WO2012042423A1 - Système de surveillance et de régulation de la cavitation de microbulles dans l'application thérapeutique d'ultrasons - Google Patents

Système de surveillance et de régulation de la cavitation de microbulles dans l'application thérapeutique d'ultrasons Download PDF

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Publication number
WO2012042423A1
WO2012042423A1 PCT/IB2011/054049 IB2011054049W WO2012042423A1 WO 2012042423 A1 WO2012042423 A1 WO 2012042423A1 IB 2011054049 W IB2011054049 W IB 2011054049W WO 2012042423 A1 WO2012042423 A1 WO 2012042423A1
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Prior art keywords
cavitation
image
therapy system
processor
locations
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PCT/IB2011/054049
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English (en)
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Francois Guy Gerard Marie Vignon
William Tao Shi
Jeffry Earl Powers
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Koninklijke Philips Electronics N.V.
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Publication of WO2012042423A1 publication Critical patent/WO2012042423A1/fr

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    • 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
    • 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
    • A61B8/06—Measuring blood flow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/13—Tomography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • 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
    • G01S7/52023—Details of receivers
    • G01S7/52036—Details of receivers using analysis of echo signal for target characterisation
    • G01S7/52038—Details of receivers using analysis of echo signal for target characterisation involving non-linear properties of the propagation medium or of the reflective target
    • 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
    • G01S7/52053—Display arrangements
    • G01S7/52057—Cathode ray tube displays
    • G01S7/52071—Multicolour displays; using colour coding; Optimising colour or information content in displays, e.g. parametric imaging
    • 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
    • A61B17/2256—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 with means for locating or checking the concrement, e.g. X-ray apparatus, imaging means
    • A—HUMAN NECESSITIES
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    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00115—Electrical control of surgical instruments with audible or visual output
    • A61B2017/00119—Electrical control of surgical instruments with audible or visual output alarm; indicating an abnormal situation
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    • 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
    • A61B2017/22008—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing used or promoted
    • A—HUMAN NECESSITIES
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    • 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
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
    • A61B34/25—User interfaces for surgical systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A61B8/0808—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/46—Ultrasonic, sonic or infrasonic diagnostic devices with special arrangements for interfacing with the operator or the patient
    • A61B8/461—Displaying means of special interest
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/52—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/5215—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data
    • A61B8/5238—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data for combining image data of patient, e.g. merging several images from different acquisition modes into one image
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0039—Ultrasound therapy using microbubbles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0078—Ultrasound therapy with multiple treatment transducers
    • 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
    • G01S15/00—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
    • G01S15/88—Sonar systems specially adapted for specific applications
    • G01S15/89—Sonar systems specially adapted for specific applications for mapping or imaging
    • G01S15/8906—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques
    • G01S15/899—Combination of imaging systems with ancillary equipment

Definitions

  • This invention relates to medical diagnostic ultrasound systems and, in particular, to ultrasound systems which perform imaging and therapy for ultrasound therapy and drug delivery.
  • Ischemic stroke is one of the most debilitating disorders known to medicine.
  • the blockage of the flow of blood to the brain can rapidly result in paralysis or death.
  • Attempts to achieve recanalization through thrombolytic drug therapy such as treatment with tissue plasminogen activator (tPA) has been reported to cause symptomatic intracerebral hemorrhage in a number of cases.
  • tPA tissue plasminogen activator
  • microbubble activity can in many instances aid in dissolving or breaking up the blood clot and return a nourishing flow of blood to the brain and other organs.
  • microbubble activity can be used to deliver drugs encapsulated in microbubble shells, and well as microbubble-mediated
  • MI High mechanical index
  • diagnostic ultrasound system have been utilized in small animal models to target drug delivery and enhance thrombolysis in the presence of intravenously infused microbubbles . These high MI impulses can induce
  • inertial cavitation (IC) of the microbubbles which may also cause unwanted bioeffects such as hemorrhage, cell death, and cardiac arrhythmias when using transthoracic or transcranial impulses.
