IMPLANTABLE MEDICAL DEVICE WITH ACOUSTIC LENS

Abstract

The invention relates to an implantable device comprising a transducer (11) for generating ultrasonic waves, and an acoustic lens (13) for modifying the phase of the ultrasonic wavefront generated by the transducer (11), the acoustic lens (13) including: a proximal layer (133) composed of a polymer matrix and hollow microspheres, and a distal layer (134) composed of a retarding material. Figure to be published with the abstract: Fig. 10

Description

Title of the invention: IMPLANTABLE MEDICAL DEVICE WITH ACOUSTIC LENS FIELD OF THE INVENTION

[0001] The present invention relates to the general technical field of ultrasonic devices for the treatment of brain tissue — human or animal — by ultrasound in order to assist a practitioner in the treatment of a pathology.

[0002] BACKGROUND OF THE INVENTION

[0003] Various techniques are known for treating brain tissue.

[0004] In particular, a known technique developed by the Applicant consists of using a treatment device comprising an implantable intracranial device.

[0005] Such an implantable intracranial device is described in particular in document WO 2021 / 105179. This intracranial device is intended to be positioned in a trephine hole made in a patient's skull. It comprises: • a support, • one (or more) transducer(s) for the generation of treatment ultrasonic waves, mounted on the support, • one (or more) electrical connection terminal(s) intended to cooperate with the connection means.

[0006] Once the intracranial device is implanted in the patient's skull, a series of treatment sessions can be provided to treat the pathology affecting him, in particular cancer. At each session, a microbubble solution can be injected into the patient to improve the effectiveness of the treatment by ultrasound waves. Indeed, the oscillations of microbubbles under the action of ultrasound cause a modulation of the permeability of the blood-brain barrier.

[0007] However, to improve the effectiveness of the treatment of brain tissue, it may be necessary to modify the shape of the wavefront generated by the transducer(s) of the intracranial device, for example: • to focus the ultrasound beam(s) generated by the transducer(s), in order to better target an area of ​​interest in the brain tissue, or • to diffuse this(these) ultrasound beam(s), in order to enlarge the treated volume of brain tissue, or even - • to modify the orientation and / or direction of propagation of this / these ultrasonic beam(s), in particular in order to compensate for the curvature and / or orientation of the transducer(s), etc.

[0008] An aim of the present invention is to propose a solution making it possible to modulate the phase of the wavefront of the acoustic beam(s) emitted by an intracranial device including one (or more) transducer(s), such as that described in document WO 2021 / 105179.

[0009] BRIEF DESCRIPTION OF THE INVENTION

[0010] To this end, the invention proposes a device implantable at the level of an opening made in the cranium of a patient, the implantable device comprising: • at least one transducer for the generation of ultrasonic waves, the transducer including a front face intended to be positioned opposite a tissue of interest to be treated, and a rear face opposite the front face, • at least one acoustic lens for modifying the phase of the ultrasonic wavefront generated by the at least one transducer, the at least one acoustic lens including a proximal face in contact with the front face of the at least one transducer and a distal face intended to be positioned opposite a tissue of interest to be treated, the distal face being opposite the proximal face, remarkable in that the at least one acoustic lens comprises: • a proximal layer composed of an accelerating material including a polymer matrix and hollow microspheres, the accelerating material having a first propagation speed of the waves generated by the transducer greater than 1500 m / s, and • a distal layer (134) composed of a retarding material, the retarding material having a second propagation speed of the waves generated by the transducer (11) less than 1500 m / s.

[0011] The presence of an acoustic lens positioned between the transducer and the tissue to be treated makes it possible to modulate the phase of the wavefront of the acoustic beam generated by the transducer. It is thus possible to modify the shape of the acoustic beam generated by the transducer in order to adapt it to the intended application.

[0012] Furthermore, the structure of this acoustic lens — including a first layer of accelerating material composed of a polymer matrix loaded with microspheres and a second layer of slowing material — makes it compatible with integration into an implantable medical device. In particular, this structure makes it possible to have an acoustic lens: • having a low thickness (typically between 0.1 and 5 millimeters, preferably between 0.5 and 4 millimeters, and even more preferably between 0.5 and 2 millimeters), and • having a smooth (non-porous) and biocompatible exterior surface, these characteristics allowing the implantation of the acoustic lens in the skull of a patient.

[0013] In the context of the present invention, the term "accelerating material" means a material in which the acoustic waves propagate at a propagation speed greater than 1500 m / s, that is to say a material in which the acoustic waves propagate faster than in the medium to be treated.

[0014] In the context of the present invention, the term "slowing material" means a material in which the acoustic waves propagate at a propagation speed of less than 1500 m / s, that is to say a material in which the acoustic waves propagate more slowly than in the medium to be treated.

[0015] The structure of the acoustic lens according to the invention also allows it to have an acoustic impedance close to that of the propagation medium (tissue to be treated). Thus, the acoustic lens according to the invention has a high transmission rate (ratio between the transmitted acoustic power divided by the incident acoustic power). This makes it possible to limit energy losses through the acoustic lens and to limit heating of the implantable device to guarantee patient safety.

