Acoustic characteristic measurement method and device

Abstract

An acoustic characteristic measurement device (10) comprises: a transducer (3) configured to cause an ultrasonic beam to be incident, through a base material (102), on an object under measurement (10) and a reference member (101), which are disposed on the base material, at a plurality of positions within a prescribed measurement region, and receive reflection waves; a reflection intensity calculation unit (55) configured to perform a deconvolution operation on the reflection waves with the incident waves and calculate the distribution of reflection intensity along the direction of the ultrasonic beam at the plurality of positions; an acoustic impedance calculation unit (57) configured to calculate the distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensity; a correction unit (56) configured to compare the acoustic impedance corresponding to the reference member with a known acoustic impedance, and correct the distribution of reflection intensity; a dispersion suppression unit (58) configured to perform a process for suppressing dispersion, with respect to the distribution of acoustic impedance calculated at each of the plurality of positions, in a plane orthogonal to the direction of the ultrasonic beam; and an image generation unit (59) configured to visualize the distribution of acoustic impedance at the plurality of positions in which dispersion is suppressed, and generate an acoustic impedance image.

Description

Acoustic characteristic measurement method and device

[0001] The present invention relates to an acoustic characteristic measuring method and apparatus for obtaining an acoustic impedance image of a measurement target such as biological tissue using ultrasonic waves.

[0002] Optical microscopes and electron microscopes have been used to observe biological tissues, but ultrasonic microscopes are being developed as a device for observing biological tissues. When using optical microscopes, there is a staining method that distinguishes differences in the chemical properties of biological tissues by changing their optical properties using chemicals. On the other hand, when using ultrasonic microscopes, differences in measured acoustic parameters, such as differences in physical properties such as tissue sound velocity and acoustic impedance, are visualized, allowing for distinction without the use of chemicals or staining. Therefore, ultrasonic microscopes have attracted attention as a so-called non-invasive measurement method that has little effect on the measurement target.

[0003] In recent years, ultrasonic microscopes have made it possible to observe biological tissues at the cellular level with a resolution approaching that of optical microscopes.

[0004] For example, Non-Patent Document 1 discloses an ultrasound imaging inspection device that uses a pulsed excitation ultrasound microscope to display an acoustic impedance image of cells. In this ultrasound imaging inspection device, biological tissue is placed on a resin film, and a reference member is provided around the biological tissue. Then, while two-dimensionally scanning the ultrasound irradiation point, ultrasound is irradiated onto the cells and the reference member through the resin film to measure the acoustic impedance, thereby obtaining a two-dimensional acoustic impedance image. Here, acoustic impedance is a parameter related to the stiffness of cells, and the properties of cells can be observed using acoustic impedance images.

[0005] Furthermore, Non-Patent Document 2 proposes a method of applying time domain reflectometry (TDR) to an ultrasonic microscope, and performing deconvolution calculations on a wave reflected from biological tissue (a target signal) and a wave reflected from a reference member (a reference signal), thereby estimating the acoustic impedance distribution in the depth direction using the acoustic impedance of the reference member as a reference.

[0006] The TDR method is a technique used to investigate the characteristics of physical media such as transmission lines and cables, and generally has the following problems.

[0007] (a) Electromagnetic wave loss Electromagnetic waves can be attenuated along a transmission line or cable. This is due to the loss of some energy when the signal is reflected or due to losses in the transmission medium itself.

[0008] (b) Cable transmission characteristics: Multiple reflections may occur, or reflections may be caused by different factors. Correctly interpreting these reflections and distinguishing between their respective causes can be difficult.

[0009] (c) Noise The TDR method is often affected by noise and interference, which are difficult to completely eliminate.

[0010] To address these issues, the following compensation methods have been proposed.

[0011] (a) Time constant compensation Since attenuation due to the characteristics of the transmission path increases with increasing distance, time constant compensation compensates the measured reflected signal according to the distance, corrects errors in the measurement results, and estimates the accurate reflection position.