  • IC inertial cavitation
  • SC stable cavitation
  • Cavitation monitoring and control techniques are required to reproducibly induce the desired state and level of cavitation to achieve the desired therapeutic bioeffects without the harmful ones. Cavitation monitoring and control are also important for thermal HIFU where both bubble generation/distribution and temperature distribution are important .
  • acoustic signatures including detection of "spikes” in received signals; post-excitation acoustic emissions; sub- and ultra- harmonic generation; broadband noise emission; increased spectral noise between harmonics;
  • Array-based imaging systems can be used as
  • cavitation detectors over a large control volume, i.e., the entire field of view of the ultrasound array.
  • a diagnostic ultrasound system and method which provide an anatomical indication of the locations of inertial and stable cavitation during ultrasonic therapy or drug delivery.
  • a cavitation image is developed from cavitation indicia of echo signals at the site of treatment.
  • the cavitation image overlays a corresponding anatomical B mode image and provides a visual indication of locations of stable and inertial cavitation in the body.
  • the clinician can then adjust the transmit energy of the ultrasound system to provide the desired therapeutic effect.
  • the adjustment can be performed automatically to maintain a desired level of cavitation activity.
  • An alert can be produced if the level of cavitation varies above a desired level.
  • FIGURE 1 illustrates in block diagram form an ultrasonic diagnostic imaging system constructed in accordance with the principles of the present invention.
  • FIGURE 2 illustrate the delivery of ultrasonic therapy in a two dimensional (2D) imaging plane
  • FIGURE 3 illustrates the delivery of ultrasonic therapy in a three dimensionally image volume.
  • FIGURE 4 illustrates the harmonic content of a cavitation echo which is used in an embodiment of the present invention.
  • FIGURE 5 is a flowchart illustrating the
  • FIGURE 6 is a flowchart illustrating treatment with cavitation monitoring and control in accordance with the principles of the present invention.
  • Two transducer arrays 10a and 10b are provided for
  • the arrays shown are two dimensional arrays of transducer elements capable of providing 3D image information although an
  • implementation of the present invention may also use two dimensional arrays of transducer element which produce 2D (planar) images.
  • the transducer arrays are coupled to microbeamformers 12a and 12b which control
  • Microbeamformers are also capable of at least partial beamforming of the signals received by groups or "patches" of transducer elements as described in US
  • implementations such as cardiac delivery a probe with a single 2D array and microbeamformer may be used.
  • Signals are routed to and from the microbeamformers by a multiplexer 14.
  • the multiplexer is coupled to a
  • T/R switch 16 which switches between transmission and reception and protects the system beamformer 20 from high energy transmit signals.
  • the transmission of ultrasonic pulses from the transducer arrays 10a and 10b under control of the microbeamformers 12a and 12b is directed by the transmit controller 18 coupled to the T/R switch, which receives input from the user's operation of the user interface or control panel 38.
  • the partially beamformed signals produced by the microbeamformers 12a, 12b are coupled to the system beamformer 20 where partially beamformed signals from the individual patches of elements of an array are combined into a fully beamformed signal.
  • the system beamformer 20 may have 128 channels, each of which receives a partially beamformed signal from a patch of 12 transducer elements. In this way the signals received by over 1500 transducer elements of a two dimensional array can contribute efficiently to a single beamformed signal.
  • the beamformed signals are coupled to a
  • the separator 22 acts to separate linear and nonlinear signals so as to enable the identification of the strongly nonlinear echo signals returned from microbubbles .
  • the separator 22 may operate in a variety of ways such as by bandpass filtering the received signals in fundamental frequency and harmonic frequency bands, or by a process known as pulse inversion harmonic separation.
  • a suitable process known as pulse inversion harmonic separation such as by bandpass filtering the received signals in fundamental frequency and harmonic frequency bands, or by a process known as pulse inversion harmonic separation.
  • the separated signals are coupled to a signal processor 24 where they may undergo additional enhancement such as speckle removal, signal compounding, and noise elimination.
  • the processed signals are coupled to a B mode processor 26 and a cavitation processor 28.
  • the B mode processor 26 employs amplitude detection for the imaging of structures in the body such as muscle, tissue, and blood cells. B mode images of structure of the body may be formed in either the harmonic mode or the fundamental mode. Tissues in the body and microbubbles both return both types of signals and the harmonic returns of microbubbles enable microbubbles to be clearly segmented in an image in most applications.
