Mosaic ultrasound array probe

Abstract

The present disclosure concerns an ultrasound 3D imaging probe (200) for imaging vascular activity dynamically at a microscopic scale in an organ of a body of a living being, the probe (200) comprising : - a mosaic ultrasound array (100) comprising a plurality of polygonal transducer element pads, each pad (101) comprising a set of transducer elements (102) distributed on a substrate (103), each transducer element (102) being configured to acquire at least a backscattered ultrasound wave from the organ following an ultrasound emission in said organ; - a support frame (10) comprising an intern surface intended to be placed facing said body; - each polygonal transducer element pad (101) being located and attached in a removable manner on said internal surface of the support frame (10).

Description

DescriptionTitle: Mosaic ultrasound array probeTechnical Field

[0001] The present disclosure relates to ultrasound imaging techniques, and in particular to a mosaic ultrasound array probe, capable of establishing a shape which conforms to a complex 3D shape of a biological organ, such as a human head for 3D volumetric imaging vascular activity with a large field of view.Background Art

[0002] The human vascular network is a complex multi-scale system, ranging from several millimeters for the largest arteries to a few micrometers for the smallest vessels. This network provides nutrients and oxygen to organs. Their activity is therefore strongly linked to organs’ functions. Thus, the ability to image or map microcirculation at the whole organ scale in 3D is crucial to improve diagnosis of vascular network pathologies. In particular, in the case of the brain, assessing microcirculation morphological and functional abnormalities may allow an early diagnosis of cerebrovascular diseases.

[0003] Cerebral vascular imaging is mainly performed via Computed Tomography scan and Magnetic Resonance Imaging. However, these technics are limited to a millimeter-scale resolution which could not sufficient to image the smallest vessels.

[0004] Ultrasound imaging offers a good spatio-temporal resolution to image blood flow dynamics at a millimeter scale resolution. Recently, ultrasound Localization Microscopy (ULM), which has been described in particular by Errico et al. [Errico, C. et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature 527, 499-+ (2015)] and Demene et al. [Demene, C. et al. Transcranial ultrafast ultrasound localization microscopy of brain vasculature in patients. Nat. Biomed. Eng 5, 219-228 (2021)] shows the ability to image the vascular network and blood-flow dynamics at a micrometer scale resolution, by imaging millions of intravenously injected microbubbles (MB).

[0005] The ULM imaging method comprises the following main steps :- acquisition of ultrasound raw data from the region to be imaged;- beamforming of the data with delay-and-sum (DAS) to reconstruct 3D images;- application of a Singular Value Decomposition (SVD) on the 3D images to reject the tissue signal;- detection of microbubbles by detecting local maxima in each 3D image;- localization of the microbubbles in each 3D image;- tracking the trajectories of the microbubbles through successive frames to establish velocity profiles;- mapping of the accumulated localizations gathered over the series of frames to produce a super-resolved image of the vascular region far beyond the diffraction limit.

[0006] By imaging isolated intravenously injected microbubbles (MB) circulating in blood vessels at ultrafast frame rates and localizing the center of their individual point spread function with a sub-resolution precision, it enables to map the microvascularization of organs with a resolution of tens of microns and blood flow dynamic velocities.

[0007] Generally, 3D imaging uses a conventional matrix ultrasound probe comprising a flat 2D array of a plurality of transducer elements or active elements able to generate individually ultrasound waves. These ultrasound waves may be directed towards a medium which may generate in response backscattered signals, which in turn may be recorded by the same array of transducers or a different array. From the backscattered signal, it may be possible to reconstruct a 3D image of the medium.

[0008] Figure 1 illustrates an example of a conventional 2D flat ultrasound array probe 2 adapted to 3D ultrasound imaging, for instance for imaging a region 10 of a medium. The ultrasound 2D array probe 2 is put in contact with a surface 1 of the medium. The medium may be a body of a living being, e.g. a human patient. The surface is an outside surface of the medium. The region 10 may be a brain and the flat 2D array may cover only a portion of the brain.

[0009] The 2D array probe 2 may have for instance a number N of few hundreds to a few thousand transducer elements Ty, with a pitch lower than 1mm. The transducers of the 2D array ultrasonic probe may present different shapes in the XY plan. In one embodiment, the shape of the transducer may be square, rectangular or circular. The thickness of the transducer element may be comprised between 10 and 1000 micrometers depending on the piezoelectric materials. The transducer elements are arranged in uniformly aligned column and rows, with uniform spacing between adjacent elements. The piezoelectric elements are identical in size and shape. In the example of Figure 1 , the transducer elements are disposed as a matrix along two perpendicular axes X, Y, transmitting ultrasound waves along an axis Z which is perpendicular to the XY plane. The transducer elements are disposed on a flat substrate and form a flat array.

[0010] Each transducer element may be driven independently by electrical current to produce ultrasound waves and receive the backscattered signals. In use, the transducer elements may be manually positioned by the clinician at the location of the organ to be imaged.

[0011] The conventional 2D flat ultrasound array probe 2 is controlled by a control unit 3 and a computer 4. In this example, the control unit 3 is used for controlling 2D array ultrasonic probe 2 and acquiring signals therefrom, while the computer 4 is used for controlling the control unit 3, generating 3D image sequences from the signals acquired by control unit 3 and determining quantification parameters therefrom.

[0012] Thus, a significant disadvantage of the conventional 2D array is that it is not adapted to the natural curvature of the organ, such as the head.