[0016] Preferred, but non-limiting aspects of the present invention are as follows: • the at least one acoustic lens may be devoid of retarding material between the front face and the proximal layer; • the proximal layer of the at least one acoustic lens may have a transverse sawtooth and / or columnar profile, the shape and dimensions of the sawtooth and / or columnar depending on a phase law to modify the phase of the ultrasonic wavefront generated by the at least one transducer; • the polymer matrix may be chosen from a polyepoxide resin, or a thermoplastic matrix based on Polyethylene (PE), or a matrix based on Poly Methyl Acrylic Methacrylate (PMMA), or a matrix based on PolyEtheretherketone (PEEK), or a matrix based on PolyEtherketone-neketone (PEKK), or a matrix based on Cyclo Olefin Copolymer (COC), or a matrix based on Cyclo Olefin Polymer (COP), or a matrix based on PolyCarbonate (PC), or a matrix based on PolyAmide (PA), or a matrix based on PolyPropylene (PP), or a matrix based on liquid crystal polymers (LCP), or a matrix based on Elium® resin (Arkema); • each hollow microsphere may consist of a microbead having a shell in which a gaseous compound has been trapped, said shell being made of glass or plastic; • the volume percentage of hollow microspheres incorporated in the polymer matrix can be between 15 and 75% of the matrix volume polymer, preferably between 30 and 60% of the volume of the polymer matrix; • the dimensions of the hollow microspheres can be between 10 and 100 microns, preferably between 20 and 60 microns, and even more preferably between 25 and 50 microns; • the retardant material can be silicone; • the device may comprise a plurality of acoustic lenses, each acoustic lens being configured according to a respective delay law.

[0017] The invention also relates to a system for imaging and / or treating brain tissue, the system including a control unit and electrical connection means, remarkable in that the system further comprises an implantable device as defined above. Brief description of the drawings

[0018] Other advantages and characteristics of the invention will emerge more clearly from the following description of several variant embodiments, given as non-limiting examples, from the attached drawings in which:

[0019] [Fig-1] is a schematic representation of an example of a treatment apparatus of a brain condition including an ultrasound device electrically connected to a remote control unit using connection means (transdermal needle + cable),

[0020] [Fig.2] is a schematic representation of the structure of a transducer of the ultrasonic device,

[0021] [Fig.3] is a schematic representation of an assembly consisting of the transducer of [Fig.2] and an acoustic lens,

[0022] [Fig.4] is a schematic representation of the structure of the acoustic lens illustrated in [Fig.3],

[0023] [Fig.5] is a representation of a first pattern of a proximal layer of the acoustic lens,

[0024] [Fig.6] is a schematic representation of a second pattern of the layer proximal of the acoustic lens,

[0025] [Fig.7] is a schematic perspective representation of a mold for the fa construction of the acoustic lens,

[0026] [Fig.8a] is an exploded view of the acoustic lens,

[0027] [Fig.8b] is a top view of the acoustic lens,

[0028] [Fig.8c] is a side view of the acoustic lens,

[0029] [Fig.9] is a representation of a normalized pressure field generated by a assembly comprising a 1 MHz planar transducer and the acoustic lens,

[0030] [Fig. 10] is a partial representation of a first example of an implantable ultrasonic device, [0031 ] [Fig. 11] is a partial representation of a second example of a device ul- implantable trasonic,

[0032] [Fig. 12] is a partial representation of a third example of an implantable ultrasound device. DETAILED DESCRIPTION OF THE INVENTION

[0033] An example of an implantable medical device will now be described with reference to the figures. In these different figures, equivalent elements are designated by the same numerical reference.

[0034] 1. General

[0035] Referring to [Fig. 1], an example of a treatment apparatus is illustrated in which the acoustic lens described hereinafter may be used. The apparatus comprises • an implantable ultrasound device 1 for the emission of ultrasound waves for imaging or treatment, • a control unit 2 for supplying electrical energy to the ultrasonic device 1, and • connection means 3 for the electrical connection of the control unit 2 to the ultrasonic device 1.

[0036] It is obvious to those skilled in the art that the acoustic lens described below can be used with other types of treatment devices. In particular, the acoustic lens described below can be used with any implantable ultrasound device including one (or more) transducer(s).

[0037] 1.1. Ultrasonic device

[0038] The ultrasonic device 1 comprises: • an electronic card (not shown) suitable for exchanging electrical power and control signals with the remote control unit 2, • one (or more) transducer(s) 11 connected to the electronic card for the generation of ultrasonic waves for treatment (or imaging) of the brain tissue of interest, and • a connection terminal 12 intended to receive a transdermal needle 31 of the electrical connection means 3, • one (or more) acoustic lens(es) associated with one (or more) transducer(s).

[0039] The ultrasound device 1 is capable of being implanted in a cranial bone 4 of a patient to enable the treatment and / or imaging of a brain tissue of interest.

[0040] To do this, the practitioner performs a craniectomy. An incision is made in the scalp, then the skin (and muscles if present) is lifted (are lifted) to expose the skull. The skull is then cut to form a bone flap. The cranial bone flap is removed to make room for a cranial opening into which the intracranial device can be positioned.

