WO2010004372A1 - Method for focusing an ultrasonic wave field - Google Patents
Method for focusing an ultrasonic wave field Download PDFInfo
- Publication number
- WO2010004372A1 WO2010004372A1 PCT/IB2008/055699 IB2008055699W WO2010004372A1 WO 2010004372 A1 WO2010004372 A1 WO 2010004372A1 IB 2008055699 W IB2008055699 W IB 2008055699W WO 2010004372 A1 WO2010004372 A1 WO 2010004372A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- medium
- scattered
- contrast agent
- signal
- focusing
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G10—MUSICAL INSTRUMENTS; ACOUSTICS
- G10K—SOUND-PRODUCING DEVICES; METHODS OR DEVICES FOR PROTECTING AGAINST, OR FOR DAMPING, NOISE OR OTHER ACOUSTIC WAVES IN GENERAL; ACOUSTICS NOT OTHERWISE PROVIDED FOR
- G10K11/00—Methods or devices for transmitting, conducting or directing sound in general; Methods or devices for protecting against, or for damping, noise or other acoustic waves in general
- G10K11/18—Methods or devices for transmitting, conducting or directing sound
- G10K11/26—Sound-focusing or directing, e.g. scanning
- G10K11/34—Sound-focusing or directing, e.g. scanning using electrical steering of transducer arrays, e.g. beam steering
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B17/225—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/48—Diagnostic techniques
- A61B8/481—Diagnostic techniques involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
- G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
- G01S7/52017—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
- G01S7/52046—Techniques for image enhancement involving transmitter or receiver
- G01S7/52049—Techniques for image enhancement involving transmitter or receiver using correction of medium-induced phase aberration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
- A61B2017/22005—Effects, e.g. on tissue
- A61B2017/22007—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
- A61B2017/22027—Features of transducers
- A61B2017/22028—Features of transducers arrays, e.g. phased arrays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
- A61B2090/3925—Markers, e.g. radio-opaque or breast lesions markers ultrasonic
Definitions
- the present invention pertains to methods for focusing ultrasonic wave fields.
- the wave field in question can consist of a wave pulse focused at one or more points of the medium, or it may involve a more complex spatio-temporal field.
- the invention relates to a method for focusing an ultrasonic wave field in a medium by an array of several transducers, said method including at least :
- each transducer i of the transducer array emits an emission signal e x (t) which corresponds to a time reversal of a signature signal S 1 (t) obtained from the scattered signal S 1 (t) received by said transducer i, to create a focused ultrasonic wave field in the medium.
- the time reversal mentioned above my consist in a direct computation of S 1 (- t) in the time domain, or in a more narrow-band treatment such as phase conjugation or delay modification applied to S 1 U) .
- step (c) This technique of time reversal enables to focus precisely the second ultrasonic wave on the scatterers in the medium.
- the method may involve repeating steps (b) and (c) , in which case the focused ultrasonic wave field of step (c) is backscattered to the transducers so that a new scattered signal S 1 (t) is captured and used to generate the subsequent signals e x (t) at the next step (c) to build a more and more precisely focused ultrasonic wave field.
- the present invention is aimed in particular at proposing a new focusing method in which one could efficiently focus the second ultrasonic wave field on focal zones which are not necessarily known in advance and which are determined by intrinsic parameters of the medium.
- a method of the type in question is characterized m that, at least before said emission step (a) , a targeted ultrasonic contrast agent is added to the medium, said targeted ultrasonic contrast agent being adapted to concentrate in areas of the medium having predetermined intrinsic characteristics (i.e. which contain particular molecules and / or have a particular physiology) .
- the focused ultrasonic field can then be used for instance for imaging purposes, or for treatment purposes, or else.