[0013] Another disadvantage of the conventional 2D array is that it requires repeated placement of the probe onto and removal from the head to map entirely the organ. In addition to being time consuming, tedious, and difficult, the repeated manipulation of the probe by placing the probe onto the organ and then removing it may also have detrimental side effects and consequences for the patient’s health.

[0014] Furthermore, the human body is made of a variety of structure which impact ultrasound propagation. For example, the ultrasound wave is reflected and distorted when propagating through the bones. Thus, the conventional arrays do not allow to perform 3D ultrasound volumetric imaging of an entire organ which may be behind bones, and with enough resolution and sensitivity to determine specific locations (e.g. disease) in the imaged organ. Prior art usually uses opening (artificial or natural) in the bones to perform ultrasound 3D imaging making difficult large field of view imaging and the possibility to determine specific location with high lateral resolution.

[0015] Another issue is the high number of elements and channels required to image 3D volumes. Indeed, the capacity to image large 3D volume is directly related to the dimension of the array of transducers. In order to not lose in spatial resolution, it is necessary to use an array of transducers, wherein the size of the transducers does not exceed the wavelength of the ultrasound wave. This requirement leads to configurations of array which are not reachable or at too high cost with the current technology. For instance, a probe with an opening of 10cmx10cm (i.e. array of 10cmx10cm) and a size of transducer around 250 micrometers (corresponding to a central frequency of 6MHz) leads to an array of 160 000 transducers in order to keep a good resolution in 3D imaging and large field of view.

[0016] Therefore, there exists a need for imaging vascular activity, in particular brain-wide vascular activity, dynamically at a microscopic scale. In particular, there is a need to provide an ultrasound probe which can be curved to form a 3D shape to wrap a 3D organ with a complex 3D shape, for example a head, to map the organ in three dimensions which enables a clinician to visualize the whole volume of the organ.

[0017] Another aim of the present disclosure is to provide an ultrasound probe which can be easily placed on the 3D organ.

[0018] Another aim of the present disclosure of the present disclosure is to provide an ultrasound probe which may be easily curved to reproduce the complex 3D shape of an organ while preserving the sensitivity of the transducer elements, i.e. the signal-noise-ratio in comparison with conventional flat probe.

[0019] Another aim of the present disclosure is to provide a probe which can be easily positioned or attached to the organ.

[0020] Another aim of the present disclosure is to provide a probe with a reduced number of transducer elements needed without loss of image quality.

[0021] Another aim of the present disclosure is to provide a probe which can emit the ultrasound signal at different frequencies.

[0022] Another aim of the present disclosure is to provide a probe which is easier and less expensive to manufacture.Summary

[0023] To this end, the present disclosure proposes an ultrasound 3D imaging probe for imaging vascular activity dynamically at a microscopic scale in an organ of a body of a living being, the probe comprising :- a mosaic ultrasound array comprising a plurality of polygonal transducer element pads, each pad comprising a set of transducer elements distributed on a substrate, each transducer element being configured to acquire at least a backscattered ultrasound wave from the organ following an ultrasound emission in said organ;- a support frame comprising an intern surface intended to be placed facing said body;- each polygonal transducer element pad being located and attached in a removable manner on said internal surface of the support frame.

[0024] The following features, can be optionally implemented, separately or in combination one with the others:

[0025] In one or more embodiments, the support frame may comprise a plurality of wires interconnected with one another via connection points, and each polygonal transducer element pad being located and attached in a removable manner on a connection point.

[0026] In one or more embodiments, the support frame may be configured to reproduce the 3D shape of the body so that the mosaic ultrasound array follows the shape of the body.

[0027] In one or more embodiments, the pads may be identical in size and / or shape.

[0028] In one or more embodiments, the mosaic array comprises at most three groups of pads different in size and / or shape, the pads in each group being identical in size and / or shape.

[0029] In one or more embodiments, the pads may have a geometric shape chosen so that the whole surface occupied by all pads is about 80% to 90 % of the surface of the mosaic ultrasound array.

[0030] In one or more embodiments, the geometric shape may a hexagonal shape or a pentagonal shape.

[0031] In one or more embodiments, each connection point may be connected to a plurality of the immediately adjacent connection point by the wires to form a plurality of triangular mesh.

[0032] In one or more embodiments, the transducer elements of the pads are distributed randomly on the substrate or distributed in a manner to form a matrix array.

[0033] In one or more embodiments, each transducer element may have a circular reception surface, said circular reception surface having a diameter comprised between 2A and 4A, where A is the wavelength of the ultrasound wave.

[0034] In one or more embodiments, each transducer element may have a circular reception surface combined with an acoustic lens designed to emulate a transducer element with a curved shape.

[0035] In one or more embodiment, each of the transducer element pads may be configured to emit ultrasound waves at a frequency different from the frequencies of the other pads so that the mosaic array probe is adapted to simultaneously emit ultrasound waves of at least two frequencies on at least two different locations of the body.

[0036] In one or more embodiments, the substrate on which the transducer elements are distributed may have a curved surface or a flat surface.

[0037] The present disclosure also concerns an ultrasound 3D imaging apparatus comprising :- an ultrasound 3D imaging probe as described above;- a control unit configured to control the pads to transmit ultrasound waves in the organ to be imaged, to acquire signals from backscattered ultrasonic waves received by the pads from the organ in response to each transmitted ultrasonic wave, the control unit being further configured for generating a 3D image based on the acquired signals.

[0038] In embodiments of the apparatus, one may use the following features, alone or in combination:

[0039] In one or more embodiment, the control unit may be configured to control the transducer element pads independently so that the ultrasound wave frequency is adjustable separately for each of the pads.

[0040] In one or more embodiment, the control unit may be configured to control the transducer element pads independently so that the moment of the ultrasound wave transmission is chosen separately for each of the pads.

