the phase of the wavefront of the ultrasound generated by the at least one transducer, wherein the at least one acoustic lens includes a proximal surface that contacts the front surface of the at least one transducer and a distal surface intended to be positioned opposite the tissue to be treated, the distal surface being opposite the proximal surface. Includes, The at least one acoustic lens, - A proximal layer comprising an accelerator material containing a polymer matrix and hollow microspheres, wherein the accelerator material has a first propagation velocity of the wave generated by the transducer that exceeds 1500 m / s, and - A distal layer (134) made of retarder material, wherein the retarder material has a second propagation velocity of less than 1500 m / s for the wave generated by the transducer (11). We propose an implantable device characterized by including the following:

[0009] The presence of an acoustic lens placed between the transducer and the tissue being treated allows for modulation of the wavefront phase of the acoustic beam generated by the transducer. This makes it possible to adjust the shape of the acoustic beam generated by the transducer to suit the intended application.

[0010] Furthermore, the structure of this acoustic lens—including a first layer composed of an accelerator material consisting of a polymer matrix loaded with microspheres, and a second layer composed of a retarder material—makes it suitable for integration into implantable medical devices. In particular, this structure is - Having a thin thickness (typically ranging from 0.1 to 5 millimeters, preferably from 0.5 to 4 millimeters, and more preferably from 0.5 to 2 millimeters), - Having a smooth (non-porous) and biocompatible outer surface, Making it possible to provide acoustic lenses, These features allow for the implantation of acoustic lenses into the patient's skull.

[0011] In the context of the present invention, "accelerator material" means a material through which acoustic waves propagate at a propagation speed greater than 1500 m / s, in other words, a material through which acoustic waves propagate faster than in the medium being treated.

[0012] In the context of this invention, "retarder material" means a material through which acoustic waves propagate at a propagation speed of less than 1500 m / s, in other words, a material through which acoustic waves propagate more slowly than in the medium being treated.

[0013] The structure of the acoustic lens according to the present invention also allows it to have an acoustic impedance close to the acoustic impedance of the propagation medium (the tissue being treated). Therefore, the acoustic lens according to the present invention has a high transmittance (ratio of transmitted acoustic power to incident acoustic power). This limits energy loss by the acoustic lens, reduces heat generation in the implantable device, and thereby ensures patient safety.

[0014] Preferred embodiments of the present invention, though not limited to them, are as follows: - At least one acoustic lens may not contain retarder material between the front and proximal layers; - The proximal layer of at least one acoustic lens may have a sawtooth and / or cylindrical cross-sectional profile, the sawtooth and / or cylindrical shape and dimensions depending on a phase law for adjusting the phase of the wavefront of the ultrasound generated by at least one transducer; - The polymer matrix can be selected from polyepoxide resin, polyethylene (PE)-based thermoplastic matrix, poly(methyl methacrylate) (PMMA)-based matrix, polyether ether ketone (PEEK)-based matrix, polyether ketone ketone (PEKK)-based matrix, cycloolefin copolymer (COC)-based matrix, cycloolefin polymer (COP)-based matrix, polycarbonate (PC)-based matrix, polyamide (PA)-based matrix, polypropylene (PP)-based matrix, liquid crystal polymer (LCP)-based matrix, or Elium® resin (Arkema)-based matrix; Each hollow microsphere may consist of a microbead having a shell in which a gaseous compound is trapped, the shell being made of glass or plastic; - The volume percentage of hollow microspheres incorporated into the polymer matrix may be in the range of 15 to 75% of the volume of the polymer matrix, preferably 30 to 60% of the volume of the polymer matrix; - The dimensions of the hollow microspheres may be in the range of 10 to 100 microns, preferably 20 to 60 microns, even more preferably 25 to 50 microns; - The retarder material may be silicone; - The device may include a plurality of acoustic lenses, each acoustic lens being configured according to an individual delay law.

[0015] The present invention also relates to a system for imaging and / or treating brain tissue, the system comprising a control unit and electrical connection means, the system further comprising the implantable device as described above.