- recourse may possibly be had moreover to one and/or other of the following arrangements: the signature signal Si (t) is equal to the scattered signal si(t) ; - the signature signal Si (t) is obtained by combining several scattered signals si(t) received by the transducer i from the medium, using any kind of linear or non linear combination of the signals; the method further includes: (a') an additional emission step in which said first ultrasonic wave field is transmitted in the medium without targeted ultrasonic contrast agent present in the medium, said first ultrasonic wave field being scattered by scatterers in said medium, which transmit a reference scattered wave to said transducer array,
- the capturing and focusing steps (b) and (c) are repeated iteratively, the scattered signals Si(t) which are captured at said capture step being generated by ultrasonic waves scattered from the focused ultrasonic wave field obtained at step (c) ;
- the targeted ultrasonic contrast agent which is added to the medium comprises a linking material adapted to enable retention by a specific chemical or physiological environment ; said linking material is chosen in the group consisting of ligands, antibodies, toxins or passive targeting materials; the ultrasonic contrast agent which is not retained in the medium by said linking material is eliminated before the emission step (a) ;
- the targeted ultrasonic contrast agent which is added to the medium is chosen in the group consisting of: encapsulated microbubbles including a shell filled with gas, the shell including said linking material
- time-reversal is performed by modifying at least one of the phase and the delay of the signature signal; - the signature signal is decomposed in a set of elementary signature signals corresponding respectively to focusing beams in different areas of the medium containing said targeted ultrasonic contrast agent, to increase antenna gain.
- Fig. 1 is a basic diagram representing an exemplary device allowing implementation of the invention
- Fig. 2 is a repartition of areas of microbubbles in a medium, in an example of use of the invention
- Fig. 3 is an image of the medium in the example of Fig. 2, showing the pressure distribution of the ultrasonic wave field emitted in the medium before performing the method of the invention;
- - Fig. 4 is a view similar to Fig. 3, showing the pressure distribution of the focused ultrasonic wave field emitted in the medium during the focusing step of the method of the invention.
- MORE DETAILED DESCRIPTION Figure 1 shows a device for implementing the invention, for instance for the purpose of imaging or treatment of a specific target area 2 in a medium 1.
- the medium 1 can be part of a human or animal body, or can be any other biological or physico-chemical medium.
- the target area 2 may be for instance an area of the medium suffering from an illness in the case of he human or animal body, or any other singular area of the medium in the general case.
- the area 2 is evidenced by a targeted ultrasonic contrast agent which may be added to the medium 1 (e.g. by injection) before the method is performed.
- a targeted ultrasonic contrast agent which may be added to the medium 1 (e.g. by injection) before the method is performed.
- Such targeted ultrasonic contrast agents are known in the art [see for instance Dayton et al . , Frontiers in Bioscience 12, 5124-5142, September 1, 2007] , and may be chosen among : - encapsulated microbubbles including a shell filled with gas, liquid droplets (which may be encapsulated in a shell too) , and solid particles.
- the targeted ultrasonic contrast agent is adapted to concentrate in areas of the medium having predetermined intrinsic characteristics, i.e. which contain particular molecules and / or have a particular physiology. More specifically, the targeted ultrasonic contrast agent may comprise a linking material adapted to enable retention by a specific chemical or physiological environment.
- This linking material may be adapted to perform active targeting, i.e. to create a chemical bond with specific molecules in the medium (then, the linking material may be for instance a ligand, an antibody or a toxin) , or the linking material may be a passive targeting material adapted to concentrate in specific areas of the medium by physiological effects.
- the targeted ultrasonic contrast agent may be in the form of encapsulated microbubbles 3 of a few micrometers in diameter, including said linking material on their outer shell.
- the ultrasonic contrast agent which is not retained in the medium by said linking material may be eliminated before the method is performed, e.g. by a natural flow of liquid such as blood or lymph in the case of the human or natural body.
- the device of Figure 1 comprises an array 4 of ultrasonic transducers 5, which may be for instance a linear echographic array including for instance a few tens of transducers (e.g. 128, or else) .
- the array 5 might also include several sub-arrays, and / or have a more complex form.
- the transducers 5 of the array 4 may be controlled individually by a central processing unit 6 (CPU) , comprising for instance a micro-computer and / or specific electronic circuits, as already known m the art.
- CPU central processing unit 6
- the focusing method of the invention is performed by this device, as follows: (a) in an initial emission step, a first ultrasonic wave field is transmitted in the medium and scattered by scatterers in said medium, which transmit a scattered wave to said transducer array (this first ultrasonic wave field may be either unfocused, or already focused) , (b) in a capture step, the transducers i of the transducer array capture respective scattered signals S 1 (t) generated by said scattered wave;
- time-reversal may be performed for instance by a pressure-release mirror.
- the time reversal may be performed by directly computing S 1 (-t) m the time domain or by more narrow-band methods such as by modifying the phase of the signature signal (m particular by phase conjugating the signature signal) and/or the delay of the signature signal, or else.
- the signature signal may be obtained by combining (linearly or nonlmearly) several scattered signals S 1 (t) received by the transducer i from the medium.
