Method, device, equipment and storage medium for measuring acoustic characteristics of contrast agent microbubbles

Abstract

The present invention discloses a method, apparatus, device, and storage medium for measuring the acoustic properties of contrast agent microbubbles. The method includes: a calibration phase, obtaining a pulse signal emitted by a transmitting probe and an echo signal received by a receiving probe, and calculating the receiving transfer function of the receiving probe using the pulse signal and the echo signal; a measurement phase, controlling the transmitting probe to sweep within a preset frequency range to emit an ultrasonic excitation signal, and controlling the receiving probe to receive scattered signals from microbubbles in a phantom blood vessel; extracting the subharmonic signal voltage amplitude from the scattered signal; using the receiving transfer function of the receiving probe to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies; and determining the optimal subharmonic driving frequency and subharmonic scattering pressure based on the actual subharmonic scattering pressure. The present invention improves the measurement accuracy of the nonlinear scattering properties of microbubbles by obtaining the receiving transfer function of the receiving probe and using it to obtain the actual scattered acoustic pressure signal.

Description

Technical Field

[0001] The present application relates to the technical field of ultrasound contrast agent characteristic measurement, and in particular to a method, device, equipment and storage medium for measuring the acoustic characteristics of contrast agent microbubbles. Background Art

[0002] In recent years, in the field of clinical medical ultrasound diagnosis and biological tissue imaging, microbubble ultrasound contrast agents have received increasing attention, and ultrasound technology has also been applied to a variety of treatment equipment. A large number of research results at home and abroad have shown that the nonlinear vibration and scattering characteristics generated by the excitation of microbubbles by sound waves can improve the efficiency of ultrasound therapy and implement intravascular thrombolysis therapy. By carrying therapeutic drugs or genes through micro-nano bubbles and using ultrasound as a mediating means, targeted delivery of anti-tumor drugs, gene location transfection or delivery, etc. can be carried out. Therefore, combining microbubbles and ultrasound to treat some major diseases has become one of the hot topics of concern in the medical community at home and abroad.

[0003] Currently, the acoustic properties of ultrasound contrast agent microbubbles are primarily evaluated using two key metrics: the attenuation coefficient and the backscattering coefficient. Because the probe transfer function is often difficult to obtain, the power spectrum of the sample scattered signal is typically divided by the power spectrum of the reference signal to eliminate the influence of the probe transfer function. The attenuation coefficient and backscattering coefficient are then calculated. However, when sound waves propagate through a medium, the forced vibration of the bubbles causes acoustic scattering, exhibiting strong nonlinear acoustic properties. While the attenuation coefficient and backscattering coefficient only reflect the linear scattering properties of microbubbles at low sound pressures (the fundamental resonance frequency and scattering intensity), they fail to capture the nonlinear scattering properties of microbubbles at high sound pressures, such as the resonance frequency and scattering intensity of the second harmonic and subharmonic components. Without the probe transfer function, the actual scattered sound pressure signal cannot be obtained. This results in strong frequency components not being at the probe's center frequency, resulting in a weak probe response at that frequency point and misinterpreting other frequency components as nonlinear resonant frequencies of the microbubbles. This ultimately leads to inaccurate assessment of the nonlinear acoustic properties of ultrasound contrast agents. Summary of the Invention

[0004] In view of this, the present application provides a method, device, equipment and storage medium for measuring the acoustic properties of contrast agent microbubbles to solve the problem of inaccurate and incomplete evaluation of the acoustic properties of existing ultrasound contrast agents.

[0005] In order to solve the above technical problems, a technical solution adopted in this application is: providing a method for measuring the acoustic characteristics of contrast agent microbubbles, including: in the calibration stage, obtaining the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe, and using the pulse signal and the echo signal to calculate the receiving transfer function of the receiving probe; in the measurement stage, controlling the transmitting probe to sweep the frequency within a preset frequency range to emit an ultrasonic excitation signal, and controlling the receiving probe to receive the scattered signal of the microbubbles in the phantom blood vessels; extracting the subharmonic signal voltage amplitude from the scattered signal; using the receiving transfer function of the receiving probe to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies; and confirming the subharmonic optimal driving frequency and subharmonic scattering pressure size based on the actual subharmonic scattering pressure.

[0006] As a further improvement of the present application, in the calibration stage, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: obtaining multiple pulse signals emitted by the transmitting probe, and summing and averaging the multiple pulse signals to obtain an average pulse signal; performing fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; converting the voltage signal amplitude spectrum into a sound pressure signal amplitude spectrum; calculating a first sound pressure spectrum on the surface of the transmitting probe based on the sound pressure signal amplitude spectrum; obtaining multiple echo signals received by the receiving probe, and summing and averaging the multiple echo signals to obtain an average echo signal; performing fast Fourier transform on the average echo signal to obtain a complex spectrum of the average echo signal; calculating a second sound pressure spectrum of the sound pressure generated by the echo signal on the surface of the receiving probe based on the first sound pressure spectrum on the surface of the transmitting probe; and calculating the receiving transfer function of the receiving probe based on the complex spectrum and the second sound pressure spectrum of the average echo signal.