  • the processor detects the signal characteristics of cavitation and produces cavitation image signals as described below.
  • the system may also include a Doppler processor which processes temporally distinct signals from tissue and blood flow for the detection of motion of substances in the image field including microbubbles.
  • cavitation signals produced by these processors are coupled to a scan converter 32 and a volume renderer 34, which produce image data of tissue structure, flow, cavitation, or a combined image of several of these characteristics.
  • the scan converter converts echo signals with polar coordinates into image signals of the desired image format such as a sector image in Cartesian coordinates.
  • the volume renderer 34 converts a 3D data set into a projected 3D image as viewed from a given reference point as described in US Pat. 6,530,885
  • This image manipulation is controlled by the user as indicated by the Display Control line between the user interface 38 and the volume renderer 34. Also described is the representation of a 3D volume by planar images of different image planes, a technique known as multiplanar reformatting.
  • the volume renderer 34 can operate on image data in either rectilinear or polar coordinates as described in US Pat. 6,723,050 (Dow et al . )
  • the 2D or 3D images are coupled from the scan converter and volume renderer to an image processor 30 for further enhancement, buffering and temporary storage for display on an image display 40.
  • a graphics processor 36 is also coupled to the image processor 30 which generates graphic overlays for displaying with the ultrasound images.
  • These graphic overlays can contain standard identifying information such as patient name, date and time of the image, imaging parameters, and the like, and can also produce a graphic overlay of a beam vector steered by the user as described below.
  • the graphics can contain standard identifying information such as patient name, date and time of the image, imaging parameters, and the like, and can also produce a graphic overlay of a beam vector steered by the user as described below. For this purpose the graphics
  • the graphics processor received input from the user interface 38.
  • the graphics processor can be used to overlay a cavitation image over a corresponding anatomical B mode image as described below.
  • the user interface is also coupled to the transmit controller 18 to control the generation of ultrasound signals from the transducer arrays 10a and 10b and hence the images produced by and therapy applied by the transducer arrays.
  • the transmit parameters controlled in response to user adjustment include the MI
  • transcranial headset implementation transmit ultrasonic waves into the cranium of a patient from opposite sides of the head, although other locations may also or alternately be employed such as the front of the head or the sub-occipital acoustic window at the back of the skull.
  • acoustic windows for transcranial ultrasound at the temporal bones around and above the ears on either side of the head.
  • the transducer arrays In order to transmit and receive echoes through these acoustic windows the transducer arrays must be in good acoustic contact at these locations which may be done by holding the transducer arrays against the head with the headset.
  • FIGURE 2 illustrates a two dimensional imaging implementation of the present invention.
  • the transducer array 122 is a one or two
  • This transducer array like the other arrays described herein, is covered with a lens 124 which electrically insulates the patient from the transducer array and in the case of a one dimensional array may also provide focusing in the elevation (out-of-plane) dimension.
  • the lens is pressed against the skinline 100 for acoustic coupling to the patient.
  • the transducer array 122 is backed with acoustic damping material 126 which
  • the device 130 may be a simple knob or tab which may be grasped by the clinician to manually rotate the circular array transducer in its rotatable transducer mount (not shown) .
  • the device 130 may also be a motor which is energized through a conductor 132 to
  • the image plane can also be steered in elevation as described in US Pat. 7,037,264.
  • Rotating the one dimensional array transducer 122 as indicated by arrow 144 will cause its image plane 140 to pivot around its central axis, enabling the
  • the planes acquired during at least a 180° rotation of the array will occupy a conical volume in front of the transducer array, which may be rendered into a 3D image of that volumetric region.
  • Other planes outside this volumetric region may be imaged by repositioning, rocking or tilting the transducer array in its headset in relation to the skull 100.
  • the therapeutic beam vector graphic 142 can be steered by the clinician to aim and focus the beam at the stenosis 144 and therapeutic pulses applied to disrupt the microbubbles at the site of the stenosis.
  • FIGURE 3 illustrates a 3D imaging implementation of the present invention which uses a 2D matrix array transducer 10a.