- the method may further include:
- step (b' ) an additional capture step in which the transducers i of the transducer array capture respective reference scattered signals SO 1 (t) generated by said reference scattered wave, and during the focusing step (c) , the signature signal S 1 (t) is based on a difference between said scattered signal S 1 (t) and said reference scattered signal SO 1 (t) (the signature signal may be equal to this difference S 1 Ct)- SO 1 Ct), or be obtained by filtering this difference S 1 Ct)- SO 1 Ct) to select harmonics of the central emission frequency, as explained above) .
- the additional steps (a' ) and (b' ) may be performed before step (a) , and before the ultrasonic contrast agent is added to the medium.
- the signature signal S 1 Ct) can be obtained by any detection method known for detecting ultrasonic contrast agents in the field of ultrasound imaging, for instance harmonics filtering, pulse inversion sequences, disruption sequences, amplitude modulation, radial modulation and other methods using nonlinear behavior of the ultrasonic contrast agent.
- the capturing and focusing steps (b) and (c) are repeated iteratively, the scattered signals S 1 (t) which are captured at said capture step being generated by ultrasonic waves scattered from the focused ultrasonic wave field obtained at step (c) : a more and more precise focusing can thus be obtained.
- the signature signal may be decomposed in a set of elementary signature signals corresponding respectively to different areas of the medium containing said targeted ultrasonic contrast agent, to increase antenna gain.
- focused ultrasonic wave field may be used for instance in a medical treatment to perform hyperthermia, cavitation, sonoporation or sonothrombolysis , when the medium 1 is the human or animal body.
- the targeted ultrasonic contrast agent may be followed by imaging (e.g. ultrasonic imaging or MRI imaging, or else) .
- a low- amplitude pulse was sent through the medium and the echoes from the different structures in its path were recorded by the array in a first set of RF data (radio- frequency data, i.e. the raw temporal data captured by each transducer) .
- a high-intensity pulse was then emitted by the array to disrupt all the bubbles on the surface of the gel .
- a second low-amplitude acquisition was performed and this bubble- less signal was subtracted from the first set of RF data for all the elements of array. The resulting subtraction was considered to be the signal from the targeted microbubbles, which was then time-reversed, amplified, elongated (to lOOus) and reemitted by the transducer array.
- the resulting increase in temperature at each point was observed using a thermosensitive gel . Pressure at each point was also measured by scanning a hydrophone. The pattern of thermal therapy was then compared to the distribution of microbubbles on the surface as observed by an optical camera.
- Figure 2 shows the two dots of microbubbles on the gelatin surface. They were slightly off the geometric center of the HIFU array. On a typical low-amplitude RF acquisition, the signal from the microbubbles represented 14% of the total signal from the surface of the gel and could easily be segmented.
- the thermosensitive paper showed a temperature- increase corresponding to the original pattern formed by the microbubbles.
- the pattern of the geometric focus of the array was obtained on the thermosensitive paper.
- the resulting pressure distributions for the control and the time-reversal experiment as measured by the hydrophone are shown in Fig.3 and Fig.4, respectively. In Fig.4, the two dots representing the higher pressures are concomitant with the placement of the microbubbles dots.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Surgery (AREA)
- Veterinary Medicine (AREA)
- Medical Informatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Remote Sensing (AREA)
- Multimedia (AREA)
- Radar, Positioning & Navigation (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- General Physics & Mathematics (AREA)
- Computer Networks & Wireless Communication (AREA)
- Acoustics & Sound (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Radiology & Medical Imaging (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Surgical Instruments (AREA)
Abstract
Method for focusing an ultrasonic wave field in a medium (1) including a targeted ultrasonic contrast agent (3), by an array (4) of several transducers (5), said method including: (a) an emission step in which a first ultrasonic wave field is transmitted in the medium and scattered by scatterers in said medium, which transmit a scattered wave to said transducer array, (b) a capture step in which the transducers i of the transducer array capture respective scattered signals Si (t) generated ed by said scattered wave; (c) a focusing step in which each transducer i of the transducer array emits an emission signal ei(t) which is a Time reversal of a signature signal Si(t) obtained from the scattered signal Si(t) received by said transducer i, to create a focused ultrasonic wave field in the medium.
Description
Method for focusing an ultrasonic wave field
FIELD OF THE INVENTION
The present invention pertains to methods for focusing ultrasonic wave fields.
The wave field in question can consist of a wave pulse focused at one or more points of the medium, or it may involve a more complex spatio-temporal field.