[0007] As a further improvement of the present application, the calculation process of the first sound pressure spectrum is expressed as follows: According to classical acoustic theory, at time t, the instantaneous sound pressure at a point r in the sound field is: Where ρ is the density of the medium, is the velocity potential. By introducing a convolution of the delta function, the velocity potential generated by the array element at point r is Among them, the spatial impulse response function of the array element is: Where S is the area of the array element, v0(t) is the surface normal velocity, r ′ is the distance between the spatial point r and the infinitesimal element dS on the array element, c is the speed of sound in the medium, then Among them, the sound pressure at a point in the sound field is: is the velocity of a particle at a position in the sound field, then the sound pressure on the surface of the transmitting probe is: The spatial impulse response function at the focus of the focused transmitting probe is: in, is the depth of the focusing probe, R is the curvature radius of the transmitting probe, a is the radius of the transmitting probe, and represents the Fourier transform. Performing a fast Fourier transform yields: Wherein, f represents frequency, j represents complex number, ω=2πf represents angular frequency, represents, represents; the calculation process of the second sound pressure spectrum is expressed as: Among them, P0() is the first sound pressure spectrum, D ref (2 ref ,) is the acoustic coupling function from the transmitting probe surface to the reference plane and then back to the probe surface, Indicates the average sound pressure on the surface of the receiving probe. When the receiving probe is a focused probe, Z ref =, then: D ref (2,ω)=-{1-exp(-jG p )[J0(G p )+jJ1( p )]}, where J0 and J1 are Bessel functions of order 0 and 1 respectively, G p =a 2 / 2 is the gain of sound pressure at the focus, represents, exp represents the exponential function, Indicates the wave number, when G p >, there are:

[0008] As a further improvement of the present application, the calculation formula of the receiving transfer function is expressed as: Among them, T R (f) is the receiving transfer function, V out (f) is the complex spectrum of the average echo signal, P R,0 (f) is the second sound pressure spectrum.

[0009] As a further improvement of the present application, in the calibration stage, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: obtaining multiple pulse signals emitted by the transmitting probe, and summing and averaging the multiple pulse signals to obtain an average pulse signal; performing fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; converting the voltage signal amplitude spectrum into a sound pressure signal amplitude spectrum; calculating the first sound pressure spectrum on the surface of the transmitting probe based on the sound pressure signal amplitude spectrum; obtaining the complex spectrum of the excitation voltage applied to the surface of the transmitting probe; calculating the transmitting transfer function of the transmitting probe based on the first sound pressure spectrum and the excitation voltage amplitude spectrum; when the transmitting probe and the receiving probe are ultrasonic transducers, the receiving transfer function of the receiving probe is calculated based on the transmitting transfer function and the reciprocity constant obtained in advance, and the reciprocity constant is a parameter of the ultrasonic transducer.

[0010] As a further improvement of the present application, the calculation formula of the transmission transfer function of the transmitting probe is expressed as: Among them, T T (f) is the transmission transfer function, P T,0 (f) is the first sound pressure spectrum, V in (f) is the complex spectrum of the excitation voltage on the surface of the transmitting probe; the calculation formula of the receiving transfer function is expressed as: Among them, R load is the resistance of the load connected to the probe, A is the effective surface area of the probe, ρ is the density of water, c is the speed of sound in water, and const is the reciprocity constant.

[0011] As a further improvement of the present application, during the measurement phase, the transmitting probe is controlled to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive the scattered signals of microbubbles in the phantom blood vessels, including: obtaining multiple sets of preset sound pressure and pressure environmental parameters; under different sound pressure and pressure environmental parameter conditions, the transmitting probe is controlled to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive the scattered signals of microbubbles in the phantom blood vessels.

[0012] To solve the above technical problems, another technical solution adopted in this application is: to provide a contrast agent microbubble acoustic characteristics measurement device, including: a calibration module, which is used to obtain the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe during the calibration stage, and use the pulse signal and the echo signal to calculate the receiving transfer function of the receiving probe; a measurement module, which is used to control the transmitting probe to sweep the frequency within a preset frequency range to emit an ultrasonic excitation signal during the measurement stage, and control the receiving probe to receive the scattered signal of the microbubbles in the phantom blood vessels; an extraction module, which is used to extract the subharmonic signal voltage amplitude from the scattered signal; a conversion module, which is used to use the receiving transfer function of the receiving probe to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies; and a confirmation module, which is used to confirm the subharmonic optimal driving frequency and subharmonic scattering pressure according to the actual subharmonic scattering pressure.

[0013] In order to solve the above technical problems, another technical solution adopted in this application is: to provide a computer device, which includes a processor and a memory coupled to the processor, wherein program instructions are stored in the memory, and when the program instructions are executed by the processor, the processor executes the steps of the contrast agent microbubble acoustic characteristics measurement method as described in any one of the above items.

[0014] In order to solve the above technical problems, another technical solution adopted by the present application is: providing a storage medium storing program instructions capable of implementing any of the above-mentioned methods for measuring the acoustic characteristics of contrast agent microbubbles.

[0015] The beneficial effects of the present application are as follows: the contrast agent microbubble acoustic property measurement method of the present application calculates the receiving transfer function of the receiving probe using the pulse emitted by the transmitting probe and the echo signal received by the receiving probe before measuring the acoustic properties of the ultrasound contrast agent, and then uses the receiving transfer function to convert the scattered signal emitted by the transmitting probe to obtain the actual subharmonic scattering pressure during the actual measurement process, and then confirms the subharmonic optimal driving frequency and subharmonic scattering pressure based on the actual subharmonic scattering pressure, thereby achieving an accurate evaluation of the nonlinear acoustic properties of the ultrasound contrast agent, filling the gaps in the existing ultrasound contrast agent microbubble acoustic property measurement, and making the ultrasound contrast agent microbubble acoustic property measurement more accurate and comprehensive. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 1 is a flow chart of a method for measuring the acoustic characteristics of contrast agent microbubbles according to an embodiment of the present invention;