[0041] The positioning of the ultrasound device 1 consists of inserting it into the cranial opening so that the transducer(s) extend(s) opposite the brain tissue of interest. Once the ultrasound device 1 is correctly positioned, it is fixed on the periphery of the cranial opening by any means known to those skilled in the art (anchoring screw 13, gluing, etc.), then the scalp and the muscles are put back in place to cover the ultrasound device 1. Thus, once implanted, the transducer(s) faces the brain tissue of interest.

[0042] 1.2. Remote control unit

[0043] The remote control unit 2 makes it possible to supply electrical energy to the ultrasonic device 1, to adjust its operating parameters, etc.

[0044] Such a control unit 2 being known to those skilled in the art, it will not be described in more detail below.

[0045] 1.3. Connection means

[0046] The connection means make it possible to electrically connect the ultrasonic device 1 and the control unit 2.

[0047] The connection means 3 comprise in particular: • the transdermal needle 31 capable of being connected to the connection terminal 12 of the ultrasound device 1, • a connection socket (not shown) capable of being connected to an additional socket of the control unit 2, and • an electrically conductive cable 32 connected to the transdermal needle 31 on the one hand, and to the connecting socket on the other hand.

[0048] 2. Transducer

[0049] With reference to [Fig.2], a partial sectional view of one of the transducers 11 of the ultrasonic device 1 is illustrated.

[0050] The nominal resonant frequency of each transducer 11 may be between 100 kHz and 20 MHz, preferably between 200 kHz and 10 MHz, and even more preferably between 0.2 and 3 MHz. Each transducer 11 allows the application of ultrasonic pulses of acoustic intensities between 1 and 50 W / cm2 (preferably between 5 and 30 W / cm2) by generating divergent or slightly convergent ultrasonic waves through the brain tissue of interest to be treated or imaged.

[0051] Each transducer 11 may be planar, convergent (concave), or divergent. (convex).

[0052] In particular, each transducer comprises one (or more) electro-acoustic element(s) 111 — such as a piezoelectric element — having a flat surface (planar transducer), cylindrical or in the form of a portion of a cylinder or sphere (convergent or divergent transducer).

[0053] In the remainder of the description, the invention will be described more precisely with reference to the use of one (or more) plane transducer(s), it being understood that the invention could be applied to the use of one (or more) convergent or divergent transducer(s).

[0054] The transducer 11 also comprises: • an external electrode intended to face the brain tissue of interest, and • an internal electrode forming a rear face 113, opposite the external electrode exterior.

[0055] Finally, the transducer 11 may comprise one (or more) adaptation layer(s) on the external electrode, for example one (or more) quarter-wave adaptation plate(s) serving to improve the transmission of acoustic energy to the brain tissue of interest.

[0056] In the case where the transducer is devoid of an adaptation layer, the external electrode forms a front face 112 of the transducer 11. In the case where the transducer comprises one (or more) adaptation layer(s), the face of the adaptation layer (the furthest away and) opposite the external electrode forms the front face 112 of the transducer 11.

[0057] The front face 112 of each transducer 11 is intended to face the brain tissue of interest to be treated. When the transducer 11 is activated, it converts the electrical energy supplied to it into acoustic waves propagating towards the outside of the front face 112 (i.e. propagation towards the brain tissue of interest).

[0058] 3. Acoustic lens

[0059] With reference to [Fig. 3], each transducer 11 is associated with one (or more) acoustic lens(es) 13.

[0060] The (Each) acoustic lens 13 is acoustically coupled to the front face 112 (i.e. radiative surface) of the transducer at a proximal face 131 of the acoustic lens 13.

[0061] The acoustic lens 13 is configured to receive the acoustic radiation generated by the transducer 11 at the proximal face 131 and to transmit the acoustic radiation through a distal face 132 of the acoustic lens 13.

[0062] When passing through the acoustic lens 13 between the proximal and distal faces 131, 132, the ultrasonic beam generated by the transducer 11 undergoes a phase modulation tending to modify the shape of its wavefront.

[0063] Depending on the type of acoustic lens chosen, this phase modulation allows: • either to modify the shape of the wavefront of the ultrasonic beam: • for example by bending it inwards (focusing) or outwards (diffusion), or • for example by flattening it, • either to modify its orientation and / or its direction of propagation.

[0064] 3.1. Structure of the acoustic lens

[0065] With reference to [Fig.4], the acoustic lens 13 comprises: • a proximal layer 133 of an “accelerator” material having a first wave propagation speed called “high” (in particular greater than the wave propagation speed in the brain tissue of interest to be treated), in particular greater than 1500 m / s, preferably greater than 1600 m / s, and even more preferably greater than 1800 m / s, • a distal layer 134 of a “slowing” material (possibly biocompatible) having a second wave propagation speed called “low” relative to the first propagation speed (in particular lower than the wave propagation speed in the brain tissue of interest to be treated), in particular lower than 1500 m / s, preferably lower than 1400 m / s, and even more preferably lower than 1300 m / s.