More particularly, the invention relates to a method for focusing an ultrasonic wave field in a medium by an array of several transducers, said method including at least :
(a) an emission step in which a first ultrasonic wave field is transmitted in the medium and scattered by scatterers in said medium, which transmit a scattered wave to said transducer array,
(b) a capture step in which the transducers i of the transducer array capture respective scattered signals S1 (t) generated by said scattered wave; (c) a focusing step in which each transducer i of the transducer array emits an emission signal ex(t) which corresponds to a time reversal of a signature signal S1 (t) obtained from the scattered signal S1 (t) received by said transducer i, to create a focused ultrasonic wave field in the medium. It should be noted that the time reversal mentioned above my consist in a direct computation of S1 (- t) in the time domain, or in a more narrow-band treatment such as phase conjugation or delay modification applied to S1U) . This technique of time reversal enables to focus precisely the second ultrasonic wave on the scatterers in the medium. Of course, the method may involve repeating steps (b) and (c) , in which case the focused ultrasonic wave field of step (c) is backscattered to the transducers so that a new scattered signal S1 (t) is captured and used
to generate the subsequent signals ex(t) at the next step (c) to build a more and more precisely focused ultrasonic wave field.
BACKGROUND OF THE INVENTION Pernot at al . [Applied Physics Letters 88, 034102,
2006] disclosed an example of such a method, m which a bubble is generated m the medium by cavitation in order to voluntarily create a scatterer in the medium at a place where the ultrasonic wave field should be focused during the focusing step (c) , thus enabling an efficient focusing of the second ultrasonic wave on said position.
However, the technique proposed by Pernot et al . supposes that one knows m advance at what position (s) the second ultrasonic wave field should be focused, which is not always the case. As a matter of fact, m some cases, the ideal position of the focusing zone(s) is determined by intrinsic parameters of the medium (such as local chemical composition, local biological parameters, etc.) which are not known m advance . OBJECTS AND SUMMARY OF THE INVENTION
The present invention is aimed in particular at proposing a new focusing method in which one could efficiently focus the second ultrasonic wave field on focal zones which are not necessarily known in advance and which are determined by intrinsic parameters of the medium.
To this end, according to the invention, a method of the type in question is characterized m that, at least before said emission step (a) , a targeted ultrasonic contrast agent is added to the medium, said targeted ultrasonic contrast agent being adapted to concentrate in areas of the medium having predetermined intrinsic characteristics (i.e. which contain particular molecules and / or have a particular physiology) .
Thanks to these dispositions, it may be possible to focus the second ultrasonic field very precisely on an area
of interest which is not necessarily known in advance.
The focused ultrasonic field can then be used for instance for imaging purposes, or for treatment purposes, or else. In preferred embodiments of the invention, recourse may possibly be had moreover to one and/or other of the following arrangements: the signature signal Si (t) is equal to the scattered signal si(t) ; - the signature signal Si (t) is obtained by combining several scattered signals si(t) received by the transducer i from the medium, using any kind of linear or non linear combination of the signals; the method further includes: (a') an additional emission step in which said first ultrasonic wave field is transmitted in the medium without targeted ultrasonic contrast agent present in the medium, said first ultrasonic wave field being scattered by scatterers in said medium, which transmit a reference scattered wave to said transducer array,
(b' ) an additional capture step in which the transducers i of the transducer array capture respective reference scattered signals sθi(t) generated by said reference scattered wave, and during the focusing step (c) , the signature signal Si(t) is based on a difference between said scattered signal Sj.(t) and said reference scattered signal sθi(t) ; the targeted ultrasonic contrast agent present in the medium is eliminated after said capture step (b) (for instance, the ultrasonic contrast agent may be disrupted by an ultrasonic pulse, or else) and wherein said additional emission step (a' ) is carried out after said capture step (b) ; the signature signal Sj. (t) is obtained by a detection method chosen in the group consisting of
harmonics filtering, pulse inversion sequences, disruption sequences, amplitude modulation, radial modulation and other methods using nonlinear behavior of the ultrasonic contrast agent ; - the capturing and focusing steps (b) and (c) are repeated iteratively, the scattered signals Si(t) which are captured at said capture step being generated by ultrasonic waves scattered from the focused ultrasonic wave field obtained at step (c) ; - the targeted ultrasonic contrast agent which is added to the medium comprises a linking material adapted to enable retention by a specific chemical or physiological environment ; said linking material is chosen in the group consisting of ligands, antibodies, toxins or passive targeting materials; the ultrasonic contrast agent which is not retained in the medium by said linking material is eliminated before the emission step (a) ; - the targeted ultrasonic contrast agent which is added to the medium is chosen in the group consisting of: encapsulated microbubbles including a shell filled with gas, the shell including said linking material , - liquid droplets, and solid particles; the focused ultrasonic wave field is used in a medical treatment to perform hyperthermia, cavitation, sonoporation or sonothrombolysis; - the targeted ultrasonic contrast agent is imaged
(e.g. by ultrasonic imaging or MRI imaging, or else) ; at the focusing step (c) , time-reversal is performed by modifying at least one of the phase and the delay of the signature signal; - the signature signal is decomposed in a set of
elementary signature signals corresponding respectively to focusing beams in different areas of the medium containing said targeted ultrasonic contrast agent, to increase antenna gain. BRIEF DESCRIPTION OF THE DRAWINGS
Other characteristics and advantages of the invention will become apparent in the course of the following description of one of its embodiments, given by way of non limiting example, with regard to the appended drawings.