[0017] Figure 2 Schematic diagram of the functional modules of the device for measuring the acoustic characteristics of contrast agent microbubbles according to an embodiment of the present invention;

[0018] Figure 3is a schematic structural diagram of a computer device according to an embodiment of the present invention;

[0019] Figure 4 It is a schematic structural diagram of a storage medium according to an embodiment of the present invention. DETAILED DESCRIPTION

[0020] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0021] The terms "first," "second," and "third" in this application are used only for descriptive purposes and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first," "second," or "third" may explicitly or implicitly include at least one of such features. In the description of this application, "multiple" means at least two, for example, two, three, etc., unless otherwise specifically defined. All directional indications in the embodiments of this application (such as up, down, left, right, front, back...) are only used to explain the relative positional relationship, movement, etc. between the components under a specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indications also change accordingly. In addition, the terms "including" and "having," as well as any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units that are not listed, or may optionally include other steps or units that are inherent to these processes, methods, products, or devices.

[0022] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0023] Figure 1 FIG. 1 is a flow chart of a method for measuring the acoustic properties of contrast agent microbubbles according to an embodiment of the present invention. It should be noted that the method of the present invention is not limited to the method of FIG. 1 if substantially the same results are obtained. Figure 1 The process sequence shown is limited. Figure 1 As shown, the method for measuring the acoustic characteristics of contrast agent microbubbles includes the following steps:

[0024] Step S101: In the calibration phase, a pulse signal transmitted by a transmitting probe and an echo signal received by a receiving probe are obtained, and a receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal.

[0025] Specifically, to eliminate the influence of the transfer function on the received signal, this embodiment requires determining the transfer function of the receiving probe, obtaining its receiving sensitivity, converting the received voltage signal into an actual sound pressure signal, and then performing appropriate signal processing on the sound pressure signal. Therefore, before measuring the acoustic properties of an ultrasound contrast agent, a pre-calibration operation is performed to obtain the probe's transfer function. In this embodiment, the probe includes a transmitting probe and a receiving probe. The transmitting transfer function of the transmitting probe can be obtained by combining the transmitting transfer function of the probe when used as a transmitting probe with the transmitting-receiving transfer function of the probe when used in a pulse-echo system. The receiving probe's transfer function can be obtained in two ways. The first method is to place a steel plate with a known reflection coefficient at the focal point of the receiving probe to serve as a reflecting surface. The plate's position is adjusted to maximize the echo signal of ultrasound perpendicularly incident on the rigid surface. The receiving transfer function of the receiving probe is then derived by combining the transmitting transfer function measured by a hydrophone with the transmitting-receiving transfer function of the pulse-echo system obtained from the reflection signal of the rigid reflecting surface. The second method is to estimate the receiving transfer function based on the transmitting transfer function when the transmitting probe and the receiving probe are reciprocal ultrasonic transducers, taking into account their reciprocity.

[0026] Furthermore, for the first method of obtaining the reception transfer function, step S101 specifically includes:

[0027] 1.1 Obtain multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal.

[0028] Specifically, during the signal acquisition phase, this embodiment utilizes a programmable arbitrary waveform generator to generate a pulse excitation signal with a center frequency of 3.5 MHz. The transmitting probe is focused with a frequency interval of 0.05 MHz. To minimize the impact of nonlinear acoustic wave propagation on the measurement, the probe excitation voltage is set to 2 Vpp. The signal at the focal point of the transmitting probe is received by a thin-film hydrophone, amplified by a 40 dB preamplifier, and then A / D converted by a high-speed acquisition card with a sampling rate of 100 MS / s. The signal is then sent to a computer for post-processing in Matlab. During post-processing, the multiple pulse signals collected are summed and averaged to obtain an average pulse signal, thereby eliminating noise. In this embodiment, the number of pulse signals is preferably 64.

[0029] 1.2 Perform fast Fourier transform on the average pulse signal to obtain the voltage signal amplitude spectrum.

[0030] 1.3 Convert the voltage signal amplitude spectrum into the sound pressure signal amplitude spectrum.

[0031] 1.4 The first sound pressure spectrum of the transmitting probe surface is obtained based on the sound pressure signal amplitude spectrum.

[0032] First, it is important to understand that for a linear acoustic system, the spatial impulse response principle can be used to accurately calculate its transmitted and scattered sound fields. Therefore, in this embodiment, it is assumed that sound propagates linearly in a homogeneous medium without attenuation, an array element of area S is embedded in an infinitely rigid baffle, and the surface normal velocity v0(t) is uniformly distributed, r ′ is the distance between the spatial point r and the infinitesimal element dS on the array element, and c is the speed of sound in the medium. Under this condition, the calculation process of the first sound pressure spectrum is expressed as:

[0033] According to classical acoustic theory, at time t, the instantaneous sound pressure at a point r in the sound field is:

[0034]

[0035] Where ρ is the density of the medium, is the velocity potential. By introducing a convolution of the delta function, the velocity potential generated by the array element at point r is:

[0036]

[0037] Among them, the spatial impulse response function of the array element is:

[0038]

[0039] Where S is the area of the array element, v0(t) is the surface normal velocity, r ′ is the distance between the spatial point r and the infinitesimal element dS on the array element, and c is the speed of sound in the medium.