  • the transducer array 10 is held against the skinline 100 of the patient with the volume 102 being imaged projected into the body. The user will see a 3D image of the volume 102 on the display of the ultrasound system in either a
  • the user can manipulate the kinetic parallax control to observe the volume rendered 3D image from different
  • the user can adjust the relative opacity of the tissue and flow components of the 3D image to better visualize the vascular structure inside the brain tissue as described in US Pat. 5,720,291 (Schwartz) or can turn off the B mode (tissue) portion of the display entirely and just visualize the flow of the vascular structure inside the 3D image volume 102.
  • a microbubble contrast agent is introduced into the patient's
  • the microbubbles in the bloodstream will be pumped through to the vasculature of the treatment site and appear in the 3D image. Therapy can then be applied by agitating or breaking
  • a therapy graphic 110 appears in the image field 102, depicting the vector path of a
  • therapeutic ultrasound beam with a graphic thereon which may be set to the depth of the thrombus.
  • therapeutic ultrasound beam is manipulated by a control on the user interface 38 until the vector graphic 110 is focused at the site of the blockage.
  • produced for the therapeutic beam can be within the energy limits of diagnostic ultrasound or in excess of the ultrasound levels permitted for diagnostic
  • the microbubbles at the site of the blood clot will be sharply broken.
  • the energy of the resulting microbubble ruptures will strongly agitate a blood clot, tending to break up the clot and dissolve it in the bloodstream.
  • insonification of the microbubbles at diagnostic energy levels will be sufficient to dissolve the clot.
  • the microbubbles may be vibrated and oscillated, and the energy from such extended
  • oscillation prior to dissolution of the microbubbles can be sufficient to break up the clot.
  • the energy level of transmitted ultrasound is monitored and controlled to produce a desired level of cavitation at the site of the therapy.
  • cavitation is indicated by the occurrence of combined sub- and ultra-harmonics, while inertial cavitation is indicated by a combination of the following features: (1) elevated noise levels between all (sub, 1st, ultra- and 2nd and higher) harmonic components (or spectral peaks) in the transducer's lower frequency band is indirectly indicative of the high-frequency noise directly associated with fast collapsing of inertially cavitating bubbles. The noise increase at the lower frequency band is not a direct indicator of inertial cavitation; (2) Doppler spectrum changes includes both bubble destruction (associated with inertial and stable cavitation) and flow velocity (speed/ direction) .
  • the degree of cavitation caused by transmitted ultrasound pulses or waves is related to the MI setting of the ultrasound transmitter.
  • MI the degree of cavitation caused by transmitted ultrasound pulses or waves.
  • microbubbles are agitated or oscillated but generally are not ruptured or dissolved. They remain stable and intact in the presence of low MI ultrasound.
  • stable cavitation can occur.
  • Stable cavitation results in significant mechanical effects of disrupted and rupturing microbubbles but without deleterious effects which can damage cells in the body. Above around an MI of 0.6, unwanted
  • bioeffects can occur.
  • FIGURE 4 illustrates a typical spectrum of an echo returned from cavitation activity at an MI of 0.3.
  • the fundamental frequency of the transmitted ultrasound is f 0 , the major peak in the spectrum of the returning echo.
  • Second (f 2 ) , third (f 4 ) , and fourth (f 6 ) harmonic peaks are also seen in the spectrum. Between the fundamental frequency of the transmitted ultrasound is f 0 , the major peak in the spectrum of the returning echo.
  • Second (f 2 ) , third (f 4 ) , and fourth (f 6 ) harmonic peaks are also seen in the spectrum. Between the fundamental
  • a series of pulses or beams are transmitted across the image field to form an anatomical image of the region of the therapy.
  • Interleaved with this standard imaging is the transmission of cavitation pulses or beams to produce echoes for the detection of cavitation at spatial locations in the image field.
  • the cavitation pulses or beams may scan the same area or volume as the imaging pulses or beams, or only a portion thereof around the therapy site.
  • the imaging pulses are
  • the cavitation pulses are transmitted at a higher MI of 0.3 or greater or at a level where the onset of cavitation is anticipated.
