WO2020128010A1 - Procédé et appareil pour imagerie de modulation radiale - Google Patents
Procédé et appareil pour imagerie de modulation radiale Download PDFInfo
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- WO2020128010A1 WO2020128010A1 PCT/EP2019/086745 EP2019086745W WO2020128010A1 WO 2020128010 A1 WO2020128010 A1 WO 2020128010A1 EP 2019086745 W EP2019086745 W EP 2019086745W WO 2020128010 A1 WO2020128010 A1 WO 2020128010A1
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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
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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
- A61B8/44—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device
- A61B8/4477—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device using several separate ultrasound transducers or probes
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- 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
- G01S15/8909—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using a static transducer configuration
- G01S15/8911—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using a static transducer configuration using a single transducer for transmission and reception
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- 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
- G01S15/8909—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using a static transducer configuration
- G01S15/8915—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using a static transducer configuration using a transducer array
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- 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
- G01S15/895—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques characterised by the transmitted frequency spectrum
- G01S15/8952—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques characterised by the transmitted frequency spectrum using discrete, multiple frequencies
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- 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
- G01S7/52019—Details of transmitters
- G01S7/5202—Details of transmitters for pulse systems
- G01S7/52022—Details of transmitters for pulse systems using a sequence of pulses, at least one pulse manipulating the transmissivity or reflexivity of the medium
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- 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
- G01S7/52039—Details of receivers using analysis of echo signal for target characterisation involving non-linear properties of the propagation medium or of the reflective target exploiting the non-linear response of a contrast enhancer, e.g. a contrast agent
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- 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
- G01S7/52079—Constructional features
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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
- A61B8/52—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
- A61B8/5246—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 combining images from the same or different imaging techniques, e.g. color Doppler and B-mode
- A61B8/5253—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 combining images from the same or different imaging techniques, e.g. color Doppler and B-mode combining overlapping images, e.g. spatial compounding
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- 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
- G01S15/8995—Combining images from different aspect angles, e.g. spatial compounding
-
- 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
- G01S15/8997—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using synthetic aperture techniques
Definitions
- the disclosure relates to methods and apparatus for radial modulation imaging.
- microbubbles were introduced as ultrasound contrast agents [Gramiak and Shah 1968] .
- the current generation of agents are formed by bubbles of perfluorocarbon gases, a few microns in size, which remain in the vasculature after being intravenously injected [Burns and Wilson 2006] .
- Their detection is based not only on the impedance mismatch between gas and liquid, but also due to their resonance in the MHz range.
- their oscillation become highly nonlinear in the diagnostic range of ultrasonic pressures and they can even be disrupted with sufficiently high pressure pulses [de Jong et al . 2002, Deng et al . 2002] .
- Microbubbles can emit harmonic components, as well as subharmonics and ultraharmonics, which falls at fraction multiple of the fundamental frequency.
- Harmonic imaging filters the echoes to extract only the content at twice the frequency of the excitation pulse to remove tissue signal [Schrope and al . 1993] .
- Different harmonic imaging schemes are now common today such as pulse inversion (PI), which implies emitting two successive pulses of inverted polarity [Hwang and al . 1999, Simpson and al . 1999, Burns and al . 2000] .
- PI pulse inversion
- linear tissue yields very limited signal while nonlinear microbubbles yield detectable signal.
- Amplitude modulation (AM) methods for which echoes from pulses of different amplitudes are combined, are also in use [Brock-Fisher and al . 1996, Caiani and al . 2001] . They can also be combined to PI methods [Eckersley and al . 2005] .
- PI methods [Eckersley and al . 2005] .
- subharmonic imaging As the nonlinear signal generated by tissue contains only harmonics components [Forsberg and al . 2000, Goertz and al . 2005] .
- the generation of very high ultraharmonics can also be implemented to separate microbubbles from tissue, allowing the reception of very high frequencies, resulting in excellent resolution as in ultrasound angiography [Gessner et al . 2013] .