[0040] Substituting the time derivative of the velocity potential into equation (1) we obtain:

[0041]

[0042] Among them, under the condition of simple harmonic wave, the sound pressure at a point in the sound field is:

[0043]

[0044] in, is the velocity of a particle at a position in the sound field, then the sound pressure on the surface of the transmitting probe is:

[0045]

[0046] Among them, the spatial impulse response function at the focus of the focused transmitting probe is:

[0047]

[0048] in, is the depth of the focusing probe, R is the curvature radius of the transmitting probe, a is the radius of the transmitting probe, and is represented by Fourier transform;

[0049] Performing fast Fourier transform on equation (4) yields:

[0050]

[0051] And, but:

[0052]

[0053] Wherein, f represents frequency, j represents complex number, ω=2πf represents angular frequency, represents, represents.

[0054] 1.5 Obtain multiple echo signals received by the receiving probe, and average the multiple echo signals to obtain an average echo signal.

[0055] Specifically, during the signal acquisition phase, this embodiment uses a programmable arbitrary waveform generator to generate pulse excitation signals with a frequency interval of 0.05 MHz. To minimize the impact of nonlinear acoustic wave propagation on measurement, the probe's excitation voltage is set to 2 Vpp. A rigid reflective surface (a 4 cm thick stainless steel block) is placed at the focal point of the transmitting probe. The reflected signal is amplified by a 20 dB preamplifier, then converted by an A / D converter using a high-speed acquisition card with a sampling rate of 100 MS / s. Afterwards, it is sent to a computer for post-processing in Matlab. During post-processing, the multiple acquired echo signals are summed and averaged to obtain an average echo signal, thereby eliminating noise.

[0056] 1.6 Perform fast Fourier transform on the average echo signal to obtain the complex spectrum of the average echo signal.

[0057] 1.7 A second sound pressure spectrum of the sound pressure generated by the echo signal on the surface of the receiving probe is calculated based on the first sound pressure spectrum on the surface of the transmitting probe.

[0058] The transfer function of a pulse-echo system can be measured by placing a rigid radiating surface as a reference plane in the near field of an unfocused probe or at the focal plane of a focused probe. In such a pulse-echo system, the distance Z from the rigid reflecting surface to the probe surface is assumed to be ref , in 2 ref There is a receiving probe that is the same as the transmitting probe at Z. ref The average sound pressure on the rigid reflective surface at 2 refThe average sound pressure on the receiving probe surface is equal. Therefore, the calculation process of the second sound pressure spectrum is expressed as:

[0059]

[0060] Among them, P0() is the first sound pressure spectrum, D ref (2 ref ,) is the acoustic coupling function from the transmitting probe surface to the reference plane and then back to the probe surface, Indicates the average sound pressure on the surface of the receiving probe;

[0061] When the receiving probe is a focusing probe, Z ref =, then:

[0062] D ref (2,ω)=-{1-exp(-jG p )[J0(G p )+jJ1( p )]}(11)

[0063] Among them, J0 and J1 are Bessel functions of order 0 and 1 respectively, G p =a 2 / 2 is the gain of sound pressure at the focus, exp represents the exponential function, Indicates the wave number, indicates;

[0064] When G p >, there are:

[0065]

[0066] 1.8 The receiving transfer function of the receiving probe is calculated based on the complex spectrum of the average echo signal and the second sound pressure spectrum.

[0067] Specifically, the calculation formula of the receiving transfer function is expressed as:

[0068]

[0069] Among them, T R (f) is the receiving transfer function, V out (f) is the complex spectrum of the average echo signal, P R,0 (f) is the second sound pressure spectrum.

[0070] Furthermore, for the second method of obtaining the reception transfer function, step S101 specifically includes:

[0071] 2.1 Obtain multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal.

[0072] 2.2 Perform fast Fourier transform on the average pulse signal to obtain the voltage signal amplitude spectrum.

[0073] 2.3 Convert the voltage signal amplitude spectrum into the sound pressure signal amplitude spectrum.

[0074] 2.4 The first sound pressure spectrum of the transmitting probe surface is obtained based on the sound pressure signal amplitude spectrum.

[0075] It should be noted that for the details of steps 2.1 to 2.4, please refer to the details of steps 1.1 to 1.4 above, which will not be repeated here.

[0076] 2.5 Obtain the complex spectrum of the excitation voltage applied to the surface of the transmitting probe.

[0077] 2.6 Calculate the transmission transfer function of the transmitting probe based on the first sound pressure spectrum and the excitation voltage amplitude spectrum.

[0078] Specifically, the calculation formula of the transmission transfer function of the transmitting probe is expressed as:

[0079]

[0080] Among them, T T (f) is the transmission transfer function, P T,0 (f) is the first sound pressure spectrum, V in (f) is the complex spectrum of the excitation voltage on the surface of the transmitting probe.

[0081] 2.7 When the transmitting probe and the receiving probe are ultrasonic transducers, the receiving transfer function of the receiving probe is calculated based on the transmitting transfer function and the pre-acquired reciprocity constant, where the reciprocity constant is a parameter of the ultrasonic transducer.

[0082] Specifically, when the transmitting probe and the receiving probe are ultrasonic transducers, it means that the transmitting probe and the receiving probe have reciprocity, and the ratio of their transfer functions is a constant. Therefore, after obtaining the transmitting transfer function, the receiving transfer function is calculated based on the transmitting transfer function and the reciprocity constant. The calculation formula of the receiving transfer function is expressed as:

[0083]

[0084] Among them, R load is the resistance of the load connected to the probe, A is the effective surface area of the probe, ρ is the density of water, c is the speed of sound in water, and const is the reciprocity constant.