[0016] Other advantages and features of the present invention will become apparent from the following description of several embodiments, given by way of non-limiting example, on the basis of the accompanying drawings. [Brief Description of the Drawings]

[0017] [Figure 1] 1 is a schematic diagram of an example of an apparatus for treating a brain condition, comprising an ultrasound device electrically connected to a remote control unit by connection means (percutaneous needle + cable). [Figure 2] 2 is a schematic diagram of the structure of a transducer of an ultrasound device. [Figure 3] FIG. 3 is a schematic diagram of an assembly consisting of the transducer of FIG. 2 and an acoustic lens. [Figure 4] FIG. 4 is a schematic diagram of the structure of the acoustic lens shown in FIG. 3. [Figure 5] FIG. 5 is a diagram of a first pattern of the proximal layer of an acoustic lens. [Figure 6] FIG. 6 is a schematic diagram of a second pattern of the proximal layer of an acoustic lens. [Figure 7]This is a schematic perspective view of a mold for manufacturing acoustic lenses. [Figure 8a] This is an exploded view of an acoustic lens. [Figure 8b] This is a top view of an acoustic lens. [Figure 8c] This is a side view of an acoustic lens. [Figure 9] This is a diagram of the normalized pressure field generated by an assembly including a 1 MHz planar transducer and an acoustic lens. [Figure 10] This is a partial diagram of the first example of an implantable ultrasound device. [Figure 11] This is a partial diagram of a second example of an implantable ultrasound device. [Figure 12] This is a partial diagram of a third example of an implantable ultrasound device. [Modes for carrying out the invention]

[0018] Examples of implantable medical devices are illustrated with reference to the figures. In these different figures, equivalent elements are indicated by the same reference number.

[0019] 1. general concept Referring to Figure 1, an example of a therapeutic device that can use the acoustic lens described below is explained. This device is - An implantable ultrasound device 1 for the emission of ultrasound for imaging or treatment, - A control unit 2 for supplying power to the ultrasonic device 1, - Connection means 3 for electrical connection of control unit 2 to ultrasonic device 1 Includes.

[0020] It will be entirely obvious to those skilled in the art that the acoustic lenses described below can be used with other types of therapeutic devices. In particular, the acoustic lenses described below can be used with any implantable ultrasound device containing one (or more) transducers.

[0021] 1.1. Ultrasonic devices Ultrasonic device 1 is, - Using the remote control unit 2, an electronic board (not shown) adapted for exchanging power and control signals, - One (or more) transducers 11 connected to an electronic board for generating ultrasound to treat (or image) the target brain tissue, and - Connection terminal 12 intended to receive the transdermal needle 31 of connection means 3, - One (or more) acoustic lenses associated with one (or more) transducers Includes.

[0022] The ultrasound device 1 is suitable for implantation in the patient's skull 4 to enable treatment and / or imaging of target brain tissue.

[0023] For this purpose, the surgeon performs a craniotomy. An incision is made in the scalp, and then the skin (and muscles, if present) is lifted to expose the skull (bone). The skull (bone) is then cut to create a bone flap. This skull flap is removed to create an opening in the skull, into which an intracranial device may be placed.

[0024] Positioning the ultrasound device 1 involves inserting it into the opening of the skull so that the transducer is positioned opposite the target brain tissue. Once the ultrasound device 1 is precisely positioned, it is secured to the outer edge of the opening of the skull by any means known to those skilled in the art (e.g., anchor screws 13, adhesive), and then the scalp and muscles are rearranged to cover the ultrasound device 1. Thus, once implanted, the transducer faces the target brain tissue.

[0025] 1.2. Remote control unit The remote control unit 2 supplies power to the ultrasonic device 1 and allows for adjustment of its operating parameters, etc.

[0026] Such a control unit 2 is known to those skilled in the art, and therefore will not be described in further detail in this specification.

[0027] 1.3. Connection means The connection means enables the ultrasonic device 1 and the control unit 2 to be electrically connected.

[0028] Connection means 3 is, in particular, - A transdermal needle 31 suitable for connecting to the connection terminal 12 of the ultrasonic device 1, - A suitable connector plug (not shown) for connecting to an additional socket on control unit 2, and - A conductive cable 32 connected to the transdermal needle 31 on one side and to the connecting plug on the other side. Includes.

[0029] 2. Transducer A partial cross-sectional view of one of the multiple transducers 11 of the ultrasonic device 1 is shown with reference to Figure 2.

[0030] The nominal resonant frequency of each transducer 11 may be in the range of 100 kHz to 20 MHz, preferably 200 kHz to 10 MHz, and more preferably 0.2 to 3 MHz. Each transducer 11 generates divergent or slightly focused ultrasound through the target brain tissue being treated or imaged, thereby producing 1 to 50 W / cm² of ultrasound. 2 (Preferably 5-30 W / cm²) 2 This enables the application of ultrasonic pulses at acoustic intensity levels within the range of ).

[0031] Each transducer 11 may be planar, converge (concave), or diverge or branch (convex).

[0032] In particular, each transducer includes one (or more) electroacoustic elements 111—for example, piezoelectric elements—having a planar surface (planar transducer), a cylindrical surface, or a surface in the form of part of a cylinder or sphere (converging or diverging transducer).

