Ultrasound image guided focused ultrasound systems and related methods

Abstract

The invention provides a transducer comprising an acoustic stack comprising a composite piezoelectric layer comprising a plurality of regions made of a piezoelectric material, each region separated by a non-piezoelectric matrix material, the composite piezoelectric layer having a length and a width defining a high aspect ratio, wherein the length and width of the composite piezoelectric layer form a high aspect ratio acoustic aperture. The acoustic stack also includes a thermally conductive and electrically conductive layer, a thermally conductive electrically isolating layer, a lens, and at least one matching layer. The acoustic stack is configured to produce a field defining an acoustic focal region having a wide lateral dimension, a narrow lateral dimension, and a low focal length to focal width ratio. The transducer also includes a backing structure in contact with the back end of the acoustic stack.

Description

Technical Field

[0001] This technical field generally relates to the field of acoustic energy, and more particularly to ultrasound image-guided focused ultrasound systems and related methods. Background Art

[0002] Since many focused ultrasound transducer (referred to as "FUS") treatment methods require specific acoustic frequencies and other parameters to achieve the desired results, there is a need for a single-element FUS that can produce a wide acoustic focus area with a relatively short focal length without changing the frequency or limiting the treatment power. Since the size and location of the subcutaneous anatomical structures vary, there is a need for different focus zones (FZs) to effectively treat different anatomical structures or parts thereof while minimizing the risk of thermal or other damage to the skin.

[0003] There is still a need for technologies, devices, equipment, and methods that alleviate or mitigate the problems of the prior art. Summary of the Invention

[0004] The present technology generally relates to a relatively high aspect ratio aperture focused ultrasound (HARFUS) transducer having high thermal efficiency, electrical isolation, and an acoustically matched lens. The present technology also relates to a modular high aspect ratio single-element focused ultrasound transducer. In some embodiments, the transducer is capable of performing a single (one shot) treatment on a wide and uniform square aspect ratio focused region, thereby allowing for a transcutaneous single sonication treatment, or treating a circular superficial nerve having a diameter greater than an ideal FUS wavelength. In some embodiments, the transducer is configured to produce an acoustically focused region having a pumpkin seed shape, i.e., wide and short in a transverse (e.g., relative to the nerve) treatment plane and relatively thin in an orthogonal direction. In some embodiments, the shape and size of the focused region can be customized to allow for neuromodulation of an entire cross-section of a nerve in a single sonication. According to one aspect, there is provided a high aspect ratio aperture focused ultrasound (HARFUS) transducer, the HARFUS transducer including a high aspect ratio acoustic stack having a front end and a back end, and a backing structure in contact with the back end of the acoustic stack. The acoustic stack includes: a composite piezoelectric layer including a plurality of regions made of a piezoelectric material, each region being separated from one another by a non-piezoelectric matrix material, the composite piezoelectric layer having a length and a width defining a high aspect ratio, wherein the length and the width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; a thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; a thermally conductive and electrically isolating layer in contact with the thermally conductive and electrically conductive layer; a lens in contact with the thermally conductive and electrically isolating layer; and at least one matching layer extending at least partially above the lens, wherein the acoustic stack is configured to generate a field defining an acoustically focused region having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio.

[0005] In some embodiments, the shape of the acoustically focused region is similar to a pumpkin seed. Geometrically, the acoustically focused region can, for example, have an axial length to lateral width ratio of less than 3:1. In some embodiments, the acoustically focused region can also have a second orthogonal lateral width that is less than 1 / 2 of a first lateral width.

[0006] In some embodiments, the at least one matching layer includes a front matching layer extending above a back matching layer.

[0007] In some embodiments, the lens has a tapered edge and a tapered width.

[0008] In some embodiments, the lens has an outer perimeter that is threaded or includes an anechoic feature.

[0009] In some embodiments, the lens curvature is a spherical curvature or an elliptical curvature.

[0010] In some embodiments, the HARFUS transducer further includes a de-matching layer in contact with the back end of the high aspect ratio acoustic stack, and the de-matching layer is in direct contact with one of: a composite piezoelectric layer and a backing structure.

[0011] In some embodiments, the backing structure is a double-layer de-matching backing structure.

[0012] In some embodiments, the HARFUS transducer further includes a heat sink.

[0013] According to one aspect, there is provided a modular system that includes a plurality of the HARFUS transducers disclosed herein, which are arranged to result in a laterally merged focal zone having an axial focal length to lateral focal width ratio lower than that of a single HARFUS transducer.

[0014] According to one aspect, there is provided a high aspect ratio aperture focused ultrasound (HARFUS) transducer that includes a high aspect ratio acoustic stack having a front end and a back end, and a backing structure in contact with the back end of the high aspect ratio acoustic stack. The acoustic stack includes a composite piezoelectric layer that includes a plurality of regions made of a piezoelectric material, each region being separated from one another by a non-piezoelectric matrix material, and the composite piezoelectric layer has a length and a width that define a high aspect ratio, wherein the length and the width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; a thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; a lens in contact with the thermally and electrically isolating layer; and at least one matching layer extending at least partially above the lens, wherein the acoustic stack is configured to generate a field that defines an acoustic focal zone having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio.

[0015] In some embodiments, the shape of the acoustic focal zone is similar to that of a pumpkin seed.

[0016] In some embodiments, the at least one matching layer includes a front matching layer extending above a back matching layer.

[0017] In some embodiments, the lens has a tapered edge and a tapered width.

[0018] In some embodiments, the lens has an outer perimeter that includes an anechoic feature, such as a wedge or a thread or an acoustic absorbing material.

[0019] In some embodiments, the lens curvature is a spherical curvature or an elliptical curvature.

[0020] In some embodiments, the HARFUS transducer further includes a de-matching layer in contact with the back end of the high aspect ratio acoustic stack, the de-matching layer being in direct contact with one of: a composite piezoelectric layer and a backing structure.

[0021] In some embodiments, the backing structure is a bilayer de-matching backing structure.

[0022] In some embodiments, the HARFUS transducer further includes a heat sink.

[0023] A modular system includes a plurality of HARFUS transducers as disclosed herein, arranged to result in a laterally merged focus zone having a lower axial focal length to lateral focal width ratio than a single HARFUS transducer.

[0024] According to one aspect, a method for aligning a treatment head including a HARFUS transducer and a diagnostic imaging system with a sample to be characterized is provided. The method includes: acoustically coupling the treatment head to an ultrasound-sensitive phantom; performing an ultrasound treatment sequence co-registered with the HARFUS transducer to determine an acoustic focus zone using the ultrasound-sensitive phantom; positioning an imaging plane of the diagnostic imaging system within the treatment head at the center of the acoustic focus zone of the HARFUS transducer; locking the position of the HARFUS transducer relative to the treatment head; acoustically coupling the treatment head to the sample to be characterized based on the locked position of the HARFUS transducer; and operating the treatment head to characterize the sample guided by the diagnostic imaging system within the treatment head.

