WO2023025165A1 - 基于超声成像的聚焦超声治疗系统 - Google Patents

基于超声成像的聚焦超声治疗系统 Download PDF

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WO2023025165A1
WO2023025165A1 PCT/CN2022/114344 CN2022114344W WO2023025165A1 WO 2023025165 A1 WO2023025165 A1 WO 2023025165A1 CN 2022114344 W CN2022114344 W CN 2022114344W WO 2023025165 A1 WO2023025165 A1 WO 2023025165A1
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blood flow
image
treatment
imaging
unit
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PCT/CN2022/114344
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French (fr)
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许凯亮
付亚鹏
郁钧瑾
郭星奕
闫少渊
他得安
王威琪
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复旦大学
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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
    • A61B8/06—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
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the present application relates to the field of ultrasound imaging therapy, in particular to focused ultrasound therapy technology based on ultrasound imaging.
  • High-intensity focused ultrasound (HIFU) technology is an ultrasonic treatment technology for the treatment of tumors, masses, nodules, polyps, etc. It has the advantages of non-invasive, non-radiation and relatively cheap.
  • High-intensity focused ultrasound utilizes the characteristics of strong ultrasound penetration and good directionality, and focuses the sound energy to the target area through ultrasound focusing, and causes coagulation necrosis of the target tissue through thermal effects and mechanical effects to achieve the purpose of treatment.
  • Magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) are usually used to locate the treatment area and monitor the treatment effect, but there are still some challenges in clinical use, including treatment
  • MRI Magnetic resonance imaging
  • PET positron emission tomography
  • CT computed tomography
  • the dynamic monitoring of the area and imaging area is difficult, the imaging speed is limited, the portability is not strong, the treatment area cannot be displayed in real time and the treatment process planning, and the detection cost is high.
  • the purpose of this application is to provide a focused ultrasound treatment system based on ultrasound imaging, which can realize dynamic and precise treatment of lesions under the cooperation of a focused ultrasound unit and an ultrasound imaging unit.
  • the present application discloses a focused ultrasound treatment system based on ultrasound imaging, including:
  • the focused ultrasound unit is configured to emit focused ultrasound to the lesion area for treatment
  • the ultrasound imaging unit is configured to transmit imaging ultrasound to the imaging area and receive corresponding echoes after the treatment, and obtain corresponding vascular blood flow images based on the echo imaging;
  • the area planning and parameter adjustment unit is configured to redefine the lesion area based on the vascular blood flow image and readjust the treatment parameters of the focused ultrasound unit for the next treatment of the redefined lesion area, the
  • the imaging area includes the lesion area.
  • the ultrasonic frame rate emitted by the ultrasonic imaging unit is ⁇ 200 frames/s, and the imaging frame rate is ⁇ 50 frames/s;
  • the vascular blood flow image is a microvascular blood flow image, and the microvascular blood flow imaging resolution is ⁇ emits ultrasonic wavelengths.
  • the area planning and parameter adjustment unit is further configured to determine the corresponding vascular blood flow network profile and corresponding vascular density indicators, blood flow velocity indicators, and blood flow indicators according to the vascular blood flow image, and Redefine the lesion area according to the outline of the vascular blood flow network and score the lesion status of the redefined lesion area according to one or more of the blood vessel density index, blood flow velocity index, and blood flow index, and The scoring result is compared with the expected result, and the treatment parameters of the focused ultrasound unit are readjusted according to the comparison result for the next treatment of the redefined lesion area.
  • the area planning and parameter adjustment unit is further configured to determine the outline of the vascular blood flow network and the direction of blood flow in the redefined lesion area according to the vascular blood flow image, and The flow network outline and the blood flow direction plan the treatment route for the next treatment of the redefined lesion area by the focused ultrasound unit.
  • system further includes an image input unit and an image fusion unit;
  • the image input unit is configured to input and obtain a registration reference image and input it to the image fusion unit, and the image fusion unit is configured to perform registration fusion of the blood vessel blood flow image and the registration reference image, Obtaining a registration fusion image; and, the area planning and parameter adjustment unit is further configured to redefine the lesion area according to the registration fusion image and readjust the treatment parameters of the focused ultrasound unit for the next time Treatment of delineated lesion areas.
  • the area planning and parameter adjustment unit is further configured to: according to the vascular blood flow network contour corresponding to the registration fusion image and the corresponding vascular density index, blood flow velocity index, and blood flow index, and according to The outline of the vascular blood flow network redefines the lesion area and scores the lesion state of the redefined lesion area according to one or more of the blood vessel density index, blood flow velocity index, and blood flow index, and the score The results are compared with the expected results, and the treatment parameters of the focused ultrasound unit are readjusted according to the comparison results for the next treatment of the redefined lesion area.
  • the area planning and parameter adjustment unit is further configured to perform binarization processing on the vascular blood flow image to obtain the outline of the vascular blood flow network;
  • the region planning and parameter adjustment unit is further configured to calculate the blood flow velocity index based on the super-resolution vascular blood flow image according to the quotient of the length of the tracer sub-trajectory and the time it takes the tracer to move along the trajectory, or obtain the blood flow velocity index from The blood flow velocity index is directly obtained from the power Doppler blood vessel blood flow image or the color Doppler blood vessel blood flow image;
  • the area planning and parameter adjustment unit is further configured to determine the center position points S(x, y) of each vessel blood flow in the vessel blood flow network outline based on the vessel blood flow network outline and obtain each center position point S
  • the area planning and parameter adjustment unit is further configured to be based on the quotient of the vascular blood flow image area formed by the vascular blood flow network outline and the current imaging image area, or the vascular blood flow image volume formed by the vascular blood flow network outline
  • the blood vessel density index is obtained by calculating the quotient with the volume of the current imaging volume.
  • the area planning and parameter adjustment unit is further configured to determine the outline of the vascular blood flow network and the direction of blood flow in the redefined lesion area according to the registration fusion image, and The flow network outline and the blood flow direction plan the treatment route for the next treatment of the redefined lesion area by the focused ultrasound unit.
  • the ultrasound imaging unit is further configured to transmit imaging ultrasound to the imaging area and receive corresponding echoes after the treatment, and obtain corresponding B-mode images based on the echo imaging, based on the The B-mode image is used to obtain the vascular blood flow image.
  • the ultrasound imaging unit is further configured to perform clutter filtering, red blood cell or tracer location tracking on the B-mode image, and detect blood vessels in the B-mode image according to the location tracking results.
  • the blood flow image is reconstructed to obtain a corresponding super-resolution vascular blood flow image, wherein the tracer is introduced into the vascular blood flow by intravenous injection after each treatment.
  • the ultrasound imaging unit is further configured to perform clutter filtering, quadrature demodulation, and frequency shift analysis on the B-mode image to obtain a corresponding power Doppler vascular blood flow image or color Doppler blood flow images of blood vessels.
  • the focused ultrasound unit, the ultrasound imaging unit, and the region planning and parameter adjustment unit sequentially operate one cycle as one treatment cycle, and each treatment stage includes a plurality of iterative cycles;
  • the ultrasound imaging unit is also configured to transmit imaging ultrasound to the imaging region and receive corresponding echoes before the treatment of the first treatment cycle in each treatment stage, and obtain corresponding B- mode image, obtaining a vascular blood flow image based on the B-mode image; and, the area planning and parameter adjustment unit is further configured to define a corresponding initial lesion area and set the focused ultrasound unit according to the vascular blood flow image initial treatment parameters.
  • system further includes an image fusion unit
  • the ultrasonic imaging unit transmits imaging ultrasound to the imaging area and receives corresponding echoes before the treatment of the first treatment cycle in each treatment stage, and obtains a corresponding B-mode image based on the echo imaging, based on The B-mode image obtains a vascular blood flow image, and the image fusion unit performs registration and fusion on the vascular blood flow image and the registration reference image received from the image input unit to obtain a registration fusion image, and the region planning and parameters
  • the adjustment unit defines the corresponding initial lesion area according to the registration fusion image and sets the initial treatment parameters of the focused ultrasound unit.
  • the registration reference image is one or more of the following:
  • the B-mode image, computed tomography image, positron emission computed tomography PET image, nuclear magnetic resonance image, X-ray computed tomography image, nuclear magnetic resonance image and X-ray computed tomography image under the cooperation of contrast agent and in Vascular images obtained from MRI images with contrast agents.
  • the treatment parameters include the focal length of the focused ultrasound, the sound intensity in the focal region, the size of the focal spot, the transmission frequency, the transmission power, the duty cycle, and the treatment duration.
  • the implementation of the present application can be used for hemodynamic analysis and functional analysis of the treatment area, and provides a new method for studying the micro-blood flow changes and therapeutic effects in the lesion area in the application of high-intensity focused ultrasound in the treatment of various lesions. At least include the following advantages:
  • the ultrasound imaging unit and the focused ultrasound unit are alternately operated in sequence, and the changes in the blood vessel blood flow in the lesion area are monitored in real time and the lesion state is calculated according to the change in the blood vessel blood flow.
  • the Determine the corresponding vascular blood flow network outline and corresponding vascular density index, blood flow velocity index, blood flow index, blood flow direction index according to the vascular blood flow image and redefine the lesion area according to the vascular blood flow network outline and according to One or more of the blood vessel density index, blood flow velocity index, and blood flow index score the lesion state of the redefined lesion area, compare the scoring result with the expected result, and readjust the
  • the treatment parameters of the focused ultrasound unit are used for the next treatment of the redefined lesion area. In this way, the dynamic monitoring of the changes in the whole process of the lesion area is realized, and the treatment parameters of the focused ultrasound are adaptively adjusted according to the real-time monitoring results of the lesion state until the treatment effect of the lesion area reaches the expectation.
  • the specific acquisition methods of blood flow velocity index, blood flow index, blood flow direction and blood vessel density index are proposed to quantify the scoring and lesion changes and improve the accuracy of treatment.
  • Ultrasound images after clutter signal separation, generate dynamic changes in vascular blood flow, which can more accurately and clearly present changes in microvascular blood flow under high-intensity focused ultrasound treatment, and can achieve 100 frames per second to tens of thousands of frames
  • Real-time imaging per second, B-mode images and color Doppler ultrasound multi-modal ultrasound imaging can also be performed according to treatment needs, and MRI, PET, CT images and ultrasound images can be fused and registered, combining the advantages of ultra-fast ultrasound imaging with HIFU technology Combined to improve the imaging effect.
  • MRI, PET, CT and other methods it has the advantages of fast imaging speed, portable equipment, low cost and no ionizing radiation.
  • the ultrafast ultrasound imaging method based on multi-angle acoustic wave composite imaging can significantly improve the temporal and spatial resolution of imaging, and has great potential in real-time monitoring of the therapeutic effect of high-intensity focused ultrasound.
  • Fig. 1 is a schematic structural diagram of a focused ultrasound therapy system based on ultrasound imaging according to an embodiment of the present application.
  • Fig. 2 is a working sequence diagram of each unit of the focused ultrasound treatment system based on ultrasound imaging involved in the present application.
  • Fig. 3 is a schematic structural diagram of a focused ultrasound therapy system based on ultrasound imaging according to another embodiment of the present application.
  • FIG. 4 is a flow chart of the operation process of the focused ultrasound therapy system based on ultrasound imaging in the embodiment of FIG. 3 .
  • Fig. 5 is a diagram of the arrangement of ultrasonic probes in an experiment for the treatment of brain lesions in rats.
  • FIG. 6 is a two-dimensional ultrafast ultrasonic power Doppler microvascular blood flow image after clutter filtering before treatment in the example of treating a rat brain lesion in Example 1.
  • FIG. 6 is a two-dimensional ultrafast ultrasonic power Doppler microvascular blood flow image after clutter filtering before treatment in the example of treating a rat brain lesion in Example 1.
  • Fig. 7 is an ultrafast ultrasonic power Doppler microvascular blood flow two-dimensional image after treating the same area of the rat brain as in Fig. 6 in the example of treating a rat brain lesion in Example 1.
  • Fig. 8 is an ultrafast ultrasonic color Doppler microvascular blood flow two-dimensional image in the treatment example for rat brain lesions in Example 1 before treatment after clutter filtering.
  • Fig. 9 is an ultrafast ultrasonic color Doppler microvascular blood flow two-dimensional image after treating the same area of the rat brain as in Fig. 8 in the example of treating a rat brain lesion in Example 1.
  • Fig. 10 is a schematic diagram of the three-dimensional imaging construction in the treatment example for rat brain lesions.
  • Fig. 11 is a three-dimensional ultrafast ultrasonic power Doppler microvascular blood flow image after clutter filtering before treatment in the example of treating a rat brain lesion in Example 1.
  • Fig. 12 is an ultrafast ultrasonic power Doppler microvascular blood flow three-dimensional image after treating the same area of the rat brain as in Fig. 11 in the example of treating a rat brain lesion in Example 1.
  • Fig. 13 is a schematic diagram of the fusion image A before treatment obtained by image fusion of the microvascular blood flow image before treatment in Fig. 6 and the B-mode image before treatment in the example of treatment for rat brain lesions in Example 1.
  • Fig. 14 is a schematic diagram of the fused image B after treatment obtained by image fusion of the microvascular blood flow image after treatment in Fig. 7 and the B-mode image after treatment in the example of treatment for rat brain lesions in Example 1.
  • Fig. 15 is a two-dimensional ultrafast ultrasonic power Doppler microvascular blood flow image after clutter filtering before treatment in the example of treating a rat brain lesion in Example 2.
  • Fig. 16 is an ultrafast ultrasonic power Doppler microvascular blood flow two-dimensional image after treating the same area of the rat brain in Fig. 15 in the example of treating a rat brain lesion in Example 2.