[0041] In one or more embodiment, the control unit may be configured to control the transducer element pads independently in such a manner that the choice of the pads to be used in a transmission sequence and in a reception sequence is defined separately for each of the pads.Brief Description of Drawings

[0042] Other features, details and advantages will be shown in the following detailed description and on the figures, on which:Fig. 1

[0043] [Fig. 1] Figure 1 illustrates a conventional flat ultrasound array probe for 3D ultrasound imaging.Fig. 2

[0044] [Fig. 2] Figure 2 illustrates an example of apparatus for ultrasound imaging comprising an ultrasound array probe according to an embodiment of the disclosure positioned on a human head.Fig. 3

[0045] [Fig. 3] Figure 3 illustrates the different components of the apparatus of Figure 2.Fig. 4

[0046] [Fig. 4] Figure 4 illustrates a top plan view of a portion of the ultrasound array probe of Figure 2, showing a mosaic array of ultrasound pads coupled with a mesh support frame.Fig. 5

[0047] [Fig. 5A] Figure 5A illustrates a perspective view of an ultrasound pad formed by a set of transducer elements, the elements being distributed on a substrate to form a hexagonal pattern.

[0048] [Fig. 5B] Figure 5B illustrates a perspective view of an ultrasound pad in a pentagonal pattern.

[0049] [Fig. 5C] Figure 5C is a schematic view of one piezoelectric transducer element used in the ultrasound pad of Figure 5A and Figure 5B.

[0050] [Fig. 5D] Figure 5D is a schematic top plan view of a portion of the ultrasound pad of Figure 5A .Description of Embodiments

[0051] In the Figures, the same references denote identical or similar elements.

[0052] In the present disclosure, the terms “conformable”, “deformable”, "flexible", "bendable" and “shapable” are used synonymously in the present description and refer to a material, structure or device component that has a bending stiffness that is sufficiently low to allow the material to adopt a curved or bent profile that follows the shape of an organ. In the example of Figure 2, the ultrasound array is shaped to reproduce the shape of a human head.

[0053] In the present disclosure, the term “substrate" or “support layer” refers to a layer having a surface that is capable of supporting one or more transducer elements. The support layer may be planar or slightly curved. In the present disclosure, the element is “bonded” to the substrate and unable to substantially move relative to the substrate surface to which it is bonded. In an embodiment, a set of transducer elements are directly or indirectly distributed and bonded to the substrate, for example, via a bonding layer, an adhesive layer or other intermediate layer positioned between the piezoelectric transducer elements and the substrate.

[0054] Figure 1 illustrates an example of apparatus for ultrasound imaging according to an embodiment.

[0055] The apparatus shown on Figure 1 may be adapted to conventional or ultrafast 3D or 4D ultrasound imaging, for instance for imaging a region of a medium. The medium may be a body of a living being, e.g. a human patient. The region to be imaged may be a brain of the living being, or may be a heart of the living being.

[0056] The apparatus comprises a mosaic ultrasound array probe 200 and a control system. The mosaic ultrasound array probe 200 is controlled by the control system to perform a conventional 3D ultrasound imaging or an ultrafast 3D ultrasound imaging.

[0057] In contrast to the conventional flat 2D ultrasound probe that may cover only a portion of the body, the mosaic array probe is configured to wrap the entire body by following the shape of the body. In the example of Figure 2, the mosaic array probe 200 is positioned on a human head.

[0058] With reference to Figure 2, the mosaic ultrasound array probe 200 comprises a support frame 10 and a plurality of ultrasound element pads 101 forming a mosaic ultrasound array. The mosaic ultrasound array probe 200 may have a number M of ultrasound element pads 101.

[0059] Each ultrasound element pad 101 may have a number N of ultrasound transducer elements 102, 112 disposed on a substrate 103, 113 as shown in Figures 5A-5B. Thus, the mosaic array probe may comprise N x M transducer elements 102.

[0060] Furthermore, each pad 101 may be configured to work as a receiver, or emitter, or emitter and receiver.

[0061] Each pad 101 may be configured to emit the ultrasound waves at a frequency comprised for instance between 0.5 and 100 MHz, for instance between 1 and 10 MHz.

[0062] The control system may for instance include a control unit 30 and a computer 40. In this example, the control unit 30 is used for controlling the mosaic ultrasound array probe 200 and acquiring signals therefrom, while the computer 40 is used for controlling the control unit 30, generating 3D image sequences from the signals acquired by the control unit 30 and generating density and velocity maps therefrom. In a variant, a single electronic device could fulfill all the functionalities of control unit 30 and computer 40.

[0063] In the case of an ULM imaging, the apparatus may further comprise an ultrasound contrast agent injection device 90. The control unit 30 may be configured to control the ultrasound contrast agent injection device 90.

[0064] The transducer elements 102 or piezoelectric elements, controlled by the control unit 30, may transmit at least one ultrasound wave in the medium. After emitting the ultrasound waves, the MxN transducer elements may be configured to receive the backscattered signals from the medium. For each transmitted signal by a transducer, backscattered signal may be generated by the medium in response to the transmitted signal and received by all the MxN transducers.

[0065] When transmitting, individual transducer elements are stimulated in particular patterns in order to form and focus one or more ultrasonic beams. When receiving, the backscattered signal received by individual transducer elements is delayed and summed in order to form electronic representations of ultrasonic beams. Therefore, the control system may comprise a multiple single line beamformers that are operated in parallel. In this configuration, each element 102 of the mosaic array 100 is connected to a channel of the beamformer. Each of these channels applies delays to the signals from its corresponding element, which delays are adapted to steer and focus the beam. The signals delayed by each channel of the beamformer are combined to form a unique beam, and the multiplebeams produced simultaneously by parallel operated beamformers are used to form an ultrasound image.