[0025] According to one aspect, a modular HARFUS transducer is provided that is configured to produce a pumpkin seed-shaped acoustic focus zone having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio. The modular HARFUS includes a plurality of HARFUS transducers arranged together to form a module. In these embodiments, the focus zones of each modular transducer can be directed to a common spot or zone such that the effective -3dB focus zone can be effectively increased in width but not in depth, resulting in a focal length to focal width ratio of 1:1. In some embodiments, the focus zone can be wider than the length. A focal length ratio of approximately 1:1 allows treatment of the entire cross-section of a nerve, and little non-intended high-intensity energy exists outside the target nerve or other structure. In some embodiments, the transducer can be used for neuromodulation. In these embodiments, the transducer can treat an entire nerve in a single ultrasound treatment. Such treatment can be facilitated by a transducer (such as the transducer described herein) capable of producing a focus zone that closely conforms to the target anatomical structure.

[0026] Other features and advantages of this specification will become clearer after reading the following non - limiting description of specific embodiments given by way of example only and with reference to the accompanying drawings. Description of the Drawings

[0027] Figure 1 An isometric view of an exemplary embodiment of a high - aspect - ratio focused ultrasound transducer having a 1:3 ratio aperture and a single focal length, resulting in a 1:3 ratio f - number ratio.

[0028] Figure 2 is Figure 1 A cross - sectional view of the HARFUS transducer in [reference], showing various aspects of the exemplary embodiment, including the cooling structure and the acoustic stack, the electrically isolated acoustic matching ceramic composite layer, and the thermal lens.

[0029] Figure 3 is a schematic diagram depicting Figure 1 the high - aspect - ratio focused region and its accompanying sound field generated by the exemplary HARFUS transducer shown in [reference].

[0030] Figure 4 is a schematic diagram of an alternative perspective showing the wide lateral dimension of the HARFUS focused region.

[0031] Figure 5 is a schematic diagram of the sound field of a 1:4.5 ratio HARFUS sound field that covers a hypothetical 3.5 - millimeter cylindrical structure (such as a nerve) bisected by the high - aspect - ratio focused region of the HARFUS transducer, where the - 3dB focused region has a width of about 4 millimeters in the lateral focus region and a focal length of about 8 millimeters at 1.5 MHz, occurring at about 50 millimeters from the surface of the HARFUS transducer.

[0032] Figure 6 is a representation of a single combined lateral focus region formed by three 1:3 f - number HARFUS transducers co - aligned, where the first - 3dB width of the single combined lateral focus region is about 12 millimeters, the second orthogonal width is 1.4 millimeters, and the height is about 18 millimeters.

[0033] Figure 7 is Figure 6 an alternative view of the three modular co - aligned HARFUS transducers shown in [reference].

[0034] Figure 8is an exemplary embodiment of a smaller HARFUS transducer that also operates at 1.5 MHz but is suitable for small animal neuromodulation, producing a focused region with a first -3dB width of 2.75 mm, a second orthogonal width of 0.8 mm, and a focused region length of 6.4 mm that occurs at approximately 18 mm from the transducer surface at an F - number ratio of 1:4.5 at 1.5 MHz. This embodiment demonstrates the ability to decouple the focused region size and location from the frequency component by controlling the focused region length and width by utilizing the aperture size and high aspect ratio.

[0035] Figure 9 is Figure 8 a cross - sectional view of the mid - HARFUS transducer. It should be noted that in this exemplary embodiment, the lens and the ground layer are not electrically isolated as in the Figure 1 exemplary embodiment.

[0036] Figure 10 is Figure 8 a close - up view of the acoustic stack of the transducer in

[0037] Figure 11 is a series of diagrams showing the Figure 1 size and location of the -3dB focused region of the exemplary 1.5 MHz HARFUS transducer shown in

[0038] Figure 12 is a series of diagrams showing the Figure 1 size and location of the -3dB focused region of the exemplary 1.5 MHz HARFUS transducer shown in Detailed Description

[0039] In the following description, like features in the figures will be denoted by like reference numerals, and, to avoid overcrowding the figures, if some elements have been labeled in one or more of the previous figures, they may not be indicated in some of the figures. It should also be understood herein that, since the focus is on clearly showing the elements and structures of this embodiment, the elements in the figures are not necessarily drawn to scale. The terms "a", "an", and "one" are defined herein to mean "at least one", that is, unless otherwise stated, these terms do not exclude a plurality of elements. It should also be noted that terms modifying numerical values, conditions, or characteristics of the features of the exemplary embodiments, such as "substantially", "generally", and "about", should be understood to mean that the numerical value, condition, or characteristic is defined within an acceptable tolerance for the normal operation of the exemplary embodiment for its intended application.

[0040] In this specification, the terms "connected", "coupled" and their variants and derivatives refer to any direct or indirect connection or coupling between two or more elements. The connection or coupling between elements can be acoustic, mechanical, physical, optical, operational, electrical, wireless or a combination thereof.

[0041] The terms "match", "matching" and "matched" are intended herein to refer to a state where two elements are the same or within a certain predetermined tolerance of each other. That is, these terms should cover not only "fully" or "identically" matching two elements, but also "substantially", "approximately" or "subjectively" matching two elements, as well as providing a higher or best match among multiple matching possibilities.

[0042] In this specification, the expression "based on" is intended to mean "at least partially based on", that is, this expression can mean "only based on" or "partially based on", and should not be construed in a restrictive manner. More specifically, the expression "based on" can also be understood to mean "depending on", "representing", "indicating", "associated with" or similar expressions.

[0043] It should be understood that the position descriptors used herein indicate the position or orientation of one element relative to another element for the purpose of facilitating description and making the description clear, and should be understood in conjunction with the accompanying drawings unless otherwise specified, and should not be regarded as limiting. It should be understood that the spatially relative terms (e.g., "outer" and "inner", "external" and "internal", "peripheral" and "center", "above" and "below", and "top" and "bottom") are intended to cover different positions and orientations in the use or operation of this embodiment, as well as the positions and orientations illustrated in the drawings.

[0044] In the context of this disclosure, the following reference numbers may be used:

[0045] 1 - Front matching layer.

[0046] 2 - Rear matching layer.

[0047] 3 - Lens. Thermally efficient aluminum or other material lens, with width and edge tapering to allow adjacent assembly into a multi-module treatment head.

[0048] 4 - Acoustic matching thermally conductive electrically insulating layer.

[0049] 5 - Thermally conductive and electrically conductive layer - can also be used as a redundant ground.

[0050] 6 - Piezoelectric composite of a specific single element with a high aspect ratio rectangular aperture, matched with aluminum, about 17 MR. Elliptical apertures or other high aspect ratio shapes can be used as needed to optimize the sound field.

[0051] 7 - Remove the matching layer - High acoustic impedance and ideally thermally and electrically conductive, for example, tungsten, tungsten carbide, or other molybdenum.

[0052] 8 - DLDB 1 / 4λ layer, low acoustic impedance and electrically and thermally conductive, such as graphite.

[0053] 9 - DLDB 1 / 4λ layer, high acoustic impedance layer, electrically and thermally conductive, such as tungsten.