  • Fig. 17 is an ultrafast ultrasonic color Doppler microvascular blood flow two-dimensional image in the treatment example for rat brain lesions in Example 2 before treatment after clutter filtering.
  • Fig. 18 is an ultrafast ultrasonic color Doppler microvascular blood flow two-dimensional image after treating the same area of the rat brain in Fig. 17 in the example of treating a rat brain lesion in Example 2.
  • Fig. 19 is a super-resolution ultrasonic localization microscopic imaging blood flow density diagram in the example of treatment for rat brain lesions in Example 2 before treatment after clutter filtering.
  • Fig. 20 is a super-resolution ultrasound localization microscopic imaging blood flow density map after treating the same area of the rat brain as in Fig. 19 in the example of treating the rat brain lesion in Example 2.
  • Fig. 21 is a super-resolution ultrasound localization microscopic imaging blood flow diagram in the example of treatment for rat brain lesions in Example 2 before treatment after clutter filtering.
  • Fig. 22 is a super-resolution ultrasonic localization microscopic imaging blood flow diagram after treating the same area of the rat brain as in Fig. 21 in the example of treating the rat brain lesion in Example 2.
  • Fig. 23 is a super-resolution ultrasonic localization microscopic imaging blood flow velocity diagram in the example of treating a rat brain lesion in Example 2 before treatment after clutter filtering.
  • Fig. 24 is a super-resolution ultrasonic localization microscopic imaging blood flow velocity map after treating the same area of the rat brain as in Fig. 23 in the example of treating the rat brain lesion in Example 2.
  • Fig. 25(a) is an enlarged image obtained by selecting a part of Fig. 19 .
  • Fig. 25(b) is a diagram of the amplitude variation of the position indicated by the white horizontal line in Fig. 25(a).
  • Fig. 26 is a three-dimensional image of ultrafast ultrasound power Doppler microvascular blood flow in the tumor before treatment in the example of mouse melanoma treatment.
  • Fig. 27 is a three-dimensional image of ultrafast ultrasound power Doppler microvascular blood flow of tumor after treatment in the example of mouse melanoma treatment.
  • FIG. 28 is a schematic diagram of a motion calibration process for an example microvascular blood flow image.
  • Fig. 29(a) is an example blood flow velocity profile before treatment.
  • Figure 29(b) is an example blood flow velocity profile after treatment.
  • Fig. 30 is a diagram showing the results of vascular blood flow contour extraction in an example vascular blood flow image.
  • Fig. 31(a) is a diagram of the three-dimensional tissue imaging results obtained by the three-dimensional probe with a center frequency of 6.25 MHz.
  • Fig. 31(b) is a diagram of three-dimensional tissue imaging results obtained by a three-dimensional probe with a center frequency of 3 MHz.
  • Ultrasonic tracer a small-sized scatterer that can swim with the blood flow in the blood vessel, and can generate scattered echo signals under the action of ultrasound.
  • red blood cells inherent in blood vessels other cells that can be injected into blood vessels, yeast cells or various types of cells after gene editing, etc.
  • artificial materials with biocompatibility such as ultrasonic microbubble contrast agents, hydrogen peroxide bubbles, nano-liquids Drip and so on.
  • Point spread function The sound field distribution formed by a single scatterer (such as an ultrasonic tracer) in the sound field after image reconstruction is called the point spread function, also known as the point spread function.
  • Focal length the distance from the focal point to the center point of the emitting element of the ultrasonic probe.
  • Ultrasonic probe also known as ultrasonic transducer array or ultrasonic probe array, related terms are different expressions of the same concept, specifically, one or more ultrasonic array elements are used, and the delay can be adjusted by a digital control unit to realize tissue
  • the device at least has the functions of transmitting and collecting ultrasonic signals.
  • Focal Sound Intensity The sound field strength in the focal area.
  • Focal spot size Or called the horizontal size of the focal area and the vertical size of the focal area, it is a parameter describing the focal area of HIFU.
  • HIFU focuses on one area, which is called the focal spot.
  • Duty cycle In a pulse cycle, the ratio of the system power-on time to the total time.
  • Image registration also known as displacement correction, during the imaging process, because the probe and the measured object have been relative to each other, especially in in-body experiments, the image displacement caused by factors such as respiration and heartbeat will affect the image quality. Therefore, image registration or displacement correction needs to be performed to compensate for the relative displacement between the probe and the measured object, so that clear imaging results can be obtained.
  • the first embodiment of the present application relates to a focused ultrasound treatment system based on ultrasound imaging. Its structural schematic diagram is shown in FIG. 1 , and the system includes a focused ultrasound unit, an ultrasound imaging unit, and an area planning and parameter adjustment unit. Specifically described as:
  • the focused ultrasound unit is configured to emit focused ultrasound to the lesion area for treatment.
  • the focused ultrasound unit processes one or more array elements through spatial or time-delayed focusing, so as to be configured to emit focused ultrasound to the lesion area to achieve local acoustic energy enhancement for treatment.
  • the treatment may be performed along the lesion area in an automatic planning manner, or the lesion area may be treated in a pre-arranged (manual) manner.
  • the ultrasound imaging unit is configured to transmit imaging ultrasound to the imaging area and receive corresponding echoes after the treatment, and obtain corresponding blood flow images of blood vessels based on the echo imaging.
  • the ultrasound imaging unit includes a B-mode imaging unit, and the B-mode imaging unit is configured to transmit imaging ultrasound to the imaging area and receive corresponding echoes after the focused ultrasound unit performs treatment.
  • the ultrasound imaging unit obtains a blood vessel blood flow image based on the B-mode image.
  • the B-mode imaging unit preferably emits a group of plane waves or curved surface acoustic waves with multiple deflection angles into the imaging area.
  • the vascular blood flow image in this application may be a two-dimensional or three-dimensional image.
  • the implementation of the three-dimensional image of the vascular blood flow image is, for example, as follows: as shown in FIG. Obtain three-dimensional images of blood vessels.
  • the implementation of the three-dimensional image of the real-time scanned vascular blood flow image is, for example: as shown in Figure 31, the system also includes a two-dimensional ultrasound array unit for real-time three-dimensional imaging; the two-dimensional ultrasound array unit is configured to be Control the delay of each array element and receive echoes ultra-fast, and obtain three-dimensional imaging.
  • the vascular blood flow image may be a microvascular blood flow image.
  • the B-mode imaging unit emits ultrasound with a frame rate of ⁇ 200 frames/s, and an imaging frame rate of ⁇ 50 frames/s.
  • the imaging resolution of microvascular blood flow ⁇ the emitted ultrasound wavelength .
  • the B-mode imaging unit emits ultrasound with a frame rate ⁇ 200 frames/s, and an imaging frame rate ⁇ 50 frames/s.
  • the vascular blood flow image can be super-resolution High-resolution microvascular blood flow images, microvascular blood flow imaging resolution ⁇ 1/50 of the emitted ultrasonic wavelength.
  • the ultrasound imaging unit also includes a filter impurity removal unit, a location tracking unit, and a super-resolution ultrasound imaging unit.
  • the imaging unit performs clutter filtering on the B-mode image by the filtering and impurity removal unit, and the location tracking unit tracks the red blood cells or tracers in the filtered image, and the super-resolution ultrasound imaging unit according to the location tracking result
  • the vascular blood flow image in the B-mode image is reconstructed to obtain a corresponding super-resolution vascular blood flow image, wherein the tracer is introduced into the vascular blood flow by intravenous injection after each treatment.
  • the ultrasonic imaging unit further includes a filtering unit and an ultrasonic Doppler imaging unit, the filtering unit performs clutter filtering on the B-mode image, and the ultrasonic Doppler imaging unit The unit performs quadrature demodulation and frequency shift analysis on the filtered B-mode image to obtain a corresponding power Doppler blood flow image or color Doppler blood flow image.
  • the super-resolution ultrasound imaging unit uses the ultrasonic tracer swimming in the blood vessel as a strong scattering source, and detects the point spread function of a single tracer from the B-mode image collected by ultrafast ultrasound;
  • the central position of the diffusion function is used as the anchor point of the tracer;
  • the positions of each tracer in each frame image are paired and connected to determine the trajectory of each tracer movement;
  • the length of the tracer track is divided by The time taken for the tracer to move along the trajectory can be used to obtain the blood flow velocity in the blood vessel that the ultrasonic tracer swims through; the blood vessel can be reconstructed by accumulating the trajectory of each tracer in thousands to millions of frames of images Super-resolution images of structures.
  • the super-resolution here refers to the center positioning of the spread function of the tracer sub-point, and the positioning accuracy obtained is much better than the wavelength of the emitted acoustic wave.
  • blood vessel density images based on tracers or the number and density of red blood cells blood flow density images that distinguish ascending blood flow and descending blood flow, and blood flow velocity images.
  • Blood flow density image based on the number of tracers or red blood cells the intensity value of each pixel in the image depends on the number of tracers or red blood cells passing through the pixel, representing blood flow; blood flow that distinguishes ascending blood flow from descending blood flow
  • Flow density image the intensity value of each pixel in the image depends on the number of upward or downward tracers or red blood cells passing through the pixel, and the upward or downward is distinguished by two different colors
  • blood flow velocity image in the image The intensity value of each pixel is determined by the average velocity of tracers or red blood cells passing through that pixel, representing blood flow velocity.
  • the area planning and parameter adjustment unit is configured to redefine the lesion area based on the vascular blood flow image (two-dimensional or three-dimensional image, etc.) and readjust the treatment parameters of the focused ultrasound unit for the next redefined lesion
  • the imaging area includes the lesion area.
  • the treatment parameters are, for example but not limited to, the probe parameters of the focused ultrasound unit, including one or more of the focal length of the focused ultrasound, the sound intensity in the focal region, the size of the focal spot, the transmission frequency, the transmission power, the duty cycle, and the treatment duration. indivual.
  • the area planning and parameter adjustment unit is further configured to determine the corresponding vascular blood flow network profile and the corresponding vascular density index, blood flow velocity index, blood flow index, and redefine the lesion area according to the outline of the vascular blood flow network, and score the lesion state of the redefined lesion area according to one or more of the vessel density index, blood flow velocity index, and blood flow index , comparing the scoring result with the expected result, and readjusting the treatment parameters of the focused ultrasound unit according to the comparison result for the next treatment of the redefined lesion area.
  • the area planning and parameter adjustment unit is further configured to determine, according to the vascular blood flow image (two-dimensional or three-dimensional image, etc.) The outline of the vascular blood flow network and the direction of blood flow plan a treatment route for the focused ultrasound unit to treat the newly defined lesion area next time.
  • the system further includes an image input unit and an image fusion unit, the image input unit is configured to input a registration reference image to the image fusion unit, and the image fusion unit is configured to use the vascular blood flow image (two-dimensional or three-dimensional image, etc.) and the registration reference image are registered and fused to obtain a registered fused image.
  • the image input unit is configured to input a registration reference image to the image fusion unit
  • the image fusion unit is configured to use the vascular blood flow image (two-dimensional or three-dimensional image, etc.) and the registration reference image are registered and fused to obtain a registered fused image.
  • the registration reference image may be, for example but not limited to, the B-mode image obtained by the aforementioned B-mode imaging unit, or a computed tomography image, a positron emission computed tomography PET image, a nuclear magnetic resonance image, an X-ray Computed tomography images, nuclear magnetic resonance images, X-ray computed tomography images with contrast agents, blood vessel images and other mode images obtained from nuclear magnetic resonance images with contrast agents.
  • the area planning and parameter adjustment unit may also be configured to: according to the vascular blood flow network contour corresponding to the registration fusion image and the corresponding vascular density index, blood flow velocity index, and blood flow index, and according to the vascular
  • the outline of the blood flow network redefines the lesion area and scores the lesion state of the redefined lesion area according to one or more of the vascular density index, blood flow velocity index, and blood flow index, and compares the scoring results with the expected results A comparison is made, and the treatment parameters of the focused ultrasound unit are readjusted according to the comparison result for the next treatment of the redefined lesion area.
  • the area planning and parameter adjustment unit is further configured to perform binarization processing on the vascular blood flow image to obtain the outline of the vascular blood flow network.
  • the above-mentioned "according to one or more of the blood vessel density index, blood flow velocity index, and blood flow index to score the lesion state of the redefined lesion area", for example, can be based on all the indicators.
  • the lesion state of the defined lesion area can be scored, and the lesion state of the redefined lesion area can also be scored according to some indicators (for example, only the blood vessel density index and the blood flow index).
  • the scoring method may be, but not limited to: pre-setting scores according to the size of each indicator and assigning corresponding weights to each indicator. The summed value.
  • the sum of each score can be calculated after scoring each indicator separately to obtain the scoring result.
  • the scoring result may also be obtained by performing weighted summation on the blood vessel density index, blood flow velocity index, and blood flow index.
  • all scoring results calculated based on the blood vessel density index, blood flow velocity index, and blood flow index are within the protection scope of the present application.
  • the above-mentioned blood vessel density index refers to the proportion of blood vessel area or volume in a unit space, that is, blood vessel area or volume/space area or volume;
  • the blood flow velocity index refers to the average blood flow of the defined lesion area speed, etc.;
  • the blood flow index refers to the average blood flow of the demarcated lesion area, etc.
  • the acquisition methods of the blood vessel density index, blood flow velocity index, and blood flow index are as follows 123: 1
  • the region planning and parameter adjustment unit is based on the super-resolution blood vessel blood flow image, according to the length of the tracer sub-trajectory
  • the blood flow velocity index is obtained by calculating the quotient with the time taken for the tracer to move along the trajectory, or the blood flow velocity index is directly obtained from a power Doppler blood vessel blood flow image or a color Doppler blood vessel blood flow image.