[0012] (b) Cable transmission characteristic compensation This is a method to compensate for attenuation and reflection due to the characteristics of transmission media such as cables and connectors. Usually, the cable transmission characteristics are calibrated in advance and modeled. Then, the measured signal is compensated using this model. The model includes system delay, gain, distortion, etc.

[0013] (c) Noise Removal Common noise removal techniques include smoothing, filtering, and waveform shaping.

[0014] (d) Multi-point compensation In addition to the above (a) to (c), measurements are taken at multiple points, and the results of these measurements are integrated and compensated to improve the reliability of the measurement results.

[0015] Yoshifumi Saijo, et al., “Ultrasound Speed ​​and Impedance Microscopy for in vivo Imaging”, Proceedings of the 29th Annual International Conference of the IEEE EMBS, 2007Edo Bagus Prastika, et al., “Three-dimensional acoustic impedance mapping of human skin by improved time-frequency domain analysis”, Japanese Journal of Applied Physics 60, SDDE22, 2021

[0016] However, there are further problems to be solved when applying the TDR method to the observation of cells or biological tissues using acoustic property measurements, which make it difficult to accurately measure the acoustic impedance distribution.

[0017] (a) Signal attenuation and scattering Biological tissues are very complex, and attenuation and scattering occur when ultrasonic waves propagate through the tissue, causing the reflected signal to weaken or exhibit a complex waveform.

[0018] (b) Tissue heterogeneity Biological tissue is heterogeneous, and the propagation speed of ultrasound changes at the boundaries between different tissues or organs. This heterogeneity affects the waveform and characteristics of the reflected signal, making it difficult to interpret the signal.

[0019] (c) Ultrasonic signal with only AC component Generally, ultrasonic waves are used to investigate only the reflection position, so AC components are acquired and DC components are ignored. There is a concern that the following problems may occur in the deconvolution calculation.

[0020] (c-1) Loss of Phase Information The DC component represents the phase information of a signal and plays an important role in the deconvolution calculation. If the DC component is ignored, the phase information of the signal is lost, and the accuracy of the deconvolution calculation decreases.

[0021] (c-2) Restoring the Baseline Since the DC component is necessary to define the baseline of a signal, if the DC component is ignored, it becomes difficult to restore the baseline, making it difficult to interpret the signal.

[0022] (c-3) Signal Bias The DC component indicates the bias (offset) of the signal. If the bias of the signal is ignored, the shape of the signal will be distorted or certain characteristics will be lost in the deconvolution calculation.

[0023] (c-4) Loss of Amplitude Information Since the DC component also contains amplitude information of the signal, if the DC component is ignored, the amplitude information of the signal is lost, making it difficult to estimate the signal strength and reflection characteristics in the deconvolution calculation.

[0024] (d) Restrictions on Observation Positions Due to their nature, cells and biological tissues that are the measurement targets cannot be used to provide measurement points inside and perform multi-point compensation.

[0025] An object of the present invention is to provide an acoustic characteristic measuring method and apparatus that can obtain a more accurate acoustic impedance image using the acoustic impedance and its distribution within a measurement object.

[0026] In order to achieve the above object, one configuration example of an acoustic property measurement method according to the present invention includes the steps of: irradiating an ultrasonic beam through a substrate at a plurality of positions within a predetermined measurement area with respect to a measurement target and a reference member placed on the substrate, and receiving reflected waves; calculating a reflection intensity distribution along the direction of the ultrasonic beam at the plurality of positions by deconvolving the reflected waves with the incident waves; calculating an acoustic impedance distribution along the direction of the ultrasonic beam from the reflection intensity distribution; correcting the reflection intensity distribution by comparing the acoustic impedance corresponding to the reference member with a known acoustic impedance; comparing the acoustic impedance distribution at a position among the plurality of positions corresponding to the reference member with the known acoustic impedance distribution to correct the reflection intensity distribution; performing processing to suppress variance in the acoustic impedance distribution calculated at each of the plurality of positions in a plane perpendicular to the direction of the ultrasonic beam; and visualizing the variance-suppressed acoustic impedance distribution at the plurality of positions to generate an acoustic impedance image.