[0033] In the following description, the present invention will be described in more detail with reference to the use of one (or more) planar transducers, so that it may be understood that the present invention may be applicable to the use of one (or more) convergent or divergent transducers.

[0034] Transducer 11 also, - External electrodes designed to face (confront) the target brain tissue, and - An inner electrode that forms a rear surface 113 on the opposite side of the outer electrode. Includes.

[0035] Finally, the transducer 11 may include one (or more) matching layers on the outer electrode, for example, one (or more) quarter-wavelength matching plates, which are used to improve the transmission of acoustic energy to the target brain tissue.

[0036] When the transducer does not have a matching layer, the outer electrode forms the front surface 112 of the transducer 11. When the transducer has one (or more) matching layers, the surface of the matching layer opposite the outer electrode (furthest from it) forms the front surface 112 of the transducer 11.

[0037] The front surface 112 of each transducer 11 is intended to face the target brain tissue to be treated. When a transducer 11 is activated, it converts the electrical energy supplied to it into acoustic waves that propagate outward from the front surface 112 (in other words, propagate toward the target brain tissue).

[0038] 3. Acoustic lens Referring to Figure 3, each transducer 11 is associated with one (or more) acoustic lenses 13.

[0039] Each acoustic lens 13 is acoustically connected to the front surface 112 of the transducer (in other words, the radiating surface) at its proximal surface 131.

[0040] The acoustic lens 13 is configured to receive acoustic radiation (rays) generated by the transducer 11 at its proximal surface 131 and to transmit the acoustic radiation (rays) through its distal surface 132.

[0041] As the ultrasonic beam generated by the transducer 11 passes through the acoustic lens 13 between the proximal and distal surfaces (131, 132), it undergoes phase modulation, which facilitates the adjustment of the shape of its wavefront.

[0042] Depending on the type of acoustic lens selected, this phase modulation will be - The shape of the wavefront of the ultrasonic beam, For example, by bending it inward (focusing) or outward (diffusing), For example, by flattening it, Adjusting, - Or, to direct and / or change the direction of its propagation. This makes it possible.

[0043] 3.1. Structure of an acoustic lens Referring to Figure 4, the acoustic lens 13 is - A proximal layer 133 of an "accelerator" material having a "high" propagation velocity (in particular, greater than the wave propagation velocity in the target brain tissue being treated), especially greater than 1500 m / s, preferably greater than 1600 m / s, and more preferably greater than 1800 m / s, - A distal layer 134 of a "retarder" material (which may optionally be biocompatible) having a second wave propagation velocity that is "lower" than the first wave propagation velocity (in particular, lower than the wave propagation velocity in the target brain tissue being treated), specifically less than 1500 m / s, preferably less than 1400 m / s, and more preferably less than 1300 m / s. Includes.

[0044] Advantageously, the accelerator and retarder materials, each constituting the proximal and distal layers (133, 134), are selected to have an acoustic impedance close to that of the target brain tissue being treated, particularly in the range of 1.1 MRayl to 1.9 MRayl, preferably in the range of 1.2 MRayl to 1.8 MRayl, and more preferably in the range of 1.4 MRayl to 1.6 MRayl (e.g., on the order of 1.5 MRayl).

[0045] The proximal layer 133, opposite the distal layer 134, defines the proximal surface 131 of the acoustic lens 13. This proximal surface 131 is intended to be mechanically coupled to the transducer 11 to which the acoustic lens 13 is associated. The distal layer 134, opposite the proximal layer 133, defines the distal surface 132 of the acoustic lens 13. This distal surface 132 is intended to be positioned opposite the target brain tissue to be treated.

[0046] Layers 133 and 134 are made from accelerator and retarder materials having different wave propagation velocities, more specifically, - Proximal layer 133 (where wave propagation speed is high), near transducer 11, and - Distal layer 134, adjacent to the brain tissue being treated (where the wave propagation speed is low) The existence of the stack is This makes it possible to accelerate the phase change of the wavefront of the acoustic wave generated by transducer 11.

[0047] Furthermore, the fact that the proximal layer 133 has a first high wave propagation velocity and the distal layer has a second low propagation velocity (in other words, c2 is much lower than c1) makes it possible to limit the thickness of the acoustic lens 13, which is desirable in terms of the use of acoustic lenses in implantable devices.

[0048] More precisely, the thickness of the acoustic lens is a function of the first and second propagation velocities c1 and c2, according to the following equations:

number

[0049] Therefore, the difference between the first and second propagation velocities (c1, c2) affects the thickness of the acoustic lens, and the larger this difference (higher c1, lower c2), the thinner the acoustic lens becomes.