[0054] 10 - DLDB 1 / 4λ layer, low acoustic impedance and electrically and thermally conductive, such as graphite.

[0055] 11 - DLDB layer, high acoustic impedance layer and electrically and thermally conductive, such as copper or tungsten or other conductive high acoustic impedance materials.

[0056] 12 - Aluminum nitride or other materials that are thermally conductive but electrically isolated.

[0057] 13 - Liquid - cooled block bases of A and B and the liquid - cooled block body for the copper liquid - cooled block. Air - based cooling solutions etc. can also be used.

[0058] 14 - Aluminum nitride or other thermally conductive and electrically insulating materials, forming a thermal return path plate to couple thermal energy from the front plate (5) to the back of the liquid - cooled block.

[0059] 15 - Copper housing cover, electrically and thermally conductive, forming an electrical shield and a possible ground connection path for the RF connector (not shown).

[0060] 16 - Liquid - cooled inlet / outlet pipe.

[0061] 17 - Electrically and thermally conductive housing, forming an electrical ground connection to the transducer and a thermal cooling path for the front of the piezoelectric composite.

[0062] 18 - Thermally and electrically conductive lens, forming a ground connection to the piezoelectric composite and the acoustic lens and a thermal cooling path for the front of the piezoelectric composite material.

[0063] 19 - Signal line connected between the RF connector and the rear electrode of the acoustic stack.

[0064] 20 - RF coaxial connector, connected to the signal line through 17 (electrically and thermally conductive housing) and grounded.

[0065] 21 - Noise - canceling feature.

[0066] 22 - Visual representation of the sound field range generated by the HARFUS transducer.

[0067] 23 - An illustrative representation of the -3dB sound field extent of the focus region of an exemplary HARFUS transducer having an F-number ratio of 1:3.

[0068] 24 - An illustrative representation of the -3dB sound field extent of the focus region of an exemplary HARFUS transducer having an F-number ratio of 1:4.5.

[0069] 25 - An exemplary cylindrical target, representing a typical nerve or other cylindrical FUS target.

[0070] While embodiments of the HARFUS transducers described in this specification will be described as including piezoelectric materials, those skilled in the art should note that the HARFUS transducers of the present disclosure may alternatively include any ferroelectric material, any single - crystal or poly - crystal material, any electro - mechanical transducer material, such materials having one or more of the following properties: ferroelectricity, pyroelectricity, piezoelectricity, electrostriction, and / or other related properties. It should be noted that in the context of this specification, the expression "piezoelectric material" may also refer to ferroelectric materials, pyroelectric materials, relaxor materials, and electrostrictive materials, which will be readily understood by those skilled in the art.

[0071] This specification generally relates to a relatively high aspect - ratio aperture focused ultrasound (HARFUS) transducer having a high thermal efficiency, electrically isolated, acoustic - matching lens. Embodiments of the HARFUS transducer described herein include an aperture having a relatively long axis in a first direction and a relatively short axis in a second direction. In some embodiments, the length of the aperture can be twice the width. In some embodiments, the length of the aperture can be three times the width. In some embodiments, the ratio can be 4.5:1. The focusing of the HARFUS transducer is adjusted by a lens. In some embodiments, the lens can be a spherical lens, an elliptical lens, or any other (one or more) refractive focusing lens that will allow the ultrasound to be adjusted to a point or a focus region. In some embodiments, the lens can have a symmetric design that will allow a high aspect - ratio focus region to be generated at (or near) the lens focus.

[0072] According to one aspect, a high aspect ratio aperture focused ultrasound (HARFUS) transducer is provided, the HARFUS transducer including a high aspect ratio acoustic stack having a front end and a back end, and a backing structure in contact with the back end of the acoustic stack. The acoustic stack includes: a composite piezoelectric layer including a plurality of regions made of a piezoelectric material, each region separated from one another by a non-piezoelectric matrix material, the composite piezoelectric layer having a length and a width defining a high aspect ratio, wherein the length and width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; a thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; a thermally conductive and electrically isolating layer in contact with the thermally conductive and electrically conductive layer; a lens in contact with the thermally conductive and electrically isolating layer; and at least one matching layer extending at least partially over the lens, wherein the acoustic stack is configured to generate a field defining an acoustic focus region having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio.

[0073] In some embodiments, the composite piezoelectric layer includes individual columns, for example, 1-3 or 2-2 composite piezoelectric columns. The aperture is associated with the high aspect ratio, that is, the entire composite piezoelectric layer is in the shape of, for example, a long and narrow strip or a high aspect ratio ellipse. Notably, the composite piezoelectric layer is acoustically matched with the thermally conductive and electrically conductive layer. In some embodiments, the thermally conductive and electrically conductive layer can only conduct heat and can be sputtered or otherwise coated with a conductive layer.

[0074] In some embodiments, the shape of the acoustic focus region is similar to a pumpkin seed.

[0075] In some embodiments, the at least one matching layer includes a front matching layer extending over a back matching layer.

[0076] In some embodiments, the lens has a tapered edge and a tapered width.

[0077] In some embodiments, the lens has an outer perimeter that is threaded or otherwise has an anechoic structure or coating.

[0078] In some embodiments, the lens curvature is a spherical curvature or an elliptical curvature.

[0079] In some embodiments, the HARFUS transducer further includes a de-matching layer in contact with the back end of the high aspect ratio acoustic stack, the de-matching layer directly contacting one of: the composite piezoelectric layer and the backing structure.

[0080] In some embodiments, the backing structure is a double layer de-matching backing structure.

[0081] In some embodiments, the HARFUS transducer further includes a heat sink.

[0082] According to one aspect, a modular system is provided that includes a plurality of the HARFUS transducers disclosed herein, which are arranged to result in a laterally merged focus region having a lower axial focal length to lateral focal width ratio than a single HARFUS transducer.

[0083] According to one aspect, a high aspect ratio aperture focused ultrasound (HARFUS) transducer is provided. The HARFUS transducer includes a high aspect ratio acoustic stack having a front end and a back end, and a backing structure in contact with the back end of the high aspect ratio acoustic stack. The acoustic stack includes a composite piezoelectric layer that includes a plurality of regions made of a piezoelectric material, each region being separated from one another by a non-piezoelectric matrix material. The composite piezoelectric layer has a length and a width that define a high aspect ratio, wherein the length and width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; a thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; a lens in contact with the thermally conductive and electrically conductive layer; and at least one matching layer extending at least partially above the lens, wherein the acoustic stack is configured to generate a field defining an acoustic focus region having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio.

[0084] In some embodiments, the shape of the acoustic focus region is similar to a pumpkin seed.

[0085] In some embodiments, the at least one matching layer includes a front matching layer extending above a back matching layer.

[0086] In some embodiments, the lens has a tapered edge and a tapered width.

[0087] In some embodiments, the lens has an outer perimeter with threads.

[0088] In some embodiments, the lens curvature is a spherical curvature or an elliptical curvature.

[0089] In some embodiments, the HARFUS transducer further includes a de-matching layer in contact with the back end of the high aspect ratio acoustic stack, the de-matching layer being in direct contact with one of the following: the composite piezoelectric layer and the backing structure.