[0027] Furthermore, one configuration example of an acoustic property measuring device according to the present invention includes: a transducer configured to irradiate an ultrasonic beam through a substrate to a measurement target and a reference member placed on the substrate at a plurality of positions within a predetermined measurement area and receive reflected waves; a reflection intensity calculation unit configured to perform a deconvolution operation on the reflected wave with the incident wave to calculate a distribution of reflection intensities along the direction of the ultrasonic beam at the plurality of positions; an acoustic impedance calculation unit configured to calculate a distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensities; a correction unit configured to compare the acoustic impedance corresponding to the reference member with a known acoustic impedance to correct the reflection intensity distribution; a variance suppression unit configured to perform processing to suppress variance in the acoustic impedance distribution calculated at each of the plurality of positions in a plane perpendicular to the direction of the ultrasonic beam; and an image generation unit configured to generate an acoustic impedance image by visualizing the variance-suppressed acoustic impedance distribution at the plurality of positions.

[0028] According to the present invention, a more accurate acoustic impedance image can be obtained using the acoustic impedance and its distribution within the measurement object.

[0029] FIG. 1 is a diagram showing an example of the configuration of an acoustic characteristics measurement apparatus according to an embodiment of the present invention. FIG. 2A is a block diagram showing an example of the configuration of a processing device. FIG. 2B is a block diagram showing an example of the configuration of a processing device. FIG. 3 is a flowchart illustrating an acoustic characteristics measurement method according to an embodiment of the present invention. FIG. 4 is a flowchart illustrating the operation of the acoustic characteristics measurement apparatus according to an embodiment of the present invention. FIG. 5 is a diagram illustrating the operation of the acoustic characteristics measurement apparatus according to an embodiment of the present invention. FIG. 6 is a diagram illustrating the principle of the acoustic characteristics measurement method according to an embodiment of the present invention. FIG. 7 is a flowchart illustrating the acoustic characteristics measurement method according to an embodiment of the present invention. FIG. 8 is a diagram schematically illustrating reflection intensity correction in the acoustic characteristics measurement method according to an embodiment of the present invention. FIG. 9 is a diagram illustrating the acoustic characteristics measurement method according to an embodiment of the present invention. FIG. 10A is a diagram showing an example of a 3D image of a measurement object without correction processing. FIG. 10B is a diagram showing an example of a 3D image of a measurement object with correction processing. FIG. 11 is a diagram showing an example of an acoustic impedance distribution without correction processing and an example of an acoustic impedance distribution with correction processing.

[0030] An acoustic characteristic measuring method and apparatus according to an embodiment of the present invention will be described below with reference to the drawings.

[0031] [Configuration of Acoustic Characteristics Measurement Apparatus] FIG. 1 is a diagram illustrating the configuration of an acoustic characteristics measurement apparatus according to an embodiment of the present invention.

[0032] 1, biological tissue 100 to be measured is supported by a substrate 102 that constitutes a part of a container 10. The substrate 102 is, for example, a resin film made of polystyrene or the like. The area around the biological tissue 100 in the container 10 is filled with a culture solution 101 that serves as a reference member. The culture solution 101 is made of a material with a known acoustic impedance, such as water.