[0066] Advantageously, the accelerating and slowing materials constituting the proximal and distal layers 133, 134 respectively are chosen so as to have an acoustic impedance close to that of the brain tissue of interest to be treated, in particular between 1.1 MRayl and 1.9 MRayl, preferably between 1.2 MRayl and 1.8 MRayl, even more preferably between 1.4 MRayl and 1.6 MRayl (for example of the order of 1.5 MRayl).

[0067] The face of the proximal layer 133 opposite the distal layer 134 defines the proximal face 131 of the acoustic lens 13. This proximal face 131 is intended to be mechanically coupled to the transducer 11 with which the acoustic lens 13 is associated. The face of the distal layer 134 opposite the proximal layer 133 defines the distal face 132 of the acoustic lens 13. This distal face 132 is intended to be positioned opposite the brain tissue of interest to be treated.

[0068] The presence of a stack of layers 133, 134 made of accelerating and slowing materials having different wave propagation speeds, and more precisely: • a proximal layer 133, close to the transducer 11, in which the speed of propagation of the waves is high, and • a distal layer 134, close to the brain tissue of interest to be treated, in which the speed of propagation of the waves is low, allows to promote the phase variations of the wavefront of the acoustic wave(s) generated by the transducer 11.

[0069] Furthermore, the fact that the proximal layer 133 has a high first wave propagation speed and that the distal layer has a low second propagation speed (i.e. c2 much lower than Ci) makes it possible to limit the thickness of the acoustic lens 13, which is desirable in the context of its use in an implantable device.

[0070] More precisely, the thickness e of the acoustic lens is a function of the first and second propagation speeds cb c2 according to the following formula: _ QX C2 fx (q ~ cz)

[0071] Where: • f is the frequency, • Ci and c2 are the sound speeds in the proximal and distal layers.

[0072] Thus, the difference between the first and second propagation speeds cb c2 has an impact on the thickness e of the acoustic lens: the greater this difference (high ci, low c2) the more the thickness e of the acoustic lens is reduced.

[0073] To modulate the phase of the wavefront of the waves generated by the transducer 11 with which the acoustic lens(es) is (are) associated, the proximal layer 133 can be shaped into different shapes. In particular, the proximal layer 133 can have a transverse sawtooth profile (as illustrated in [Fig. 5]), or a columnar profile (as illustrated in [Fig. 6]). Of course, those skilled in the art will have understood that the dimensions and shapes of these “sawtooth” or “columns” depend on the intended application for the acoustic lens (flattening of the wavefront, modification of the orientation and / or the direction of propagation of the wavefront, etc.). In all cases, those skilled in the art will know how to adapt the shape of the proximal layer 133 according to the intended application.The fact that the transverse profile of the proximal layer 133 is arranged in a sawtooth or columnar pattern makes it possible to limit its thickness on the same principle as the stepped lenses known as “Fresnel lenses”.

[0074] 3.2. Proximal layer

[0075] The accelerator material constituting the proximal layer 133 can advantageously include a polymer matrix 1331 loaded with hollow microspheres 1332. As will become apparent below, the integration of hollow microspheres 1332 into a polymer matrix 1331 makes it possible to obtain a material: • having a “high” wave propagation speed (greater than the speed of wave propagation in the brain tissue of interest to be treated), • while maintaining an acoustic impedance close to that of the brain tissue of interest to be treated.

[0076] 3.2.1. Polymer matrix

[0077] The polymer matrix 1331 can be chosen from: • polyepoxide resins (or epoxy resin), for example Epotek 301-2 resin (Epoxy Technologies), and / or • thermoplastic materials based on Polyethylene (or PE), Poly Methyl Acrylic Methacrylate (or PMMA), PolyEtheretherketone (or PEEK, an acronym for the term “PolyEtherEtherKetone”), Poly-Etherketoneketone (or PEKK, an acronym for the term “PolyEtherKetoneKetone”), Cyclo Olefin Copolymer (or COC, an acronym for the term “Cyclic Olefin Copolymer”), Cyclo Olefin Polymer (or COP, an acronym for the term “Cyclic Olefin Polymer”), PolyCarbonate (or PC), PolyAmide (or PA), Poly-Propylene (or PP), liquid crystal polymers (or LCP, an acronym for the term “Liquid Crystal Polymer”), or resin Elium® (Arkema).

[0078] The polymer matrix 1331 chosen may have a viscosity before polymerization of between 100 and 600 cPs at 23°C, in particular of between 200 and 500 cPs at 23°C. This makes it easier to manufacture the proximal layer of the acoustic lens 13. More specifically, the choice of such a viscosity makes it easier to implement degassing and molding steps in the method for manufacturing the acoustic lens 13 which will be described below. Of course, those skilled in the art may choose a polymer matrix having a viscosity outside the ranges mentioned above.

[0079] 3.2.2. Hollow microspheres

[0080] The hollow microspheres 1332 may be microbeads formed by a shell—made of glass or a thermoplastic material such as a copolymer—within which a liquid or gaseous compound, such as air, has been trapped.