[0085] Step S102: During the measurement phase, the transmitting probe is controlled to sweep the frequency within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive scattered signals of microbubbles in the phantom blood vessel.

[0086] Specifically, during the measurement, a programmable arbitrary waveform generator is used to sweep the frequency range of 2-6 MHz with a frequency change step of 0.05 MHz to generate a series of ultrasonic pulse signals with different frequencies, 16 cycles, a pulse repetition frequency of 1 kHz, and a phase of 0°. The power amplifier further amplifies the signal generated by the programmable arbitrary waveform generator and transmits the ultrasonic excitation signal through a single-element focused ultrasonic transducer (transmitting probe) with a center frequency of 3.5 MHz, a focal length of 25.4 mm, -6 dB, and a bandwidth range of 2.58 MHz to 5.47 MHz. Another single-element focused ultrasound transducer (receiving probe) with a center frequency of 2.25 MHz, a -6 dB gain, a bandwidth of 1.29-2.99 MHz, and a focal length of 25.4 mm receives scattered signals from microbubbles in the phantom vessel. It is located at a 90° angle to the transmitting transducer and in the same plane perpendicular to the phantom vessel. The focal points of both ultrasound transducers are located at the same center point of the phantom vessel. The scattered signals received by the receiving probe are further amplified by a preamplifier with a gain of 40 dB and low-pass filtered. The signals are then digitized by an acquisition card at a sampling frequency of 100 MHz and stored in a computer. Ten sets of data are collected continuously for each measurement, each containing 500 received signals.

[0087] Furthermore, the acoustic properties of existing ultrasound contrast agent microbubbles are generally measured at standard atmospheric pressure (ambient pressure 0 mmHg), while the blood pressure in the human body varies within the range of 0-200 mmHg. That is, the blood pressure variation range in the human body is not standard. Therefore, to ensure measurement accuracy, step S102 specifically includes:

[0088] 1. Obtain multiple sets of preset sound pressure and pressure environment parameters;

[0089] 2. Under different sound pressure and pressure environmental parameter conditions, the transmitting probe is controlled to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive the scattered signals of microbubbles in the phantom blood vessels.

[0090] Specifically, by collecting signals under different sound pressure and pressure environment parameters, the nonlinear acoustic characteristics of the ultrasound contrast agent can be evaluated under different sound pressure and pressure environment parameters, further improving the accuracy of the evaluation results.

[0091] Step S103: extracting the subharmonic signal voltage amplitude from the scattered signal.

[0092] Specifically, MATLAB 7.0 was used to post-process the received pulse echo signal data, and a fourth-order Butterworth bandpass filter was used to filter the collected scattered signals to extract the subharmonic components. The fast Fourier transform was then used to further calculate the average subharmonic amplitude of the subharmonic components of 500 received signals to obtain the subharmonic signal voltage amplitude.

[0093] Step S104: using the receiving transfer function of the receiving probe to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies.

[0094] Specifically, the obtained subharmonic signal voltage amplitude is converted by the receiving transfer function of the probe to obtain the actual subharmonic scattering pressure, and the subharmonic scattering pressure at each driving frequency within the sweep frequency range is further obtained, and a curve of the subharmonic scattering pressure changing with the driving frequency is plotted.

[0095] Step S105: confirming the subharmonic optimal driving frequency and the subharmonic scattering pressure according to the actual subharmonic scattering pressure.

[0096] The method for measuring the acoustic properties of contrast agent microbubbles in an embodiment of the present invention calculates the receiving transfer function of the receiving probe using the pulse emitted by the transmitting probe and the echo signal received by the receiving probe before measuring the acoustic properties of the ultrasound contrast agent. Then, during the actual measurement process, the receiving transfer function is used to convert the scattered signal emitted by the transmitting probe to obtain the actual subharmonic scattering pressure, and then the subharmonic optimal driving frequency and subharmonic scattering pressure are determined based on the actual subharmonic scattering pressure. This achieves an accurate evaluation of the nonlinear acoustic properties of the ultrasound contrast agent, fills the gaps in the existing measurement of the acoustic properties of ultrasound contrast agent microbubbles, and makes the measurement of the acoustic properties of ultrasound contrast agent microbubbles more accurate and comprehensive.

[0097] Figure 2 FIG. 1 is a functional module diagram of a device for measuring the acoustic characteristics of contrast agent microbubbles according to an embodiment of the present invention. Figure 2 As shown, the contrast agent microbubble acoustic characteristic measurement device 20 includes a calibration module 21 , a measurement module 22 , an extraction module 23 , a conversion module 24 and a confirmation module 25 .

[0098] The calibration module 21 is used to obtain the pulse signal transmitted by the transmitting probe and the echo signal received by the receiving probe during the calibration phase, and calculate the receiving transfer function of the receiving probe using the pulse signal and the echo signal;

[0099] The measuring module 22 is used to control the transmitting probe to sweep the frequency within a preset frequency range to transmit the ultrasonic excitation signal, and control the receiving probe to receive the scattered signals of the microbubbles in the phantom blood vessels during the measurement phase;

[0100] An extraction module 23 is used to extract the subharmonic signal voltage amplitude from the scattered signal;

[0101] A conversion module 24 is configured to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies using a receiving transfer function of the receiving probe;

[0102] The confirmation module 25 is used to confirm the subharmonic optimal driving frequency and the subharmonic scattering pressure according to the actual subharmonic scattering pressure.