[0090] In some embodiments, the backing structure is a double-layer de-matching backing structure.

[0091] In some embodiments, the HARFUS transducer further includes a heat sink.

[0092] A modular system includes a plurality of HARFUS transducers as described herein, which are arranged to result in a laterally merged focus region having a lower axial focal length to lateral focal width ratio than a single HARFUS transducer.

[0093] In some embodiments, the system may include a liquid-cooled FUS transducer, which is incorporated in an articulated treatment head that further includes a micropositioning and clamping mechanism configured to co-register the imaging plane of a suitable high-resolution diagnostic imaging ultrasound (DIUS) with the focal zone (FZ) of the FUS transducer, or in other diagnostic imaging scan heads (such as wobbler-based scanners). Additionally, the system may further include a water bath and a small animal handling platform with a positioning system for orienting the co-registered FUS and imaging transducers relative to a small animal (e.g., a rat), enabling precise visualization of the peripheral nerve and subsequent insonation to achieve accurate peripheral nerve block. In some embodiments, the liquid-cooled FUS transducer may incorporate acoustic stack technology, enabling highly efficient thermal operation and capable of performing FUS treatment for extended periods at a duty cycle of up to 100% with little or minimal heating of the device or lens surface, thus enabling the testing of a very wide parameter space. The FUS transducer of the system includes a high transverse aspect ratio aperture and lens technology, resulting in a relatively short focal length while providing the required focal width to treat the entire peripheral nerve in a single sonication. For this purpose, an exemplary embodiment of a 1.5 MHz HARFUS transducer with an f-number ratio of 1:4.5 and a focal depth of 18 mm is configured to produce a focal spot suitable for small animal PNB studies, having a nominal -3 dB azimuthal focal width of approximately 2.5 mm, an elevation focal width of less than approximately 1.0 mm, and a nominal -3 dB focal length of approximately 6.5 mm, with the focal spot center occurring approximately 18 mm from the transducer surface. These FZ parameters are expected to facilitate accurate treatment of the small animal peripheral nerve through a single sonication while minimizing the likelihood of skin burns. Co-registration (CR) of the high-resolution diagnostic imaging array with the FZ of the FUS transducer can be achieved by positioning the DIUS while performing real-time imaging of an echo object placed in a visible lesion created at the FZ of the FUS transducer in a HIFU phantom, which is placed in the water bath and made of a sonolucent polymer container filled with a commercially available optically clear HIFU phantom gel (Onda Corporation). The USgFUS device can be positioned such that the FZ of the FUS transducer falls within the interior of the HIFU phantom. Subsequently, operating the FUS transducer at a high enough intensity will raise the temperature of the HIFU phantom gel near the FUS FZ above 70 degrees Celsius, resulting in the formation of a persistent, visible opaque thermal lesion corresponding to the FZ of the FUS transducer.The resulting lesion located at the FZ of the FUS transducer can be imaged in real time by DIUS, and the imaging methods include direct imaging or imaging by placing echo markers within the lesion boundary. The multi-axis positioning system of the operation co-registration alignment system can position the DIUS so that the lesion image appears at a predetermined position within the ultrasound image, thereby realizing the real-time visualization of the FUS FZ. When the desired alignment between the DIUS and the FUS FZ has been obtained, the CR positioning system can be locked in place to maintain the co-registration of the DIUS and the FUS transducer when the USgFUS treatment head is positioned for subsequent treatment.

[0094] The FUS transducer includes a structure that allows active cooling of the piezoelectric crystal from the front and back of the piezoelectric layer (e.g., 1-3 composite piezoelectric layer), which means that the FUS transducer is equipped with a thermal management module or structure. This enables the transducer to operate at high intensity (at the piezoelectric) and high duty cycle for a long time up to continuous wave ultrasound treatment without thermal damage or performance drift. In addition, the FUS transducer also incorporates a highly thermally efficient electrical isolation lens technology that allows heat to be removed from the treatment site through the transducer while the transducer is in operation. In some embodiments, the configuration of this structure may be similar to the structure described in PCT / CA2020 / 051563, the content of which is incorporated herein by reference. This ensures the minimization of bubble formation at the lens surface and reduces the water flow rate required to keep the skin cool. The transducer includes a high transverse aspect ratio aperture and is focused by a single highly thermally efficient lens, thereby providing an FUS beam with a composite f-value that can be optimized to provide the focal width required for a single PNB treatment without using the usually long focal lengths produced by circular or square focus zones. In some embodiments, the transducer can produce a -3dB focus zone with a transverse dimension of 4.5 mm and a longitudinal dimension of 1.4 mm, and the focal length is approximately 18 mm. It is speculated that this focus zone is sufficient to treat, for example, small peripheral nerves less than 5 mm, and in clinical applications or animal studies, a single ultrasound treatment is sufficient without scanning or treating subsequent positions to cover the entire cross-section of the PN. This method is much more cost-effective than the high-element number rectangular matrix arrays that may also be used in this way. In addition, the focus zone can be created to achieve low energy in the near field and a relatively wide parameter space to optimize the treatment of the target PN while simplifying the acoustic coupling and minimizing the possibility of skin burns.

[0095] Taking 1.5 MHz ultrasound as an example of a typical focused ultrasound treatment frequency, considering the typical anatomical depth relative to the skin line, the upper limit of the circular spherical focused transducer is an f-value approximately equal to 4. The theory shows that for a spherical focused transducer, the -3dB emission focal length and focal width are respectively equal to:

[0096] -3dB Focal length=7.08λ(Fnumber ) 2

[0097] -3dB Focal width = 1.28λF number

[0098] As can be seen from these equations, the growth of the focal length is proportional to the square of the f-value compared to the focal width, while the growth of the focal width is proportional to the f-value. This poses challenges for FUS treatment and the translation from small animal targets to, for example, clinical targets, or from small clinical targets to larger targets, because the size of the focal region is frequency-dependent and, as the f-value increases, the growth of the lateral dimension is much slower than that in the length direction. This leaves only the possibilities of using a focal zone of reasonable length that will be scanned over the desired anatomy or changing the frequency of the FUS transducer to match the desired anatomy. If a single ultrasound treatment or a limited number of ultrasound treatments are required to fully treat a nerve cross-section in a short time at a predetermined frequency, for example, with optimized acoustic parameters (such as frequency, PRF, duty cycle, or other ultrasound parameters that may have been proven optimal for FUS treatment purposes), then neither of these solutions is ideal because they both require changing the FUS treatment parameters between different anatomy sizes or depths. For example, multiple ultrasound treatments may be required over time, or a lower frequency may be used for larger anatomies, to perform a single ultrasound treatment on different anatomical targets.

[0099] For example, when produced by a circular aperture transducer using a spherical focusing lens, a 4 mm wide -3dB FZ can produce a -3dB focal length with a depth between 75 mm and 100 mm at 1.5 MHz. For example, this focal zone may cause accidental ultrasound treatment of long cylindrical tissue segments above and below the target nerve.