  • cavitation pulse sequences are processed as shown by the flowchart of FIGURE 5.
  • This implementation of the present invention produces an anatomical image of the location of cavitation in the image field by combining a B mode image with detected cavitation at spatial
  • the RF echo data from the B mode pulses is processed starting at 60.
  • the echo data is filtered at 62 (generally by the signal processor 24) and envelope detected at 64 to produce a B mode image at 66, the latter being performed by the B mode processor 26.
  • the RF data may all be at the second harmonic, or at the fundamental frequency for tissue with an overlay of second harmonic signals from microbubbles.
  • Processing of the RF echo data from the cavitation pulse sequence begins at 70. Filtering is performed to detect the signal content at three spectral locations: the fundamental frequency (f 0 ) at 72, between the first ultra-harmonic frequency and the second harmonic ( fi . 75 ) at 74, and the first ultraharmonic frequency ( fi .
  • the filtered RF signals are envelope detected to produce Fundamental data at 82, Noise data at 84 and Ultraharmonic data at 86. These detected signals are then combined and analyzed as shown at 92 and 94 to detect the presence of inertial and stable cavitation. If the ratio of the detected
  • Ultraharmonic data at a location in the image field to the Noise data at that location is greater than 6dB
  • stable cavitation is determined to be present at that location (94) .
  • This determination is essentially based on the assessment that the Ultraharmonic data being much greater than the Noise data at a spectral location that should be low in harmonic content indicates a strong echo return from microbubble activity, but insufficient Noise data to indicate strong bubble ruptures. If this ratio is less than 6dB and the ratio of the Noise data to the Fundamental data at the location is greater than or equal to 25dB, then inertial cavitation is determined to be present at that location.
  • This determination is essentially based on the assessment that Ultraharmonic data from microbubble activity is much less than the Noise data and that the Noise data level is
  • the picture element at that location is colored green in this example as indicated at 154.
  • the picture element at that location is colored red as indicated at 152.
  • the picture elements of the B mode image are all nominally gray in this example as
  • the picture elements in the B mode image may be replaced by red and green picture elements at locations where inertial and stable cavitation are determined in the image field.
  • an inertial cavitation image is formed of just the red picture elements
  • a stable cavitation image is formed of just the green picture elements and the inertial and stable cavitation images overlaid over the B mode image to spatially present the cavitation locations to the viewer.
  • Another alternative is to combine the inertial and stable cavitation images into one cavitation image for overlay over the B mode image. Each approach shows the user where cavitation has been detected in the image field, and the type of cavitation detected by the color coding and brightness.
  • FIGURE 6 is an exemplary flowchart of a therapy procedure which may be performed in accordance with the present invention.
  • a microbubble contrast agent is introduced into the bloodstream of the patient and at 160 low MI harmonic imaging is performed to visualize the microbubbles in the bloodstream and to locate the target, the thrombus, blood clot, or site where drug delivery is to take place.
  • the probe and/or the image field may be scanned and moved until the site of the procedure is visualized and the clinician sees that microbubbles are present at the site.
  • the clinician turns up the power of the ultrasound system to a higher MI and performs cavitation imaging.
  • Cavitation imaging may also use a different pulse than the initial harmonic imaging. For example, the initial survey imaging may use a short pulse for good spatial
  • cavitation imaging may use a longer pulse (greater number of cycles) to provide good
  • Coded pulses and chirp (variable frequency) pulses accompanied by deconvolution filtering may also be suitable.
  • Cavitation imaging is performed while the MI is adjusted until at least some stable cavitation is seen by green colorizing in the B mode image.
  • the clinician increases the power further until stable cavitation is seen where microbubbles are present and little or no inertial cavitation is seen (red color) . If the power is turned up too far and a
  • the clinician turns down the power so that most or all of the cavitation seen is stable cavitation. Therapy may then continue at this setting at 166.
  • Another possibility is that the moderate, diagnostic level setting for cavitation imaging is insufficient for the needed therapy and more power is needed, or different pulses or pulse sequences are used for the therapy.