[0081] The hollow microspheres 1332 with a thermoplastic shell have the advantage of having a lower density (density of microspheres with a thermoplastic shell of the order of 40 kg / m3) than the hollow microspheres 1332 with a glass shell (density of microspheres with a glass shell greater than or equal to 100 kg / m3). This is why the use of hollow microspheres 1332 with a thermoplastic shell may be preferred for the production of an acoustic lens 13 of an implantable ultrasound device. The hollow microspheres 1332 with a glass shell may nevertheless be used, these also having interesting properties in the context of the present invention, particularly in terms of thermal resistance.

[0082] This type of hollow microspheres 1332 is notably represented by the “Expancel” range from the company AkzoNobel and is described in document WO 01 / 07154. The hollow microspheres are for example of the “Expancel 920 DET20 d40” type, with a density of 40 kg / m3.

[0083] It is known that the incorporation of hollow microspheres into a polymer matrix (syntactic foam) makes it possible to obtain a low-density composite material having high acoustic attenuation. Such a composite material is commonly used as an acoustic absorber in water. Surprisingly, the inventors have discovered that the use of such a composite material can be advantageous in an acoustic lens. Indeed, even if the acoustic attenuation of this composite material makes its use in an acoustic lens counterintuitive, when the thickness of this composite material is limited, this attenuation becomes acceptable and is largely counterbalanced by the other properties of the composite material (high speed, impedance close to that of water, fine optimization of the properties by adjusting the size and dose of spheres, solidity).An acoustic lens structure composed of layers made of accelerating and slowing materials with high contrast in sound propagation speed allows very thin thicknesses, and the use of syntactic foam is therefore advantageous.

[0084] To facilitate the adjustment of the acoustic impedance (and possibly limit the attenuation of the acoustic waves generated by the transducer 11) of the acoustic lens, the diameter of the hollow microspheres (used in the context of the present invention) is between 10 and 100 microns, preferably between 20 and 60 microns, and even more preferably between 25 and 50 microns.

[0085] To reduce the acoustic impedance of the accelerator material obtained so that it tends towards the acoustic impedance of the brain tissue of interest to be treated, the volume percentage of hollow microspheres 1332 incorporated in the polymer matrix is ​​between 15 and 75% of the volume of polymer matrix, preferably between 30 and 60% of the volume of the polymer matrix. This makes it possible to obtain a polymer matrix 1331 loaded with hollow microspheres 1332 having an acoustic impedance of between 1.2 and 1.8 MRayl, using a polymer matrix such as: • a polyepoxide resin whose acoustic impedances are between 2.6 MRayl and 2.9 MRayl, or • polyethylene with an acoustic impedance of the order of 2 MRayl, or • PMMA with an acoustic impedance of around 3.2 MRayl, or • PEEK with an acoustic impedance of around 3.1 MRayl.

[0086] 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 brain tissue of interest to be treated (i.e. approximately 1.5MRayl) and therefore having a high transmission rate (greater than or equal to 70% of the acoustic waves generated by the transducer associated with the acoustic lens) by minimizing acoustic reflections on the proximal face 131 of the acoustic lens 13.

[0087] 3.3. Distal layer

[0088] The distal layer 134 may be made of a non-porous material, with a high contrast in sound speed compared to the accelerating material of the proximal layer, i.e. a low sound speed (<1500 m / s) and possibly biocompatible such as silicone.

[0089] For example, the distal layer 134 can be made of Wagnersil 26LE silicone, which has the advantage of being easily shapeable (in particular easy to mold) for the manufacture of the acoustic lens.

[0090] The distal layer 134 can extend over all the faces of the proximal layer 133 with the exception of the proximal face 131. In particular, the distal layer 134 can extend both: • on the face of the proximal layer 133 opposite the proximal face 131, and • on the edges of the proximal layer 133.

[0091] This makes it possible to "coat" the proximal layer 133 in a biocompatible, impermeable and smooth material to make the outer surface of the lens flat and without asperities. This also makes it possible to limit discomfort, the risk of injury to the tissues in contact with the implant, facilitates decontamination, and prevents unwanted tissue growth caused by the implantation of the acoustic lens 13 in the patient's skull.

[0092] 3.4. Example of a manufacturing process for the acoustic lens

[0093] 3.4.1. Formation of the accelerating material constituting the proximal layer

[0094] 3.4.1.1. Use of existing composite material

[0095] There is a commercially available composite material composed of a polyepoxide resin (or epoxy resin) loaded with hollow microspheres having a glass shell: Stycast 1090 SI + CAT 24 LV from the company LOCTITE.

[0096] This type of existing composite material can be used as an accelerator material for the production of the proximal layer 133 of the acoustic lens 13.

[0097] However, the high viscosity of Stycast 1090 SI + CAT 24 LV (between 30 and 50 Pa.s) makes it difficult to produce the proximal layer 133, in particular for molding sawtooth or columnar shapes of the proximal layer 133 such as illustrated in FIGS. 5 and 6, under laboratory conditions.

[0098] Furthermore, the concentration of hollow microspheres is fixed and cannot be modified depending on the intended application.