[0066] The mosaic array probe comprises N x M transducer elements. Each of the M x N elements 102 has a channel on which any received signals are transmitted to the control unit 30. In other words, the control unit 30 has M X N channels to control independently each transducer element 102 within each pad 101.

[0067] Therefore and as shows in Figure 3, the control unit 30 may include for instance a NxM number of analog / digital converters 50 individually connected to the N number of transducer elements distributed in each of the M pad 101 of mosaic array ultrasonic probe 200, a NxM number of buffer memories 60 respectively connected to the NxM number of analog / digital converters 50, a central processing unit 70 communicating with the buffer memories 60 and the computer 40, a memory 80 connected to the central processing unit 70, and a digital signal processor 90 connected to the central processing unit 70.

[0068] The control system may be programmed (or configured) such that the ultrasound waves may be transmitted at a rate more than 100 ultrasonic waves per second, for instance hundreds to several thousands of ultrasonic waves per second.

[0069] The M ultrasound pads of the mosaic array, controlled by the control unit 30, may have the transducer elements transmitting at least one ultrasound wave in the medium. After each emitting the ultrasonic wave, the M pads may be configured to receive the backscattered signals generated from the organ wrapped by the mosaic array probe. The transmitted ultrasound wave may be a spherical wave, a plane wave, a divergent wave or a more complex wave (Hadamard emission).

[0070] In one embodiment, all M pads have been used to transmit an ultrasound wave in the medium and to receive the generated backscattered signal. In each pad, all N transducer elements have been used to transmit an ultrasound wave in the medium and to receive the generated backscattered signal. In other words, the control unit 30 may be configured to active the M pads to simultaneously emit ultrasound wave and to simultaneously receive backscattered signals.

[0071] In another embodiment, the mosaic array probe 200 may be configured to use only one pad every K pads for emissions and all pads for reception. For instance, the ultrasonic 2D array may use every two pads (K=2), or every four transducers (K=4) in emission. In other words, the control unit 30 may be configured to active one pad every K pads for emissions and all pads for reception.

[0072] For each signal by transmitted a pad, backscattered signals may be generated by the medium in response to the transmitted signal. The generated backscattered signalscontain information about scatters in the region. The generated backscattered signals may be received by all the N pads and may be then respectively digitized by the N analog-digital converters and memorized in the N buffer memories. The data stored in the N buffer memories are called hereafter the raw signal data. Then, the raw signal data may be beamformed at all image points to form a 3D image.

[0073] The architecture of the mosaic array probe will be described in detail below with reference to Figures 4-5.

[0074] Fig. 4 is a top plan view of a portion of the probe 200 of Figure 2.

[0075] The probe 200 is composed of two parts coupled together for imaging an organ by wrapping entirely said organ which may be located behind bones or located deeply from the skin surface.

[0076] The probe comprises a mosaic array 100 of transducer element pads 101 for emitting and receiving ultrasound waves coupled with a support frame 10. The support frame 10 is configured to follow the shape of a living body so that the mosaic array can encircle the organ to be imaged.

[0077] For example, the shape and the dimension of the support frame 10 is not plane and conforms to the placement site of the body. The support frame comprises an outer surface and an intern surface on which are attached the plurality of transducer element pads 101. Each pad 101 comprises an outer surface and an intern surface.

[0078] In the present disclosure, the “intern surface” of the pads 101 refers to a surface that is intended to be in contact with the outer surface of the body receiving the probe.

[0079] In the present disclosure, the “outer surface” of the pads 101 refers to a surface that is intended to be coupled with the intern surface of the support frame 10.

[0080] In use, the probe 200 may be positioned on the surface of the patient’s body and the pads 101 may be put in contact with a surface of the body. Therefore, the shape and the dimension of the support frame 10 reproduce substantially the shape and the dimension of the outer surface of the body, close to the region to be imaged, e.g. a brain. In other words, when the probe is placed on the patient’s body, the intern surface of the support frame follows the shape of the outer surface of the body.

[0081] In the example of the Figure 2, the body is a human head and the region to be imaged is a brain. The shape and the dimensions of the support frame 10 reproduces the shape of the human head so that it can be placed on the head. Thus, the mosaic array 100 which is coupled to the intern surface of the support frame 10 is also shaped to encircle completely the brain.

[0082] In another exemplary application (not illustrated), the shape of the support frame 10 can follow the shape of a human chest. In this use, the mosaic array may be used to encircle the entire heart.

[0083] Preferably, this support frame 10 is of a single piece. By not resulting from the assembling of separate components, this support frame advantageously exhibits increases mechanical strength and stability to ensure the support of the pads.

[0084] In another embodiment, the support frame 10 may comprise a plurality of connection point 11 connected with one another by a plurality of wires 12 to form a plurality of unitary triangular mesh 14. Each connection point is connected to a plurality of the immediately adjacent connection point by the wires 12. The resulting support frame 10 is a mesh support frame. Each connection point is located at every intersection of wires.

[0085] The connection point may be an eyelet. It should be noted that, as used herein, the term “eyelet” means an opening having a substantially closed perimeter, but it is not limited to a particular shape. Thus, eyelets can be round, square, rectangular, trapezoidal, hexagonal, oval, elliptical or any other suitable shape. Of course, other types of attachment apertures or other fastening points may be used in place of the eyelets.