  • the vector graphic 110, 142 may then be turned on and set for the therapy site and therapy is enabled at 166 to direct the requisite ultrasonic therapy pulses to the indicated therapy site. Echoes returning from the higher level therapy pulses may also be processed to form a cavitation image in response to the higher level therapy pulses.
  • Anatomical imaging, cavitation imaging, and therapy transmission are time-interleaved so that the progress of the therapy can be monitored by
  • the cavitation imaging data can be used as feedback in an automated implementation, automatically keeping the cavitation in the stable cavitation regime should the detected
  • therapy is paused to allow blood flow to replenish the supply of microbubbles at the therapy site.
  • desired result of the therapy e.g., release of the desired amount of a drug or dissipation of a thrombus, is seen, the therapy is terminated.
  • the ultrasound system of FIGURE 1 also includes an inertial cavitation detector 50 and a loudspeaker 42. These features are useful in an automated or monitoring implementation to alert a user when undesired inertial cavitation is occurring.
  • the inertial cavitation data e.g., red picture elements indicative of inertial cavitation, are applied to the inertial cavitation detector. When this data such as the number of red pixels in a cavitation image is greater that a preset level, preferably one that is user-adjustable, an alert is sounded by the loudspeaker 42, is displayed on the display screen 40, or both. This alerts the clinician that an undesired level of inertial cavitation has been sensed, giving the clinician the immediate opportunity to correct the situation by adjusting the transmit level setting of the ultrasound system.

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Abstract

L'invention concerne un système d'imagerie diagnostique ultrasonore, qui met en œuvre une thérapie utilisant des microbulles telle que la sonothrombolyse ou l'apport d'un médicament encapsulé. Le site de la procédure thérapeutique est imagé par une imagerie harmonique. Le type et la quantité de cavitation présente dans le champ d'image sont détectés par la mise en œuvre d'une imagerie de cavitation, qui détecte des caractéristiques d'écho indiquant différents types de cavitation dans des emplacements du champ d'image. Un élément de superposition d'image colorisée est produit, dans lequel une couleur indique les emplacements de cavitation stable, et une autre couleur indique les emplacements de cavitation inertielle. L'image colorisée est superposée ou combinée à une image en mode B pour indiquer à l'utilisateur les emplacements et le type de cavitation. Une alerte d'utilisateur est produite quand le système détecte un niveau indésirable de cavitation inertielle.
PCT/IB2011/054049 2010-09-30 2011-09-16 Système de surveillance et de régulation de la cavitation de microbulles dans l'application thérapeutique d'ultrasons WO2012042423A1 (fr)

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WO2015000953A1 (fr) 2013-07-03 2015-01-08 Bracco Suisse S.A. Dispositifs et procédés pour le traitement par ultrasons d'un accident cérébral ischémique
WO2016075586A1 (fr) * 2014-11-14 2016-05-19 Koninklijke Philips N.V. Dispositif à ultrasons pour sonothrombolyse
CN105943087A (zh) * 2016-07-26 2016-09-21 飞依诺科技(苏州)有限公司 超声微泡空化设备的成像处理方法及处理系统
DE102015003704A1 (de) * 2015-03-20 2016-09-22 Martin-Luther-Universität Halle-Wittenberg Kopfhalterung für Duplex- und Dopplersonden
EP2962642A4 (fr) * 2013-02-28 2016-11-23 Alpinion Medical Systems Co Procédé de détection de cavitation et appareil médical ultrasonore correspondant