  • the V/V 0 value may be further divided into multiple different scoring intervals.
  • the quotient of the area of the vascular blood flow image formed by the area planning and parameter adjustment unit according to the outline of the vascular blood flow network and the area of the current imaging image, or the volume of the vascular blood flow image formed by the outline of the vascular blood flow network and the current is calculated to obtain the blood vessel density index.
  • ⁇ the blood vessel density ⁇ of this area can be obtained.
  • the value of ⁇ is between 0 and 1, 1 means that the whole area is full of blood vessels, and 0 means that the area has no blood vessels.
  • the ratio of ⁇ to ⁇ 0 during treatment can be used for normalized evaluation The degree of treatment, so as to complete the dynamic treatment planning and treatment process.
  • the value of ⁇ / ⁇ 0 can be further divided into multiple different scoring intervals, etc.
  • the area planning and parameter adjustment unit is further configured to determine the vascular blood flow network outline and blood flow direction in the redefined lesion area according to the registration fusion image, and determine the vascular blood flow network outline and blood flow direction according to the vascular blood flow network outline and The flow direction plans the treatment route for the next treatment of the redefined lesion area by the focused ultrasound unit.
  • the system may also include a display unit for displaying the vascular blood flow image (two-dimensional or three-dimensional image, etc.) output by the ultrasound imaging unit and/or the fused image output by the image fusion unit for manual adjustment of the treatment probe and/or Or the position and angle of the imaging probe.
  • a display unit for displaying the vascular blood flow image (two-dimensional or three-dimensional image, etc.) output by the ultrasound imaging unit and/or the fused image output by the image fusion unit for manual adjustment of the treatment probe and/or Or the position and angle of the imaging probe.
  • the focused ultrasound unit, the ultrasound imaging unit, and the region planning and parameter adjustment unit sequentially operate a cycle as a treatment cycle, and each treatment stage includes a plurality of iterative cycles, as shown in Figure 2, where the timing only Represents related basic logic.
  • the ultrasound imaging unit is also configured to transmit imaging ultrasound to the imaging region and receive corresponding echoes before the treatment of the first treatment cycle in each treatment stage, and obtain the corresponding B based on the echo imaging.
  • -mode image obtaining a vascular blood flow image (two-dimensional or three-dimensional image, etc.) based on the B-mode image; ) delineate the corresponding initial lesion area and set the initial treatment parameters of the focused ultrasound unit.
  • the ultrasonic imaging unit transmits imaging ultrasound to the imaging area and receives corresponding echoes before the treatment of the first treatment cycle in each treatment stage, and obtains a corresponding B-mode image based on the echo imaging, based on
  • the B-mode image obtains a vascular blood flow image (two-dimensional or three-dimensional image, etc.); and the image fusion unit performs registration fusion on the blood vessel blood flow image (two-dimensional or three-dimensional image, etc.) and a registration reference image;
  • the area planning and parameter adjustment unit defines the corresponding initial lesion area according to the registration fusion image and sets the initial treatment parameters of the focused ultrasound unit.
  • the registration reference image can be, for example but not limited to, B-mode image, computed tomography image, positron emission computed tomography PET image, nuclear magnetic resonance image, X-ray computerized tomography image, nuclear magnetic resonance image and contrast imaging Blood vessel images obtained from X-ray computed tomography images with contrast agents and nuclear magnetic resonance images with contrast agents, etc.
  • FIG. 3 an embodiment of a focused ultrasound treatment system based on vascular blood flow imaging is shown. As shown in Figure 3, it specifically includes the following parts:
  • the computer control terminal is an implementation of the regional planning and parameter adjustment unit. After each ultrasound imaging and before high-intensity focused ultrasound treatment, the system uses the computer control terminal to configure the signal transmitting/receiving module to adjust the imaging frame rate, imaging depth, ultrasound deflection angle and other parameters of the ultra-fast ultrasound imaging unit to stimulate the ultrasound transducer
  • the device emits a group of ultrasonic waves with multiple deflection angles (preferably plane waves or curved surface acoustic waves) into the imaging area, and observes the micro blood flow images of the treatment area (or lesion area) and surrounding normal tissues.
  • ultrasound images image registration and fusion can be performed with images obtained by existing imaging methods such as MRI, PET, and CT to obtain multi-modal images to enhance the observation effect of the treatment area and surrounding tissues; according to ultrasound images or multi-modal Ultrasound images can be used to judge blood flow changes in the lesion area, analyze the treatment effect in this area, and dynamically adjust the treatment parameters such as the ultrasound emission intensity, duration, frequency, and excitation mode of the high-intensity focused ultrasound unit in real time, thereby changing the overall mechanical index of the system. , MI), thermal index (thermal index, TI), spatial peak time average sound intensity (spatial temporal average intensity, Ispta), spatial peak pulse average intensity (spatial peak pulse average intensity, Isppa), etc. Treatment.
  • MI thermal index
  • TI spatial peak time average sound intensity
  • Ispta spatial peak pulse average intensity
  • Isppa spatial peak pulse average intensity
  • High-intensity focused ultrasound unit including waveform generator, power amplifier and high-intensity focused ultrasound probe.
  • the waveform generator can receive the trigger signal, waveform setting, sound field strength, frequency and other control signals from the computer control terminal and generate ultrasonic signals in corresponding timing;
  • the power amplifier is used to provide power output for the high-intensity focused ultrasound probe;
  • the high-intensity focused ultrasound probe Used to transmit ultrasound to the treatment area.
  • Ultrafast ultrasonic imaging unit Compared with the conventional ultrasonic imaging system of 100 frames per second, the imaging frame rate of the ultrafast ultrasonic imaging unit can range from 100 frames per second to tens of thousands of frames per second, specifically including: signal transmission / receiving module, array ultrasonic transducer and software processing module. It is used to sample and store ultrasonic radio frequency echo signals reflected or backscattered within a certain period of time in the imaging area; for example, beamforming, coherent compounding, image registration, Clutter filtering, orthogonal demodulation, image generation, and real-time display of ultrafast power Doppler and ultrafast color Doppler blood flow changes in the treatment area on the monitor.
  • beamforming, coherent compounding, image registration, clutter filtering, quadrature demodulation, ultrasonic tracer positioning, and ultrasonic tracer tracking can be performed on the collected ultrasonic radio frequency echo signals through the software processing module , super-resolution image reconstruction, generate super-resolution images, and perform blood flow density images based on the number of ultrasonic tracers in the treatment area on the monitor, blood flow density images that distinguish ascending blood flow and descending blood flow, and blood flow velocity images display.
  • the signal transmitting/receiving module may further include a waveform generator, a D/A converter, an A/D converter, a data memory, a signal amplifier, etc.; according to the current imaging sequence, after the waveform generator generates a signal of a specific waveform and frequency, the The D/A converter is converted into an analog signal, and after passing through the signal amplifier, the ultrasonic transducer is excited to excite the ultrasonic pulse signal, and the pulse transmission time interval is greater than the longest time required for the ultrasonic wave to go back and forth in the target imaging area once; according to the established imaging Depth, amplifies, samples and stores ultrasonic radio frequency echo signals for a period of time after the ultrasonic signal is transmitted.
  • a waveform generator after the waveform generator generates a signal of a specific waveform and frequency, the The D/A converter is converted into an analog signal, and after passing through the signal amplifier, the ultrasonic transducer is excited to excite the ultrasonic pulse signal, and the pulse transmission time interval is greater than
  • the array ultrasonic transducer can not only vibrate to generate ultrasonic signals under the excitation of electrical signals, but also receive ultrasonic signals and convert them into electrical signals; in order to achieve imaging in a certain area, it is often necessary to use multiple ultrasonic transducer array elements
  • Ultrasonic transducer arrays include commonly used ultrasonic probes such as one-dimensional linear array probes, convex array probes, and two-dimensional area array probes. The present invention does not limit the types of ultrasonic transducer arrays used.
  • the software processing module may further include a beamforming module, a coherent compounding module, an image registration module, a clutter filtering module, and an orthogonal demodulation module; image, the beamforming algorithm includes a time-delay superposition algorithm, a frequency domain-beam domain migration algorithm for beamforming, etc.; preferably, coherently compounding a group of images obtained by a single or multiple deflection angle planes or curved surface acoustic waves can effectively improve The signal-to-noise ratio and resolution of the image to obtain a high-quality B-mode ultrasonic image; when sampling the ultrasonic radio frequency echo signal, preferably, use 2 times, 3 times or 4 times or more of the center frequency of the transmitted signal as the sampling frequency, Thereby, the band-pass signal (RF) with the carrier frequency of the center frequency can be obtained, the carrier signal is filtered out by the quadrature demodulation step, and the in-phase component and the quadrature component (IQ) are obtained; during the imaging process, the probe and the measured object There
  • image
  • Fig. 4 is the operation flow diagram of the treatment system of the embodiment shown in Fig. 3, comprises the following steps:
  • step 401 the ultrasonic imaging unit emits imaging ultrasound to the imaging area, obtained by ultrasonic Doppler imaging or super-resolution ultrasonic imaging Microvascular blood flow image; then enter step 402, determine the corresponding vascular blood flow network profile and corresponding vascular density index, blood flow velocity index and blood flow index, demarcate the lesion area according to the outline of the vascular blood flow network, and score the lesion state of the demarcated lesion area according to one or more of the blood vessel density index, blood flow velocity index, and blood flow index Then enter step 403 to judge whether the scoring result has reached the expected therapeutic effect; if not, then enter step 404, under the guidance of the microvascular blood flow image or fusion image, emit high-intensity focused ultrasound to the lesion area, otherwise the treatment ends. Wherein, after the step 404, return to the step 401 until whether the scoring result reaches the expected therapeutic effect.
  • ultrasound Doppler imaging or super-resolution ultrasound imaging can be manually selected to obtain microvascular blood flow images according to needs, and for example, the initial treatment cycle can be configured at each treatment stage to select super High-resolution ultrasound imaging is used for imaging and treatment, and subsequent treatment cycles are configured to select ultrafast ultrasound imaging or ultrasound Doppler imaging for imaging and treatment.
  • imaging ultrasound can be emitted to the imaging area to obtain a B-mode image
  • super-resolution ultrasound imaging or ultrasound Doppler imaging can be selected based on the B-mode image to obtain a microvascular blood flow image .
  • imaging ultrasound is emitted to the imaging area and imaged to obtain a B-mode image
  • power Doppler and color Doppler microvascular blood flow images are obtained based on the obtained B-mode image.
  • imaging ultrasound can also be emitted to the imaging area and imaged to obtain a B-mode image.
  • ultra- High-resolution microvascular blood flow images Based on the obtained B-mode image, ultra- High-resolution microvascular blood flow images. For example, if ultrasonic tracers are injected, imaging ultrasound is emitted to the imaging area and imaged to obtain a B-mode image. Super-resolution microvascular blood flow images can be obtained through ultrasonic tracer positioning, tracking, and image reconstruction.
  • This example uses the focused ultrasound therapy system based on ultrasound imaging of this application to perform high-intensity focused ultrasound treatment and imaging experiments on the blood flow in the brain of adult rats and surrounding tissues, but the application is not limited to rat brains Department of therapy and imaging.
  • the specific operation steps are as follows:
  • the high-intensity focused ultrasound probe used in this example is a single-element probe with a center frequency of 956kHz and a focal length of 6.0mm. In practical applications, according to the size and intensity of different treatment areas, high-intensity focused ultrasound probes with different center frequencies, focal lengths, and array elements can be freely selected.
  • the ultrasonic probe is connected with the multi-channel ultrasonic transmitting and receiving equipment.
  • the depth of the imaging area is d
  • the total length of the probe array is L
  • the propagation speed of ultrasound in soft tissue is c
  • the shortest time interval between two transmissions of ultrasonic plane waves is
  • the number of a group of inclined plane waves is N
  • the highest frame rate is In practical applications, according to the size and intensity of different treatment areas, ultrasonic imaging probes with different center frequencies, focal lengths, and array elements are selected.
  • the frequency domain-beam domain migration algorithm is used for beamforming, and the stored echo signals are used for image reconstruction. Then, the 23 images reconstructed from the echo signals of plane waves with 23 deflection angles in each group were coherently combined to obtain a high-quality ultrasonic B-mode image.
  • the composite imaging frame rate is 500 Hz
  • the sampling time is 0.6 s
  • a total of 300 composite images can be obtained. Parameters for image reconstruction such as imaging frame rate and sampling time can be selected according to actual needs.
  • the singular value decomposition method is used for clutter filtering.
  • ⁇ is a diagonal matrix with dimension (n x ⁇ n z , n t ), and the number on the diagonal is the singular value of Y.
  • U and V are orthogonal identity matrices with two-dimensional scales (n x ⁇ n z ,n x ⁇ n z ) and (n t ,n t ) respectively, and their column vectors correspond to the space and time domains of Y The singular value vector of .
  • U i (x, z) and V i (t) respectively represent the column vectors in the matrices U and V in the formula (1) corresponding to the singular value ⁇ i .
  • the dynamic blood flow signal extracted after clutter filtering is processed by orthogonal demodulation, frequency shift analysis, modulus, logarithm, etc., and the contrast is adjusted to obtain the power Doppler two-dimensional imaging results before treatment, as shown in Figure 6
  • the display and color Doppler two-dimensional imaging results are shown in Figure 8.
  • a three-dimensional mobile unit as shown in FIG. 10 is set, and the power Doppler three-dimensional imaging result of imaging the same area of the rat brain by clamping and controlling the imaging probe by the three-dimensional mobile unit is shown in FIG. 11 .
  • the above-mentioned Figures 6, 8, and 11 can all clearly show the microvascular blood flow images of the rat brain before the high-intensity focused ultrasound, and the three-dimensional imaging results are better than the two-dimensional imaging results.