[0086] As used herein, the term “wire” refers to a rod, strut, or similar structure having a length that is relatively long compared to its width in the cross-sectional plane. For example, a “wire,” as used herein, can have a circular, oval, rectangular, or other cross-sectional shape. Each individual wire may be in the form of a single, continuous structure.

[0087] In one embodiment, the wires have the same width along their entire length. In another embodiment, the width of the wire is not identical in the frame. Some wires may have a reduced width to provide a greater flexibility, while others have increased width in order to provide regions of greater rigidity.

[0088] In one embodiment, the wires and the eyelets will generally have the same thickness.

[0089] The support frame may also be formed in any of a variety of manners such as forging, casting, molding, extrusion, cutting, etching, stamping, 3D printing.

[0090] In another embodiment, the support frame may made of any material having a suitable combination of rigidity and flexibility to allow the frame to be deformable to reproduce the shape of the organ, while providing a rigid support for the pads.

[0091] For example, the wires may be made from any of a variety of materials suitable for use on a patient and to provide a flexibility, such as various metals, or composite materials of two or more metals.

[0092] Each unitary triangular mesh may be regular, e,g a traingle having sides of equal length.

[0093] In one embodiment, the support frame 10 may be shaped at the time of fabrication.

[0094] In the case where the support frame 10 is made of material shapable, it can be shaped at another time prior to be positioned on an organ.

[0095] In one embodiment, the support frame may be rigid and is shaped during the manufacturing step to reproduce the shape of the body on which the mosaic probe is applied to perform the ultrasound imaging.

[0096] According to an embodiment, the pads are identical in size and / or shape.

[0097] In another embodiment, the mosaic array comprises at most three groups of pads different in size and / or shape, the pads in each group being identical in size and / or shape.

[0098] In order to maximize the compactness of the mosaic array probe, most of polygonal pads are identical in size and shape.

[0099] In one embodiment, the geometric shape of the pads is chosen so that the whole surface occupied by all pads is about 80% to 90% of the surface of the mosaic array, in order to maximize the reception surface and the transmission surface. For instance, in one example, the pads may have a hexagonal shape. In another example, the pads may have a pentagonal shape.

[0100] In another embodiment, the mosaic array probe may comprise a first group composed of hexagonal pads and a second group composed of pentagonal pads.

[0101] As result, the eyelets 11 are distributed in a pattern having the same geometric shape than that of the pad.

[0102] In the example of Figure 4, six triangular unitary mesh 14 are connected to form a regular hexagonal configuration. In other words, the eyelets 11 are distributed in a hexagonal pattern. In this configuration, six connection eyelets are 11 connected by a wire 12 and surround a connection eyelet located at the center of the hexagonal configuration. This hexagonal configuration is particularly adapted to support a mosaic array forming from a plurality of hexagonal pads to maximize the compactness.

[0103] In another example, five triangular unitary mesh are connected to form a regular pentagonal configuration. In other words, the eyelets 11 are distributed in a pentagonal pattern. In this configuration, five connection eyelets are connected by a wire and surround a connection eyelet located at the center of the pentagonal configuration. This pentagonalconfiguration is particularly adapted to support a mosaic array forming from a plurality of pentagonal pads to maximize the compactness.

[0104] Advantageously, each pad 101 is removably attached to a connection point 11 . For instance, each pad 101 is attached to a connection point 11 by a fastening screw. Thus, the ultrasound pads 101 are individually coupled to the support frame 10 via the connection points 11 and are interchangeable, enabling an easy reparation of the array.

[0105] The resulting mosaic array of pads is conformable to various curved shapes in order to match that of a patient’s body.

[0106] Figure 5A represents a perspective view of a hexagonal pad 101 formed by a set of transducer elements 102 distributed and assembled on a substrate 103. The substrate 103 has a hexagonal shape, and the distribution of the elements 102 forms a hexagonal pattern in the matrix array. For each pad, the number of elements distributed in the matrix array may be between 50 and 500.

[0107] In another example and with reference to Figure 5B, the pad 111 has a pentagonal shape formed by a set of transducer element 112 distributed and assembled on a substrate 113. The substrate113 has a pentagonal shape, and the distribution of the elements forms a pentagonal pattern in the matrix array.

[0108] Figure 5C is a schematic view of one single piezoelectric transducer element used in the pad.

[0109] The transducer elements may have different shapes in the plan of the substrate. In one embodiment, the shape of the transducer element may be square, rectangular or circular. In the example of Figures 5A-5C, the transducer element has a circular shape in the plan of the substrate. The thickness of the transducer element may be comprised between 10 and 1000 micrometers depending on the piezoelectric materials.

[0110] Each transducer element has a circular emission and reception surface with a diameter D of 350pm to 6.5 mm. For instance, the cylindrical element may have a diameter of 2A, where A is the wavelength of the ultrasound wave. In another example, the transducer element may have a diameter of 4A to maximize energy in transmission and reception mode.

[0111] In another embodiment, each transducer element has a circular surface combined with an acoustic lens designed to emulate a transducer element with a curved shape. By element with a curved shape, it should be understood a transducer element with a curved transmitting or / and receiving surface. The acoustic lens may be a compound acoustic lens comprising several materials associated respectively to several sound velocities.

[0112] Thus, the elements may enable to transmit and / or receive ultrasound waves with high amplitude due to the diameter larger than 2A. In addition, the curved shape may enable to maintain a low directivity by transmitting divergent ultrasound waves in the region and which may increase image quality in terms of field of view.

[0113] According to an embodiment, the surface of each pad 101 may be larger than 400A2allowing to increase the field of view.