- microbubbles detection approaches have been used. The oldest [Gramiak and Shah 1968] is the detection of the microbubble decorrelation through their motion. It was recently exploited for ultrasound localization microscopy [Couture et al . 2011, Errico et al . 2015, Couture et al . 2018] to detect microbubbles with respect to tissue before the localization step which improved the resolution by an order of magnitude as compared to the diffraction limit. For this, spatiotemporal filters were implemented on stacks of ultrafast imaging. Singular-value decomposition of large ensembles of ultrafast images was proved to be superior to nonlinear techniques for flow within the mm/s range, both in-vitro and the clinic [Desailly and al .
- RMI Radial modulation imaging
- a particular application of a dual frequency band technique is based on the observations of an increase of the microbubbles' amplitude in radio-frequency data in presence of a superimposed ultrasound excitations, say 10 MHz and 0.5 MHz [Deng et al . 2000] .
- a superimposed ultrasound excitations say 10 MHz and 0.5 MHz [Deng et al . 2000] .
- a low-frequency pulse induces oscillation of microbubbles and modify its size.
- the microbubbles are simultaneously interrogated using a high-frequency pulse (the imaging pulse) .
- RMI radial modulation on a single microbubble has an effect on microbubble's radius and echoes' amplitude [Bouakaz et al . 2004] .
- the predominant effect in RMI was found to be microbubble size and not microbubble resonance or compression-only effect [Emmer and al . 2009] . Simulations suggested that a 10% variation of bubble diameter induced by the modulation excitation is sufficient for radial modulation imaging [Cherin et al . 2008] .
- RMI showed a 35 dB microbubbles signal enhancement [Shariff et al . 2006] .
- Angelsen et al . [Angelsen et al . 2007, Hansen et al . 2009] demonstrated numerically that SURF imaging (RMI with a frequency separation between the modulation and the imaging pulses of a factor of 10) with correction of the dispersion of the imaging pulse by the modulation pulse provided higher contrast than PI.
- RMI SURF imaging
- the imaging pulse presented a distortion which was different than for conventional harmonic distortion [Hansen et al . 2011] .
- This technique showed promising results in-vitro with a 20 MHz single-element intravascular ultrasound catheter [Yu et al .
- Tanter M (2018), “Ultrasound localization microscopy and super-resolution: A state of the art", IEEE transactions on ultrasonics, ferroelectrics , and frequency control. Vol. 65(8), pp. 1304-1320. IEEE
- Embodiments described therein provide for enhanced methods and apparatus for radial modulation imaging.
- the radial modulation imaging method is particularly efficient and also simpler to implement compared to classical radial modulation imaging.
- the efficiency and accuracy of the method is obtained in particular because at least three different phases of the modulation of the microbubbles are interrogated by the unfocused ultrasonic pulses, thus avoiding the need to synchronize the unfocused ultrasonic pulses with a predetermined state of the microbubbles as in classical radial modulation imaging (notably compression and rarefaction phases and not between them) .
- the method of the present disclosure enables to obtain images in a very short time.
- the method may further include one and / or other of the following features:
- said bandpass filter has a bandpass of x.f ⁇ , x being comprised between 0.01 and 0.3;
- step (c) after being filtered by said bandpass filter, said set of basic data is multiplied by a sinusoidal signal at said modulation frequency and filtered by a lowpass filter having a cutoff frequency lower than the modulation frequency f2, thus obtaining said filtered data;
- said cutoff frequency is comprised between 0.05 and 0.2 times the modulation frequency f2;
- said modulation ultrasonic wave has a mechanical index MI comprised between 0.005 and 0.3, wherein:
- said modulation ultrasonic wave is a sinusoidal wave having a known phase
- said constant phases cp j are spread over the range 0-2n and a maximum difference between said constant phases cp being at least n/2;
- said microbubbles have a resonance frequency and said modulation frequency f is comprised between 0.3 and 3 times said resonance frequency;
- N is at least 500
- A 3;
- said medium is a living body having a vasculature and said microbubbles are contained in said vasculature;
- the method further comprises, before the filtering step (c) :
- said number A is 1 and said at least one image corresponds to said filtered basic data
- said number A is more than 1 and said at least one image is obtained by coherently summing said filtered basic data corresponding respectively to the propagation directions ;
- said basic data are said raw data and said imaging step (d) includes computing said at least one image from said filtered data by synthetic imaging;
- a set of images is obtained over time and said set of images is filtered by a bandpass filter around m.f2, wherein m is an integer equal to or larger than 2 such that m.f2 is lower than PRF/ (2.A.S), where PRF is a frequency of repetition of the unfocused ultrasonic pulses .