In the drawings :
Fig. 1 is a basic diagram representing an exemplary device allowing implementation of the invention;
Fig. 2 is a repartition of areas of microbubbles in a medium, in an example of use of the invention;
Fig. 3 is an image of the medium in the example of Fig. 2, showing the pressure distribution of the ultrasonic wave field emitted in the medium before performing the method of the invention; - Fig. 4 is a view similar to Fig. 3, showing the pressure distribution of the focused ultrasonic wave field emitted in the medium during the focusing step of the method of the invention.
MORE DETAILED DESCRIPTION Figure 1 shows a device for implementing the invention, for instance for the purpose of imaging or treatment of a specific target area 2 in a medium 1. The medium 1 can be part of a human or animal body, or can be any other biological or physico-chemical medium. The target area 2 may be for instance an area of the medium suffering from an illness in the case of he human or animal body, or any other singular area of the medium in the general case.
In the present method, the area 2 is evidenced by a targeted ultrasonic contrast agent which may be added to the medium 1 (e.g. by injection) before the method is
performed. Such targeted ultrasonic contrast agents are known in the art [see for instance Dayton et al . , Frontiers in Bioscience 12, 5124-5142, September 1, 2007] , and may be chosen among : - encapsulated microbubbles including a shell filled with gas, liquid droplets (which may be encapsulated in a shell too) , and solid particles. The targeted ultrasonic contrast agent is adapted to concentrate in areas of the medium having predetermined intrinsic characteristics, i.e. which contain particular molecules and / or have a particular physiology. More specifically, the targeted ultrasonic contrast agent may comprise a linking material adapted to enable retention by a specific chemical or physiological environment.
This linking material may be adapted to perform active targeting, i.e. to create a chemical bond with specific molecules in the medium (then, the linking material may be for instance a ligand, an antibody or a toxin) , or the linking material may be a passive targeting material adapted to concentrate in specific areas of the medium by physiological effects.
In the present case, the targeted ultrasonic contrast agent may be in the form of encapsulated microbubbles 3 of a few micrometers in diameter, including said linking material on their outer shell.
The ultrasonic contrast agent which is not retained in the medium by said linking material may be eliminated before the method is performed, e.g. by a natural flow of liquid such as blood or lymph in the case of the human or natural body.
The device of Figure 1 comprises an array 4 of ultrasonic transducers 5, which may be for instance a linear echographic array including for instance a few tens
of transducers (e.g. 128, or else) . The array 5 might also include several sub-arrays, and / or have a more complex form.
The transducers 5 of the array 4 may be controlled individually by a central processing unit 6 (CPU) , comprising for instance a micro-computer and / or specific electronic circuits, as already known m the art.
The focusing method of the invention is performed by this device, as follows: (a) in an initial emission step, a first ultrasonic wave field is transmitted in the medium and scattered by scatterers in said medium, which transmit a scattered wave to said transducer array (this first ultrasonic wave field may be either unfocused, or already focused) , (b) in a capture step, the transducers i of the transducer array capture respective scattered signals S1 (t) generated by said scattered wave;
(c) and in a focusing step, each transducer i of the transducer array emits an emission signal eα(t) which is correspond to a time reversal of a signature signal S1 (t) obtained from the scattered signal S1 (t) received by said transducer i, to create a focused ultrasonic wave field in the medium (ex (t) =SX (-t) or may be proportional to S1 (-a. t) where a is a positive constant) . At the focusing step (c) , time-reversal may be performed for instance by a pressure-release mirror. More generally, the time reversal may be performed by directly computing S1 (-t) m the time domain or by more narrow-band methods such as by modifying the phase of the signature signal (m particular by phase conjugating the signature signal) and/or the delay of the signature signal, or else.