[0114] In one embodiment, the N transducer elements 102 may be disposed as a regular matrix on the substrate 103 with a pitch p between 350um to 6.5 mm. In another embodiment, the N transducer elements 102 may be disposed randomly on the substrate 103. In the case where the substrate 103 extends in a XY plane, the N transducer elements may be disposed as a matrix along two perpendicular axes X, Y, transmitting ultrasound waves along an axis Z which is perpendicular to the XY plane.

[0115] Figure 5D is a schematic view of the element distribution in the matrix array. The elements are distributed in a matrix array with an inter-element pitch p of 350um to 6.5 mm. In the example of Figure 5D, the elements are distributed in a hexagonal pattern to maximize the compactness.

[0116] In one embodiment, the pads are identical in size and / or shape, and in number of elements. In another embodiment, the mosaic array probe may comprise at least two pads different in shape and / or in size. For example, the peripheral region of the probe may have pentagonal pads, while the center region of the probe may have hexagonal pads.

[0117] In one embodiment, the element count and the element size are identical for each pad. In another embodiment, the mosaic array may comprise at least two pads different in element count and in element size.

[0118] The transducer element pads are configured to be controlled independently to adapt the frequency of the ultrasound waves with respect to the medium of propagation and the bone thickness.

[0119] The control unit 30 is configured to control the transducer element pads 101 independently so that the wave frequency is adjustable separately for each of the pads. Thus, the frequency of the emitted ultrasound wave may be different for at least two element pads. Thus, the pads are adapted with respect to the propagation medium, e.g. the body part.

[0120] Indeed, whole brain 3D clinical ULM remains challenging due to transcranial energy loss which significantly reduces the imaging sensitivity and leads to a low signal-to-noise ratio. This is because of several effects including phase aberration, variations in the speedof sound in the skull, scattering at the bone interface, the acoustic impedance mismatch, and absorption of the three-layer medium made up of soft tissues, the skull and the brain.

[0121] Thus, higher frequency waves are not able to adequately penetrate through the skull. Lower transmit frequency, e.g. between 1 MHz and 2 MHz, is chosen to limit bone aberration and to image large volumes in term of imaging depth. However, the thickness of the bone varies from one region to another of the skull for a patient, and from one patient to another. Therefore, these characteristics limit imaging through thinner region of the skull, called acoustic windows. In general, four acoustic windows are commonly used in transcranial ultrasound imaging: the transtemporal window, the transorbital window, the submandibular window, and the suboccipital window. However, these windows of a few centimeter squares limit the aperture size of the probe, and thus resolution and sensitivity.

[0122] For transcranial imaging, furthermore, there is the existence of a critical angle defined as the greatest angle of incidence for which an ultrasound beam can strike the bone interface without being totally reflected.

[0123] Therefore, it is necessary to adapt the wave frequency and the incidence angle of the transmitted wave generated by each pad to the position of the pads positioned on the bone by taking account the bone thickness, the curvature of the bone and the medium.

[0124] In the case of the conventional flat probe, the wave frequency remains the same for all elements transducers, regardless of where they are located with respect to the bone thickness and the medium. For instance, the frequency if the transducer elements is chosen to be 1 MHz to limit the attenuation coefficient of the wave in the skull bone (10dB / cm).

[0125] In the present disclosure, advantageously, the use of the pads that are controlled independently by the control unit 30 to adapt the frequency of the ultrasound waves with respect to the bone thickness and the medium allows to overcome the limits imposed by the acoustic windows, to enlarge aperture size to image organs in large volume through the bones while keeping a high sensitivity.

[0126] According to one embodiment, the pads which are located in front of the thin bones, may be configured to emit an ultrasound wave with a frequency lower than that of the pads which are located in front of the thick bone.

[0127] For instance, in the example of the figure 2, the mosaic array probe is positioned on the patient’s head. The pads located in front the temporal window are configured to emit ultrasound waves with higher frequency whereas the pads located on the summit of the skull are configured to emit ultrasound waves with lower frequence.

[0128] In order to favorize the transmission and the reception of the ultrasound waves between the head’s surface and the probe, a liquid or gel may be applied on the intern surface of the pads.

[0129] In one embodiment, the pad curvature may be configured to adapt the angle of incidence for which an ultrasound wave can strike the bone interface in order to limit the reflectivity. In other words, the curvature of each pad may be adapted to the location of the pad in front of the bone so that the angle incidence between the wave transmitted by the elements of said pad and the body surface limits the reflectivity. For instance, the pads can be curved to lower the incidence angle between the transmitted ultrasound wave and the body surface.

[0130] To do so, a wave propagation model calculates frequency dependent transmission coefficient and angle incidence dependent transmission coefficient for a given skin, bone thickness and pad curvature.

[0131] Thereby, the mosaic probe presented in the figure 2 allows to increase the aperture size of the probe, and therefore, to increase the resolution and the sensitivity of the probe.

[0132] However, the use of the probe with a curved shape may introduce interference between the ultrasound signal at the transmission for pads which are located on the travel path of the incident wave of the other pads. Therefore, the pads are configured to emit the ultrasound waves at different moments. In other words, it may be required to determine the pads that are located on the travel path of the incidence wave of the other pads. These pads are defined as pads that cannot send ultrasound waves at the same time.

[0133] Furthermore, the use of the probe with a curved shape may introduce interference between the ultrasound signal at the reception and lead to difficulty for constructing the focused beamforming at the reception. In other words, the pads can send ultrasound waves at same time, but their received signals do not interfere constructively. Therefore, it may be required to determine pads that do not insonifiate the same part of the region.