- an apparatus for radial modulation imaging including an array ultrasonic probe having a plurality of ultrasonic transducers (2a) and a modulation ultrasonic probe, said array ultrasonic probe and said modulation ultrasonic probe being both controlled by a control system which is adapted to perform:
- the apparatus may further include one and / or other of the following features:
- said bandpass filter has a bandpass of x.f2, x being comprised between 0.01 and 0.3;
- control system is adapted to, at step (c) , after filtering by said bandpass filter, multiplying said set of basic data by a sinusoidal signal at said modulation frequency f and filtering it by a lowpass filter having a cutoff frequency lower than the modulation frequency f 2 , thus obtaining said filtered data;
- said cutoff frequency is comprised between 0.05 and 0.2 times the modulation frequency f ;
- said modulation ultrasonic wave has a mechanical index MI comprised between 0.005 and 0.3, wherein:
- said modulation ultrasonic wave is a sinusoidal wave having a known phase
- said constant phases cp j are spread over the range 0-2n and a maximum difference between said constant phases cp being at least n/2;
- N is at least 500
- A 3;
- control system is adapted to, before the filtering step (c) :
- said number A is 1 and said at least one image corresponds to said filtered basic data
- said control system is adapted to obtained said at least one image by coherently summing said filtered basic data corresponding respectively to the propagation directions;
- said basic data are said raw data and at said imaging step (d) , the control system is adapted to compute said at least one image from said filtered data by synthetic imaging;
- the control system is adapted to obtain a set of images over time and to filter said set of images by a bandpass filter around m.f2, wherein m is an integer equal to or larger than 2 such that m.f2 is lower than PRF/ (2.A.S), where PRF is a frequency of repetition of the unfocused ultrasonic pulses.
- FIG. 1 is a schematic drawing showing an apparatus for radial modulation imaging
- FIG. 2 is a block diagram showing part of the apparatus of Figure 1;
- FIG. 3 is a schematic drawing illustrating operation of the apparatus of Figures 1-2;
- FIG. 4 is graph showing scattered pressure from simulations of a microbubble in MA (modulation of amplitude) imaging, microbubble disruption and RMI as a function of the mechanical index MI;
- the black and white rectangles correspond to the region of interest (ROI) of the vessel phantom and the agar, respectively.
- the scale bar represents 1 mm and the colorbar is in dB;
- the plain black and white rectangles correspond to the ROI of the vessel phantom and the agar, respectively.
- the dotted black and white rectangles correspond to the ROI in the center of the vessel phantom and the agar, respectively.
- the scale bar represents 1 mm and the colorbar is in dB .
- the dotted lines show the limits of the bandpass filter;
- the black and white rectangles correspond to the ROI of the vessel phantom and the agar, respectively.
- the scale bar represents 1 mm and the colorbar is in dB .
- the dotted lines show the limits of the bandpass filter;
- the black and white rectangles correspond to the ROI of the vessel phantom and the agar, respectively.
- the scale bar represents 1 mm and the colorbar is in dB .
- the dotted lines show the limits of the bandpass filter;
- the black and white rectangles correspond to the ROI of the vessel phantom and the agar, respectively.
- the scale bar represents 1 mm and the colorbar is in dB;
- the apparatus shown on Figures 1 and 2 is adapted to ultrafast radial modulation imaging of a medium 1.
- the medium 1 can be tissues of a living being, for instance a mammal and in particular a human.
- the apparatus may include for instance at least a ID or 2D array ultrasonic probe 2 having a plurality of ultrasonic transducers 2a and a modulation ultrasonic probe 11, said array ultrasonic probe 2 and said modulation ultrasonic probe 11 being both controlled by a control system 3 , 4 , 12.
- the array ultrasonic probe 2 may have for instance a few tens to a few thousands transducer elements 2a (T ki , or T k in the case of a ID probe) , with a pitch which can be for instance lower than 1mm.
- the transducer elements 2a of the array ultrasonic probe 2 may transmit for instance at a central imaging frequency fi comprised between 1 and 40 MHz, for instance of 15 MHz or close to 15 MHz.