[0050] To modulate the phase of the wavefront of a wave generated by a transducer 11 to which one or more acoustic lenses are associated, the proximal layer 133 can be shaped in different forms. In particular, the proximal layer 133 can have a sawtooth cross section (as shown in Figure 5) or a cylindrical cross section (as shown in Figure 6). Naturally, those skilled in the art will understand that these “sawtooth” or “cylindrical” dimensions and shapes depend on the intended use of the acoustic lens (e.g., wavefront flattening, wavefront orientation, and / or adjustment of the direction of propagation). In all cases, those skilled in the art will be able to adapt the shape of the proximal layer 133 according to the intended use. The fact that the cross-sectional profile of the proximal layer 133 can be arranged in a sawtooth or cylindrical shape allows its thickness to be limited in the same way as stepped lenses known as “Fresnel lenses”.

[0051] 3.2. Proximal layer The accelerator material constituting the proximal layer 133 may, advantageously, include a polymer matrix 1331 loaded with hollow microspheres 1332. As will become clear later, the integration of hollow microspheres 1332 into the polymer matrix 1331 is - Having a "high" wave propagation velocity (greater than the wave propagation velocity in the target brain tissue being treated), - At the same time, maintain an acoustic impedance close to that of the brain tissue being treated. It makes it possible to obtain the materials.

[0052] 3.2.1. Polymer matrix Polymer matrix 1331 is - Polyepoxy resin (or epoxy resin), e.g., Epotek 301-2 resin (Epoxy Technologies), and / or - Polyethylene (PE), poly(methyl methacrylate) (PMMA), polyether ether ketone (PEEK), polyether ketone ketone (PEKK), and cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polycarbonate (PC), polyamide (PA), polypropylene (PP), liquid crystal polymer (LCP), or Elium® resin (Arkema) based thermoplastic materials It can be selected from the following.

[0053] The selected polymer matrix 1331 may have a prepolymerization viscosity in the range of 100 to 600 cPs at 23°C, particularly in the range of 200 to 500 cPs at 23°C. This facilitates the production of the proximal layer of the acoustic lens 13. More specifically, selecting such a viscosity simplifies the degassing and molding steps in the method for manufacturing the acoustic lens 13, as described later. Of course, those skilled in the art can select a polymer matrix with a viscosity outside the above range.

[0054] 3.2.2. Hollow Microsphere Hollow microspheres 1332 can be microbeads formed by a shell—made from glass or a thermoplastic material (such as a copolymer)—in which a liquid compound or a gaseous compound such as air is trapped inside.

[0055] The hollow microsphere 1332 having a thermoplastic shell is a glass shell (100 kg / m³ 3 Hollow microspheres 1332 with a density lower than (40 kg / m³) (glass-shelled microsphere density greater than or equal to) 3 It has the advantage of having a thermoplastic shell microsphere density of the order of . Therefore, the use of hollow microspheres 1332 having a thermoplastic shell may be preferred for the manufacture of acoustic lenses 13 for implantable ultrasonic devices. However, hollow microspheres 1332 having a glass shell can also be used, as they have important properties within the scope of the present invention, particularly in terms of heat resistance.

[0056] This type of hollow microsphere 1332 is particularly represented by the "Expancel" series manufactured by AkzoNobel, described in document WO01 / 07154. Hollow microspheres can be, for example, 40 kg / m³. 3 It is a type called "Expancel 920 DET 20 d40" with a density of [value missing].

[0057] It is known that incorporating hollow microspheres into a polymer matrix (syntactic foam) yields low-density composite materials with high acoustic attenuation. Such composite materials are commonly used as sound absorbers in water. Surprisingly, the inventors have found that the use of such composite materials can be advantageous in acoustic lenses. In fact, even if the acoustic attenuation of this composite material makes its use in acoustic lenses counterintuitive, if the thickness of the composite material is limited, this attenuation becomes acceptable and is largely compensated for by the other properties of the composite material (high speed, impedance close to that of water, fine-grained optimization of properties by adjusting the size and density of the spheres, and strength). Acoustic lens structures consisting of layers made from accelerator and retarder materials with high contrast in sound propagation velocity allow for very thin thicknesses, and therefore the use of syntactic foam is advantageous.

[0058] To facilitate the adjustment of the acoustic impedance of the acoustic lens (and optionally limit the attenuation of acoustic waves generated by the transducer 11), the diameter of the hollow microsphere (as used in the context of this invention) is in the range of 10 to 100 microns, preferably 20 to 60 microns, and more preferably 25 to 50 microns.