The signature signal S1 (t) may be equal to the scattered signal S1 (t) (m which case the emitted signal is βj. (t) =sx ( -t) ) , or the signature signal S1 (t) may be obtained by filtering said scattered signal S1 (t) to select at least
one harmonic of the central frequency of the transducers, which enables to efficiently select the scattered signals coming from the ultrasonic contrast agent .
In a variant, the signature signal may be obtained by combining (linearly or nonlmearly) several scattered signals S1 (t) received by the transducer i from the medium. In particular, the method may further include:
(a') an additional emission step in which said first ultrasonic wave field is transmitted in the medium without targeted ultrasonic contrast agent present in the medium, said first ultrasonic wave field being scattered by scatterers in said medium, which transmit a reference scattered wave to said transducer array,
(b' ) an additional capture step in which the transducers i of the transducer array capture respective reference scattered signals SO1 (t) generated by said reference scattered wave, and during the focusing step (c) , the signature signal S1 (t) is based on a difference between said scattered signal S1 (t) and said reference scattered signal SO1 (t) (the signature signal may be equal to this difference S1Ct)- SO1Ct), or be obtained by filtering this difference S1Ct)- SO1Ct) to select harmonics of the central emission frequency, as explained above) . The additional steps (a' ) and (b' ) may be performed before step (a) , and before the ultrasonic contrast agent is added to the medium. Alternately, these additional steps could be performed after elimination (e.g. after destruction) of the microbubbles, after steps (a) and (b) . More generally, the signature signal S1Ct) can be obtained by any detection method known for detecting ultrasonic contrast agents in the field of ultrasound imaging, for instance harmonics filtering, pulse inversion sequences, disruption sequences, amplitude modulation, radial modulation and other methods using nonlinear
behavior of the ultrasonic contrast agent.
In another variant, the capturing and focusing steps (b) and (c) are repeated iteratively, the scattered signals S1 (t) which are captured at said capture step being generated by ultrasonic waves scattered from the focused ultrasonic wave field obtained at step (c) : a more and more precise focusing can thus be obtained.
In still another variant, the signature signal may be decomposed in a set of elementary signature signals corresponding respectively to different areas of the medium containing said targeted ultrasonic contrast agent, to increase antenna gain.
After performing the above process, focused ultrasonic wave field may be used for instance in a medical treatment to perform hyperthermia, cavitation, sonoporation or sonothrombolysis , when the medium 1 is the human or animal body.
During and after the above focusing process, the targeted ultrasonic contrast agent may be followed by imaging (e.g. ultrasonic imaging or MRI imaging, or else) .
One example of use of the method of the invention will now be decribed. In this example, droplets of avidinated-microbubbles were deposited on an agar gel covered with biotinylated gelatin. Disks, 2.5 mm in diameter, with high surface density of microbubbles were obtained. The agar gel was then immersed in a water tank equipped with 80 "HIFU" [High Intensity Focused Ultrasound] transducers fully programmable in both emission and reception. The dots of microbubbles were placed within 2 cm of the geometrical focus of the transducer array. A low- amplitude pulse was sent through the medium and the echoes from the different structures in its path were recorded by the array in a first set of RF data (radio- frequency data, i.e. the raw temporal data captured by each transducer) . A high-intensity pulse was then emitted by the array to
disrupt all the bubbles on the surface of the gel . A second low-amplitude acquisition was performed and this bubble- less signal was subtracted from the first set of RF data for all the elements of array. The resulting subtraction was considered to be the signal from the targeted microbubbles, which was then time-reversed, amplified, elongated (to lOOus) and reemitted by the transducer array. The resulting increase in temperature at each point was observed using a thermosensitive gel . Pressure at each point was also measured by scanning a hydrophone. The pattern of thermal therapy was then compared to the distribution of microbubbles on the surface as observed by an optical camera.