- One example of usable array ultrasonic probe 2 is a 15 MHz linear (ID) transducer array from Vermon, France (128 elements, pitch: 0.11mm and bandwidth: 9-24 MHz at -10 dB) .
- the modulation ultrasonic probe 11 may further include at least one ultrasonic transducer T, or more, transmitting for instance at a central modulating frequency f2 comprised between 0.1 and 5 MHz, for instance 1 MHz or close to 1 MHz.
- a central modulating frequency f2 comprised between 0.1 and 5 MHz, for instance 1 MHz or close to 1 MHz.
- Such ultrasonic modulation probe 11 may be either unitary with or separate from the array ultrasonic probe 2.
- the imaging frequency fi is at least 4 times said modulation frequency f 2 .
- the imaging frequency fi is at least 10 times said modulation frequency f 2 .
- the control system may for instance include a specific control unit 3, a function generator 12 (FG) and a computer 4.
- FG function generator 12
- control unit 3 is used for controlling the array ultrasonic probe 2 and acquiring signals therefrom
- function generator 12 is used for controlling modulation ultrasonic probe 11 while the computer 4 is used for controlling control unit 3 and possibly function generator 11 (function generator 11 may also be autonomous and thus controlled independently of the control unit 3, provided the phase thereof remains constant), and generating image sequences from the signals acquired by control unit 3.
- control unit 3 could fulfill all the functionalities of control unit 3 and computer 4.
- control unit 3 or the above single electronic device could include the function generator 12.
- control unit 3 may include for instance (in the case of a n*n 2D array - the description would be the same, mutatis mutandis, in the case of a n ID array) :
- ADi j individually connected to the n transducers Tj j of 2D array ultrasonic probe 2;
- CPU central processing unit
- MEM memory 8
- DSP digital signal processor 9
- control unit 3 is 256 the Vantage ® system (Verasonics, Kirkland, WA) .
- array ultrasonic probe 2 may be controlled to transmit unfocused ultrasonic pulses at said imaging frequency fi in the medium 1, at a number A of propagation directions Pi.
- A is an integer which can be 1 or more, for instance not more than 25, in particular not more than 7.
- Each unfocused ultrasonic pulse can be in particular a plane ultrasonic wave.
- the propagation directions Pi may be defined by their respective angles eg with the normal N to the array ultrasonic probe 2.
- the angles eg are the respective inclinations of the plane waves with respect to the array ultrasonic probe 2, as shown on Figure 3.
- A 3 and the angles eg may be -10°, 0°, +10°.
- the array ultrasonic probe 2 is able to image a certain field Ci in the medium 1, in order to image blood vessels 21 in the medium 1 (including the smallest ones of very small diameter d) by detecting microbubbles 22 in the blood 23 of the blood vessels 21.
- the modulation ultrasonic probe 11 may be disposed to transmit the modulation ultrasonic wave, for instance a plane or diverging wave, in the medium 1, in a certain field C2 covering the field Ci at least in part.
- the modulation ultrasonic probe 11 may be controlled by the function generator 12 to transmit the modulation ultrasonic wave for instance as a sinusoidal wave of known phase, which is either continuous during all the acquisition or continuous at least during transmission of the unfocused ultrasonic pulses in the medium 1 by array ultrasonic probe 2.
- function generator 12 is the DG1022A, RIGOL, Beaverton, OR, USA.
- the modulation ultrasonic probe 11 may usually be required that the modulation ultrasonic probe 11 be inclined on the surface of the medium 1 so that the field C2 covers the field Ci, in which case this inclination can be obtained by any support 11a made in a material transparent to ultrasonic waves.
- the modulation ultrasonic wave has a mechanical index MI comprised between 0.005 and 0.3, wherein:
- MI P mg lJ (1) ,
- P ne g being the maximum negative pressure of the modulation ultrasonic wave in MPa and f2 being expressed in MHz.
- the microbubbles may be for instance Sonovue ® microbubbles (Bracco) .
- the microbubbles may have a resonance frequency and said modulation frequency f2 may be comprised between 0.3 and 3 times said resonance frequency. Operation - first mode :
- the apparatus may operate as follows.
- the array ultrasonic probe 2 and modulation ultrasonic probe 11 are placed on the surface of the medium 1. While the modulation ultrasonic probe 11 is controlled by the function generator 12 to transmit the modulation ultrasonic wave having the modulation frequency f2 in the medium 1, the array ultrasonic probe 2 is controlled by the control unit 3 to transmit the unfocused ultrasonic pulses having said imaging frequency fi in the medium 1.