US9555268B2 (en) 2011-05-18 2017-01-31 Koninklijke Philips N.V. Spherical ultrasonic HIFU transducer with modular cavitation sense element
WO2018109652A1 (fr) * 2016-12-16 2018-06-21 Koninklijke Philips N.V. Impulsions adaptatives pour traitement par sonothrombolyse
WO2020083725A1 (fr) 2018-10-24 2020-04-30 Commissariat A L'energie Atomique Et Aux Energies Procédé et système d'analyse spectrale et de détermination d'un marqueur permettant d'assurer la sécurité d'interventions d'ultrasons thérapeutiques
CN111093520A (zh) * 2017-09-19 2020-05-01 医视特有限公司 局部空化信号测量
CN111134719A (zh) * 2019-12-19 2020-05-12 西安交通大学 一种聚焦超声辐照相变纳米液滴的主被动超声复合成像方法及系统
CN113040814A (zh) * 2021-03-11 2021-06-29 飞依诺科技(苏州)有限公司 超声微泡空化设备的成像处理方法及成像处理系统
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6450752B2 (ja) 2013-06-28 2019-01-09 コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． 画像誘導超音波血栓溶解のためのトランスデューサ配置及び位置合わせ
WO2016092396A1 (fr) * 2014-12-11 2016-06-16 Koninklijke Philips N.V. Réglage de puissance de sortie d'ultrasons de sono-thrombolyse
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US10575816B2 (en) 2017-01-25 2020-03-03 Insightec, Ltd. Cavitation localization
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US20220287733A1 (en) * 2021-03-15 2022-09-15 Covidien Lp Devices, systems, and methods for disrupting obstructions in body lumens

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5181514A (en) 1991-05-21 1993-01-26 Hewlett-Packard Company Transducer positioning system
US5720291A (en) 1996-03-22 1998-02-24 Advanced Technology Laboratories, Inc. Three dimensional medical ultrasonic diagnostic image of tissue texture and vasculature
US5997479A (en) 1998-05-28 1999-12-07 Hewlett-Packard Company Phased array acoustic systems with intra-group processors
US6013032A (en) 1998-03-13 2000-01-11 Hewlett-Packard Company Beamforming methods and apparatus for three-dimensional ultrasound imaging using two-dimensional transducer array
US6530885B1 (en) 2000-03-17 2003-03-11 Atl Ultrasound, Inc. Spatially compounded three dimensional ultrasonic images
US6623432B2 (en) 2000-08-24 2003-09-23 Koninklijke Philips Electronics N.V. Ultrasonic diagnostic imaging transducer with hexagonal patches
US6723050B2 (en) 2001-12-19 2004-04-20 Koninklijke Philips Electronics N.V. Volume rendered three dimensional ultrasonic images with polar coordinates
WO2005074805A1 (fr) 2004-02-05 2005-08-18 Koninklijke Philips Electronics N.V. Imagerie ultrasonore d'irrigation et de debit sanguin au moyen d'agents de contraste harmoniques
US7037264B2 (en) 2000-08-17 2006-05-02 Koninklijke Philips Electronics N.V. Ultrasonic diagnostic imaging with steered image plane
WO2008017997A2 (fr) 2006-08-11 2008-02-14 Koninklijke Philips Electronics, N.V. Système à ultrasons pour l'imagerie de la circulation sanguine cérébrale et la lyse de caillot sanguin au moyen de microbulles
US20100056924A1 (en) * 2006-11-20 2010-03-04 Koninklijke Philips Electronics N.V. Control and display of ultrasonic microbubble cavitation

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5181514A (en) 1991-05-21 1993-01-26 Hewlett-Packard Company Transducer positioning system
US5720291A (en) 1996-03-22 1998-02-24 Advanced Technology Laboratories, Inc. Three dimensional medical ultrasonic diagnostic image of tissue texture and vasculature
US6013032A (en) 1998-03-13 2000-01-11 Hewlett-Packard Company Beamforming methods and apparatus for three-dimensional ultrasound imaging using two-dimensional transducer array
US5997479A (en) 1998-05-28 1999-12-07 Hewlett-Packard Company Phased array acoustic systems with intra-group processors
US6530885B1 (en) 2000-03-17 2003-03-11 Atl Ultrasound, Inc. Spatially compounded three dimensional ultrasonic images