[0100] In view of the above, it is necessary to decouple the focal zone from the focal length of the single-element FUS transducer in at least one axis.

[0101] Note that as the upper limit of the focal width is approached, a limiting factor is the reduced focusing gain achieved with high f-number lenses. To achieve high focusing intensity, the transducer needs to be driven at high emission power. To this end, an exemplary embodiment described herein includes a highly thermally conductive lens (such as aluminum) that is in contact with an acoustically matching, thermally conductive but electrically insulating ceramic composite material (such as a 1-3 composite of aluminum nitride, beryllium oxide, or alumina), which is interposed between piezoelectric composite transducer elements that are themselves bonded to a thermally conductive and electrically conductive ground plane (such as an aluminum plate of a suitable thickness, such as 1 / 4λ, 1 / 3λ, or several wavelengths thick). The 1-3 composite acoustic matching and electrical isolation layer allows the lens to be actively cooled by the transducer cooling solution while maintaining a patient current leakage level that is safe for medical devices, such as less than 100 μA for a body-floating device.

[0102] The combination of cooling on both sides of the piezoelectric crystal and the transducer lens also enables the FUS transducer to operate at an extremely high duty cycle, further enhancing the available treatment parameter space provided by the device. For example, an exemplary embodiment of the present technology can operate continuously at pressure and intensity levels sufficient for treatment while only a few degrees Celsius of temperature rise occurs at the lens and without any degradation in thermal performance.

[0103] In some embodiments, the HARFUS transducer according to the present technology utilizes a lateral f-number of 6 and a longitudinal f-number of 1.7 to produce a -3dB focal width that is 4.5 mm x 1.4 mm wide and has a high aspect ratio, while the focal length is only 1.66 cm deep. This enables the treatment of anatomical structures that are relatively close to the skin and up to 4 to 4.5 mm in size with a single ultrasound treatment. In some embodiments, several of these HARFUS transducers can be juxtaposed such that the focal regions merge laterally into a very wide focal region. For example, in some embodiments, three modular HARFUS transducers at 1.5 MHz can produce a -3dB focal region with a width >10 mm at a focal length of 1.6 cm.

[0104] Reference Figure 1 , an embodiment of the HARFUS transducer is shown in the figure. The HARFUS transducer includes a front matching layer 1, a rear matching layer 2, and a high thermal efficiency aluminum or other material lens 3. In some embodiments, the width and edges of the lens 3 can be tapered for adjacent assembly into a multi-module treatment head. The HARFUS transducer also includes an acoustically matching thermally conductive composite electrical isolation layer 4 and a thermally conductive and electrically conductive layer - also used as a redundant ground 5. Still referring to Figure 1, the HARFUS transducer includes a single-element piezoelectric composite material 6 specific to a high aspect ratio rectangular aperture, which is matched to aluminum (at approximately 17 MR). It is noted that the aperture can be an elliptical aperture or other high aspect ratio shapes to optimize the sound field as needed. The HARFUS transducer also includes a de-matching layer 7, which preferably has a high acoustic impedance. The de-matching layer 7 is preferably thermally and electrically conductive and can be made of materials such as tungsten, tungsten carbide, or other molybdenum, etc. The HARFUS transducer also includes a double-layer de-matching backing (DLDB) 1 / 4λ layer 8 (with a low acoustic impedance, layer 8 is made of a thermally and electrically conductive material such as graphite), such as the layer described in PCT / CA2020 / 051563. The HARFUS transducer also includes a DLDB 1 / 4λ layer 9 (with a high acoustic impedance layer, layer 9 is made of a thermally and electrically conductive material such as tungsten). The HARFUS transducer also includes a DLDB 1 / 4λ layer 10 (with a low acoustic impedance, layer 10 is made of a thermally and electrically conductive material such as graphite). The HARFUS transducer also includes a DLDB layer 11 (with a high acoustic impedance layer, this layer 11 is made of a thermally and electrically conductive material such as copper, tungsten, or any other (one or more) electrically conductive and high acoustic impedance materials). The HARFUS transducer also includes an aluminum nitride layer 12. Layer 12 can be replaced with a layer made of any other thermally conductive and also electrically insulating material, such as boron nitride, beryllium oxide, aluminum oxide, or other suitable thermally conductive and electrically insulating materials. The HARFUS transducer also includes a heat sink, which can be embodied as a liquid-cooled block base 13A and a liquid-cooled block body 13B for the liquid-cooled block 13A, or a finned air heat sink including multiple fins. In some embodiments, air can be used as the cooling mechanism. In some embodiments, the cooling water block can be composed of a single component or multiple components. The HARFUS transducer also includes an aluminum nitride layer 14. This layer 14 can be replaced with a layer made of any other thermally conductive and electrically insulating material, which can form a thermal return path plate to couple thermal energy from the front plate (5) to the back of the liquid-cooled block. The HARFUS transducer also includes an electrical shield 15, which can be implemented using a copper outer shell cover. The shield 15 is made of a thermally and electrically conductive material, enabling it to form an electrical shield and can form a ground connection path for an RF connector (not shown in the figure). The HARFUS transducer also includes a liquid-cooled inlet / outlet tube 16. The HARFUS transducer also includes a thermally and electrically conductive outer shell 17, which forms both an electrical ground connection to the transducer and a thermal cooling path for the front of the piezoelectric composite material.

[0105] Other visual representations of the HARFUS transducer are as Figures 2 to 7 shown.

[0106] Now refer to Figures 8 to 10, a modular HARFUS transducer will be described. These figures show a three-module FUS treatment system with co-aligned focal zones positioned so that the -3dB lateral focal zones of each module can be merged on the same axis. The lateral merged focal zone has a -3dB focal width that is approximately 3 times that of a single module. It is noteworthy that the three focal zones maintain approximately the same focal width in the direction orthogonal to the lateral field, and maintain approximately the same -3dB focal length as a single module. The resulting wide focal zone is many times wider, but many times shorter, than the focal zone that a single-element FUS transducer can produce at a given frequency.

[0107] Now go to Figure 11 and 12 , the figure shows the results that can be obtained using this technology (lateral results, -3dB). Figure 11 The lateral focal zone of a high aspect ratio FUS transducer is shown, with a focal zone of 4.5 mm wide x 1.4 mm wide and only 1.66 cm long, occurring at a depth of approximately 3.5 cm-4 cm from the skin line. The HARFUS transducer is capable of directly translating single-shot sonication neuromodulation (NM) studies of peripheral nerves (PNs) at, for example, 1.5 MHz to studies in subjects from, for example, rats to larger animal models, and to clinical studies using the same frequency and sonication parameters. Translational studies from small animals to clinical studies can be performed using a single set of FUS parameters at a single frequency (e.g., 1.5 MHz). This can be accomplished by using multiple exemplary HARFUS transducers disclosed herein, for example, first using Figure 8 The transducer shown is then used Figure 1 The transducer shown is then used Figure 6 transducer shown. In this sequence of multiple HARFUS transducers, for example, each transducer operating at 1.5 MHz, one transducer optimized for small animal based HARFUS therapy produces a relatively small focal zone, approximately 2.5 mm x less than 1 mm x approximately 6.7 mm long; and a larger 1.5 MHz HARFUS treatment head produces a wider focal zone, for example 4.5 mm x 1.3 mm x approximately 17 mm; and finally, using a multi-modular treatment head containing multiple 1.5 MHz HARFUS transducers, these transducers are co-placed into a lateral merged focal zone, obtaining a -3 dB FZ of up to 10.6 mm x 1.3 mm wide x 1.66 cm long. It will of course be appreciated that in addition to neuromodulation, the present technology can also be applied to many possible FUS applications over a wide range of frequencies. A key aspect of the present technology is the ability to linearly scale the lateral width and axial length of the focal zone within a wide parameter space at a given frequency, thereby enabling translational studies between small animals and enabling the use of optimal acoustic parameters to a variety of anatomical structures at different depths below the skin line.