- a series of unfocused (e.g. planar) ultrasonic pulses are transmitted at said number A of successive propagation directions Pi, and for the or each propagation direction, a number S of unfocused ultrasonic pulses are successively transmitted in the medium respectively at instants corresponding to constant phases cp of the modulation wave, j being an index comprised between 1 and
- the phases cp j may be spread over the range 0-2n.
- a maximum difference between said constant phases cpj may be at least n/2.
- the phases cpj may substantially equally spread over the range 0-2n.
- Each raw data set corresponds to one propagation direction Pi and one phase cp j .
- the acquired signals sensed by ultrasonic transducers 2a may be sampled for instance at 31.25 MHz.
- a number N of successive data frames is acquired in the acquisition step, corresponding to N images.
- N may be at least 20, for instance at least 500.
- a specific example of N is 1000.
- the raw data sets corresponding to the or each propagation direction Pi are then beamformed by the control system (e.g. by computer 4) as well known in the art
- set of basic data This set of beamformed data will be called hereafter "set of basic data”.
- Each of the A sets of basic data (corresponding respectively to the A propagation directions Pi) is then filtered over time by the control system (e.g. by computer 4), by a bandpass filter having a bandpass around the modulation frequency 2, thus obtaining filtered basic data .
- the bandpass filter may have a bandpass of x.f2, x being comprised between 0.01 and 0.3.
- the bandpass may be between 0.9 f2 and 1.1 f2.
- An example of bandpass filter usable here is a butterworth filter with cut-off frequencies of 0.9 f2 and 1.1 f2 with an order of 48.
- each set of basic data after being filtered by said bandpass filter, each set of basic data may be multiplied by a sinusoidal signal at said modulation frequency f2 and filtered by a lowpass filter having a cutoff frequency lower than the modulation frequency f2, thus obtaining a set of filtered basic data for each propagation direction Pi (the whole filtering process then forms a lock-in amplifier) .
- Said cutoff frequency may be comprised between 0.05 f2 and 0.2 f , for instance 0.1 f2 .
- An example of lowpass filter usable here is a butterworth filter with cut-off frequency of 0.1 f2 with an order of 48.
- At least one image is then created by the control system (e.g. by computer 4) on the basis of said filtered basic data.
- the control system e.g. by computer 4
- said at least one image corresponds to said filtered basic data.
- said at least one image in practice a set of N images over time is 5 obtained by coherently summing said sets of filtered basic data corresponding respectively to the A different propagation directions.
- the set of images may also be filtered over time by a bandpass filter around m.f2, wherein m is an integer 35 equal to or larger than 2, thus obtaining multiband uRMI .
- the number m may be:
- the number m is such that m.f2 is lower than
- PRF/ (2.A.S) where PRF is a pulse frequency repetition of the unfocused ultrasonic pulses.
- the filtering step could be applied to the successive sets of raw data without beamforming.
- the method could be as follows:
- the acquisition step of the second mode may be the same as in the first mode.
- the beamforming step is omitted before filtering.
- the A sets of raw data corresponding respectively to the A propagation directions Pi constitute the A sets of basic data which are filtered in step (c) .
- Each set of basic data is then filtered over time by the control system (e.g. by computer 4), as described for the first mode.
- At least one image is then created by the control system (e.g. by computer 4) on the basis of said filtered basic data.
- said at least one image is obtained by beamforming as well known in the art (beamforming in reception) .
- said at least one image is obtained by synthetic imaging (also called compound imaging) as taught for instance in the publications cited in step (d) of the first mode.
- the set of images may also be filtered over time by a bandpass filter around m.f2, wherein m is an integer equal to or larger than 2, thus obtaining multiband uRMI .
- the number m may be:
- the number m is such that m.f2 is lower than PRF/ (2.A.S), where PRF is a pulse frequency repetition of the unfocused ultrasonic pulses.
- Tests were made with an experimental setup in which Sonovue microbubbles (Bracco) , diluted at 1/3000 (with an approximate concentration of 30,000 to 16.104 microbubbles/mL) circulated at a flow rate between 0 and 20 mL/min in a 2 mm diameter vessel phantom by syringe pump or by gravity.