  • Quadrature demodulation can get IQ signal.
  • the image data after the clutter filtering is a band-pass signal with the center frequency fc , the data is multiplied by After low-pass filtering, the low-pass signal IQ after quadrature demodulation can be obtained, the real part is the in-phase component I, and the imaginary part is the quadrature component Q:
  • Ultrasonic power Doppler imaging Based on the B-mode image obtained by the ultrafast ultrasonic imaging unit, through clutter filtering and orthogonal demodulation, the corresponding Doppler vascular blood flow image is obtained.
  • PDI represents the power Doppler blood flow image
  • NF is the number of frames used for the original image
  • f c is the center frequency of the transmitted ultrasonic signal.
  • ⁇ represents the time interval between two frames of images.
  • the Doppler velocity can be given by the formula Calculated, the obtained Doppler velocity is greater than 0, which means moving towards the probe direction, and less than 0, which means moving away from the probe direction, and PRF is the pulse transmission frequency.
  • the high-intensity focused ultrasound probe used destroys (or treats) the tissue on the left side of the rat brain on the same plane as the ultrafast ultrasound imaging probe.
  • the excitation signal amplitude is 30V
  • the frequency is 956kHz
  • the action time is 150s
  • the focus is located 2mm below the left cerebral cortex of the rat.
  • the ultrafast ultrasonic imaging unit obtains the microvascular blood flow image, and determines the corresponding blood vessel density, blood flow change, blood flow velocity, etc. based on the microvascular blood flow image indicators, and then calculate the treatment effect (that is, the tissue destruction effect) of the treatment area based on these indicators, and adjust the treatment parameters of the focused ultrasound unit adaptively according to the treatment effect, so as to realize the interaction between the high-intensity focused ultrasound unit and the ultrafast ultrasound imaging unit.
  • the treatment effect that is, the tissue destruction effect
  • the fusion image A before treatment obtained by image fusion of the microvascular blood flow image before treatment in Figure 6 and the B-mode image before treatment, and the microvascular blood flow image after treatment in Figure 7 and The fused image B after treatment obtained by image fusion of the B-mode image after treatment (as shown in Figure 14) compares the fused images A and B, and it can be seen that the fused image obtained according to the embodiment of the present application is compared with The microvascular blood flow image before fusion is clearer, so the accuracy of indicators such as blood vessel density, blood flow change, and blood flow velocity can be further improved, thereby improving the accuracy of the calculated treatment effect and the accuracy of the adjusted treatment parameters.
  • the present application is not limited to the treatment and imaging of rat brains, as it can also be used for the treatment and imaging of tumors.
  • the ultrafast ultrasound power Doppler microvascular blood flow three-dimensional image of the tumor before the treatment of mouse melanoma and the three-dimensional ultrafast ultrasound power Doppler microvascular blood flow of the tumor after the treatment of mouse melanoma image.
  • This example uses the focused ultrasound therapy system based on ultrasound imaging of this application to perform high-intensity focused ultrasound treatment and imaging experiments on the blood flow in the brain of adult rats and surrounding tissues, but the application is not limited to rat brains Department of therapy and imaging.
  • the specific operation steps are as follows:
  • Probe placement Fix the probe of the high-intensity focused ultrasound unit and the probe of the ultrafast ultrasound imaging unit on the same vertical plane, place the ultrasound probe for imaging directly above the head of the rat, and place the high-intensity focused ultrasound probe for treatment on one side , the angle between the high-intensity focused ultrasound probe and the vertical direction can be changed according to the requirements, as shown in Figure 5, and the medical ultrasonic coupling agent is used for coupling.
  • the high-intensity focused ultrasound probe used in this example is a single-element probe with a center frequency of 967kHz and a focal length of 6.0mm. In practical applications, according to the size and intensity of different treatment areas, high-intensity focused ultrasound probes with different center frequencies, focal lengths, and array elements can be freely selected.
  • the ultrasonic probe is connected with the multi-channel ultrasonic transmitting and receiving equipment.
  • the depth of the imaging area is d
  • the total length of the probe array is L
  • the propagation speed of ultrasound in soft tissue is c
  • the shortest time interval between two transmissions of ultrasonic plane waves is
  • the number of a group of inclined plane waves is N
  • the highest frame rate is In practical applications, according to the size and intensity of different treatment areas, ultrasonic imaging probes with different center frequencies, focal lengths, and array elements are selected.
  • the Delay And Sum (DAS) algorithm is used for beamforming, and the stored echo signals are used for image reconstruction. Then, the 21 images reconstructed from the echo signals of plane waves at each group of 21 deflection angles are coherently combined to obtain a high-quality ultrasonic B-mode image.
  • the composite imaging frame rate is 500 Hz
  • the sampling time is 0.4 s
  • a total of 200 composite images can be obtained. Parameters for image reconstruction such as imaging frame rate and sampling time can be selected according to actual needs.
  • ⁇ is a diagonal matrix with dimension (n x ⁇ n z , n t ), and the number on the diagonal is the singular value of Y.
  • U and Y are orthogonal identity matrices with two-dimensional scales (n x ⁇ n z ,n x ⁇ n z ) and (n t ,n t ) respectively, and their column vectors correspond to the space and time domains of Y The singular value vector of .
  • the singular values are distributed from large to small.
  • the singular values corresponding to the tissue signal are larger, the singular values of the noise signal are smaller, and the singular values in the middle correspond to the blood flow dynamic signal.
  • the microvascular blood flow image is obtained.
  • U i (x, z) and V i (t) respectively represent the column vectors in the matrices U and V in the formula (1) corresponding to the singular value ⁇ i .
  • the dynamic blood flow signal extracted after clutter filtering is processed by orthogonal demodulation, frequency shift analysis, modulus, and logarithm, and the contrast is adjusted to obtain the power Doppler two-dimensional imaging results before treatment, as shown in Figure 15.
  • the display and color Doppler two-dimensional imaging results are shown in Figure 17. Both Figure 15 and Figure 17 above can clearly show the microvascular blood flow images of rat brains before the action of high-intensity focused ultrasound.
  • the intensity value of the ultrasonic tracer is an intensity profile centered on its maximum value, and the intensity gradient of each point always points to the maximum value.