[0108] It should be noted that in order to obtain an acoustically focused region 3.5 mm wide at 1.5 MHz using a single-element FUS transducer (e.g., having a circular aperture) according to prior art methods, a focal length of approximately 80 mm long (-3 dB) will be generated, occurring at approximately 7.5 cm from the skin line. This result can be easily simulated using a circular single-element FUS model having a nominal aperture with an f value of approximately 4.5, but with a short focal length and a relatively small required k-wave number aperture product of only 65, resulting in a diffraction-limited focal width less than the f value. It should be noted that to achieve a wider focused region using a transducer of this type in the prior art, a much larger transducer aperture will be required, while the focused region moves much deeper. Although diffraction correction lenses beyond those used in the present technology can also be used, it is unlikely to significantly overcome the problem of the exponential growth of the focal length with respect to the focal width for increasing f values. Such prior art devices cannot be safely used to treat small targets such as nerves, especially near the skin or above or below sensitive organs or structures, with a focal length of 8 cm.

[0109] Using finite element modeling techniques, it can be demonstrated that a traditional circular single-element FUS transducer geometry has an upper -3 dB focused region width limit of approximately 4 mm at 1.5 MHz and is hardly usable when the focal length exceeds 80 mm. These numbers are consistent with theoretical predictions that the lateral focused region is proportional to the f value multiplied by the wavelength, and the focal length is proportional to a constant (approximately 7 for a typical single-element FUS transducer) multiplied by the f value squared multiplied by λ. This is the key reason why it is extremely challenging to achieve a 4 - 5 mm focused region required for ultrasonic treatment of, for example, even a relatively small 4 mm diameter peripheral nerve. Those skilled in the art understand that many neuromodulation studies are conducted at 1.5 MHz and further understand that at 1.5 MHz, λ in tissue is approximately 1 mm, which means an f value of 4 - 5 is required to achieve a focused region width capable of ultrasonic treating a 4 mm diameter nerve in a single ultrasonic treatment, and this also means that the focused region will be approximately 7 times (4 to 5 times) the size of the lateral focused region, or approximately 14 cm in length when the focused region length is 4.5 mm.

[0110] Using the present HARFUS transducer allows for the generation of a much shorter focal length of 16.6 mm long, while generating a focused region 4.5 mm wide by 1.4 mm thick.

[0111] An exemplary embodiment of the technology is a small animal ultrasound-guided focused ultrasound (USgFUS) device that includes a liquid-cooled FUS transducer that is incorporated within an articulated treatment head that further includes a micropositioning and clamping mechanism that is configured to co-register the imaging plane of a suitable high-resolution US diagnostic imaging ultrasound (DIUS) with the focus zone (FZ) of the FUS transducer. Additionally, the device includes a water bath and a small animal manipulation platform that has a positioning system for positioning the co-registered FUS and imaging transducers relative to the rat to enable precise visualization of the PN and subsequent ultrasound treatment to obtain an accurate PNB.

[0112] In this exemplary embodiment, the liquid-cooled FUS transducer includes an acoustic stack that comprises a stack of material-specific piezoelectric composites and may or may not include a composite dielectric isolation layer located between the material-specific composite piezoelectric, an aluminum ground enhancement electrode, and a cooling layer, as well as an aluminum acoustic lens, to enable highly efficient operation and to enable FUS treatment to be performed for extended periods of time with a duty cycle of up to 100% with little heating of the device or lens surfaces, thereby enabling the testing of a very wide parameter space. Non-limiting examples of stacks, structures, and materials are provided in PCT / CA2019 / 051046, PCT / CA2020 / 051563, and / or PCT / CA2022 / 050387.

[0113] In addition, the FUS transducer includes a high lateral aspect ratio aperture and lens technology, with an elevation aperture (or short-axis aperture) of 4 mm, an azimuth aperture (or long-axis aperture) of 18 mm, and a focal depth of 15 mm, resulting in a relatively short focal length while providing the desired focal width to treat, for example, an entire peripheral nerve in a small animal model (e.g., a rat) in a single ultrasound treatment. In an embodiment intended for small animal experiments, the transducer provides a focal spot with a nominal -3dB azimuthal focal width of approximately 2.8 mm, an elevation focal width of <1.0 mm, and a nominal -3dB focal length of approximately 6.8 mm, where the center of the focal spot appears at approximately 15 mm from the transducer surface. These FZ parameters are expected to facilitate, for example, accurate neuromodulation of the peripheral PN in a small animal model (e.g., a rat) in a single ultrasound treatment while minimizing the likelihood of skin burns. High-resolution DIUS-FUS transducer FZ co-registration (CR) is achieved by localizing DIUS while performing real-time imaging of an echo object placed in a visible lesion created at the FZ of the FUS transducer in a HIFU phantom, which is placed in a water bath and made of an acoustically transparent polymer container filled with a commercially available optically clear HIFU phantom gel (Onda Corporation). The USgFUS device can be positioned such that the FZ of the FUS transducer falls within the interior of the HIFU phantom. Subsequently, operating the FUS transducer at a high enough intensity will raise the temperature of the HIFU phantom gel near the FUS FZ to above 70 degrees Celsius, resulting in the formation of a persistent, visible opaque thermal lesion corresponding to the FZ of the FUS transducer. The resulting lesion, which can be located at the FZ of the FUS transducer, can be imaged in real time by DIUS, including direct imaging or imaging by placing an echo marker within the lesion boundary. Operating the multi-axis positioning system of the co-registration alignment system can position DIUS such that the lesion image appears at a predetermined location within the ultrasound image, thereby enabling real-time visualization of the FUS FZ. When the desired alignment of DIUS and the FUS FZ has been achieved, the co-registration (CR) positioning system can be locked in place to maintain the co-registration of DIUS with the FUS transducer when the USgFUS treatment head is positioned for subsequent treatment.