Figure 2 shows the two dots of microbubbles on the gelatin surface. They were slightly off the geometric center of the HIFU array. On a typical low-amplitude RF acquisition, the signal from the microbubbles represented 14% of the total signal from the surface of the gel and could easily be segmented. When the time-reversed HIFU pulses were emitted, the thermosensitive paper showed a temperature- increase corresponding to the original pattern formed by the microbubbles. As a control, when simultaneous pulses were sent through all the transducers, the pattern of the geometric focus of the array was obtained on the thermosensitive paper. The resulting pressure distributions for the control and the time-reversal experiment as measured by the hydrophone are shown in Fig.3 and Fig.4, respectively. In Fig.4, the two dots representing the higher pressures are concomitant with the placement of the microbubbles dots.
Claims
1. Method for focusing an ultrasonic wave field in a medium (1) by an array (4) of several transducers (5), said method including at least :
(a) an emission step in which a first ultrasonic wave field is transmitted in the medium (1) and scattered by scatterers in said medium, which transmit a scattered wave to said transducer array (4), (b) a capture step in which the transducers i of the transducer array (4) capture respective scattered signals Si(t) generated by said scattered wave;
(c) a focusing step in which each transducer i of the transducer array (4) emits an emission signal ei(t) which corresponds to a time reversal of a signature signal Si(t) obtained from the scattered signal si(t) received by said transducer i, to create a focused ultrasonic wave field in the medium, characterized in that, at least before said emission step (a), a targeted ultrasonic contrast agent (3) is added to the medium, said targeted ultrasonic contrast agent being adapted to concentrate in areas of the medium having predetermined intrinsic characteristics.
2. Method according to claim 1, wherein the signature signal Si (t) is equal to the scattered signal
Si(t) .
3. Method according to claim 1, wherein the signature signal Si(t) is obtained by combining several scattered signals Si(t) received by the transducer i from the medium (1) .
4. Method according to claim 1, further including: (a' ) an additional emission step in which said first ultrasonic wave field is transmitted in the medium without targeted ultrasonic contrast agent present in the medium, said first ultrasonic wave field being scattered by scatterers in said medium, which transmit a reference scattered wave to said transducer array,
(b' ) an additional capture step in which the transducers i of the transducer array capture respective reference scattered signals sθi(t) generated by said reference scattered wave, and during the focusing step (c) , the signature signal Si(t) is based on a difference between said scattered signal Si(t) and said reference scattered signal SO1 (t) .
5. Method according to claim 4, wherein the targeted ultrasonic contrast agent present in the medium is eliminated after said capture step (b) , and wherein said additional emission step (a') is carried out after said capture step (b) .
6. Method according to any one of the preceding claims, wherein the signature signal Si (t) is obtained by a detection method chosen in the group consisting of harmonics filtering, pulse inversion sequences, disruption sequences, amplitude modulation, radial modulation and other methods using nonlinear behavior of the ultrasonic contrast agent .
7. Method according to any one of the preceding claims, wherein the capturing and focusing steps (b) and (c) are repeated iteratively, the scattered signals Si(t) which are captured at said capture step being generated by ultrasonic waves scattered from the focused ultrasonic wave field obtained at step (c) .
8. Method according to any one of the preceding claims, wherein the targeted ultrasonic contrast agent which is added to the medium comprises a linking material adapted to enable retention by a specific chemical or physiological environment.
9. Method according to claim 8, wherein said linking material is chosen in the group consisting of ligands, antibodies, toxins or passive targeting materials.
10. Method according to claim 9, wherein the ultrasonic contrast agent (3) which is not retained in the medium by said linking material is eliminated before the emission step (a) .
11. Method according to any one of the preceding claims, wherein the targeted ultrasonic contrast agent (3) which is added to the medium is chosen in the group consisting of: encapsulated microbubbles including a shell filled with gas, the shell including said linking material, liquid droplets, and solid particles.
12. Method according to any one of the preceding claims, wherein the targeted ultrasonic contrast agent (3) is imaged.
13. Method according to any one of the preceding claims, wherein at the focusing step (c) , time-reversal is performed by modifying at least one of the phase and the delay of the signature signal.
14. Method according to any one of the preceding claims, wherein the signature signal is decomposed in a set of elementary signature signals corresponding respectively to focusing beams in different areas of the medium containing said targeted ultrasonic contrast agent .