- the flow rate was determined by measuring the volume of outflow over 1 minute of flow. To guarantee the absence of flow when required, the flow was stopped 30 seconds before acquisition.
- This microbubble wall-less vessel phantom was included in a 4 cm thick 5% (w/w) agar phantom comprising 1% (w/w) sigma-cell (20 pm particles, Sigma-Aldrich, Saint Louis, MO) to mimic tissue scattering.
- a 15 MHz linear transducer array (Vermon, France, 128 elements, pitch: 0.11mm and bandwidth: 9-24 MHz at -10 dB) was placed above the agar phantom and a 1-MHz modulation transducer was positioned next to it, in a way that their pressure fields overlapped at the vessel phantom location.
- the pulse-repetition-frequency (PRF) was of 1/ (60 ps) .
- the imaging voltage was 300 kPa peak-negative pressure.
- Ultrafast radial-modulation imaging consisted in addressing the microbubbles at different stage of their oscillations. Several numbers of microbubble modulation- states were tested, each fitted within the same imaging angle.
- the low- frequency was generated, via the 1-MHz transducer, by a function generator (DG1022A, RIGOL, Beaverton, OR, USA) .
- the low-frequency was chosen in a way that high-frequency pulses every 60 ps reached microbubble in 3, 4, 5 or 10 modulation-states and the corresponded frequencies were 0.988889, 1.004167, 1.003333 and 1.001667 MHz, respectively.
- the amplitude pressures of the low-frequency were between 50 and 250 kPa.
- a lock-in amplifier was implemented on the channel data in the slow time.
- the demodulation process consisted to filter each channel data around the modulation frequency using a bandpass filter (using a butterworth filter with cut-off frequencies of 0.9 and 1.1 time the modulation frequency with an order of 48) .
- the modulation frequency is the sampling frequency in the slow time divided by the number of microbubble modulation- states.
- the filtered signals were multiplied with a sinusoidal signal at the modulation frequency before to be filtered by a lowpass filter in the slow time (butterworth filter with a cut-off frequency of 0.1 time the sampling frequency with an order of 48) .
- Reconstruction of images was performed by combining coherently the summing angles.
- the beamformed images were also filtered at the modulation frequency multiplied by 2 (for 5 and 10 microbubbles modulation-states), 3 (for 10 microbubbles modulation-states) and 4 (for 10 microbubbles modulation-states) .
- the reconstructed set of images correspond to the product of the filtered images for the modulation frequency and its multiples.
- the amplitudes of the signal in the agar and in the vessel phantom were estimated for the sum in intensity of these 1000 processed images. Acquisitions were repeated 3 times .
- the uRMI results were compared with other techniques to detect microbubbles: amplitude modulation, microbubbles disruption and SVD spatiotemporal filter.
- a Verasonic plane-waves amplitude modulation sequence with the 15-MHz transducer was implemented. In this sequence for each angles of each image with an amplitude of 300 kPa, 3 pulses were defined: a first 1 cycle 15 MHz pulses with all elements, a second with only odd elements and a third with only even elements.
- the amplitude modulation image was estimated by subtracting the RF data from odd and even elements to the image with all elements prior to beamforming these different images.
- the PRF was 1/ (3*60) ps, the same as PRF from uRMI imaging for 3 angles. One thousand images were acquired and the amplitude of the signal in the agar and in the vessel phantom were estimated for the sum in intensity of these 1000 images. Acquisitions were repeated 3 times. 2) Microbubble disruption
- the contrast-to-tissue ratio obtained by microbubbles disruption should be the difference in contrast in presence to in absence of microbubbles.
- 1000 images were acquired before and after microbubbles injection in the vessel phantom.
- the amplitude of the signal in the agar and in the vessel phantom were estimated on the sum in intensity of the images before microbubbles injection and on the sum in intensity of images after microbubble injection.
- the microbubble contrast corresponding to the subtraction of the contrast-to-tissue ratio after injection to the microbubble contrast before injection.
- the ROI used were two times smaller than for amplitude modulation, uRMI or SVD filterting in order to limit the presence of artefacts in the vessel ROI. In comparison, the other techniques naturally limit the amplitude of the phantom.