[0134] In a similar manner, it may be necessary to determine pads that can send ultrasound at the same time to insonifiate the same part of the region, because their received signals can interfere constructively.

[0135] Therefore, the control unit is configured to control the transducer element pads independently so that the moment of the ultrasound wave transmission and the choice of the pads to be used are defined separately for each of the pads. The moment of the ultrasound wave transmission for each of the pads and the choice of the pads to be used are defined with respect to the position of the pads with respect one another once the probe is placed on the patient’s body.

[0136] In one embodiment, the positions of the pads with respect to one another in the mosaic array of the probe may be determined by a preliminary step of rough calibration. For instance, the rough calibration may be performed by using a simulation to calculate the positions, or a vitro calibration.

[0137] In another embodiment, the positions of the pads with respect to one another in the mosaic array of the probe may be determined by a preliminary step of precise calibration. For instance, the precise calibration may be performed by using in vitro or in vivo calibration by tracking the microbubbles signals.

[0138] An example of 3D ultrasound localization microscopy (ULM) using the apparatus of Figure 2 will be explained below.

[0139] The Ultrasound 3D imaging apparatus comprises an ultrasound 3D imaging probe 200 described above, a control unit 30 configured to control the pads 100 to transmit ultrasound waves in the organ to be imaged, to acquire signals from backscattered ultrasonic waves received by the pads from the organ in response to each transmitted ultrasonic wave, and a computer configured to generate a 3D image based on the acquired signals and determine quantification parameters.

[0140] In addition, the apparatus 200 may include an ultrasound contrast agent injection device 40 and the controller 30 may be configured to control the ultrasound contrast agent injection device.

[0141] The ultrasound contrast agent injection device may comprise ultrasound contrast agents. The ultrasound contrast agents may be microbubbles, as for instance described by Dayton et al., [Dayton, PA et al. Molecular ultrasound imaging using microbubble contrast agent. Frontiers in Bioscience 12, 5124-5142 (2007)], or equivalent ultrasound contrast agents. In some embodiments, the ultrasound contrast agents may be based on SonoVue®.

[0142] The ultrasound agent injection device 40 may be a push syringe in the example considered here. The ultrasound agent injection device 40 may comprise a magnet in order to mix a solution comprising the ultrasound contrast agents.

[0143] The mosaic array probe with ultrasound 3D imaging apparatus presented above may allow to perform 3D (or 4D) ultrasound image. Particularly, it may be possible to perform 3D ultrasound imaging, with a high resolution, of whole organ which may be located behind bones or located deeply from the skin surface, as for instance the brain. Indeed, the use of large transducer elements combined with a respective curved shape may guarantee a high energy transmission as well as a high reception sensitivity while keeping a large aperture, and therefore a high resolution and a large field of view of the organs to imaged.

[0144] The mosaic ultrasound array 100 which is shaped so that it conforms to the shape of a human head. In other words, the structure has been deformed to match the patient’s cranium. In addition, the support frame is shaped such that it surrounds entirely the head that it is not necessary to attach the support frame to the patient’s head. In this example of use, the support frame forms a hemi-sphere.

[0145] The probe 200 may be positioned on the patient’s head for brain imaging. In or more embodiments. The frequency (or the central frequency) of the emission may be comprised between 0.5 and 3 MHz. In order to favorize the transmission and the reception of the ultrasound waves between the head’s surface and the probe, a liquid / gel may be used to create a coupling surface between the intern surface of the pads and the surface of the patient’s head.

[0146] Thanks to the support frame and the mosaic array of ultrasound element pads, the probe can be deformed to reproduce the shape of the patient’s head as illustrated in Figure 2. Thus, the probe is place on the head and the pads may wrap entirely the patient’s head, and the brain to be imaged. In the prior art, the flat prob can cover only one portion of the organ. It is necessary to adjust the location of the probe.

[0147] The ultrasound 3D imaging method may be carried out as follow:-acquiring signals from backscattered ultrasonic waves propagated in the region to image in response to each transmitted ultrasonic wave,- generating a 3D image based on the acquired signals, said backscattered ultrasonic waves having said wavelength A.- applying a corrective delay on the acquired signals obtained after each transmitted ultrasonic wave to obtain a corrected acquired signals, said corrective delay taking into account the curved shape of the transmission surface,- applying beamforming on the corrected acquired signals to perform dynamic focusing and generating the 3D image; the beamforming may be performed in reception for each transmitted wave to perform coherent compounding or synthetic aperture imaging.

[0148] The ultrasonic waves may be transmitted in the region to image according to a known synthetic aperture method.

[0149] The 3D generated ultrasound image may be, for instance, a 3D image of a vasculature of a whole organ. An 3D image of vasculature of a whole organ may be obtained by using a superlocalization algorithms (or ultrasound localization algorithm) to localize or / and track microbubbles injected in the blood flow of the region to image, e.g. the vasculature of an organ to image. Such use of superlocalization algorithm with microbubbles may allow to generate vascular maps with a high spatial resolution. Indeed,it may be possible to obtain a resolution of the vasculature of an organ as small as ten micrometers, over an order of magnitude smaller than the ultrasound diffraction limit, and at depths much greater than the traditionally frequency-limited imaging depth. The 3D ultrasound generated image using a superlocalization algorithm may be called a 3D superresolution ultrasound image.