  • the method locates this center (ie, is orthogonal to the gradient) by minimizing the distance from the center to the equipotential line.
  • This example tracks ultrasound tracers using the Kuhn-Munkres algorithm based on the Hungarian distribution method.
  • the algorithm calculates the distance between each ultrasound tracer and all ultrasound tracers in the next frame, and minimizes the total distance, thus connecting all the locations of the ultrasound tracers to form a trajectory.
  • the blood flow density image based on the number of ultrasonic tracers before treatment is obtained as shown in Figure 19
  • the blood flow density image for distinguishing ascending blood flow and descending blood flow is shown in Figure 21
  • the blood flow velocity image is shown in Figure 23 .
  • the above-mentioned Figures 19, 21, and 23 can display the microvascular blood flow images of rat brains before the action of high-intensity focused ultrasound with very high resolution.
  • the extraction of related blood vessel parameters includes: as shown in Figure 29, a schematic diagram of blood flow velocity measurement results is given, (a) is the blood flow velocity distribution map in the blood vessel before treatment; (b) blood flow in the blood vessel after treatment Velocity profile.
  • the gray value corresponds to the blood flow velocity in the blood vessel at different positions.
  • the outline extraction of the blood vessel image can obtain the outline of the blood vessel network, calculate the ratio of the area or volume of the local blood vessel image to the total image area or volume space, and determine the radius and density index of the blood vessel.
  • the blood flow velocity image can be obtained through Doppler imaging processing; the blood flow index can be obtained by time integrating the blood flow velocity image.
  • HIFU treatment the ultrasonic tracer has been injected.
  • a high-intensity focused ultrasound probe is used to examine the left side of the brain tissue of the rat on the same plane as the ultrafast ultrasonic imaging probe. To destroy (or heal). Using sine wave excitation, the excitation signal amplitude is 30V, the frequency is 967kHz, the action time is 90s, and the focus is located 2mm below the left cerebral cortex of the rat.
  • the ultrafast ultrasonic imaging unit obtains the microvascular blood flow image, and determines the corresponding blood vessel density, blood flow change, blood flow velocity, etc. based on the microvascular blood flow image indicators, and then calculate the treatment effect (that is, the tissue destruction effect) of the treatment area based on these indicators, and adjust the treatment parameters of the focused ultrasound unit adaptively according to the treatment effect, so as to realize the interaction between the high-intensity focused ultrasound unit and the ultrafast ultrasound imaging unit.
  • the treatment effect that is, the tissue destruction effect
  • Figure 25(a) is an enlarged image of a selected area in Figure 19, and the three curves in Figure 25(b) correspond to the amplitude changes at the three white horizontal lines in Figure 25(a), and the three horizontal lines
  • the thread passes through three blood vessels respectively.
  • the widths of blood vessel 1 and blood vessel 2 are 16 microns and 21 microns respectively.
  • the super-resolution microvascular blood flow image can distinguish blood vessels within 20 microns; blood vessel 3 has two bifurcations The distance between the blood vessels is 40 microns, and the super-resolution microvascular blood flow images can also be resolved.
  • an action is performed according to a certain element, it refers to the meaning of performing the action based on at least the element, which includes two situations: performing the action only based on the element and performing the action based on the element and other The element performs the behavior.
  • Expressions such as multiple, multiple, and multiple include 2, 2 times, 2 types, and 2 or more, 2 or more times, or 2 or more types.

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Abstract

一种基于超声成像的聚焦超声治疗系统，包括：聚焦超声单元，被配置为向病灶区域发射聚焦超声波进行治疗；超声成像单元，被配置为在治疗后，发射成像超声波至成像区域并接收相应的回波，基于回波成像得到对应的血管血流图像；区域规划与参数调整单元，被配置为基于血管血流图像重新划定病灶区域以及重新调整聚焦超声单元的治疗参数，以用于下一次对重新划定的病灶区域的治疗，成像区域包含病灶区域。

Description

基于超声成像的聚焦超声治疗系统 技术领域
本申请涉及超声成像治疗领域，特别涉及基于超声成像的聚焦超声治疗技术。
背景技术
高强度聚焦超声(High intensity focused ultrasound，HIFU)技术是一种用于肿瘤、肿块、结节、息肉组织等治疗的一种超声治疗技术，具有无创、无辐射及相对价廉等优势。高强度聚焦超声利用超声穿透性强、方向性好等特点，通过超声聚焦的方式将声能汇聚到目标区域，通过热效应、机械效应等使目标组织发生凝固性坏死而达到治疗的目的。
目前高强度聚焦超声技术已经被广泛应用于肌瘤、肿瘤、帕金森和遗传性震颤等疾病治疗中。通常采用核磁共振成像(MRI)、正电子发射计算机断层显像(PET)和计算机断层扫描(CT)等技术来定位治疗区域、监测治疗效果，但目前临床使用中仍存在一定挑战，具体包括治疗区域与成像区域动态监测困难、成像速度有限、便携性不强、无法实时呈现治疗区域并进行治疗过程规划、检测成本较高等问题。
发明内容
本申请的目的在于提供一种基于超声成像的聚焦超声治疗系统，实现聚焦超声单元和超声成像单元的配合下对病灶的动态精准治疗。
本申请公开了一种基于超声成像的聚焦超声治疗系统，包括：
聚焦超声单元，被配置向病灶区域发射聚焦超声波进行治疗；
超声成像单元，被配置为在所述治疗后，发射成像超声波至成像区域并接收相应的回波，基于所述回波成像得到对应的血管血流图像；
区域规划与参数调整单元，被配置为基于所述血管血流图像重新划定病灶区域以及重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗，所述成像区域包含所述病灶区域。
在一个优选例中，所述超声成像单元发射的超声波帧率≥200帧/s，成像帧率≥50帧/s；所述血管血流图像为微血管血流图像，微血管血流成像分辨率≤发射超声波波长。
在一个优选例中，所述区域规划与参数调整单元还被配置为根据所述血管血流图像确定对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据所述血管血流网络轮廓重新划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据比较结果重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
在一个优选例中，所述区域规划与参数调整单元还被配置为根据所述血管血流图像确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据所述血管血流网络轮廓和血流方向规划治疗路线以用于所述聚焦超声单元下一次对重新划定的病灶区域的治疗。
在一个优选例中，所述系统还包括图像输入单元和图像融合单元；
所述图像输入单元被配置为输入获取配准参考图像并输入至所述图像融合单元，所述图像融合单元被配置为将所述血管血流图像和所述配准参考图像进行配准融合，得到配准融合图像；以及，所述区域规划与参数调整单元还被配置为根据所述配准融合图像重新划定病灶区域以及重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
在一个优选例中，所述区域规划与参数调整单元还被配置为根据所述配准融合图像对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据所述血管血流网络轮廓重新划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据所述比较结果重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
在一个优选例中，所述区域规划与参数调整单元还被配置为对所述血管血流图像进行二值化处理，得到所述血管血流网络轮廓；
所述区域规划与参数调整单元还被配置为基于超分辨率血管血流图像，根据示踪子轨迹的长度与示踪子沿轨迹运动所用时间的商计算得到所述血流速度指标，或者从功率多普勒血管血流图像或彩色多普勒血管血流图像中直接获取所述血流速度指标；
所述区域规划与参数调整单元还被配置为基于所述血管血流网络轮廓确定所述血管血流网络轮廓中各血管血流的中心位置点S(x,y)并获取各中心位置点S(x,y)处的血管血流半径r(x,y)，根据公式Q＝∑ s(x,y)v(x,y)*πr(x,y) 2计算得到所述血流量指标；
所述区域规划与参数调整单元还被配置为根据所述血管血流网络轮廓形成的血管血流图像面积与当前成像图像面积的商、或者所述血管血流网络轮廓形成的血管血流图像体积与当前成像体空间体积的商计算得到所述血管密度指标。
在一个优选例中，所述区域规划与参数调整单元还被配置为根据所述配准融合图像确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据所述血管血流网络轮廓和血流方向规划治疗路线以用于所述聚焦超声单元下一次对重新划定的病灶区域的治疗。
在一个优选例中，所述超声成像单元还被配置为在所述治疗后，发射成像超声波至成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到所述血管血流图像。
在一个优选例中，所述超声成像单元还被配置为对所述B-mode图像进行杂波滤除、红细胞或示踪子定位追踪，根据定位追踪结果对所述B-mode图像中的血管血流图像进行重建，得到对应的超分辨率血管血流图像，其中所述示踪子在每次治疗后通过静脉注射的方式引入血管血流中。
在一个优选例中，所述超声成像单元还被配置为对所述B-mode图像进行杂波滤除、正交解调、频移分析，得到对应的功率多普勒血管血流图像或彩色多普勒血管血流图像。
在一个优选例中，所述聚焦超声单元、所述超声成像单元和所述区域规划与参数调整单元顺序操作一个循环为一个治疗周期，每个治疗阶段包含迭代的多个循环；
所述超声成像单元还被配置为在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至所述成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到血管血流图像；以及，所述区域规划与参数调整单元还被配置为根据该血管血流图像划定对应的初始病灶区域和设置所述聚焦超声单元的初始治疗参数。
在一个优选例中，所述系统还包括图像融合单元；
所述超声成像单元在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至所述成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到血管血流图像，所述图像融合单元将该血管血流图像和接收自图像输入单元的配准参考图像进行配准融合得到配准融合图像，所述区域规划与参数调整单元根据该配准融合图像划定对应的初始病灶区域和设置所述聚焦超声单元的初始治疗参数。
在一个优选例中，所述配准参考图像为以下的一者或多者：
所述B-mode图像、计算机断层显像图像、正电子发射计算机断层扫描PET图像、核磁共振图像、X射线计算机断层扫描图像、核磁共振图像与在造影剂配合下X射线计算机断层扫描图像和在造影剂配合下的核磁共振图像所获得的血管图像。
在一个优选例中，所述治疗参数包括聚焦超声的焦距、焦域声强、焦斑尺寸、发射频率、发射功率、占空比、治疗时长。
本申请的实施方式可以用于治疗区域的血流动力学分析和功能分析，为研究高强度聚焦超声在各类病灶治疗等应用中的病灶区域微血流变化和治疗效果提供了新的方法，至少包括以下优点：