[0059] To reduce the acoustic impedance of the resulting accelerator material so that it approaches the acoustic impedance of the target brain tissue being treated, the volume percentage of hollow microspheres 1332 incorporated into the polymer matrix is ​​in the range of 15-75%, preferably 30-60%, of the volume of the polymer matrix. - Polyepoxy resin having an acoustic impedance in the range of 2.6 MRayl to 2.9 MRayl, or - Polyethylene with an acoustic impedance of approximately 2Mayl, or - PMMA with an acoustic impedance of the order of 3.2 MRayl, or - PEEK, whose acoustic impedance is on the order of 3.1 MRayl Using polymer matrices such as the above, it is possible to obtain a polymer matrix 1331 loaded with hollow microspheres 1332 having an acoustic impedance in the range of 1.2 to 1.8 MRayl.

[0060] In conclusion, the integration of hollow microspheres 1332 into the polymer matrix 1331 makes it possible to obtain an accelerator material (whose acoustic impedance is close to that of the target brain tissue being treated, in other words, about 1.5 MRayl), which in turn allows for a high transmittance (greater than or equal to 70% of the acoustic waves generated by the transducer associated with the acoustic lens) while minimizing acoustic reflection at the proximal surface 131 of the acoustic lens 13.

[0061] 3.3. Distal layer The distal layer 134 has a distinct difference in sound velocity compared to the accelerator material of the proximal layer, namely a lower sound velocity (<1500 m / s), and can be made from a non-porous material, such as silicone, which may be biocompatible.

[0062] For example, the distal layer 134 can be made from Wagnersil 26LE silicone, which has the advantage of being easily moldable (especially easy to make by molding) for the manufacture of acoustic lenses.

[0063] The distal layer 134 may exist so as to cover all surfaces of the proximal layer 133 except for the proximal surface 131. In particular, the distal layer 134, - On the surface of the proximal layer 133 opposite to the proximal surface 131, and - Above the edge of Proximal Formation 133 It can exist in both cases.

[0064] This allows the proximal layer 133 to be "encapsulated" in a biocompatible, impermeable, and flat material, resulting in a flat and defect-free outer surface of the lens. This also limits the risk of discomfort and injury to tissues in contact with the implant, facilitates decontamination, and helps prevent undesirable tissue growth caused by the implantation of the acoustic lens 13 in the patient's skull.

[0065] 3.4. Examples of methods for manufacturing acoustic lenses 3.4.1. Formation of accelerator materials constituting the proximal layer 3.4.1.1. Use of existing composite materials A commercially available composite material made from polyepoxy resin (or epoxy resin) loaded with hollow microspheres containing glass shells is Stycast 1090 SI+CAT 24 LV from LOCTITE.

[0066] Existing composite materials of this type can be used as accelerator materials for creating the proximal layer 133 of the acoustic lens 13.

[0067] However, the high viscosity of Stycast 1090 SI + CAT 24 LV (ranging in the range of 30–50 Pa.s) makes it difficult to create the proximal layer 133, particularly under laboratory conditions, when forming the sawtooth or cylindrical shape of the proximal layer 133 as shown in Figures 5 and 6.

[0068] Furthermore, the concentration of hollow microspheres is fixed and cannot be adjusted according to the intended use.

[0069] Therefore, another solution may involve producing accelerator materials from a polymer matrix on the one hand and hollow microspheres on the other. This makes it possible to obtain accelerator materials with lower viscosity (less than 600 cPa·s), thereby facilitating their handling (particularly their degassing and molding).

[0070] 3.4.1.2. Manufacturing of composite materials 3.4.1.2.1. How to execute The processes involved in the manufacturing of accelerator materials may be as follows: - Creation of polymer matrix, - Vacuum degassing of the polymer matrix alone, - Prepolymerization of the prepared polymer matrix alone at 80°C for 15 minutes. - Incorporation of hollow microspheres into the created polymer matrix, - Vacuum degassing of a mixture consisting of a polymer matrix and hollow microspheres. - Prepolymerization of the mixture: at 80°C for 15 minutes, - Complete polymerization at room temperature for 48 hours.

[0071] The polymer matrix preparation process involves mixing its components. The polymer matrix used may be Epo-tek® 301-2 resin from Epoxy Technologies. Epo-tek® 301-2 resin from Epoxy Technologies has low viscosity. This facilitates the microsphere incorporation and degassing processes. Its low viscosity also facilitates the molding of the proximal layer. Epo-tek® 301-2 resin from Epoxy Technologies also has a very long polymerization time (48 hours).

[0072] Hollow microspheres can be glass-shelled or plastic-shelled microspheres.

[0073] Naturally, other polymer matrices or microspheres can be used. In this case, the process (in particular, their presence or absence) and their parameters (e.g., duration and temperature) must be adapted.