[0033] The acoustic property measuring device according to the embodiment includes a transducer 3 that converts electrical energy into ultrasonic waves and vice versa, an acoustic lens 2 that focuses the ultrasonic waves emitted from the transducer 3 and irradiates the target biological tissue 100 with an ultrasonic beam 20, a scanning stage 4 that can move the transducer 3 in the axial direction of the ultrasonic beam 20 and in a horizontal direction perpendicular to this axis (hereinafter, the direction perpendicular to the axis of the ultrasonic beam 20 irradiated to the biological tissue 100 is referred to as the "horizontal direction"), a processing device 5 that processes the ultrasonic waves received by the transducer 3 and converted into electrical signals to generate a three-dimensional (3D) image of the target biological tissue 100, and a display device 6 that displays the 3D image generated by the processing device 5. Distilled water 103 is used as a propagation medium for ultrasonic waves between the bottom of the resin film 102 and the acoustic lens 2.

[0034] By mounting the transducer 3 on the scanning stage 4, the transducer 3 can be scanned across the biological tissue 100 on the substrate 102, and the ultrasonic beam 20 can be incident through the substrate 102 at multiple positions within a predetermined measurement region. The scanning stage 4 can be a linear stage using a stepping motor, a piezo stage, or the like. Alternatively, a beam manipulation mechanism such as a galvanometer mirror can be used instead of the scanning stage 4.

[0035] As shown in FIG. 2A , the processing device 5 is composed of a transmitting unit 50, a receiving unit 51, a control unit 52, a memory unit 53, a reference area extraction unit 54, a reflection intensity calculation unit 55, a correction unit 56, an acoustic impedance calculation unit 57, a dispersion suppression unit 58, and an image generation unit 59.

[0036] Here, the transmitting unit 50 is a circuit configured to supply a driving transmission pulse to the transducer 3, thereby causing the transducer 3 to transmit an ultrasonic pulse. The receiving unit 51 is a circuit configured to store the signal of the reflected wave output from the transducer 3 in the memory unit 53.

[0037] The control unit 52 is a control circuit that controls the movement of the scanning stage 4. The control unit 52 allows the scanning stage 4 to move the transducer 3 along the axial direction of the ultrasonic beam irradiated onto the biological tissue 100, and simultaneously move the transducer 3 along a direction perpendicular to the axial direction. The control unit 52 can also adjust the position of the transducer 3 so that the absolute value of the intensity of the reflected wave is maximized.

[0038] The storage unit 53 is a storage device that stores various data. The reference region extraction unit 54 extracts, as a reference region, a region within a predetermined measurement region that does not contain biological tissue 100, based on the intensity of the waveform of the reflected wave. For example, the reference region extraction unit 54 can extract, as a reference region, a region in which the maximum absolute value of the intensity is equal to or greater than a predetermined threshold.

[0039] The reflection intensity calculation unit 55 is configured to perform a deconvolution operation on the reflected wave with the incident wave to calculate the distribution of reflection intensity along the direction of the ultrasonic beam at a plurality of positions.

[0040] The correction unit 56 is configured to correct the distribution of reflection intensity by comparing the distribution of acoustic impedance at a position among the multiple positions corresponding to the culture solution 101, which is a reference member, with the distribution of known acoustic impedance of the culture solution 101.

[0041] The acoustic impedance calculation unit 57 is configured to calculate the distribution of acoustic impedance along the direction of the axis of the ultrasonic beam 20 from the distribution of the corrected reflection intensity.

[0042] The dispersion suppression unit 58 is configured to perform processing to suppress dispersion in a plane perpendicular to the direction of the axis of the ultrasonic beam for the acoustic impedance distribution calculated at each of a plurality of positions within the measurement region. The image generation unit 59 is configured to visualize the dispersion-suppressed acoustic impedance distribution at a plurality of positions to generate an acoustic impedance image and display it on the display device 6.

[0043] As shown in FIG. 2B, such a processing device 5 is realized by cooperation between a computer including an arithmetic unit (CPU) 500, a memory device 501, and various interface circuits (I / F) 502, and a computer program installed on the computer.

[0044] [Operation of Acoustic Characteristics Measuring Apparatus] Next, the operation of the acoustic characteristics measuring apparatus and the acoustic characteristics measuring method will be described.