[0099] Therefore, another solution may consist of manufacturing the material acce aerator from a polymer matrix on the one hand, and hollow microspheres on the other. This makes it possible to obtain an accelerator material with a lower viscosity (less than 600 cPa.s), which facilitates its handling (in particular its degassing and molding).

[0100] 3.4.1.2. Manufacture of the composite material

[0101] 3.4.1.2.1. Method implemented

[0102] The steps implemented for the manufacture of the accelerator material can be the following: • creation of the polymer matrix, • vacuum degassing of the polymer matrix created alone, • pre-polymerization of the polymer matrix created alone for 15 min at 80°C, • incorporation of hollow microspheres into the created polymer matrix, • vacuum degassing of the mixture composed of the polymer matrix and the hollow microspheres, • pre-polymerization of the mixture 15 min at 80°C, • complete polymerization 48 hours in ambient air.

[0103] The step of creating the polymer matrix consists of mixing components constituting it. The polymer matrix used can be an Epo-tek® 301-2 Epoxy Technologies resin. The low viscosity of the Epo-tek® 301-2 Epoxy Technologies resin facilitates the incorporation of the microspheres and the degassing steps. Furthermore, this low viscosity facilitates the molding of the proximal layer. The Epo-tek® 301-2 Epoxy Technologies resin also has a very long polymerization time (48 h).

[0104] The hollow microspheres may be glass or plastic shell microspheres.

[0105] Of course, other polymer matrices or microspheres can be used. In this case, the steps (in particular their presence or absence), as well as their parameters (for example duration and temperature) must be adapted.

[0106] The degassing steps allow the air bubbles formed to be evacuated: • when mixing the components constituting the polymer matrix to create it, • when mixing the polymer matrix with the hollow microspheres, • during the polymerization of the resin which can cause a release gaseous.

[0107] Even if the incorporation step consists of integrating hollow microspheres containing air into the polymer matrix, it is preferable to limit the quantity of air bubbles formed during the creation and incorporation steps. Indeed, since the size and number of these air bubbles are neither controlled nor controllable, it is preferable to avoid their presence to guarantee obtaining an accelerator material having an acoustic impedance close to that of the brain tissue of interest to be treated (i.e. 1.5 MRayl) and a high transmission rate (greater than or equal to 70%) of the acoustic waves generated by the transducer associated with the acoustic lens.

[0108] The pre-polymerization steps make it possible to vary the viscosities of the polymer matrix and of the mixture composed of the polymer matrix and the hollow microspheres. It is thus possible to limit the rise of the microspheres to the surface of the polymer matrix following their incorporation. The durations (15 minutes) and the temperature (80°C) are chosen so as to limit the risks of heat release likely to denature the hollow microspheres and / or deform the proximal layer following its molding.

[0109] 3.4.1.2.2. Accelerating material obtained

[0110] Epo-tek® 301-2 Epoxy Technologies resin was chosen as the polymer matrix to produce a mixture: • having substantially the same properties as the composite material Stycast 1090 SI + CAT 24 LV from LOCTITE, but • having a lower viscosity than the composite material Stycast 1090 SI + CAT 24 LV from LOCTITE.

[0111] The acoustic characteristics for three different ratios of hollow microspheres are available in the table below. Material %voi MCV Density Speed ​​@25°C Impedance x 1e-6 (kg.s~1.nr2) Attenuation @ 1 MHz Epoxy Henkei with MCV ? 0.65 2456 1.6 3.2 Epoxy 301-2 alone 0 1.12 2387 2.7 2.3 20 0.91 1943 1.8 8.2 Epoxy 301-2 with MCV 25 0.86 1986 17 7.8 30 0.81 1974 1.6 5.5 MCV - Hollow Glass Microspheres

[0112] The incorporation of hollow microspheres into the polyepoxide resin makes it possible to obtain an accelerator material with an acoustic impedance (1.6 MRayl) lower than that of the polyepoxide resin alone (2.7 MRayl), while maintaining a relatively high acoustic wave propagation speed (1974 m / s, instead of 2387 m / s for the polyepoxide resin alone).

[0113] The speed of propagation of the waves in the accelerator material thus obtained does not vary more than 20% compared to that of the Epoxy 301-2 Henkel resin alone, while maintaining a maximum load of 50% vol in microspheres.

[0114] The incorporation of 30% of hollow microspheres makes it possible to obtain an accelerator material with very good acoustic characteristics. The microspheres increase the attenuation of the sample and also reduce the propagation speed of ultrasonic waves.

[0115] Microspheres make it possible to reduce the density (impedance = density x speed) of the accelerator material.

[0116] In the case of the accelerator material, the density is calculated based on the densities of the hollow microspheres and the polyepoxide resin as well as their volume ratio.

[0117] In view of the properties of PMMA and PEEK, it would be interesting to consider the same approach with an unpolymerized version of these two materials and to also consider other thermosetting polymers. Indeed, PMMA and PEEK have much lower attenuations than polyepoxide resins, for a similar density and a higher acoustic wave propagation speed.