- a set of 1000 ultrafast Bmode images were obtained. From these Bmode images, the vessel phantom and a phantom location were determined. The selected vessel and phantom region-of-interest had the same dimensions and the same depth.
- the uRMI technique was applied in presence and absence of microbubbles, with and without low-frequency excitation to evaluate their effect on the modulation and demodulation process.
- Example of microbubbles images acquired are presented in Figure 6.
- microbubbles in the vessel phantom are clearly observed in the image ( Figure 6 (b) ) .
- Figure 6 (c) When the sum of the 1000 images is used, the entire vessel phantom is well defined in the uRMI image ( Figure 6 (c) ) .
- microbubbles Figure 6d) and (e)
- low-frequency excitation Figure 6(d) and (f)
- microbubbles cannot be detected.
- the corresponded contrast-to-tissue ratios are listed in Table 1.
- the contrast-to-tissue ratio in the Bmode image shows an increase around 3 dB .
- the contrast-to-tissue ratio for uRMI is close to 0 dB .
- the contrast-to-tissue ratio for uRMI is 2.41 dB without microbubbles and 12.65 dB with microbubbles.
- Table 1 Contrast-to-tissue ratio between microbubbles in the vessel and the phantom for a 3 angles high-frequency excitation to evaluate the modulation/demodulation process: with and without microbubbles and with and without a low- frequency excitation (4 microbubble modulation-states, 100 kPa) .
- contrast-to-tissue ratio is slightly higher for flow speed until 5 mL/min, and the decrease of contrast-to-tissue ratio with flow speed is more pronounced.
- the contrast-to-tissue ratio was estimated with other techniques and compared to the contrast-to-tissue ratio obtained with uRMI for 4 modulation-states, 3 angles high- frequency excitation and a 100 kPa low-frequency excitation. Amplitude modulation was applied for the same amplitude of excitation of the high-frequency than the one used for uRMI, 300 kPa.
- the SVD filter was applied on acquisitions with the same conditions as for uRMI but without low-frequency excitation. Microbubbles maximum contrast after their disruption was evaluated by acquiring an image without microbubbles and with microbubbles, without flow only. Results are presented in Figure 12 as well as example of images obtained with these techniques.
- SVD filter provided higher contrast-to-tissue ratios than other techniques (around 16 to 17 dB in our conditions) .
- uRMI provided the best contrast-to-tissue ratio (around 10 dB) . Contrast-to-tissue ratios obtained with amplitude modulation were close to 4 dB and close to 6 dB for microbubbles disruption.
- a lock-in amplifier selective bandpass filter combined with a demodulation stage
- a selective bandpass filter without demodulation stage allowed to increase the relative contrast-to-tissue ratio from 26 to 48 % on average (examples are presented on Fig. 13), and up to 65%.
- the lock-in amplifier was particularly interesting for the low amplitudes of the modulation excitation, a limited number of compounding angles and modulation states, along with the slow flow.
- the microbubbles videos obtained after demodulation with the lock-in amplifier presented fewer artifacts as compared to a simple bandpass filter.
- the minimum number of images for the lock-in amplifier was 144 (defined by the Matlab® functions used) .
- the number of images may be optimized as a function of the number of modulation states, angles and imaging depth, to attain sufficient image repetition frequency.
- the increase in the number of images led to an increase of microbubbles contrast (Fig. 14 (b) ) .
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Abstract
Des impulsions ultrasonores non focalisées présentant une certaine fréquence d'imagerie f1 sont transmises dans un milieu contenant des microbulles selon un certain nombre A de directions de propagation (Pi), tandis qu'au moins une onde ultrasonore de modulation présentant une fréquence de modulation f2 inférieure est transmise dans le milieu, et des données brutes provenant des ondes ultrasonores rétrodiffusées sont acquises. Pour chaque direction de propagation (Pi), un certain nombre S d'impulsions sont successivement transmises dans le milieu (1), respectivement selon des phases constantes φj de l'onde de modulation, et les signaux rétrodiffusés correspondants sont acquis. Ensuite, un ensemble de données de base correspondant aux données brutes pour chaque direction de propagation (Pi) est filtré au fil du temps par un filtre passe-bande autour de la fréquence de modulation f2, et une image est créée à partir des données filtrées.
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