[0074] The degassing process is, - Mix the components that make up the polymer matrix, and while the polymer matrix is ​​being created, - While mixing the polymer matrix and hollow microspheres, - During the polymerization of the resin, which may generate gas release, This makes it possible to remove the bubbles that have formed.

[0075] Even if the integration process involves integrating air-containing hollow microspheres into a polymer matrix, it is preferable to limit the number of bubbles formed between the creation and integration processes. Since the size and number of these bubbles are neither controlled nor even controllable, it is best to eliminate the presence of bubbles in order to ensure the creation of an accelerator material that has an acoustic impedance close to the acoustic impedance of the target brain tissue being treated (i.e., 1.5 MRayl) and a high transmission rate (greater than or equal to 70%) of acoustic waves generated by a transducer associated with an acoustic lens.

[0076] The prepolymerization step allows for variations in the viscosity of the polymer matrix, as well as the mixture consisting of the polymer matrix and hollow microspheres. This allows for limiting the upward migration of microspheres to the surface of the polymer matrix after their incorporation. The duration (15 minutes) and temperature (80°C) are selected to minimize the risk of heat generation that could deform the hollow microspheres and / or deform the proximal layer after molding.

[0077] 3.4.1.2.2. Obtainable accelerator materials Epo-tek® 301-2 resin from Epoxy Technologies, - It has virtually the same properties as the composite material Stycast 1090 SI + CAT 24 LV manufactured by LOCTITE, - Has a lower viscosity than LOCTITE's composite material Stycast 1090 SI + CAT 24 LV. It was selected as the polymer matrix for creating the mixture.

[0078] The acoustic characteristics for three different ratios of hollow microspheres are available in the table below.

[0079] [Table 1]

[0080] Incorporating hollow microspheres into polyepoxy resins makes it possible to obtain accelerator materials with a lower acoustic impedance (1.6 MRayl) than that of polyepoxy resin alone (2.7 MRayl), while maintaining a relatively high acoustic wave propagation velocity (1974 m / s compared to 2387 m / s for polyepoxy resin alone).

[0081] The wave propagation velocity in the accelerator material obtained in this way does not fluctuate by more than 20% compared to that of Henkel Epoxy 301-2 resin alone, and maintains a maximum charge of 50 volume percent in the microsphere.

[0082] The incorporation of 30% hollow microspheres results in an accelerator material with superior acoustic properties. The microspheres increase sample attenuation and reduce the propagation speed of ultrasound.

[0083] Microspheres make it possible to reduce the density (impedance = density × velocity) of accelerator materials.

[0084] In the case of accelerator materials, density is calculated based on the densities of hollow microspheres and polyepoxide resin, as well as their volume ratio.

[0085] Given the properties of PMMA and PEEK, it would be worthwhile to consider the same approach with unpolymerized versions of these two materials, as well as to explore other thermosetting polymers. Indeed, PMMA and PEEK have significantly lower attenuation than polyepoxide resins, despite having similar densities and high acoustic wave propagation velocities to polyepoxide resins.

[0086] Therefore, using PMMA or PEEK to create accelerator materials that form the proximal layer allows for thinner acoustic lenses with less attenuation than using polyepoxide resins.

[0087] 3.4.2. Manufacturing of acoustic lenses The resulting accelerator material can be used to generate a proximal layer 133 by molding, and the shape of the mold can be determined by three-dimensional (3D) modeling according to the intended application.

[0088] Refer to Figure 7 for an example of type M. Numerous models were used to determine the appropriate shape for phase shift and, therefore, for deflecting the ultrasonic beam generated by a planar transducer emitting at 1 MHz by 30°.

[0089] Type M, shown in Figure 7, was printed using a 3D printer as a result of the modeling performed.

[0090] Once the mold M is printed, the retarder material that will form the distal layer 134 can be poured into the mold M. The retarder material is first prepared, degassed under vacuum in a container, and then poured into the mold M. After curing (i.e., polymerization), the distal layer 134 can be removed from the mold. The distal layer 134 removed from the mold forms an impression (mold) for the formation of the proximal layer 133.

[0091] Specifically, the accelerator material can be poured into the distal layer 134 removed from the mold. A heat gun can be used to remove any bubbles that have risen to the surface of the accelerator material. Once poured into the mold, the accelerator material can undergo an additional degassing process.

[0092] This yields an acoustic lens 13, as shown in Figures 8a-8c, which is flattened on its proximal and distal surfaces (131, 132). The resulting acoustic lens 13 has a thickness ranging from 3.8 to 4 mm. Optionally, layers of parylene can be deposited on top of the proximal and distal layers (133, 134).