[0118] Thus, the use of PMMA or PEEK for the production of the accelerator material forming the proximal layer makes it possible to obtain a thinner and less attenuating acoustic lens than with a polyepoxide resin.

[0119] 3.4.2. Manufacture of the acoustic lens

[0120] From the accelerator material obtained, it is possible to produce the proximal layer 133 by molding, the shape of the mold being determinable by three-dimensional (3D) modeling depending on the intended application.

[0121] With reference to [Fig.7], an example of mold M is illustrated. A numerical model made it possible to determine the phase shift and therefore the appropriate shape for deflecting by 30° a beam of ultrasonic waves generated by a flat transducer emitting at 1 MHz.

[0122] The mold M illustrated in [Fig.7] was printed using a 3D printer as well as the results of the modeling carried out.

[0123] Once the mold M has been printed, the retarder material forming 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 hardening (i.e. after polymerization), the distal layer 134 can be demolded. This demolded distal layer 134 constitutes an imprint for the formation of the proximal layer 133.

[0124] More specifically, the accelerator material may be poured into the demolded distal layer 134. A heat gun may be used to remove bubbles rising to the surface of the accelerator material. Once poured into the mold, the accelerator material may undergo an additional degassing step.

[0125] This gives the acoustic lens 13, as illustrated in figures 8a to 8c, this- being flat on its proximal and distal faces 131, 132. The acoustic lens 13 obtained has a thickness of between 3.8 and 4 mm. Optionally, a layer of parylene can be deposited on the proximal and distal layers 133, 134.

[0126] In summary, the manufacture of the acoustic lens 13 may comprise the following steps: • determination of the desired shape for the proximal 133 and distal 134 layers depending on the intended application, • production of the mold M from the determined shape, for example by 3D printing, • pouring the retarder material in the liquid state into the mold M to form the distal layer 134, • hardening and demolding of the distal layer 134, • pouring the accelerating material into the distal layer 134 and hardening the accelerating material to form the acoustic lens 13.

[0127] 3.4.3. Performances

[0128] An acoustic lens as previously described (including a proximal layer composed of a mixture of Epo-tek® 301-2 Epoxy Technologies resin and hollow plastic microspheres and a distal layer composed of Wagnersil 26LE silicone) was combined with a planar transducer to study the performances associated therewith.

[0129] More precisely, an acoustic field generated by an assembly comprising: • a transducer 11 including a front face 112 at the level of which are generated the acoustic waves, and a rear face 113 opposite the front face 112, and • an acoustic lens 13 whose proximal face 131 is in contact with the front face 112 of the transducer 11, was measured.

[0130] The acoustic lens 13 makes it possible to deflect the acoustic beam generated by the transducer 11 by 30°. As illustrated [Fig.9], 90% of the energy emitted by the assembly composed of the transducer 11 and the acoustic lens 13 propagates in the desired direction. The geometry of the field is generally preserved and only off-axis.

[0131] The attenuation of the acoustic lens 11 results here in a reduction ranging from 30 to 60% of the maximum acoustic pressure generated, in comparison with the capacities of the transducer 11 alone. An optimization of the manufacturing process of the acoustic lens 13 makes it possible to reduce this loss of power, while retaining these same materials.

[0132] 4. Example of an implantable ultrasound device including at least one lens acoustic

[0133] With reference to [Fig. 10], a first example of an ultrasound device is illustrated. This implantable ultrasound device comprises a single transducer 11 associated with an acoustic lens 13 fixed on its front face 112.

[0134] The transducer 11 may be of any technology known to those skilled in the art. For example, the transducer 11 may be of the CMUT (or “Capacitive Micro Machined Transducer”) PMUT (“Piezoelectric MUT”) or MMUT (Magnetostrictive MUT) type. Alternatively, the transducer may be a piezoelectric transducer (PZT) or a piezocomposite transducer, etc.

[0135] In the embodiment illustrated in [Fig. 10], the transducer 11 comprises a quarter-wave adaptation plate 114 whose face opposite the electroacoustic element 111 forms the front face 112.

[0136] The proximal face 131 of the acoustic lens 13 is fixed by gluing to the front face 112 of the transducer 11.

[0137] The shapes and dimensions of the proximal and distal layers 133, 134 define a phase law for the phase modulation of the ultrasonic wavefront produced by the transducer 11. The phase law implemented depends on the indication and the targeted brain tissue of interest, for example: • deflection to target an area of ​​brain tissue of interest that is not located under the implantable ultrasound device 1 (i.e. an area of ​​brain tissue not extending under the burr hole made in the patient's skull), • single or multiple focusing of the ultrasound beam generated by the transducer, to target precise areas of the brain tissue of interest, • defocusing of the ultrasound beam generated by the transducer (divergence) to target a large area of ​​brain tissue of interest.

[0138] The phase law can be implemented using different techniques. In particular, the phase law can be: • calculated geometrically, • calculated by “time reversal” or acoustic holography techniques, simulated or measured, • bounded between -pi and pi, or between -2*pi and 2*pi (partially unrolled), • continuous (“sawtooth”), or discretized (stair steps / columns)

[0139] In the embodiment illustrated in [Fig. 10], the acoustic lens 13 has a single continuous phase law over its entire surface, said phase law having been calculated to induce a focusing of the ultrasonic beam generated by the transducer.