US7037264B2 (en) 2000-08-17 2006-05-02 Koninklijke Philips Electronics N.V. Ultrasonic diagnostic imaging with steered image plane
US6623432B2 (en) 2000-08-24 2003-09-23 Koninklijke Philips Electronics N.V. Ultrasonic diagnostic imaging transducer with hexagonal patches
US6723050B2 (en) 2001-12-19 2004-04-20 Koninklijke Philips Electronics N.V. Volume rendered three dimensional ultrasonic images with polar coordinates
WO2005074805A1 (fr) 2004-02-05 2005-08-18 Koninklijke Philips Electronics N.V. Imagerie ultrasonore d'irrigation et de debit sanguin au moyen d'agents de contraste harmoniques
WO2008017997A2 (fr) 2006-08-11 2008-02-14 Koninklijke Philips Electronics, N.V. Système à ultrasons pour l'imagerie de la circulation sanguine cérébrale et la lyse de caillot sanguin au moyen de microbulles
US20100056924A1 (en) * 2006-11-20 2010-03-04 Koninklijke Philips Electronics N.V. Control and display of ultrasonic microbubble cavitation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HODNETT AND B ZEQIRI M: "A detector for monitoring the onset of cavitation during therapy-level measurements of ultrasonic power", JOURNAL OF PHYSICS: CONFERENCE SERIES, INSTITUTE OF PHYSICS PUBLISHING, BRISTOL, GB, 1 January 2004 (2004-01-01), pages 112 - 117, XP007919966, ISSN: 1742-6596, DOI: 10.1088/1742-6596/1/1/027 *
M. HODNETT ET AL.: "A detector for monitoring the onset of cavitation during therapy-level measurements of ultrasonic power", JOURNAL OF PHYSICS: CONFERENCE SERIES, vol. 1, 2004, pages 112 - 17, XP007919966, DOI: doi:10.1088/1742-6596/1/1/027

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EP2962642A4 (fr) * 2013-02-28 2016-11-23 Alpinion Medical Systems Co Procédé de détection de cavitation et appareil médical ultrasonore correspondant
WO2015000953A1 (fr) 2013-07-03 2015-01-08 Bracco Suisse S.A. Dispositifs et procédés pour le traitement par ultrasons d'un accident cérébral ischémique
US10926112B2 (en) 2013-07-03 2021-02-23 Koninklijke Philips N.V. Devices and methods for the ultrasound treatment of ischemic stroke
WO2016075586A1 (fr) * 2014-11-14 2016-05-19 Koninklijke Philips N.V. Dispositif à ultrasons pour sonothrombolyse
US10799723B2 (en) 2014-11-14 2020-10-13 Koninklijke Philips N.V. Ultrasound device for sonothrombolysis therapy
DE102015003704A1 (de) * 2015-03-20 2016-09-22 Martin-Luther-Universität Halle-Wittenberg Kopfhalterung für Duplex- und Dopplersonden
CN105943087A (zh) * 2016-07-26 2016-09-21 飞依诺科技(苏州)有限公司 超声微泡空化设备的成像处理方法及处理系统
US11950958B2 (en) 2016-12-16 2024-04-09 Koninklijke Philips N.V. Adaptive pulsing for sonothrombolysis treatment
US11259781B2 (en) 2016-12-16 2022-03-01 Koninklijke Philips N.V. Adaptive pulsing for sonothrombolysis treatment
WO2018109652A1 (fr) * 2016-12-16 2018-06-21 Koninklijke Philips N.V. Impulsions adaptatives pour traitement par sonothrombolyse
CN111093520A (zh) * 2017-09-19 2020-05-01 医视特有限公司 局部空化信号测量
CN111093520B (zh) * 2017-09-19 2024-03-08 医视特有限公司 局部空化信号测量
FR3087642A1 (fr) 2018-10-24 2020-05-01 Commissariat A L'energie Atomique Et Aux Energies Alternatives Procede et systeme d'analyse spectrale et de determination d'un marqueur permettant d'assurer la securite d'interventions d'ultrasons therapeutiques
WO2020083725A1 (fr) 2018-10-24 2020-04-30 Commissariat A L'energie Atomique Et Aux Energies Procédé et système d'analyse spectrale et de détermination d'un marqueur permettant d'assurer la sécurité d'interventions d'ultrasons thérapeutiques
CN113015488A (zh) * 2018-10-24 2021-06-22 原子能和辅助替代能源委员会 用于谱分析和确定使得能够确保治疗性超声介入的安全性的标记的方法和系统
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CN111134719B (zh) * 2019-12-19 2021-01-19 西安交通大学 一种聚焦超声辐照相变纳米液滴的主被动超声复合成像方法及系统
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