[0093] In summary, the manufacturing of the acoustic lens 13 involves the following steps: - A step of determining the desired shape for the proximal layer 133 and distal layer 134 according to the intended use, - For example, the process of creating a mold M from a determined shape using 3D printing, - A step of pouring liquid retarder material into mold M to form a distal layer 134, - The process of hardening the distal layer 134 and removing it from the mold. - A step of pouring accelerator material into the distal layer 134 and curing the accelerator material to form the acoustic lens 13. It may include.

[0094] 3.4.3. performance The acoustic lens described above (containing a proximal layer made of a mixture of Epo-tek® 301-2 resin manufactured by Epoxy Technologies, and a distal layer made of hollow plastic microspheres and Wagnersil 26LE silicone) was associated with a planar transducer, and its associated performance was studied.

[0095] More specifically, - The transducer 11 includes a front surface 112 from which acoustic waves are generated, and a rear surface 113 opposite to the front surface 112, and - The acoustic lens 13 whose proximal surface 131 is in contact with the front surface 112 of the transducer 11 The acoustic field generated by the assembly containing the component was measured.

[0096] The acoustic lens 13 allows the acoustic beam generated by the transducer 11 to be deflected by 30°. As shown in Figure 9, 90% of the energy radiated by the assembly consisting of the transducer 11 and the acoustic lens 13 propagates in the desired direction. The overall shape of the field is preserved, only slightly off-axis.

[0097] The attenuation of the acoustic lens 11 results in a 30-60% reduction in the maximum sound pressure compared to the capability of the transducer 11 alone. By optimizing the manufacturing method of the acoustic lens 13, it is possible to reduce this output loss while using the same materials.

[0098] 4. Example of an implantable ultrasonic device including at least one acoustic lens Refer to Figure 10 to show a first example of an ultrasonic device. This implantable ultrasonic device includes a single transducer 11 associated with an acoustic lens 13 fixed to its front surface 112.

[0099] The transducer 11 may be of any technology known to those skilled in the art. For example, the transducer 11 may be a CMUT (i.e., a "capacitive micro-used transducer"), a PMUT ("piezoelectric MUT"), or an MMUT (magnetostrictive MUT). Alternatively, the transducer may be a piezoelectric transducer (PZT) or a piezo-composite transducer, etc.

[0100] In the embodiment shown in Figure 10, the transducer 11 includes a quarter-wavelength matching plate 114, and the opposite side of the electroacoustic element 111 forms a front surface 112.

[0101] The proximal surface 131 of the acoustic lens 13 is coupled to the front surface 112 of the transducer 11.

[0102] The shape and dimensions of the proximal and distal layers (133, 134) determine the phase law for the phase modulation of the wavefront of the ultrasound generated by transducer 11. The phase law performed depends on the pathological condition and the target brain tissue, e.g., - Deflection for targeting areas of target brain tissue not located beneath implantable ultrasound device 1 (in other words, areas of brain tissue not extending beneath the burr hole created in the patient's skull), - Single or multiple focus settings of the ultrasound beam generated by the transducer to target specific regions of the target brain tissue. - Focus blurring (divergence) of the ultrasound beam generated by the transducer to target a large area of ​​the target brain tissue. It depends on.

[0103] Phase laws can be applied using different techniques. In particular, phase laws are... - Can be calculated geometrically, - Can be calculated, simulated, or measured using time reversal or acoustic holography techniques. - - Between pi and pi, or -2 * pi (2*pi) and 2 * The pies can be joined together (partially unwrapped). - It can be continuous ("sawtooth") or discrete (stepped / cylindrical).

[0104] In the embodiment shown in Figure 10, the acoustic lens 13 has a single continuous phase law across its entire surface, which is calculated to guide the focusing of the ultrasonic beam generated by the transducer.

[0105] Refer to Figure 11 to see a second example of the ultrasonic device 1. The transducer 11 is - A single electroacoustic element 111, - Four adjacent internal electrodes 116a, 116b, 116c, 116d, which form the rear surface of the transducer, and - External electrodes 117 forming the front surface of the transducer (i.e., the outer surface of the tube) Includes.

[0106] In the embodiment shown in Figure 11, four acoustic lenses 13a, 13b, 13c, and 13d, each having its own individual phase law (different from other phase laws), are associated with the transducer 11.

[0107] Referring to Figure 12, a third example of an implantable ultrasonic device is shown. The transducer 11 includes four electroacoustic elements 111a, 111b, 111c, and 111d, each element associated with an individual electrode (not shown) of the transducer.

[0108] In the embodiment shown in Figure 12, a single acoustic lens 13 having a continuous phase law across its entire surface is associated with a transducer 11 to deflect the ultrasonic beam generated by the transducer by 30°.

[0109] 5. conclusion The acoustic lens 13 described above makes it possible to adjust the phase of the acoustic wavefront generated by the transducer 11 according to a phase law determined according to the intended application.