[0114] In another embodiment aimed at single-site, single-shot ultrasound treatment for neuromodulation of small peripheral nerves about 4 mm in size, the USgFUS transducer includes an elevation aperture of about 7 mm and an azimuth aperture of about 24 mm, with the focal depth occurring at about 3.5 cm. This investigational ultrasound-guided FUS device can be used, for example, to perform percutaneous nerve conduction block (PNB) on peripheral nerves up to 4 mm in diameter using single-shot ultrasound treatment from a single position. The device includes a custom 1.5 MHz liquid-cooled, high lateral aspect ratio aperture FUS transducer that provides a low aspect ratio FZ for safe single-shot treatment of PNs located, for example, 2 cm to 5 cm subcutaneously. Additionally, the device includes a multi-jointed locking articulating arm or robotic arm to facilitate placement of the FUX FZ relative to the anatomical structure to be treated. Guidance to the treatment location can be provided by a co-registered high-resolution diagnostic imaging array (DIA) (e.g., Sonosite L38 10-5 linear array) and a diagnostic ultrasound (DUS) system. Methods for co-registering the DIUS and FUS FZ include provisions for placing an HIFU-compatible phantom into the device, which is filled with, for example, a thermosensitive HIFU phantom gel (Onda Corporation) to enable visualization of the focal zone of the FUS transducer. Once co-registration is complete, the treatment head, which includes the FUS transducer, the DIUS co-registration mechanism, and the DIUS, as well as the means for acoustically coupling the US transducer to the subject, can be positioned via the articulating arm, using the DIUS and US imaging systems to provide real-time guidance to the PN to be treated. When the optimal position and acoustic treatment window are achieved, the articulating arm can be locked in place for precise treatment during FUS ultrasound treatment.

[0115] The FUS transducer includes a structure that allows for active cooling of the piezoelectric crystal from both the front and back sides of the piezoelectric. This enables the transducer to operate at high intensity (at the piezoelectric) and high duty cycle for extended periods, up to continuous wave sonication, without thermal damage or performance drift. Additionally, the FUS transducer incorporates a highly thermally efficient electrically isolated lens technology that allows heat to be removed from the treatment site through the transducer while the transducer is in operation. This ensures minimization of bubble formation at the lens surface and reduces the water flow rate required to keep the skin cool. The design includes a high lateral aspect ratio aperture and is focused through a single highly thermally efficient lens, providing an FUS beam with a composite f-number that can be optimized to provide the focal width required for a single FUS treatment without the typically long focal lengths that would result from using circular or square focus zones. An exemplary embodiment includes a single FUS transducer that produces a -3dB focus zone that is 4.5 mm laterally and 1.3 mm longitudinally and has a -3dB focal length of approximately 17 mm. It is hypothesized that this focus zone is sufficient to treat nerves that are at least 1.5 cm, 4 mm or less than 4 mm below the skin line without scanning the FZ or treating subsequent positions to cover the entire cross-section of the PN. This approach is much more cost-effective than high element count rectangular matrix arrays that may also be used in this manner. Additionally, the focus zone can be created to achieve low energy in the near field and a relatively wide parameter space to optimize treatment of the target PN while simplifying acoustic coupling and minimizing the likelihood of skin burns.

[0116] Ultrasound image guidance for FUS treatment is crucial for achieving accurate percutaneous ultrasound treatment of target anatomical structures (such as peripheral nerves). Notably, without the use of contrast agents, and in some cases, elastography or ARFI techniques or MRI methods, FUS ultrasound treatment cannot be directly visualized in vivo during the treatment process. However, all of these options are costly, and due to the relatively low level of acoustic wave action associated with NM FUS, certain limitations may render these techniques ineffective. In an exemplary embodiment, the FUS transducer is mounted within a system that includes means for registering high-resolution DIUS with the focal region of the FUS transducer through an acoustically transparent hollow cylindrical tissue phantom, the phantom having an outer diameter of approximately 5 cm, an inner diameter of approximately 4 cm, and an absorbing back wall. The phantom will be filled with a transparent HIFU phantom gel (from ONDA Corporation), which will turn into a stable opaque material when the temperature of the gel increases due to thermal FUS ablation inside the gel. The treatment head of the FUS transducer will be positioned above the custom HIFU phantom, and both the FUS transducer and the DIUS transducer will be acoustically coupled to the phantom using the same acoustic coupling method as for treating, for example, peripheral nerves. Then, the FUS transducer will be driven at an appropriate level to rapidly induce a thermal lesion in the phantom that will correspond to the FZ of the FUS transducer. Then, the lesion will be visualized through the DIUS and the ultrasound imaging system, and the relative position of the DIUS within the treatment head can be adjusted to center the lesion on the screen of the ultrasound imaging system. When the relative positioning is achieved as desired, for example, the longitudinal FZ is centered on the DUS image, the relative position of the DIUS will be locked, enabling the operator to freely position the treatment head on the subject using the co-registered DUS image to find the optimal treatment position for FUS treatment. When the optimal position is obtained, the articulated arm can be locked via a remote switch (such as a foot switch or a button on the treatment head). Then the treatment can continue.

[0117] According to one aspect, there is provided a method for aligning a treatment head including a HARFUS transducer and a diagnostic ultrasound imaging system with a sample to be characterized, the method comprising acoustically coupling the treatment head to an ultrasound-sensitive phantom; performing a co-registered ultrasound treatment sequence with the HARFUS transducer to determine an acoustic focal region using the ultrasound-sensitive phantom; positioning an imaging plane of the treatment head at the center of the acoustic focal region of the HARFUS transducer; locking the position of the HARFUS transducer relative to the treatment head; acoustically coupling the treatment head to the sample to be characterized based on the locked position of the HARFUS transducer; and operating the treatment head to characterize the sample.

[0118] Using at the transducer element at over 30W / cm 2The model verified under the strength of, the initial design of the FUS transducer has been simulated using OnScale numerical simulation software. The focusing area of the proposed transducer can be achieved using a high aspect ratio aperture with dimensions of approximately 6 mm x 20 mm and a focal depth of approximately 3.5 cm for a hybrid F-number of 6 / 1.8. According to the simulation results, the initial design provides a longitudinal -3dB focal width of 1.3 mm (relative to the peripheral nerve) and a transverse -3dB focal width of 4.5 mm in the focusing area. The simulation of the -3dB focusing area is shown below.

[0119] During the development process, the focal depth and the size of the FZ can be adjusted by changing the size and aspect ratio of the aperture and the focusing characteristics of the lens.

[0120] The FUS device can achieve sub-millimeter positioning accuracy of the treatment head and sub-millimeter co-registration with high-frequency DIUS and DIS, enabling FUS treatments such as neuromodulation to be performed with a high degree of spatial accuracy in a short space of time with a minimal amount of training. In addition, when paired with a suitable radio frequency power source such as 150W, the FUS transducer should be able to generate a peak intensity of over 1000 W / cm 2 in the focusing area of 4.5 mm x 16 mm for several minutes.

[0121] It should be noted that the present technology or at least some embodiments thereof are compatible with the technologies described in PCT / CA2019 / 051046, PCT / CA2020 / 051563, and PCT / CA2022 / 050387, the contents of which are incorporated herein by reference.

[0122] Now let's talk about the advantages and benefits of the present technology. In a cost-effective single-element solution, the need to decouple the frequency of focused ultrasound therapy from the size of the focusing area is crucial. There is a real need to combine such devices in a modular manner to laterally expand the focusing area without increasing the risk of skin burns, or to add expensive two-dimensional arrays and associated electronics, treatment planning software, and image guidance, which has hindered the clinical adoption of FUS.