[0103] Optionally, the calibration module 21 performs an operation in the calibration phase to obtain the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe, and uses the pulse signal and the echo signal to calculate the receiving transfer function of the receiving probe, specifically including: obtaining multiple pulse signals emitted by the transmitting probe, and summing and averaging the multiple pulse signals to obtain an average pulse signal; performing fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; converting the voltage signal amplitude spectrum into a sound pressure signal amplitude spectrum; calculating a first sound pressure spectrum on the surface of the transmitting probe based on the sound pressure signal amplitude spectrum; obtaining multiple echo signals received by the receiving probe, and summing and averaging the multiple echo signals to obtain an average echo signal; performing fast Fourier transform on the average echo signal to obtain a complex spectrum of the average echo signal; calculating a second sound pressure spectrum of the sound pressure generated by the echo signal on the surface of the receiving probe based on the first sound pressure spectrum on the surface of the transmitting probe; and calculating the receiving transfer function of the receiving probe based on the complex spectrum and the second sound pressure spectrum of the average echo signal.

[0104] Optionally, the calculation process of the first sound pressure spectrum is expressed as follows: According to classical acoustic theory, at time t, the instantaneous sound pressure at a point r in the sound field is: Where ρ is the density of the medium, is the velocity potential. By introducing a convolution of the delta function, the velocity potential generated by the array element at point r is Among them, the spatial impulse response function of the array element is: Where S is the area of the array element, v0(t) is the surface normal velocity, r ′ is the distance between the spatial point r and the infinitesimal element dS on the array element, c is the speed of sound in the medium, then Among them, the sound pressure at a point in the sound field is: is the velocity of a particle at a position in the sound field, then the sound pressure on the surface of the transmitting probe is: The spatial impulse response function at the focus of the focused transmitting probe is: in, is the depth of the focusing probe, R is the curvature radius of the transmitting probe, a is the radius of the transmitting probe, and represents the Fourier transform. Performing a fast Fourier transform yields: Wherein, f represents frequency, j represents complex number, ω=2πf represents angular frequency, represents, represents;

[0105] The calculation process of the second sound pressure spectrum is expressed as: |D ref (2Z ref ,ω)|, where P0(ω) is the first sound pressure spectrum, D ref (2Z ref ,ω) is the acoustic coupling function from the transmitting probe surface to the reference plane and then back to the probe surface, Indicates the average sound pressure on the surface of the receiving probe. When the receiving probe is a focused probe, Z ref =R, then: D ref (2R,ω)=-{1-exp(-jG p )[J0(G p )+jJ1(G p )]}, where J0 and J1 are Bessel functions of order 0 and 1 respectively, G p =ka 2 / 2R is the gain of sound pressure at the focus, and exp represents the exponential function. Indicates the wave number, indicating that when G p When >π, we have:

[0106] Optionally, the calculation formula of the receiving transfer function is expressed as:

[0107]

[0108] Among them, T R (f) is the receiving transfer function, V out (f) is the complex spectrum of the average echo signal, P R,0 (f) is the second sound pressure spectrum.

[0109] Optionally, the calibration module 21 performs an operation in the calibration phase to obtain the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe, and uses the pulse signal and the echo signal to calculate the receiving transfer function of the receiving probe, specifically including: obtaining multiple pulse signals emitted by the transmitting probe, and summing and averaging the multiple pulse signals to obtain an average pulse signal; performing fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; converting the voltage signal amplitude spectrum into a sound pressure signal amplitude spectrum; calculating the first sound pressure spectrum on the surface of the transmitting probe based on the sound pressure signal amplitude spectrum; obtaining the complex spectrum of the excitation voltage applied to the surface of the transmitting probe; calculating the transmitting transfer function of the transmitting probe based on the first sound pressure spectrum and the excitation voltage amplitude spectrum; when the transmitting probe and the receiving probe are ultrasonic transducers, calculating the receiving transfer function of the receiving probe based on the transmitting transfer function and a pre-acquired reciprocity constant, where the reciprocity constant is a parameter of the ultrasonic transducer.

[0110] Optionally, the calculation formula of the transmission transfer function of the transmitting probe is expressed as:

[0111]

[0112] Among them, T T (f) is the transmission transfer function, P T,0 (f) is the first sound pressure spectrum, V in (f) is the complex spectrum of the excitation voltage on the surface of the transmitting probe;

[0113] The calculation formula of the receiving transfer function is expressed as:

[0114]

[0115] Among them, R load is the resistance of the load connected to the probe, A is the effective surface area of the probe, ρ is the density of water, c is the speed of sound in water, and const is the reciprocity constant.

[0116] Optionally, during the measurement phase, the measurement module 22 controls the transmitting probe to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and controls the receiving probe to receive scattered signals of microbubbles in the phantom blood vessels, including: obtaining multiple sets of preset sound pressure and pressure environmental parameters; and controlling the transmitting probe to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and controlling the receiving probe to receive scattered signals of microbubbles in the phantom blood vessels under different sound pressure and pressure environmental parameter conditions.

[0117] For other details of the technical solutions for implementing each module in the device for measuring acoustic characteristics of contrast agent microbubbles in the above embodiment, please refer to the description of the method for measuring acoustic characteristics of contrast agent microbubbles in the above embodiment, which will not be repeated here.

[0118] It should be noted that the various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. Similarities between the various embodiments can be referred to in conjunction with each other. For device embodiments, since they are generally similar to method embodiments, their description is relatively simple, and for relevant details, reference can be made to the description of the method embodiments.