[0110] The presence of a proximal layer 133, which consists of an accelerator material containing a polymer matrix 1331 loaded with hollow microspheres 1332, enables the creation of an acoustic lens 13 having a thickness ranging from 0.5 to 4 mm (preferably less than 2 mm), which makes the acoustic lens suitable for use in an implantable ultrasonic device.

[0111] Furthermore, the presence of a distal layer 134 composed of a retarder material such as silicone allows the acoustic lens 13 to be biocompatible, flat, and non-porous at its distal surface, which also makes it suitable for use in an implantable ultrasonic device.

[0112] The acoustic lens 13 obtained in this way has the following advantages: - High transmission efficiency (greater than or equal to 70% of the acoustic waves generated by the transducer associated with the acoustic lens), and - Acoustic impedance close to the acoustic impedance of the brain tissue being treated (on the order of 1.5 MRayl) To provide.

[0113] The acoustic lens 13 also has other advantages, such as being MRI compatible, stable over time, stable against sterilization (e.g., ethylene oxide), and stable against radiation exposure in radiotherapy.

[0114] Readers will understand that many modifications can be made to the invention described above without substantially departing from the new knowledge and advantages presented herein.

Claims

1. A device (1) that can be implanted in an opening created in the patient's skull, wherein the implantable device (1) - A transducer (11) for generating ultrasound, wherein the transducer (11) includes a front surface (112) intended to be positioned opposite to the tissue to be treated, and a rear surface (113) opposite to the front surface (112), - At least one acoustic lens (13) for adjusting the phase of the wavefront of the ultrasound generated by the at least one transducer (11), wherein the at least one acoustic lens (13) includes a proximal surface (131) that contacts the front surface (112) of the at least one transducer (11), and a distal surface (132) intended to be positioned opposite the tissue to be treated, wherein the distal surface (132) is opposite the proximal surface (131). Includes, The at least one acoustic lens (13) - A proximal layer (133) comprising an accelerator material including a polymer matrix (1331) and hollow microspheres (1332), wherein the accelerator material has a first propagation velocity of more than 1500 m / s for the wave generated by the transducer (11), and - A distal layer (134) made of retarder material, wherein the retarder material has a second propagation velocity of less than 1500 m / s for the wave generated by the transducer (11). An implantable device characterized by including the following:

2. The implantable device according to claim 1, wherein the at least one acoustic lens (13) does not include a retarder material between the front surface (112) and the proximal layer (133).

3. The implantable device according to any one of claims 1 or 2, wherein the proximal layer (133) of the at least one acoustic lens (13) has a sawtooth and / or cylindrical cross-sectional profile, and the sawtooth and / or cylindrical shape and dimensions depend on a phase law for adjusting the phase of the wavefront of the ultrasonic wave generated by the at least one transducer (11).

4. An embeddable device according to any one of claims 1 to 3, wherein the polymer matrix is ​​selected from a polyepoxide resin, a polyethylene (PE)-based thermoplastic matrix, a poly(methyl methacrylate) (PMMA)-based matrix, a polyetheretherketone (PEEK)-based matrix, a polyetherketoneketone (PEKK)-based matrix, a cycloolefin copolymer (COC)-based matrix, a cycloolefin polymer (COP)-based matrix, a polycarbonate (PC)-based matrix, a polyamide (PA)-based matrix, a polypropylene (PP)-based matrix, a liquid crystal polymer (LCP)-based matrix, or an Elium® resin (Arkema)-based matrix.

5. The embeddable device according to any one of claims 1 to 4, wherein each hollow microsphere consists of a microbead having a shell in which a gaseous compound is trapped, and the shell is made of glass or plastic.

6. The embeddable device according to any one of claims 1 to 5, wherein the volume percentage of hollow microspheres (1332) incorporated into the polymer matrix (1331) is in the range of 15 to 75% of the volume of the polymer matrix (1331), preferably 30 to 60% of the volume of the polymer matrix (1331).

7. The implantable device according to any one of claims 1 to 6, wherein the dimensions of the hollow microsphere (1332) are in the range of 10 to 100 microns, preferably 20 to 60 microns, and more preferably 25 to 50 microns.

8. The implantable device according to any one of claims 1 to 7, wherein the retarder material (134) is silicone.

9. The implantable device according to claim 3, comprising a plurality of acoustic lenses (13a to 13d), each acoustic lens (13a to 13d) configured according to an individual delay rule.

10. A system for imaging and / or treating brain tissue, wherein the system comprises a control unit and electrical connection means, and the system further comprises an implantable device (1) according to any one of claims 1 to 9.

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