[0123] In addition, the need to translate preclinical research results using the same parameters for small animals into clinical studies with much larger anatomical structures but similar tissues is a major obstacle to translating preclinical FUS results into clinical applications. The HARFUS device disclosed herein is capable of generating the same acoustic characteristics in the focusing area, which can vary by a full order of magnitude, which has the potential to be a breakthrough for translating preclinical FUS research into clinical applications.

[0124] All of these are enhanced by the ability to use diagnostic ultrasound to guide these HARFUS devices to the target anatomical structure. The safety and utility of US-guided FUS (USgFUS) are significantly improved by the ability to control the focal length to the target while matching the width of the focal zone to the target anatomical structure, meaning that there is no need for complex treatment planning for a small focal zone within a larger anatomical structure, which typically requires complex software and MRI guidance and long treatment times.

[0125] This technology presents high aspect ratio apertures that produce wide lateral focal zones at relatively short focal lengths, combined with excellent cooling on both sides of the piezoelectric elements and the lens, enabling FUS research and clinical treatment to be carried out at lower cost and higher efficacy, where single ultrasound treatments of anatomical structures are of significance and can reduce treatment time and cost compared to treatments based on complex two-dimensional arrays.

[0126] Several alternative embodiments and examples have been described and illustrated herein. The above embodiments are for reference only. Those skilled in the art can understand the features of each embodiment and the possible combinations and variations of the components. Those skilled in the art can also understand that any embodiment can be arbitrarily combined with other embodiments disclosed herein. Therefore, these examples and embodiments should be considered illustrative rather than restrictive in all respects. Thus, although specific embodiments have been illustrated and described, many modifications can still be envisioned without significantly departing from the scope defined by this specification and the appended claims.

Claims

1. A high aspect ratio aperture focused ultrasound (HARFUS) transducer, the HARFUS transducer comprising: A high aspect ratio acoustic stack having a front end and a back end, the acoustic stack comprising: A composite piezoelectric layer, the composite piezoelectric layer comprising a plurality of regions made of piezoelectric material, each region being separated from each other by a non-piezoelectric matrix material, the composite piezoelectric layer having a length and a width defining a high aspect ratio, wherein the length and the width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; A thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; A thermally conductive and electrically insulating layer in contact with the thermally conductive and electrically conductive layer; A lens in contact with the thermally conductive and electrically insulating layer; and At least one matching layer extending at least partially above the lens, wherein the acoustic stack is configured to generate a field defining an acoustic focus region, the acoustic focus region having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio; and A backing structure in contact with the back end of the acoustic stack.

2. The HARFUS transducer according to claim 1, wherein, The shape of the acoustic focus region is similar to a pumpkin seed.

3. The HARFUS transducer according to claim 1 or 2, wherein The at least one matching layer includes a front matching layer extending above a back matching layer.

4. The HARFUS transducer according to any one of claims 1 to 3, wherein The lens has a tapered edge and a tapered width.

5. The HARFUS transducer according to any one of claims 1 to 4, wherein, The lens has an outer perimeter that is threaded or includes an anechoic feature.

6. The HARFUS transducer according to any one of claims 1 to 5, wherein, The curvature of the lens is a spherical curvature or an elliptical curvature.

7. The HARFUS transducer according to any one of claims 1 to 6, further comprising a de-matching layer in contact with the back end of the high aspect ratio acoustic stack, the de-matching layer directly contacting one of the composite piezoelectric layer and the backing structure.

8. The HARFUS transducer according to any one of claims 1 to 7, wherein, The backing structure is a double-layer de-matching backing structure.

9. The HARFUS transducer according to any one of claims 1 to 8, further comprising a heat sink.

10. A modular system, the modular system comprising a plurality of HARFUS transducers according to any one of claims 1 to 9, the HARFUS transducers being arranged to result in a laterally merged focus region having an axial focal length to lateral focal width ratio lower than that of a single HARFUS transducer.

11. A high aspect ratio aperture focused ultrasound (HARFUS) transducer, the HARFUS transducer comprising: A high aspect ratio acoustic stack having a front end and a back end, the acoustic stack comprising: A composite piezoelectric layer, the composite piezoelectric layer comprising a plurality of regions made of piezoelectric material, each region being separated from each other by a non-piezoelectric matrix material, the composite piezoelectric layer having a length and a width defining a high aspect ratio, wherein the length and the width of the composite piezoelectric layer form a high aspect ratio acoustic aperture; A thermally conductive and electrically conductive layer in physical contact with the piezoelectric layer, the composite piezoelectric layer being acoustically matched with the thermally conductive and electrically conductive layer; A lens in contact with the thermally conductive and electrically conductive layer; At least one matching layer extending at least partially above the lens, wherein the acoustic stack is configured to generate a field defining an acoustic focus region, the acoustic focus region having a relatively wide lateral dimension, a relatively narrow lateral dimension, and a relatively low focal length to focal width ratio; and A backing structure in back-end contact with the acoustic stack.

12. The HARFUS transducer according to claim 11, wherein, The shape of the acoustic focusing region is similar to a pumpkin seed.

13. The HARFUS transducer according to claim 11 or 12, wherein, The at least one matching layer includes a front matching layer extending over a back matching layer.

14. The HARFUS transducer according to any one of claims 11 to 13, wherein, The lens has a tapered edge and a tapered width.

15. The HARFUS transducer according to any one of claims 11 to 14, wherein, The lens has an outer perimeter that is threaded or includes an anechoic feature.

16. The HARFUS transducer according to any one of claims 11 to 15, wherein, The curvature of the lens is spherical curvature or elliptical curvature.

17. The HARFUS transducer according to any one of claims 11 to 16, further comprising a de-matching layer in back-end contact with the high aspect ratio acoustic stack, the de-matching layer being in direct contact with one of the composite piezoelectric layer and the backing structure.

18. The HARFUS transducer according to any one of claims 11 to 17, wherein, The backing structure is a double-layer de-matching backing structure.

19. The HARFUS transducer according to any one of claims 11 to 18, further comprising a heat sink.

20. A modular system comprising a plurality of HARFUS transducers according to any one of claims 11 to 19, the HARFUS transducers being arranged to result in a laterally combined focusing region having an axial focal length to lateral focal width ratio lower than that of a single HARFUS transducer.

21. A method for aligning a treatment head including a HARFUS transducer and a diagnostic imaging system with a sample to be characterized, the method comprising: Acoustically coupling the treatment head to an ultrasound-sensitive phantom; Performing an ultrasound treatment sequence co-registered with the HARFUS transducer to determine an acoustic focusing region using the ultrasound-sensitive phantom; Positioning an imaging plane of the treatment at the center of the acoustic focusing region of the HARFUS transducer; Locking the position of the HARFUS transducer relative to the treatment head; Based on the locked position of the HARFUS transducer, acoustically coupling the treatment head to the sample to be characterized; and Operating the treatment head to characterize the sample.

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