[0119] See also Figure 3 , Figure 3 FIG. 1 is a schematic diagram of the structure of a computer device according to an embodiment of the present invention. Figure 3 As shown, the computer device 30 includes a processor 31 and a memory 32 coupled to the processor 31. The memory 32 stores program instructions. When the program instructions are executed by the processor 31, the processor 31 executes the steps of the contrast agent microbubble acoustic characteristics measurement method described in any of the above embodiments.

[0120] The processor 31 may also be referred to as a CPU (Central Processing Unit). The processor 31 may be an integrated circuit chip having signal processing capabilities. The processor 31 may also be a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or other programmable logic device, a discrete gate or transistor logic device, or a discrete hardware component. The general-purpose processor may be a microprocessor or any conventional processor.

[0121] See Figure 4 , Figure 4 Schematic diagram of the structure of the storage medium of the embodiment of the present invention. The storage medium of the embodiment of the present invention stores program instructions 41 that can realize the above-mentioned contrast agent microbubble acoustic property measurement method, wherein the program instructions 41 can be stored in the above-mentioned storage medium in the form of a software product, including a number of instructions for causing a computer device (which can be a personal computer, server, or network device, etc.) or a processor (processor) to execute all or part of the steps of the method described in each embodiment of the present application. The aforementioned storage medium includes: various media that can store program codes, such as a USB flash drive, a mobile hard disk, a read-only memory (ROM, Read-Only Memory), a random access memory (RAM, Random Access Memory), a magnetic disk or an optical disk, or a computer device such as a computer, a server, a mobile phone, or a tablet.

[0122] In the several embodiments provided in this application, it should be understood that the disclosed computer devices, apparatuses and methods can be implemented in other ways. For example, the device embodiments described above are merely illustrative. For example, the division of units is merely a logical function division. In actual implementation, there may be other division methods, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be an indirect coupling or communication connection through some interface, device or unit, which can be electrical, mechanical or other forms.

[0123] In addition, the functional units in the various embodiments of the present invention may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit. The above-mentioned integrated units may be implemented in the form of hardware or in the form of software functional units. The above is only an implementation method of the present application and does not limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the description and drawings of this application, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A method for measuring the acoustic properties of contrast agent microbubbles, characterized in that: The method comprises: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal; During the measurement phase, the transmitting probe is controlled to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive scattered signals of microbubbles in the phantom blood vessel; Extracting the subharmonic signal voltage amplitude from the scattered signal; Converting the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies using a receiving transfer function of the receiving probe; Determine the subharmonic optimal driving frequency and subharmonic scattering pressure according to the actual subharmonic scattering pressure; wherein: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: Acquire multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal; Performing a fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; Converting the voltage signal amplitude spectrum into an acoustic pressure signal amplitude spectrum; Obtaining a first sound pressure spectrum on the surface of the transmitting probe according to the sound pressure signal amplitude spectrum; Acquire multiple echo signals received by the receiving probe, and sum and average the multiple echo signals to obtain an average echo signal; Performing a fast Fourier transform on the average echo signal to obtain a complex spectrum of the average echo signal; Calculating a second sound pressure spectrum of the sound pressure generated by the echo signal on the surface of the receiving probe based on the first sound pressure spectrum on the surface of the transmitting probe; Calculating a receiving transfer function of the receiving probe according to the complex spectrum of the average echo signal and the second sound pressure spectrum; The calculation formula of the receiving transfer function is expressed as: Among them, T R (f) is the receiving transfer function, V out (f) is the complex spectrum of the average echo signal, P R,0 (f) is the second sound pressure spectrum.

2. The method for measuring the acoustic characteristics of contrast agent microbubbles according to claim 1, wherein: During the measurement phase, controlling the transmitting probe to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and controlling the receiving probe to receive scattered signals of microbubbles in the phantom blood vessel, includes: Obtain multiple sets of preset sound pressure and pressure environment parameters; Under different acoustic pressure and pressure environment parameter conditions, the transmitting probe is controlled to sweep frequency within a preset frequency range to transmit ultrasonic excitation signals, and the receiving probe is controlled to receive scattered signals of microbubbles in the phantom blood vessels.

3. A method for measuring the acoustic properties of contrast agent microbubbles, characterized in that: The method comprises: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal; During the measurement phase, the transmitting probe is controlled to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and the receiving probe is controlled to receive scattered signals of microbubbles in the phantom blood vessel; Extracting the subharmonic signal voltage amplitude from the scattered signal; Converting the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies using a receiving transfer function of the receiving probe; Determine the subharmonic optimal driving frequency and subharmonic scattering pressure according to the actual subharmonic scattering pressure; wherein: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: Acquire multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal; Performing a fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; Converting the voltage signal amplitude spectrum into an acoustic pressure signal amplitude spectrum; Obtaining a first sound pressure spectrum on the surface of the transmitting probe according to the sound pressure signal amplitude spectrum; Acquiring a complex spectrum of an excitation voltage applied to the surface of the transmitting probe; Calculating a transmission transfer function of the transmitting probe according to the first sound pressure spectrum and the excitation voltage amplitude spectrum; When the transmitting probe and the receiving probe are ultrasonic transducers, the receiving transfer function of the receiving probe is calculated according to the transmitting transfer function and a pre-acquired reciprocity constant, where the reciprocity constant is a parameter of the ultrasonic transducer; The calculation formula of the transmission transfer function of the transmitting probe is expressed as: Among them, T T (f) is the transmission transfer function, P T,0 (f) is the first sound pressure spectrum, V in (f) is the complex spectrum of the excitation voltage on the surface of the transmitting probe; The calculation formula of the receiving transfer function is expressed as: Among them, R load is the resistance of the load connected to the probe, A is the effective surface area of the probe, ρ is the density of water, c is the speed of sound in water, and const is the reciprocity constant.