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IB2008/055699 WO2010004372A1 (en) | 2008-07-10 | 2008-07-10 | Method for focusing an ultrasonic wave field |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IB2008/055699 WO2010004372A1 (en) | 2008-07-10 | 2008-07-10 | Method for focusing an ultrasonic wave field |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010004372A1 true WO2010004372A1 (en) | 2010-01-14 |
Family
ID=41226656
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2008/055699 WO2010004372A1 (en) | 2008-07-10 | 2008-07-10 | Method for focusing an ultrasonic wave field |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2010004372A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5092336A (en) * | 1989-02-08 | 1992-03-03 | Universite Paris Vii-Bureau De La Valorisation Et De Relations Industrielle | Method and device for localization and focusing of acoustic waves in tissues |
EP1449563A1 (en) * | 2003-02-19 | 2004-08-25 | Biosense Webster, Inc. | Externally-applied high intensity focused ultrasound (hifu) for therapeutic treatment |
US20050260189A1 (en) * | 2002-07-11 | 2005-11-24 | Klibanov Alexander L | Microbubble compositions, and methods for preparing and using same |
-
2008
- 2008-07-10 WO PCT/IB2008/055699 patent/WO2010004372A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5092336A (en) * | 1989-02-08 | 1992-03-03 | Universite Paris Vii-Bureau De La Valorisation Et De Relations Industrielle | Method and device for localization and focusing of acoustic waves in tissues |
US20050260189A1 (en) * | 2002-07-11 | 2005-11-24 | Klibanov Alexander L | Microbubble compositions, and methods for preparing and using same |
EP1449563A1 (en) * | 2003-02-19 | 2004-08-25 | Biosense Webster, Inc. | Externally-applied high intensity focused ultrasound (hifu) for therapeutic treatment |
Non-Patent Citations (1)
Title |
---|
PAUL A. DAYTON, JOSHUA J. RYCHAK: "Molecular ultrasound imaging using microbubble contrast agents", FRONTIERS IN BIOSCIENCE, vol. 12, 1 September 2007 (2007-09-01), pages 5124 - 5142, XP002554263 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100990011B1 (en) | Contrast agent manipulation with medical ultrasound imaging | |
US20190350562A1 (en) | Customized cosmetic treatment | |
OˈReilly et al. | A super‐resolution ultrasound method for brain vascular mapping | |
Tanter et al. | Compensating for bone interfaces and respiratory motion in high-intensity focused ultrasound | |
US6716168B2 (en) | Ultrasound drug delivery enhancement and imaging systems and methods | |
JP5451819B2 (en) | Method of using combined imaging and therapy transducers to dissolve clots | |
EP2091438B1 (en) | Apparatus for 3d ultrasound imaging and therapy | |
CN102281918B (en) | The drafting of cavitation activity and sign | |
Hynynen et al. | Feasibility of using ultrasound phased arrays for MRI monitored noninvasive surgery | |
Gâteau et al. | Transcranial ultrasonic therapy based on time reversal of acoustically induced cavitation bubble signature | |
EP2991556B1 (en) | Systems and methods for super-resolution ultrasound imaging | |
US20150258352A1 (en) | Frequency compounding ultrasound pulses for imaging and therapy | |
US20070167798A1 (en) | Contrast agent augmented ultrasound therapy system with ultrasound imaging guidance for thrombus treatment | |
US20080125657A1 (en) | Automated contrast agent augmented ultrasound therapy for thrombus treatment | |
Coviello et al. | Thin-film sparse boundary array design for passive acoustic mapping during ultrasound therapy | |
Boulos et al. | Weighting the passive acoustic mapping technique with the phase coherence factor for passive ultrasound imaging of ultrasound-induced cavitation | |
Lu et al. | Enhanced-cavitation heating protocols in focused ultrasound surgery with broadband split-focus approach | |
Lu et al. | Delay multiply and sum beamforming method applied to enhance linear‐array passive acoustic mapping of ultrasound cavitation | |
WO2010004372A1 (en) | Method for focusing an ultrasonic wave field | |
Sutin et al. | Prospective medical applications of nonlinear time reversal acoustics | |
US20210015511A1 (en) | System and method for comminution of biomineralizations using microbubbles | |
Bancel et al. | Adaptive Ultrasound Focusing Through the Cranial Bone for Non-invasive Treatment of Brain Disorders | |
JP5520150B2 (en) | Ultrasonic measuring device and ultrasonic treatment system | |
Ebbini et al. | Self-guided ultrasound phased arrays for noninvasive surgery | |
Maleke et al. | An all-ultrasound-based system for real-time monitoring and sonication of temperature change and ablation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 08875977 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 08875977 Country of ref document: EP Kind code of ref document: A1 |