(1)在实施高强度聚焦超声治疗过程中，按照超声成像单元与聚焦超声单元交替时序操作，通过实时监测病灶区域的血管血流的变化并根据血管血流的变化计算病灶状态，例如根据所述血管血流图像确定对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标、血流方向指标，并根据所述血管血流网络轮廓重新划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据比较结果重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。如此实现对病灶区域全程情况变化进行动态监测，根据病灶状态的实时监测结果适应性地调整聚焦超声的治疗参数直至病灶区域治疗效果达到预期，这可以避免辐照过度造成正常组织受到损伤、体内不必要的能量积累或辐照强度不足影响治疗效果，实现聚焦超声单元和超声成像单元的相互配合下对病灶的动态精准治疗。此外，提出了血流速度指标、血流量指标、血流方向和血管密度指标的具体获取方法，为评分及病灶变化情况进行量化，提高治疗的准确度。
(2)在向血管中注射或者不注射超声造影剂的条件下，均可对治疗区域微血流进行高帧率、高信号噪声功率比质量成像、超分辨率超声成像，通过得到连续多帧超声图像，经过杂波信号分离，生成血管血流的动态变化图，对于高强度聚焦超声治疗下的微血管血流变化情况能有更精确清晰的呈现，且可以实现100帧每秒至数万帧每秒的实时成像，同时也可以根据治疗需要进行B-mode图像和彩超多模态超声成像，将MRI、PET、CT图像和超声图像进行融合配准，将超快超声成像优势和HIFU技术相结合，提高成像效果。相较于MRI、PET、CT等方法具有成像速度快、设备便携、成本低和无电离辐射等优点。
(3)基于多角度声波复合成像的超快超声成像方法可以显著提升成像的时间和空间分辨率，在实时监测高强度聚焦超声治疗效果中具有很大潜力。
本申请的说明书中记载了大量的技术特征，分布在各个技术方案中，如果要罗列出本申请所有可能的技术特征的组合(即技术方案)的话，会使得说明书过于冗长。为了避免这个问题，本申请上述发明内容中公开的各个技术特征、在下文各个实施方式和例子中公开的各技术特征以及附图中公开的各个技术特征，都可以自由地互相组合，从而构成各种新的技术方案(这些技术方案均因视为在本说明书中已经记载)，除非这种技术特征的组合在技术上是不可行的。例如，在一个例子中公开了特征A+B+C，在另一个例子中公开了特征A+B+D+E，而特征C和D是起到相同作用的等同技术手段，技术上只要择一使用即可，不可能同时采用，特征E技术上可以与特征C相组合，则，A+B+C+D的方案因技术不可行而应当不被视为已经记载，而A+B+C+E的方案应当被视为已经记载。
附图说明
图1是根据本申请一个实施例的基于超声成像的聚焦超声治疗系统结构示意图。
图2是使用本申请涉及的基于超声成像的聚焦超声治疗系统的各单元工作时序图。
图3是根据本申请的另一个实施例的基于超声成像的聚焦超声治疗系统结构示意图。
图4是图3的实施例的基于超声成像的聚焦超声治疗系统的操作过程流程图。
图5是针对大鼠脑部病灶治疗示例的实验中超声探头位置摆放图。
图6是实施例1中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超快超声功率多普勒微血管血流二维图像。
图7是实施例1中针对大鼠脑部病灶治疗示例中对与图6大鼠脑部相同区域进行治疗后的超快超声功率多普勒微血管血流二维图像。
图8是实施例1中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超快超声彩色多普勒微血管血流二维图像。
图9是实施例1中针对大鼠脑部病灶治疗示例中对与图8大鼠脑部相同区域进行治疗后的超快超声彩色多普勒微血管血流二维图像。
图10是针对大鼠脑部病灶治疗示例中三维成像构建示意图。
图11是实施例1中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超快超声功率多普勒微血管血流三维图像。
图12是实施例1中针对大鼠脑部病灶治疗示例中对与图11大鼠脑部相同区域进行治疗后的超快超声功率多普勒微血管血流三维图像。
图13是实施例1中针对大鼠脑部病灶治疗示例中将图6治疗前的微血管血流图像 与治疗前的B-mode图像进行图像融合得到的治疗前的融合图像A的示意图。
图14是实施例1中针对大鼠脑部病灶治疗示例中将图7治疗后的微血管血流图像与治疗后的B-mode图像进行图像融合得到的治疗后的融合图像B的示意图。
图15是实施例2中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超快超声功率多普勒微血管血流二维图像。
图16是实施例2中针对大鼠脑部病灶治疗示例中对图15大鼠脑部相同区域进行治疗后的超快超声功率多普勒微血管血流二维图像。
图17是实施例2中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超快超声彩色多普勒微血管血流二维图像。
图18是实施例2中针对大鼠脑部病灶治疗示例中对图17大鼠脑部相同区域进行治疗后的超快超声彩色多普勒微血管血流二维图像。
图19是实施例2中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超分辨率超声定位显微成像血流密度图。
图20是实施例2中针对大鼠脑部病灶治疗示例中对与图19大鼠脑部相同区域进行治疗后的超分辨率超声定位显微成像血流密度图。
图21是实施例2中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超分辨率超声定位显微成像血流方向图。
图22是实施例2中针对大鼠脑部病灶治疗示例中对与图21大鼠脑部相同区域进行治疗后的超分辨率超声定位显微成像血流方向图。
图23是实施例2中针对大鼠脑部病灶治疗示例中治疗前杂波滤除后的超分辨率超声定位显微成像血流速度图。
图24是实施例2中针对大鼠脑部病灶治疗示例中对与图23大鼠脑部相同区域进行治疗后的超分辨率超声定位显微成像血流速度图。
图25(a)是选取图19中的一部分放大所获得的图像。
图25(b)是图25(a)中白色横线所指位置的幅度变化情况图。
图26是针对小鼠黑色素瘤治疗实例中治疗前的肿瘤超快超声功率多普勒微血管血流三维图像。
图27是针对小鼠黑色素瘤治疗实例中治疗后的肿瘤超快超声功率多普勒微血管血流三维图像。
图28是示例微血管血流图像的运动校准过程示意图。
图29(a)是治疗前示例血流速度分布图。
图29(b)是治疗后示例血流速度分布图。
图30是示例血管血流图像中的血管血流轮廓提取结果图。
图31(a)是中心频率为6.25MHz的三维探头所获得的三维组织成像结果图。
图31(b)是中心频率为3MHz的三维探头所获得的三维组织成像结果图。
具体实施方式
在以下的叙述中，为了使读者更好地理解本申请而提出了许多技术细节。但是，本领域的普通技术人员可以理解，即使没有这些技术细节和基于以下各实施方式的种种变化和修改，也可以实现本申请所要求保护的技术方案。
部分概念的说明：
超声示踪子：可在血管内随血流游动的小尺寸散射子，在超声作用下可产生散射回波信号。例如：血管内固有的红细胞；可注入血管的其它细胞，酵母细胞或经基因编辑后的各类细胞等等；具备生物相融性的人工材料，如超声微泡造影剂、双氧水气泡、纳米液滴等。
点扩散函数：声场中的单个散射子(例如超声示踪子)，经过图像重建后所形成的声场分布，称为点扩散函数，也称点扩展函数。
焦距：焦点到超声探头发射阵元中心点的距离。
超声探头：又被称为超声换能器阵列或超声探头阵列，相关术语系同一概念的不同表述，具体为采用一个或者多个超声阵元，经过延时可调节的数字控制单元，实现对组织中感兴趣区域的成像或者聚焦治疗的装置。所述装置至少具备超声信号发射与采集的功能。
焦域声强：焦点区域的声场强度。
焦斑尺寸：或者说称为焦域横向尺寸、焦域纵向尺寸，是描述HIFU焦点区域的参数，一般HIFU聚焦在一个区域，称为焦斑。
占空比：在一个脉冲循环内，系统通电时间相对于总时间所占的比例。
图像配准：又被称为位移校正，在成像的过程中，因为探头与被测物体的相对去过，特别是在体实验时，呼吸作用和心跳等因素引起的图像位移会影响图像质量，因此需要进行图像配准或者位移校正，以补偿探头与被测物体之间的相对位移，从而可以获得清晰的成像结果。为使本申请的目的、技术方案和优点更加清楚，下面将结合附图对本申请的实施方式作进一步地详细描述。
本申请的第一实施方式涉及一种基于超声成像的聚焦超声治疗系统，其结构示意图如图1所示，该系统包括聚焦超声单元、超声成像单元和区域规划与参数调整单元。具体描述为：
该聚焦超声单元被配置向病灶区域发射聚焦超声波进行治疗。具体的，该聚焦超声单元将一个或者多个阵元经空间或时间延时聚焦处理，从而被配置向病灶区域发射聚焦超声波达到局部声能增强从而进行治疗。
可选地，该聚焦超声单元向病灶区域发射聚焦超声波进行治疗时，例如可以采用自动规划方式沿着病灶区域进行治疗，也可以按照预先约定(人工)方式对病灶区域进行治疗。
该超声成像单元被配置为在所述治疗后，发射成像超声波至成像区域并接收相应的回波，基于所述回波成像得到对应的血管血流图像。具体的，该超声成像单元包括B模式成像单元，通过该B模式成像单元被配置为在该聚焦超声单元进行治疗后，发射成像超声波至成像区域并接收相应的回波，基于该回波成像得到对应的B模式图像(B-mode图像)，超声成像单元基于该B模式图像得到血管血流图像。其中，该B模式成像单元优选地向成像区域内发射一组多个偏转角度的平面波或者曲面声波。
可选地，本申请的血管血流图像可以是二维或三维图像等。其中血管血流图像的三维图像的实现方式例如为：如图10所示，该系统还包括三维移动单元，该三维移动单元被配置为夹持并控制超声成像单元的成像探头进行三维空间移动以得到血管血流三维图像。其中实时扫查的血管血流图像的三维图像的实现方式例如为：如图31所示，该系统还包括用于实时三维成像的二维超声阵列单元；该二维超声阵列单元被配置为可控制各阵元延时与超快接收回波，并获得三维成像。
可选地，该血管血流图像可以为微血管血流图像。在一个实施例中，该B模式成像单元发射超声波帧率≥200帧/s，成像帧率≥50帧/s，通过如图1所示的成像框图，微血管血流成像分辨率≤发射超声波波长。在另一个实施例中，该B模式成像单元发射超声波帧率≥200帧/s，成像帧率≥50帧/s，通过如图1所示的成像框图，该血管血流图像可以为超分辨率微血管血流图像，微血管血流成像分辨率≥1/50的发射超声波波长。
基于该B模式图像得到血管血流图像(例如微血管血流图像)的实现方式多种多样，在一个实施例中，所述超声成像单元还包括滤波杂除单元、定位追踪单元和超分辨率超声成像单元，由滤波杂除单元对所述B-mode图像进行杂波滤除，由定位追踪单元对滤波后的图像中红细胞或示踪子定位追踪，由超分辨率超声成像单元根据定位追踪结果对所 述B-mode图像中的血管血流图像进行重建，得到对应的超分辨率血管血流图像，其中所述示踪子在每次治疗后通过静脉注射的方式引入血管血流中。在另一个实施例中，所述超声成像单元还包括滤波杂除单元和超声多普勒成像单元，由滤波杂除单元对所述B-mode图像进行杂波滤除，由超声多普勒成像单元对滤波后的所述B-mode图像进行正交解调、频移分析，得到对应的功率多普勒血管血流图像或彩色多普勒血管血流图像。
其中，所述超分辨率超声成像单元利用在血管中游动的超声示踪子作为强散射源，从超快超声采集的B模式图像中检测到单个示踪子的点扩散函数；以其点扩散函数的中心位置作为示踪子的定位点；将各帧图像中的各个示踪子的位置进行配对和连接，从而确定每个示踪子运动的轨迹；将示踪子轨迹的长度除以示踪子沿轨迹运动所用时间，可以得到超声示踪子游过的血管中的血流速度；通过积累数千帧至数百万帧图像中的各个示踪子运动的轨迹，即可重建血管结构的超分辨率图像。此处的超分辨率是指通过示踪子点扩散函数的中心定位，获得的定位精度远优于发射声波波长。并且，基于示踪子或红细胞数量和密度的血流血管密度图像、分辨上行血流和下行血流的血流密度图像、血流速度图像。基于示踪子或红细胞数量的血流密度图像：图像中每个像素的强度值取决于经过该像素的示踪子或红细胞的数量，代表着血流量；分辨上行血流和下行血流的血流密度图像：图像中每个像素的强度值取决于经过该像素的向上或向下的示踪子或红细胞的数量，向上或向下用两种不同的颜色区分；血流速度图像：图像中每个像素的强度值取决于经过该像素的示踪子或红细胞的平均速度，代表着血流速度。
该区域规划与参数调整单元被配置为基于该血管血流图像(二维或三维图像等)重新划定病灶区域以及重新调整该聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗，该成像区域包含该病灶区域。可选地，该治疗参数例如但不限于是聚焦超声单元的探头参数，包括聚焦超声的焦距、焦域声强、焦斑尺寸、发射频率、发射功率、占空比、治疗时长中一个或多个。
可选地，该区域规划与参数调整单元还被配置为根据该血管血流图像(二维或三维图像等)确定对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据该血管血流网络轮廓重新划定病灶区域以及根据该血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据比较结果重新调整该聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
可选地，该区域规划与参数调整单元还被配置为根据该血管血流图像(二维或三维 图像等)确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据该血管血流网络轮廓和血流方向规划治疗路线以用于该聚焦超声单元下一次对重新划定的病灶区域的治疗。
可选地，该系统还包括图像输入单元和图像融合单元，该图像输入单元被配置为输入配准参考图像至该图像融合单元，该图像融合单元被配置为将该血管血流图像(二维或三维图像等)和该配准参考图像进行配准融合，得到配准融合图像。其中，该配准参考图像例如但不限于可以是前述B模式成像单元成像得到的该B-mode图像，或者是计算机断层显像图像、正电子发射计算机断层扫描PET图像、核磁共振图像、X射线计算机断层扫描图像、核磁共振图像与在造影剂配合下的X射线计算机断层扫描图像和在造影剂配合下的核磁共振图像所获得的血管图像等其它模式图像。
可选地，该区域规划与参数调整单元还可以被配置为：根据该配准融合图像对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据该血管血流网络轮廓重新划定病灶区域以及根据该血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据该比较结果重新调整该聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
可选地，所述区域规划与参数调整单元还被配置为对所述血管血流图像进行二值化处理，得到所述血管血流网络轮廓。
其中，上述的“根据该血管密度指标、血流速度指标、血流量指标的中的一者或多者对重新划定的病灶区域的病灶状态进行评分”，例如可以是根据所有指标对重新划定的病灶区域的病灶状态进行评分，也可以根据部分指标(例如仅血管密度指标和血流量指标)对重新划定的病灶区域的病灶状态进行评分。在一个实施例中，评分方式可以但不限于为：预先为按照各指标的大小设置分值以及为各指标分配相应权重，该重新划定的病灶区域的病灶状态的评分可以等于各指标的加权求和的值。上述“根据该血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分”的具体方法多种多样。例如，可以对每个指标单独评分后计算每个评分的和来得到评分结果。或者，也可以对该血管密度指标、血流速度指标、血流量指标进行加权求和得到所述评分结果。且不限于此两种评分例子，所有基于该血管密度指标、血流速度指标、血流量指标计算的评分结果均在本申请的保护范围内。
需要说明的是，上述血管密度指标指的是单位空间中血管面积或者体积占比，即血 管面积或者体积/空间面积或者体积；血流速度指标指的是所划定的病灶区域的平均血流速度等；血流量指标指的是所划定的病灶区域的平均血流量等。可选地，所述血管密度指标、血流速度指标、血流量指标的获取方法如下①②③：①由所述区域规划与参数调整单元基于超分辨率血管血流图像，根据示踪子轨迹的长度与示踪子沿轨迹运动所用时间的商计算得到所述血流速度指标，或者从功率多普勒血管血流图像或彩色多普勒血管血流图像中直接获取所述血流速度指标。②由所述区域规划与参数调整单元基于所述血管血流网络轮廓确定所述血管血流网络轮廓中各血管血流的中心位置点S（x,y)并获取各中心位置点S(x,y)处的血管血流半径r(x,y)，根据公式Q＝∑ S(x,y)v(x,y)*πr(x,y) 2计算得到所述血流量指标。进一步地，通过对照治疗各阶段总血流量V的变化可以了解该区域的治疗量化情况，若选定区域治疗前总血流量为V 0，治疗过程中的V与V 0比值可用于归一化评价治疗程度，从而完成动态治疗规划与治疗过程。若V/V 0＝0则表示该选定区域全部血流为零，判定为无需进一步治疗，例如评分为a；若V/V 0＝1则表示该选定区域血流量与治疗前相同，即尚未形成有效治疗，评分为c；若V/V 0值介于0至1之间，评分为b，a＜b＜c。例如还可以进一步把V/V 0值划分为多个不同评分区间等。③由所述区域规划与参数调整单元根据所述血管血流网络轮廓形成的血管血流图像面积与当前成像图像面积的商、或者所述血管血流网络轮廓形成的血管血流图像体积与当前成像体空间体积的商计算得到所述血管密度指标。进一步地，基于给定阈值对超声多普勒图像或超分辨率超声定位显微血管图像，如大于0.1则判定为血管区域，小于0.1则判定为非血管区域，从而可对图像中有血流与无血流进行二值化处理，将有血流处标记为1，无血流处标记为0。计算相关区域中1的个数占全图像素点的比值，则可获得该区域的血管密度ρ。ρ值介于0至1之间，为1则表示全区域均为血管，为0表示该区域无血管。通过对照治疗各阶段总血流平均密度ρ的变化可以了解该区域的治疗量化情况，若选定区域治疗前总平均密度为ρ 0，治疗过程中的ρ与ρ 0比值可用于归一化评价治疗程度，从而完成动态治疗规划与治疗过程。若ρ/ρ 0＝0则表示该选定区域全部血流为零，判定为无需进一步治疗，评分为x；若ρ/ρ 0＝1则表示该选定区域血流密度与治疗前相同，即尚未形成有效治疗，评分为z，ρ/ρ 0值介于0至1之间，评分为y，x＜y＜z。例如还可以进一步把ρ/ρ 0值划分为多个不同评分区间等。