[0150] Such superlocalization algorithm may be carried out as follow: / a / detecting the microbubbles including:- applying a SVD clutter filter on 3D B-mode volumes to remove signal from the tissue and only keep microbubbles,- detecting local maxima in in each 3D B-mode volumes,- applying an energy level threshold based on the mean energy level of a microbubble to remove false positive microbubbles,- applying a correlation value threshold based on 3D Point Spread Function (PSF) correlation to remove false positive microbubbles, / b / tracking the microbubbles by:- detecting the exact center of a microbubble by using a 3D paraboloid interpolation on the voxels around the microbubble maximum,- using coordinates of exact centers, tracking bubbles frame to frame- recovering location and speed of track, / c / generating a super-resolved volume by:- reconstructing a super-resolved volume on a grid, the density of the superresolved volume is the number of microbubbles in each voxel of the grid, the speed of the super-resolved volume is the average speed in each voxel of the grid,

[0151] / d / generating a 3D super resolved image based on the super resolved volume. The 3D image may a density map based on the number of microbubbles in each voxel. The 3D image may be a velocity map by averaging bubbles velocities in each voxel.

[0152] In the example of figure 2, the mosaic array probe is used to image whole cerebral vascular network. In or more embodiment, the mosaic probe may be used to cardiac or liver imaging for which imaging the entire organ through the bones is also challenging.

[0153] Thanks to the use of a mosaic array probe of independent ultrasound pads coupled with a support frame that can be deformed to wrap entirely the organ, it is possible to image the whole microcirculation network of an organ at micrometer scale. The probe of thepresent disclosure may be used in the diagnostic of a neurodegenerative disease in an early stage and also in the monitoring of a medical treatment against a predetermined disease, for example in the case of a post-stroke recovery.

Claims

Claims

1. Ultrasound 3D imaging probe (200) for imaging vascular activity dynamically at a microscopic scale in an organ of a body of a living being, the probe (200) comprising :- a mosaic ultrasound array (100) comprising a plurality of polygonal transducer element pads, each pad (101) comprising a set of transducer elements (102) distributed on a substrate (103), each transducer element (102) being configured to acquire at least a backscattered ultrasound wave from the organ following an ultrasound emission in said organ;- a support frame (10) comprising an intern surface intended to be placed facing said body;- each polygonal transducer element pad (101) being located and attached in a removable manner on said internal surface of the support frame (10).

2. Ultrasound 3D imaging probe according to claim 1 , wherein the support frame (10) comprises a plurality of wires (12) interconnected with one another via connection points (11), and each polygonal transducer element pad (101) being located and attached in a removable manner on a connection point (11).

3. Ultrasound 3D imaging probe according to claim 1 or 2, wherein the support frame (10) is configured to reproduce the 3D shape of the body so that the mosaic ultrasound array follows the shape of the body.

4. Ultrasound 3D imaging probe according to any of claim 1 to 3, wherein the pads are identical in size and / or shape.

5. Ultrasound 3D imaging probe according to any of claims 1 to 3, wherein the mosaic array comprises at most three groups of pads different in size and / or shape, the pads in each group being identical in size and / or shape.

6. Ultrasound 3D imaging probe according to any of claims 1 to 5, wherein the pads have a geometric shape chosen so that the whole surface occupied by all pads is about 80% to 90 % of the surface of the mosaic ultrasound array.

7. Ultrasound 3D imaging probe according to claim 6, wherein the geometric shape is a hexagonal shape or a pentagonal shape.

8. Ultrasound 3D imaging probe according to any of claims 2 to 7, wherein each connection point (11) is connected to a plurality of the immediately adjacent connection point by the wires (12) to form a plurality of triangular mesh (14).

9. Ultrasound 3D imaging probe according to any of claims 1 to 8, wherein the transducer elements of the pads are distributed randomly on the substrate (103) or distributed in a manner to form a matrix array.

10. Ultrasound 3D imaging probe according to any of claims 1 to 9, wherein each transducer element (102, 112) has a circular reception surface, said circular reception surface having a diameter comprised between 2A and 4A, where A is the wavelength of the ultrasound wave.

11. Ultrasound 3D imaging probe according to any of claims 1 to 9, wherein each transducer element (102, 112) has a circular reception surface combined with an acoustic lens designed to emulate a transducer element with a curved shape.

12. Ultrasound 3D imaging probe according to any of claims 1 to 11 , wherein each of the transducer element pads (101) is configured to emit ultrasound waves at a frequency different from the frequencies of the other pads so that the mosaic array probe is adapted to simultaneously emit ultrasound waves of at least two frequencies on at least two different locations of the body.

13. Ultrasound 3D imaging probe according to any of claims 1 to 12 wherein the substrate (103, 113) on which the transducer elements (102, 112) are distributed has a curved surface or a flat surface.

14. Ultrasound 3D imaging apparatus comprising :- an ultrasound 3D imaging probe (200) according to any of preceding claims;- a control unit (30) configured to control the pads (101) to transmit ultrasound waves in the organ to be imaged, to acquire signals from backscattered ultrasonic waves received by the pads from the organ in response to each transmitted ultrasonic wave, the control unit being further configured for generating a 3D image based on the acquired signals.

15. Ultrasound 3D imaging apparatus according to claim 14, wherein the control unit (30) is configured to control the transducer element pads (101) independently so that the ultrasound wave frequency is adjustable separately for each of the pads.

16. Ultrasound 3D imaging apparatus according to claim 14 or 15, wherein the control unit (30) is configured to control the transducer element pads (101) independently so that the moment of the ultrasound wave transmission is chosen separately for each of the pads.

17. Ultrasound 3D imaging apparatus according to any of claims 14 to 16, wherein the control unit (30) is configured to control the transducer element pads (101) independently in such a manner that the choice of the pads to be used in a transmission sequence and in a reception sequence is defined separately for each of the pads.

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