[0045] [Measurement of Reflected Waves] In the acoustic property measuring device according to this embodiment, as shown in FIG. 3 , an ultrasonic beam 20 is irradiated from a transducer 3 via an acoustic lens 2, and a predetermined area of ​​a resin film 102 carrying a biological tissue 100 is scanned. The ultrasonic beam 20 is irradiated onto the biological tissue 100 and the culture solution 101 at a plurality of positions Pa and Pb, and the reflected waves are received.

[0046] More specifically, as shown in FIG. 4 , the scanning stage 4 carrying the transducer 3 is controlled by the control unit 52 to move to the measurement position ( FIG. 4 , step S10), and the transducer 3 is positioned at that measurement position ( FIG. 4 , step S20). Next, the transmitter 50 supplies a driving transmission pulse to the transducer 3 to transmit an ultrasonic pulse ( FIG. 4 , step S30), and receives a reflected wave ( FIG. 4 , step S40). The reflected wave signal output from the transducer 3 is stored in the memory unit 53 by the receiver 51 ( FIG. 4 , step S50). If the measurement of the reflected wave has not been completed at all measurement positions ( FIG. 4 , step S60: No), the stage is moved to the next measurement position ( FIG. 4 , step S10). If the measurement has been completed ( FIG. 4 , step S60: Yes), the series of measurement processes is terminated. This process allows the ultrasound beam 20 to scan the measurement area, including the entire biological tissue 100.

[0047] [Transducer Positioning] When irradiating an ultrasonic beam 20 in an area including biological tissue 100 as viewed from the transducer 3 side and receiving the resulting reflected waves, the position of the transducer 3 in the axial direction of the ultrasonic beam is fixed as follows.

[0048] First, the transmitter 50 supplies a driving transmission pulse to the transducer 3, causing the transducer 3 to emit an ultrasonic pulse (FIG. 5, step S200). The acoustic lens 2 focuses the ultrasonic waves emitted from the transducer 3 into a beam and irradiates the beam onto the biological tissue 100 or the culture solution 101 through the resin film 102. The transducer 3 receives the reflected waves from the biological tissue 100 or the culture solution 101.

[0049] The receiving unit 51 receives the signal of the reflected wave received by the transducer 3 and stores it in the storage unit 53 (FIG. 5, step S201).

[0050] The control unit 52 controls the scanning stage 4 to move the transducer 3 along the axial direction of the ultrasonic beam irradiated onto the biological tissue 100, and simultaneously move the transducer 3 along a direction perpendicular to the axial direction (FIG. 5, step S202). The control unit 52 adjusts the axial position of the transducer 3 so that the absolute value of the intensity of the reflected wave is maximized (FIG. 5, step S203). The direction perpendicular to the axial direction of the ultrasonic beam irradiated onto the biological tissue 100 is sometimes referred to as the horizontal direction.

[0051] [Principle of Acoustic Characteristic Measurement] Here, the principle of acoustic characteristic measurement will be described.

[0052] 1 and 3, the peripheral portion of the biological tissue 100 within the range scanned by the ultrasonic waves is filled with a culture solution 101. In the acoustic property measuring device described above, the transducer 3 is moved in the horizontal direction to change its position relative to the resin film 102, and ultrasonic waves are irradiated onto the biological tissue 100 and the culture solution 101 via the resin film 102, and reflected waves are received from each.

[0053] At this time, the relationship of equation (1) holds between the ultrasonic wave S0 irradiated to the culture solution 101 at an angle perpendicular to the surface thereof and the reflected wave Sr from the culture solution 101.

[0054] Sr=(Zs−Zr) / (Zs+Zr)S0 (1) Zs is the acoustic impedance of the resin film 3 , and Zr is the acoustic impedance of the culture solution 101 .