可选地，该区域规划与参数调整单元还被配置为根据该配准融合图像确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据该血管血流网络轮廓和血流方向规划治疗路线以用于该聚焦超声单元下一次对重新划定的病灶区域的治疗。
可选地，该系统还可以包括显示单元，用于显示超声成像单元输出的血管血流图像(二维或三维图像等)和/或图像融合单元输出的融合图像，供人工调整治疗探头和/或成像探头的位置和角度。
可选地，该聚焦超声单元、该超声成像单元和该区域规划与参数调整单元顺序操作一个循环为一个治疗周期，每个治疗阶段包含迭代的多个循环，如图2所示，其中时序只表示相关基本逻辑，具体实现中，HIFU治疗过程与超声成像过程时间重叠或者不重叠不做限定。可选地，该超声成像单元还被配置为在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至该成像区域并接收相应的回波，基于该回波成像得到对应的B-mode图像，基于所述B-mode图像得到血管血流图像(二维或三维图像等)；以及该区域规划与参数调整单元还被配置为根据该血管血流图像(二维或三维图像等)划定对应的初始病灶区域和设置该聚焦超声单元的初始治疗参数。
可选地，该超声成像单元在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至该成像区域并接收相应的回波，基于该回波成像得到对应B-mode图像，基于所述B-mode图像得到血管血流图像(二维或三维图像等)；以及该图像融合单元将该血管血流图像(二维或三维图像等)和配准参考图像进行配准融合；该区域规划与参数调整单元根据该配准融合图像划定对应的初始病灶区域和设置该聚焦超声单元的初始治疗参数。其中，该配准参考图像例如但不限于可以是B-mode图像、计算机断层显像图像、正电子发射计算机断层扫描PET图像、核磁共振图像、X射线计算机断层扫描图像、核磁共振图像与在造影剂配合下X射线计算机断层扫描图像和在造影剂配合下的核磁共振图像所获得的血管图像等。
如图3所示为一个实施例的基于血管血流成像的聚焦超声治疗系统。如图3所示，具体包括以下部分：
a.计算机控制端，为区域规划与参数调整单元的一种实现方式。系统在每次超声成像后以及高强度聚焦超声治疗前，利用计算机控制端配置信号发射/接收模块，调整超快超声成像单元的成像帧率、成像深度、超声波偏转角度等参数，激励超声换能器向成像区域内发射一组多个偏转角度的超声波(优选地为平面波或者曲面声波)，观测治疗区域(或病灶区域)和周围正常组织的微血流图像。对于上述超声图像，可以和MRI、PET、CT等现有成像方法得到的图像进行图像配准融合以得到多模态图像，增强对治疗区域和周围组织的观测效果；根据超声图像或多模态超声图像判断病灶区域血流变化，分析该区域的治疗效果，对应实时动态调整高强度聚焦超声单元的超声发射强度、时长、频率、 激励方式等治疗参数，从而改变系统整体的机械指数(mechanical index，MI)、热指数(thermal index，TI)、空间峰值时间平均声强(spatial temporal average intensity，Ispta)、空间峰值脉冲平均强度(spatial peak pulse average intensity，Isppa)等主要声输出指标，进行合适的治疗。
b.高强度聚焦超声单元：包括波形发生器、功率放大器和高强度聚焦超声探头。其中波形发生器可以接收计算机控制端的触发信号、波形设置、声场强度、频率等控制信号并以相应的时序产生超声信号；功率放大器用于为高强度聚焦超声探头提供功率输出；高强度聚焦超声探头用于发射超声波到治疗区域。
c.超快超声成像单元：其与常规的百帧每秒的超声成像系统相比，超快超声成像单元的成像帧率可从100帧每秒至数万帧每秒，具体包括：信号发射/接收模块、阵列超声换能器和软件处理模块。用于采样和存储成像区域一定时间内反射或背散射的超声射频回波信号；例如，可选地通过软件处理模块对采集到的超声射频回波信号进行波束合成、相干复合、图像配准、杂波滤除、正交解调，生成图像，并在显示器上进行治疗区域超快功率多普勒、超快彩色多普勒血流变化图像的实时显示。或者，可选地通过软件处理模块对采集到的超声射频回波信号进行波束合成、相干复合、图像配准、杂波滤除、正交解调、超声示踪子定位、超声示踪子追踪、超分辨率图像重建，生成超分辨率图像，并在显示器上进行治疗区域基于超声示踪子数量的血流密度图像、分辨上行血流和下行血流的血流密度图像、血流速度图像的显示。其中信号发射/接收模块可以进一步包括波形发生器、D/A转换器、A/D转换器、数据存储器、信号放大器等；依照当前成像序列，波形发生器产生特定波形和频率的信号后，经D/A转换器转换为模拟信号，再经过信号放大器后，激励超声换能器激发超声脉冲信号，脉冲发射时间间隔要大于超声波在目标成像区域内往返一次所需的最长时间；按照既定成像深度，放大、采样和存储超声信号发射后一段时间的超声射频回波信号。其中，阵列超声换能器既可以在电信号激发下振动产生超声信号，也可以接收超声信号并转化为电信号；为了实现一定区域内的成像，往往需要使用多个超声换能器阵元组成超声换能器阵列，常用的超声探头有一维线阵、凸阵探头和二维面阵探头等，本发明不限定使用超声换能器阵列的种类。其中，软件处理模块可以进一步包括波束合成模块、相干复合模块、图像配准模块、杂波滤除模块、正交解调模块；在采集到超声射频回波数据后，需要先进行波束合成得到初始图像，波束合成算法包括延时叠加算法、频域-波束域迁移算法进行波束合成等；优选地，将一组单个或者多个偏转角度平面或者曲面声波所得的图像进行相干复合，可以有效地提高图像的信噪 比和分辨率，得到高质量的B模式超声图像；在采样超声射频回波信号时，优选地，使用2倍、3倍或4倍或以上的发射信号中心频率为采样频率，从而可得到以该中心频率载频的带通信号(RF)，正交解调步骤滤除了载波信号，并得到同相分量和正交分量(IQ)；在成像的过程中，探头与被测物体往往会产生一定的相对位移，特别是在体实验时，呼吸作用引起的图像位移会影响图像质量，因此需要进行图像配准以补偿探头与被测物体之间的相对位移；接收到的回波数据包含静态组织的回波信号、血流的回波信号和噪声；为了在图像中清晰地观察到微血流，从运动校准之后的图像数据中滤除噪声和静态组织信号数据；目前常用的方法有高通滤波、自适应滤波、奇异值分解、鲁棒主成分分析、独立成分分析等。
操作流程：
图4为图3示出的实施例的治疗系统的操作流程图，包括以下步骤：在步骤401中，超声成像单元向成像区域发射成像超声波，通过超声多普勒成像或超分辨率超声成像得到微血管血流图像；之后进入步骤402，基于该微血管血流图像或该微血管血流图像与配准参考图像的融合图像确定对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标和血流量指标，根据所述血管血流网络轮廓划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对划定的病灶区域的病灶状态进行评分；之后进入步骤403，判断评分结果是否达到预期治疗效果；若否则之后进入步骤404，在该微血管血流图像或融合图像的引导下，向病灶区域发射高强度聚焦超声波，否则治疗结束。其中，所述步骤404之后返回步骤401直至达到所述评分结果是否达到预期治疗效果。
可选地，该操作流程中的步骤401中，例如可以根据需要人工选择超声多普勒成像或超分辨率超声成像得到微血管血流图像，又例如可以在每个治疗阶段配置初始治疗周期选择超分辨率超声成像进行成像和治疗，并配置后续治疗周期选择超快超声成像或超声多普勒成像进行成像和治疗。
可选地，该操作流程中的步骤401中，具体的可以向成像区域发射成像超声波得到B模式图像，基于B模式图像选择采用超分辨率超声成像或者超声多普勒成像来得到微血管血流图像。例如，若不注射超声示踪子，则向成像区域发射成像超声波并成像得到B-mode图像，基于所得B-mode图像得到功率多普勒和彩色多普勒微血管血流图像。例如，在不注射超声示踪子的条件下，还可向成像区域发射成像超声波并成像得到B-mode图像后，还可基于所得B-mode图像，通过红细胞定位、追踪和图像重建，得到超分辨率 微血管血流图像。例如，若注射超声示踪子，向成像区域发射成像超声波并成像得到B-mode图像，通过超声示踪子定位、追踪和图像重建，可得到超分辨率微血管血流图像。
实施例1
为了能够更好地理解本申请的技术方案，下面结合一个具体的例子来进行说明。该例子是利用本申请的基于超声成像的聚焦超声治疗系统，对成年大鼠脑部血流进行高强度聚焦超声治疗区域和周围组织的治疗和成像实验，但本申请并不限于对大鼠脑部的治疗和成像。具体操作步骤如下：
(1)将高强度聚焦超声单元的探头和超快超声成像单元的探头固定在同一垂直平面，用于成像的超声探头置于大鼠头部正上方，用于治疗的高强度聚焦超声探头置于一侧，可根据需求改变高强度聚焦超声探头与垂直方向的夹角，如图5，均用医用超声耦合剂进行耦合。本例中使用的高强度聚焦超声探头为单阵元探头，中心频率为956kHz，焦距为6.0mm。实际应用中根据不同的治疗区域大小及强度等需求，可自由选择不同中心频率、焦距、阵元数的高强度聚焦超声探头。超声探头与多通道超声发射与接收设备连接。
(2)多角度相干平面波的发射和回波数据采集。本例中使用中心频率为15.6MHz，128通道的线阵超声探头，每组发射23个偏转角度的平面波。回波信号经超声换能器转化为电压信号，并由模拟信号放大器和滤波器对回波信号进行处理，继而进行模数转换和数据存储，其中模数转换采样频率为4倍的用于超声成像的发射信号中心频率。成像区域深度为d、探头阵列的总长度为L，超声波在软组织中的传播速度为c，则两次发射超声平面波之间的最短的时间间隔为
Figure PCTCN2022114344-appb-000001
一组倾斜平面波的个数为N，则最高帧频为
Figure PCTCN2022114344-appb-000002
实际应用中根据不同的治疗区域大小及强度等需求，选择不同中心频率、焦距、阵元数的超声成像探头。
(3)波束合成。本例中使用频域-波束域迁移算法进行波束合成，将存储的回波信号进行图像重建。然后将每组23个偏转角度的平面波的回波信号重建出的23张图像进行相干复合，得到一张高质量的超声B模式图像。本实施例复合成像帧率是500Hz，采样时间为0.6s，一共可得到300张复合后的图像。成像帧率、采样时间等用于图像重建的参数可根据实际需求选择。
(4)杂波滤除。本例中使用奇异值分解方法进行杂波滤除。S(x,z,t)是一个(n x×n z×n t)的三维时空矩阵，用于表示相干复合后的300张图像信息，其中x＝960，z＝128，t＝300。将三维矩阵S(x,z,t)转化为(n x×n z,n t)的二维矩阵形式Y，然后对其进行奇异值分解，如式(1)所示：
Y＝U*Σ*V T                              (1)
其中，Σ是维度为(n x×n z,n t)的对角矩阵，对角线上的数为Y的奇异值。U和V分别是二维尺度为(n x×n z,n x×n z)和(n t,n t)的正交单位矩阵，它们的列向量分别对应于Y的空间和时域上的奇异值向量。
在对300帧图像矩阵奇异值分解之后，将奇异值从大到小分布，组织信号对应的奇异值较大，噪声信号的奇异值较小，中间的奇异值对应的是血流动态信号。设置低阶和高阶阈值(n 1,n 2)提取血流动态信号，本实施例中令n 1＝20，n 2＝240，再按照式(2)进行计算，就可以达到杂波滤除的效果，获得微血管血流图像。
Figure PCTCN2022114344-appb-000003
其中，U i(x,z)和V i(t)分别代表了奇异值λ i对应的公式(1)中矩阵U和V中的列向量。
对杂波滤除后提取出的动态血流信号进行正交解调、频移分析、取模、取对数等处理，调整对比度，得到治疗前功率多普勒二维成像结果如图6所示、彩色多普勒二维成像结果如图8所示。同时，设置如图10的三维移动单元，通过该三维移动单元夹持并控制成像探头针对大鼠脑部相同区域进行成像的功率多普勒三维成像结果如图11所示。上述图6、图8、图11均可以清晰地显示出高强度聚焦超声作用前大鼠脑部微血管血流图像，且三维比二维成像结果更佳。
(5)血流速度正交解调
正交解调：正交解调可得到IQ信号。经杂波滤除后的图像数据是中心频率为f c的带通信号，将该数据乘上
Figure PCTCN2022114344-appb-000004
再经过低通滤波即可得到正交解调后的低通信号IQ，其实部为同相分量I，虚部为正交分量Q:
Figure PCTCN2022114344-appb-000005
其中，A和
Figure PCTCN2022114344-appb-000006
分别表示图像中每个像素点的回声强度和相位，A可由IQ信号取模得到。
Figure PCTCN2022114344-appb-000007
超声功率多普勒成像：基于超快超声成像单元所得B-mode图像，经由杂波滤除、正交解调，从而得到对应的多普勒血管血流图像。
Figure PCTCN2022114344-appb-000008
其中，PDI表示功率多普勒血流图像，
Figure PCTCN2022114344-appb-000009
表示IQ信号的复数共轭。
彩色多普勒成像，基于IQ信号自相关实现彩色多普勒成像。IQ信号的自相关函数为：
Figure PCTCN2022114344-appb-000010
其中，
Figure PCTCN2022114344-appb-000011
为IQ信号的自相关矩阵，NF为用于原图像的帧数，
Figure PCTCN2022114344-appb-000012
表示第k+1帧图像IQ信号的共轭信号。
假设对
Figure PCTCN2022114344-appb-000013
Figure PCTCN2022114344-appb-000014
Figure PCTCN2022114344-appb-000015
为常数，则
Figure PCTCN2022114344-appb-000016
可以记作：
Figure PCTCN2022114344-appb-000017
根据对数法则，可得
Figure PCTCN2022114344-appb-000018
即
Figure PCTCN2022114344-appb-000019
根据多普勒方程
Figure PCTCN2022114344-appb-000020
其中，f c为发射超声信号的中心频率。频移与相移有如下关系
Figure PCTCN2022114344-appb-000021
其中，Δτ表示两帧图像之间的时间间隔。多普勒速度可以由公式
Figure PCTCN2022114344-appb-000022
计算得到，所得的多普勒速度大于0表示向着探头方向运动，小于0表示远离探头方向运动，PRF为脉冲发射频率。
(6)使用的高强度聚焦超声探头对超快超声成像探头同一平面的大鼠脑部左侧组织进行破坏(或治疗)。采用正弦波激励，激励信号幅度为30V，频率956kHz，作用时间150s，焦点位于大鼠左侧大脑皮层下方2mm。
(7)重复上述(2)至(5)，进行一次治疗后重新对成像区域进行超快超声成像得到的功率多普勒二维成像结果如图7所示、彩色多普勒二维成像结果如图9所示、功率多普勒三维成像结果如图12所示，并基于所得到的微血管血流成像结果确定对应的血管密度、血流量变化、血流速度等指标，进而基于这些指标分析该治疗区域的治疗效果(即组织破坏效果)若组织破坏效果未达到预期，可调整高强度聚焦超声治疗参数后继续重复上述(5)进行治疗。