[0140] With reference to [Fig. 11], a second example of an ultrasonic device 1 has been illustrated. The transducer 11 comprises: • a single electro-acoustic element 111, • four adjacent internal electrodes 116a, 116b, 116c, 116d forming the rear face of the transducer and • an external electrode 117 forming the front face of the transducer (i.e. the external face of the tube).

[0141] In the embodiment illustrated in [Fig. 11], four acoustic lenses 13a, 13b, 13c, 13d each having a respective phase law (different from the other phase laws) are associated with the transducer 11.

[0142] With reference to [Fig. 12], a third example of an implantable ultrasound device is illustrated. The transducer 11 comprises four electro-acoustic elements 111a, 111b, 111c, 111d each associated with respective electrodes (not shown).

[0143] In the embodiment illustrated in [Fig. 12], a single acoustic lens 13 having a continuous phase law over its entire surface is associated with the transducer 11 to deflect by 30° the beam of ultrasonic waves generated by the transducer.

[0144] 5. Conclusions

[0145] The acoustic lens 13 described above makes it possible to modify the phase of the acoustic wave front generated by the transducer 11 according to a phase law determined as a function of the intended application.

[0146] The presence of a proximal layer 133 of accelerating material including a polymer matrix 1331 loaded with hollow microspheres 1332 makes it possible to produce an acoustic lens 13 whose thickness is between 0.5 and 4 mm (preferably less than 2 mm), which makes it compatible with use in an implantable ultrasound device.

[0147] Furthermore, the presence of a distal layer 134 of retarding material, such as silicone, allows the acoustic lens 13 to be biocompatible, smooth and non-porous on its distal face, which also makes it compatible with use in an implantable ultrasound device.

[0148] The acoustic lens 13 thus obtained advantageously has: • a high transmission rate (greater than or equal to 70% of the acoustic waves generated by the transducer(s) associated with the acoustic lens), and • an acoustic impedance close to that of the brain tissue of interest to be treated (of the order of 1.5 MRayl).

[0149] This acoustic lens 13 also has other advantages such as being MRI compatible, stable over time, stable to sterilization (for example with ethylene oxide) and stable to radiotherapy irradiation.

[0150] The reader will have understood that numerous modifications can be made to the invention described above without materially departing from the new teachings and advantages presented here.

Claims

1.

2.

3. Claims An implantable device (1) at an opening in a patient's skull, the implantable device (1) comprising: • at least one transducer (11) for generating ultrasonic waves, the transducer (11) including a front face (112) intended to be positioned opposite a tissue of interest to be treated, and a rear face (113) opposite the front face (112), • at least one acoustic lens (13) for modifying the phase of the ultrasonic wavefront generated by the at least one transducer (11), the at least one acoustic lens (13) including a proximal face (131) in contact with the front face (112) of the at least one transducer (11) and a distal face (132) intended to be positioned opposite a tissue of interest to be treated, the distal face (132) being opposite the proximal face (131), characterized in that the at least one acoustic lens (13) comprises • a proximal layer (133) composed of an accelerating material including a polymer matrix (1331) and hollow microspheres (1332), the accelerating material having a first propagation speed of the waves generated by the transducer (11) greater than 1500 m / s, and • a distal layer (134) composed of a retarding material, the retarding material having a second propagation speed of the waves generated by the transducer (11) less than 1500 m / s. An implantable device according to claim 1, wherein the at least one acoustic lens (13) is free of retarding material between the front face (112) and the proximal layer (133). An 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 transverse sawtooth and / or columnar profile, the shape and dimensions of the sawtooth and / or columnar depending on a phase law to modify the phase of the front ultrasonic waves generated by the at least one transducer (11).

4. An implantable device according to any one of claims 1 to 3, wherein the polymer matrix is ​​selected from a polyepoxide resin, or a thermoplastic matrix based on Polyethylene (PE), or a matrix based on Poly Methyl Acrylic Methacrylate (PMMA), or a matrix based on PolyEtheretherketone (PEEK), or a matrix based on PolyEtherketoneketone (PEKK), or a matrix based on Cyclo Olefin Copolymer (COC), or a matrix based on Cyclo Olefin Polymer (COP), or a matrix based on Poly-Carbonate (PC), or a matrix based on PolyAmide (PA), or a matrix based on PolyPropylene (PP), or a matrix based on liquid crystal polymers (LCP), or a matrix based on Elium® resin (Arkema).

5. An implantable 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 has been trapped, said shell being made of glass or plastic.

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

7. Implantable device according to any one of claims 1 to 6, wherein the dimensions of the hollow microspheres (1332) are between 10 and 100 microns, preferably between 20 and 60 microns, and even more preferably between 25 and 50 microns.

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

9. An implantable device according to claim 3, which comprises a plurality of acoustic lenses (13a-13d), each acoustic lens (13a-13d) being configured according to a respective delay law.

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

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