4. The method for measuring the acoustic characteristics of contrast agent microbubbles according to claim 3, wherein: During the measurement phase, controlling the transmitting probe to sweep within a preset frequency range to transmit an ultrasonic excitation signal, and controlling the receiving probe to receive scattered signals of microbubbles in the phantom blood vessel, includes: Obtain multiple sets of preset sound pressure and pressure environment parameters; Under different acoustic pressure and pressure environment parameter conditions, the transmitting probe is controlled to sweep frequency within a preset frequency range to transmit ultrasonic excitation signals, and the receiving probe is controlled to receive scattered signals of microbubbles in the phantom blood vessels.

5. A device for measuring the acoustic properties of contrast agent microbubbles, characterized in that: The device comprises: The calibration module is used to obtain the pulse signal transmitted by the transmitting probe and the echo signal received by the receiving probe during the calibration phase, and calculate the receiving transfer function of the receiving probe using the pulse signal and the echo signal; A measuring module, configured to control the transmitting probe to sweep the frequency within a preset frequency range to transmit an ultrasonic excitation signal, and to control the receiving probe to receive scattered signals of microbubbles in the phantom blood vessel during a measurement phase; An extraction module, configured to extract a subharmonic signal voltage amplitude from the scattered signal; a conversion module, configured to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies using a receiving transfer function of the receiving probe; A confirmation module is used to confirm the subharmonic optimal driving frequency and the subharmonic scattering pressure according to the actual subharmonic scattering pressure; wherein: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: Acquire multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal; Performing a fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; Converting the voltage signal amplitude spectrum into an acoustic pressure signal amplitude spectrum; Obtaining a first sound pressure spectrum on the surface of the transmitting probe according to the sound pressure signal amplitude spectrum; Acquire multiple echo signals received by the receiving probe, and sum and average the multiple echo signals to obtain an average echo signal; Performing a fast Fourier transform on the average echo signal to obtain a complex spectrum of the average echo signal; Calculating a second sound pressure spectrum of the sound pressure generated by the echo signal on the surface of the receiving probe based on the first sound pressure spectrum on the surface of the transmitting probe; Calculating a receiving transfer function of the receiving probe according to the complex spectrum of the average echo signal and the second sound pressure spectrum; The calculation formula of the receiving transfer function is expressed as: Among them, T R (f) is the receiving transfer function, V out (f) is the complex spectrum of the average echo signal, P R,0 (f) is the second sound pressure spectrum.

6. A device for measuring the acoustic properties of contrast agent microbubbles, characterized in that: The device comprises: The calibration module is used to obtain the pulse signal transmitted by the transmitting probe and the echo signal received by the receiving probe during the calibration phase, and calculate the receiving transfer function of the receiving probe using the pulse signal and the echo signal; A measuring module, configured to control the transmitting probe to sweep the frequency within a preset frequency range to transmit an ultrasonic excitation signal, and to control the receiving probe to receive scattered signals of microbubbles in the phantom blood vessel during a measurement phase; An extraction module, configured to extract a subharmonic signal voltage amplitude from the scattered signal; a conversion module, configured to convert the subharmonic signal voltage amplitude into actual subharmonic scattering pressure at different frequencies using a receiving transfer function of the receiving probe; A confirmation module is used to confirm the subharmonic optimal driving frequency and the subharmonic scattering pressure according to the actual subharmonic scattering pressure; wherein: In the calibration phase, the pulse signal emitted by the transmitting probe and the echo signal received by the receiving probe are obtained, and the receiving transfer function of the receiving probe is calculated using the pulse signal and the echo signal, including: Acquire multiple pulse signals emitted by the transmitting probe, and sum and average the multiple pulse signals to obtain an average pulse signal; Performing a fast Fourier transform on the average pulse signal to obtain a voltage signal amplitude spectrum; Converting the voltage signal amplitude spectrum into an acoustic pressure signal amplitude spectrum; Obtaining a first sound pressure spectrum on the surface of the transmitting probe according to the sound pressure signal amplitude spectrum; Acquiring a complex spectrum of an excitation voltage applied to the surface of the transmitting probe; Calculating a transmission transfer function of the transmitting probe according to the first sound pressure spectrum and the excitation voltage amplitude spectrum; When the transmitting probe and the receiving probe are ultrasonic transducers, the receiving transfer function of the receiving probe is calculated according to the transmitting transfer function and a pre-acquired reciprocity constant, where the reciprocity constant is a parameter of the ultrasonic transducer; The calculation formula of the transmission transfer function of the transmitting probe is expressed as: Among them, T T (f) is the transmission transfer function, P T,0 (f) is the first sound pressure spectrum, V in (f) is the complex spectrum of the excitation voltage on the surface of the transmitting probe; The calculation formula of the receiving transfer function is expressed as: Among them, R load is the resistance of the load connected to the probe, A is the effective surface area of the probe, ρ is the density of water, c is the speed of sound in water, and const is the reciprocity constant.

7. A computer device, characterized in that: The computer device includes a processor and a memory coupled to the processor, wherein program instructions are stored in the memory. When the program instructions are executed by the processor, the processor performs the steps of the method for measuring the acoustic characteristics of contrast agent microbubbles as described in claim 1 or 3.

8. A storage medium, characterized in that: The device stores program instructions capable of implementing the method for measuring the acoustic characteristics of contrast agent microbubbles as claimed in claim 1 or 3.

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