从上述示例可以知道：本申请的实施方式在病灶治疗过程中，通过超快超声成像单元得到微血管血流图像，并基于该微血管血流图像确定对应的血管密度、血流量变化、血流速度等指标，进而基于这些指标计算该治疗区域的治疗效果(即组织破坏效果)，并根据治疗效果适应性地调整聚焦超声单元的治疗参数，可以实现高强度聚焦超声单元和超快超声成像单元的相互配合下对病灶的精准治疗。为了更好的说明本发明的效果，将图6和图7进行比对以及将图8和图9进行比对，可以看出：根据本申请实施方式得到的治疗后的微血管血流图像清晰完整，可准确地确定对应的血管密度、血流量变化、血流速度等指标，从而保证了所计算的治疗效果和所调整的治疗参数的可靠性，一定程度 上表明本申请实施方式的可实施性和可靠性。进一步地，将图6、图7与图11、图12进行比对，可以看出：三维微血管血流图像的成像结果好于二维，三维成像结果可以提高血管密度、血流量变化、血流速度等指标的准确度，进而可以提高所计算的治疗效果准确度和所调整的治疗参数的准确度。进一步地，将图6治疗前的微血管血流图像与治疗前的B-mode图像进行图像融合得到的治疗前的融合图像A(如图13)，以及将图7治疗后的微血管血流图像与治疗后的B-mode图像进行图像融合得到的治疗后的融合图像B(如图14)，将融合图像A和B进行比对，可以看出：根据本申请的实施方式得到的融合图像相比融合前的微血管血流图像更清晰，因此可以进一步提高血管密度、血流量变化、血流速度等指标的准确度，进而可以提高所计算的治疗效果准确度和所调整的治疗参数的准确度。本申请并不限于对大鼠脑部的治疗和成像，如也可用于肿瘤的治疗和成像。如图26、27，分别是对小鼠黑色素瘤治疗前的肿瘤超快超声功率多普勒微血管血流三维图像和对小鼠黑色素瘤治疗后的肿瘤超快超声功率多普勒微血管血流三维图像。
实施例2
为了能够更好地理解本申请的技术方案，下面结合另一个具体的例子来进行说明。该例子是利用本申请的基于超声成像的聚焦超声治疗系统，对成年大鼠脑部血流进行高强度聚焦超声治疗区域和周围组织的治疗和成像实验，但本申请并不限于对大鼠脑部的治疗和成像。具体操作步骤如下：
(1)探头放置。将高强度聚焦超声单元的探头和超快超声成像单元的探头固定在同一垂直平面，用于成像的超声探头置于大鼠头部正上方，用于治疗的高强度聚焦超声探头置于一侧，可根据需求改变高强度聚焦超声探头与垂直方向的夹角，如图5，均用医用超声耦合剂进行耦合。本例中使用的高强度聚焦超声探头为单阵元探头，中心频率为967kHz，焦距为6.0mm。实际应用中根据不同的治疗区域大小及强度等需求，可自由选择不同中心频率、焦距、阵元数的高强度聚焦超声探头。超声探头与多通道超声发射与接收设备连接。
(2)多角度相干平面波的发射和回波数据采集。本例中使用中心频率为15.6MHz，128通道的线阵超声探头，每组发射21个偏转角度的平面波。回波信号经超声换能器转化为电压信号，并由模拟信号放大器和滤波器对回波信号进行处理，继而进行模数转换和数据存储，其中模数转换采样频率为4倍的用于超声成像的发射信号中心频率。成像区域深度为d、探头阵列的总长度为L，超声波在软组织中的传播速度为c，则两次发射超声平面波之间的最短的时间间隔为
Figure PCTCN2022114344-appb-000023
一组倾斜平面波的个数为N，则最高帧 频为
Figure PCTCN2022114344-appb-000024
实际应用中根据不同的治疗区域大小及强度等需求，选择不同中心频率、焦距、阵元数的超声成像探头。
(3)波束合成。本例中使用Delay And Sum(DAS)算法进行波束合成，将存储的回波信号进行图像重建。然后将每组21个偏转角度的平面波的回波信号重建出的21张图像进行相干复合，得到一张高质量的超声B模式图像。本实施例复合成像帧率是500Hz，采样时间为0.4s，一共可得到200张复合后的图像。成像帧率、采样时间等用于图像重建的参数可根据实际需求选择。
(4)杂波滤除得到微血管血流图像。本例中使用奇异值分解方法进行杂波滤除。S(x,z,t)是一个(n x×n z×n t)的三维时空矩阵，用于表示相干复合后的200张图像信息，其中x＝880，z＝128，t＝200。将三维矩阵S(x,z,t)转化为(n x×n z,n t)的二维矩阵形式Y，然后对其进行奇异值分解，如式(1)所示：
Y＝U*Σ*V T                         (1)
其中，Σ是维度为(n x×n z,n t)的对角矩阵，对角线上的数为Y的奇异值。U和Y分别是二维尺度为(n x×n z,n x×n z)和(n t,n t)的正交单位矩阵，它们的列向量分别对应于Y的空间和时域上的奇异值向量。
在对200帧图像矩阵奇异值分解之后，将奇异值从大到小分布，组织信号对应的奇异值较大，噪声信号的奇异值较小，中间的奇异值对应的是血流动态信号。设置低阶和高阶阈值(n 1,n 2)提取血流动态信号，本实施例中令n 1＝20,n 2＝180，再按照式(2)进行计算，就可以达到杂波滤除的效果，获得微血管血流图像。
Figure PCTCN2022114344-appb-000025
其中，U i(x,z)和V i(t)分别代表了奇异值λ i对应的公式(1)中矩阵U和V中的列向量。
对杂波滤除后提取出的动态血流信号进行正交解调、频移分析、取模、取对数等处理，调整对比度，得到治疗前功率多普勒二维成像结果如图15所示、彩色多普勒二维成像结果如图17所示。上述图15、图17均可以清晰地显示出高强度聚焦超声作用前大鼠脑部微血管血流图像。
(5)超分辨率超声成像。通过静脉注射的方式将超声示踪子注入大鼠的血流中，重复上述(2)至(4)，但是每组发射5个角度的平面波，复合成像帧率为1000Hz，采样时间0.6s，1s可得到600张复合之后的图像。对杂波滤除后提取的动态血路信号正交解调得到正交分量IQ。杂波滤除的低阶和高阶阈值分别为n 1＝30,n 2＝500，可以得到超声示踪子分离出组织信号后的图像。对超声示踪子定位，找到每个超声示踪子中心 点的位置。本例使用的是径向对称的定位方法。波束合成后，超声示踪子的强度值是以其最大值为中心对称的强度剖面，其中每一点的强度梯度总是指向该最大值。该方法通过最小化该中心到等势线的距离来定位这个中心(即与梯度正交)。找到超声示踪子的中心之后，对帧与帧之间的超声示踪子追踪，获得它们的运动轨迹。本例使用基于匈牙利分配法的Kuhn-Munkres算法追踪超声示踪子。该算法计算每个超声示踪子与下一帧中所有超声示踪子之间的距离，将总距离最小化，从而将超声示踪子的所有位置连接起来，形成轨迹。最终，得到治疗前基于超声示踪子数量的血流密度图像如图19所示、分辨上行血流和下行血流的血流密度图像如图21所示、血流速度图像如图23所示。上述图19、21、23可以以很高的分辨率显示出高强度聚焦超声作用前大鼠脑部微血管血流图像。
其中，相关血流血管参数提取包括：如图29，给出了血流速度测量结果示意图,(a)图为治疗前血管中的血流速度分布图；(b)治疗后血管中的血流速度分布图。灰度值对应了不同位置血管中的血流速度。
如图30对血流血管图像进行轮廓提取可以获得血管血流网络轮廓计算局部血管图像面积或者体积占全图像面积或者体空间的比例值，可以确定血管半径、密度指标。经由多普勒成像处理可获得血流速度图像；对血流速度图像进行时间积分，可获得血流量指标。
(6)HIFU治疗。本实施例中已经注射超声示踪子，为避免超声示踪子空化待超声示踪子排出体外后，使用高强度聚焦超声探头对超快超声成像探头同一平面的大鼠脑部左侧组织进行破坏(或治疗)。采用正弦波激励，激励信号幅度为30V，频率967kHz，作用时间90s，焦点位于大鼠左侧大脑皮层下方2mm。
(7)HIFU治疗后超快超声成像。重复上述(2)至(4)，进行一次治疗后重新对成像区域进行超快超声成像得到的功率多普勒二维成像结果如图16所示、彩色多普勒二维成像结果如图18所示，并基于所得到的微血管血流成像结果确定对应的血管密度、血流量变化、血流速度等指标，进而基于这些指标分析该治疗区域的治疗效果(即组织破坏效果)。若组织破坏效果未达到预期，可调整高强度聚焦超声治疗参数后继续重复上述(6)进行治疗。
(8)HIFU治疗后的超分辨率超声成像。重复上述步骤(5)，进行一次治疗后重新对成像区域进行超分辨率超声成像，得到的基于超声示踪子数量的血流密度图像如图20所示、分辨上行血流和下行血流的血流密度图像如图22所示、血流速度图像如图24所示，并基于所得到的超分辨率微血管血流成像结果确定对应的血管密度、血流量变化、 血流速度等指标，进而基于这些指标分析该治疗区域的治疗效果(即组织破坏效果)。若组织破坏效果未达到预期，可调整高强度聚焦超声治疗参数后继续重复上述(6)进行治疗。
从上述示例可以知道：本申请的实施方式在病灶治疗过程中，通过超快超声成像单元得到微血管血流图像，并基于该微血管血流图像确定对应的血管密度、血流量变化、血流速度等指标，进而基于这些指标计算该治疗区域的治疗效果(即组织破坏效果)，并根据治疗效果适应性地调整聚焦超声单元的治疗参数，可以实现高强度聚焦超声单元和超快超声成像单元的相互配合下对病灶的精准治疗。为了更好的说明本发明的效果，将图15和图16进行比对以及将图17和图18进行比对，可以看出：根据本申请实施方式得到的治疗后的微血管血流图像清晰完整，可准确地确定对应的血管密度、血流量变化、血流速度等指标，从而保证了所计算的治疗效果和所调整的治疗参数的可靠性，一定程度上表明本申请实施方式的可实施性和可靠性。进一步地，将图15、图16与图19、图20进行比对，可以看出：超分辨率微血管血流图像结果好于一般微血管血流图，超分辨率微血管血流图像提高了图像的分辨率。图25(a)是选取的图19中一块区域并放大的图像，图25(b)的三个曲线对应于图25(a)中三个白色横线处的幅值变化情况，三个横线分别经过三根血管。由图25(b)可以看出，血管1和血管2的宽度分别为16微米和21微米，由此可见，超分辨微血管血流图像可以分辨20微米以内的血管；血管3具有两个分叉的血管，彼此间的距离为40微米，超分辨微血管血流图像也可以分辨。由图19、图20、图21、图22、图23、图24可以看出，超分辨率成像结果可以提高血管密度、血流量变化、血流速度等指标的准确度，进而可以提高所计算的治疗效果准确度和所调整的治疗参数的准确度。
需要说明的是，在本专利的申请文件中，诸如第一和第二等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其它变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者设备不仅包括那些要素，而且还包括没有明确列出的其它要素，或者是还包括为这种过程、方法、物品或者设备所固有的要素。在没有更多限制的情况下，由语句“包括一个”限定的要素，并不排除在包括所述要素的过程、方法、物品或者设备中还存在另外的相同要素。本专利的申请文件中，如果提到根据某要素执行某行为，则是指至少根据该要素执行该行为的意思，其中包括了两种情况：仅根据该要素执行该行为与根据该要素 和其它要素执行该行为。多个、多次、多种等表达包括2个、2次、2种以及2个以上、2次以上、2种以上。
在本申请提及的所有文献都被认为是整体性地包括在本申请的公开内容中，以便在必要时可以作为修改的依据。此外应理解，在阅读了本申请的上述公开内容之后，本领域技术人员可以对本申请作各种改动或修改，这些等价形式同样落于本申请所要求保护的范围。

Claims (15)

  1. 一种基于超声成像的聚焦超声治疗系统，其特征在于，包括：
    聚焦超声单元，被配置向病灶区域发射聚焦超声波进行治疗；
    超声成像单元，被配置为在所述治疗后，发射成像超声波至成像区域并接收相应的回波，基于所述回波成像得到对应的血管血流图像；
    区域规划与参数调整单元，被配置为基于所述血管血流图像重新划定病灶区域以及重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗，所述成像区域包含所述病灶区域。
  2. 如权利要求1所述的系统，其特征在于，所述超声成像单元发射的超声波帧率≥200帧/s，成像帧率≥50帧/s；所述血管血流图像为微血管血流图像，微血管血流成像分辨率≤发射超声波波长。
  3. 如权利要求2所述的系统，其特征在于，所述区域规划与参数调整单元还被配置为根据所述血管血流图像确定对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据所述血管血流网络轮廓重新划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据比较结果重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
  4. 如权利要求3所述的系统，其特征在于，所述区域规划与参数调整单元还被配置为根据所述血管血流图像确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据所述血管血流网络轮廓和血流方向规划治疗路线以用于所述聚焦超声单元下一次对重新划定的病灶区域的治疗。
  5. 如权利要求2所述的系统，其特征在于，所述系统还包括图像输入单元和图像融合单元；
    所述图像输入单元被配置为输入获取配准参考图像并输入至所述图像融合单元，所述图像融合单元被配置为将所述血管血流图像和所述配准参考图像进行配准融合，得到配准融合图像；以及，所述区域规划与参数调整单元还被配置为根据所述配准融合图像重新划定病灶区域以及重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
  6. 如权利要求5所述的系统，其特征在于，所述区域规划与参数调整单元还被配置 为根据所述配准融合图像对应的血管血流网络轮廓和相应的血管密度指标、血流速度指标、血流量指标，并根据所述血管血流网络轮廓重新划定病灶区域以及根据所述血管密度指标、血流速度指标、血流量指标中的一者或多者对重新划定的病灶区域的病灶状态进行评分，将评分结果与预期结果进行比较，根据所述比较结果重新调整所述聚焦超声单元的治疗参数以用于下一次对重新划定的病灶区域的治疗。
  7. 如权利要求3或6所述的系统，其特征在于，所述区域规划与参数调整单元还被配置为对所述血管血流图像进行二值化处理，得到所述血管血流网络轮廓；
    所述区域规划与参数调整单元还被配置为基于超分辨率血管血流图像，根据示踪子轨迹的长度与示踪子沿轨迹运动所用时间的商计算得到所述血流速度指标，或者从功率多普勒血管血流图像或彩色多普勒血管血流图像中直接获取所述血流速度指标；
    所述区域规划与参数调整单元还被配置为基于所述血管血流网络轮廓确定所述血管血流网络轮廓中各血管血流的中心位置点S(x,y)并获取各中心位置点S(x,y)处的血管血流半径r(x,y)，根据公式Q＝∑ S(x,y)v(x,y)*πr(x,y) 2计算得到所述血流量指标；
    所述区域规划与参数调整单元还被配置为根据所述血管血流网络轮廓形成的血管血流图像面积与当前成像图像面积的商、或者所述血管血流网络轮廓形成的血管血流图像体积与当前成像体空间体积的商计算得到所述血管密度指标。
  8. 如权利要求6所述的系统，其特征在于，所述区域规划与参数调整单元还被配置为根据所述配准融合图像确定重新划定的病灶区域内的血管血流网络轮廓和血流方向，并根据所述血管血流网络轮廓和血流方向规划治疗路线以用于所述聚焦超声单元下一次对重新划定的病灶区域的治疗。
  9. 如权利要求1所述的系统，其特征在于，所述超声成像单元还被配置为在所述治疗后，发射成像超声波至成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到所述血管血流图像。
  10. 如权利要求9所述的系统，其特征在于，所述超声成像单元还被配置为对所述B-mode图像进行杂波滤除、红细胞或示踪子定位追踪，根据定位追踪结果对所述B-mode图像中的血管血流图像进行重建，得到对应的超分辨率血管血流图像，其中所述示踪子在每次治疗后通过静脉注射的方式引入血管血流中。
  11. 如权利要求9所述的系统，其特征在于，所述超声成像单元还被配置为对所述B-mode图像进行杂波滤除、正交解调、频移分析，得到对应的功率多普勒血管血流图像或彩色多普勒血管血流图像。
  12. 如权利要求1所述的系统，其特征在于，所述聚焦超声单元、所述超声成像单元和所述区域规划与参数调整单元顺序操作一个循环为一个治疗周期，每个治疗阶段包含迭代的多个循环；
    所述超声成像单元还被配置为在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至所述成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到血管血流图像；以及，所述区域规划与参数调整单元还被配置为根据该血管血流图像划定对应的初始病灶区域和设置所述聚焦超声单元的初始治疗参数。
  13. 如权利要求12所述的系统，其特征在于，所述系统还包括图像融合单元；
    所述超声成像单元在每个治疗阶段的第一个治疗周期的治疗前，发射成像超声波至所述成像区域并接收相应的回波，基于所述回波成像得到对应的B-mode图像，基于所述B-mode图像得到血管血流图像，所述图像融合单元将该血管血流图像和配准参考图像进行配准融合得到配准融合图像，所述区域规划与参数调整单元根据该配准融合图像划定对应的初始病灶区域和设置所述聚焦超声单元的初始治疗参数。
  14. 如权利要求5或13所述的系统，其特征在于，所述配准参考图像为以下的一者或多者：
    所述B-mode图像、计算机断层显像图像、正电子发射计算机断层扫描PET图像、核磁共振图像、X射线计算机断层扫描图像、核磁共振图像与在造影剂配合下X射线计算机断层扫描图像和在造影剂配合下的核磁共振图像所获得的血管图像。
  15. 如权利要求1-13中任意一项所述的系统，其特征在于，所述治疗参数包括聚焦超声的焦距、焦域声强、焦斑尺寸、发射频率、发射功率、占空比、治疗时长。
PCT/CN2022/114344 2021-08-23 2022-08-23 基于超声成像的聚焦超声治疗系统 WO2023025165A1 (zh)

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