[0055] The relationship of Equation (2) holds between the ultrasonic wave S0 irradiated onto the biological tissue 100 at an angle perpendicular to the surface of the biological tissue 100 and the reflected wave St from the biological tissue 100.

[0056] St=(Zs-Zt) / (Zs+Zt)S0 (2) Zt is the acoustic impedance of the biological tissue 100. Therefore, from equations (1) and (2), the acoustic impedance Zt of the biological tissue 100 can be calculated by equation (3).

[0057] 1, the acoustic impedance Zt can be measured while moving the transducer 3 using the scanning stage 4, thereby obtaining the acoustic impedance at multiple positions distributed two-dimensionally. The acoustic impedance Zt of the biological tissue 100 is a parameter related to the stiffness of the biological tissue 100.

[0058] [Acoustic Characteristic Measurement Method] Hereinafter, an acoustic characteristic measurement method according to this embodiment will be described with reference to FIGS.

[0059] Generally, biological tissue 100 is composed of multiple thin layers. Figure 6 shows a schematic diagram of the reflection of ultrasound waves in biological tissue 100. If the acoustic impedances of each layer of biological tissue 100 are Z1, Z2, ... Zi-1, Zi (i is an integer equal to or greater than 2), an incident wave S0 from transducer 3 is reflected at the interface between two layers with different acoustic impedances (Rs1, R12, R23, ...), and the reflected wave from biological tissue 100 received by transducer 3 includes reflections from the interfaces of multiple layers of biological tissue 100, which are distributed along the time axis as t0, t1, t2, ... ti-1, ti.

[0060] On the other hand, in the culture solution 101, a reflected wave for the incident wave S0 from the transducer 3 is generated only at the interface between the resin film 102, which is the base material, and the culture solution 101. The acoustic impedance Zs of the resin film 102, which is the base material, is a known value. The acoustic impedance of the culture solution 101, which acts as a reference member, is also known.

[0061] Therefore, the reflection intensity calculation unit 55 sequentially calculates the acoustic impedances Z1, Z2, . . . Zi-1, Zi (i is an integer of 2 or more) of each layer of the biological tissue 100 shown in FIG. 6 as follows.

[0062] First, the reflection intensity calculation unit 55 performs a process of deconvolving the incident wave S0 with the reflected wave Sout for each measurement position to calculate the reflection intensity q along the axis direction of the ultrasonic beam 20 at multiple positions (Figure 7, step S30).

[0063] 6, Zp is the acoustic impedance of the resin film 102, Zn (n is a natural number equal to or greater than 1) is the acoustic impedance of each of the multiple layers constituting the biological tissue 100, and Zm is the acoustic impedance of the culture solution 101 acting as a reference member. The reflectance Rin→out and transmittance Tin→out at the interface between two adjacent media having different acoustic impedances can be expressed as the following equations (4) and (5), where Zin and Zout are the acoustic impedances of the two adjacent media, respectively.

[0064]

[0065] The transmittance when the incident ultrasonic beam 20 is received by the transducer 3 as a reflected wave is the product of the transmittance Tin→out on the outward path and the transmittance Tout→in on the return path, and can be expressed from equation (5) as the following equation (6).

[0066]

[0067] On the other hand, the incident intensity Sin of the ultrasonic beam 20 is expressed by the following equations (7) and (8), where Sref is the intensity of the reflected wave reflected at the interface between the resin film 102 and the culture solution 101.

[0068]

[0069] Furthermore, the reflection intensity can be expressed by the following formula (9) from the definition, and when this is subjected to an inverse Fourier transform to make it a function of time, it can be expressed as formula (10).

[0070]

[0071] Furthermore, in FIG. 6, when the relationship between time (t0, t1, ..., ti) and reflection intensity (q0, q1, ..., qi) is shown, the reflection intensity, reflectivity, acoustic impedance, and round-trip transmittance can be expressed as follows:

[0072]

[0073] From the above, the acoustic impedance Zn of the n-th layer counted from the resin film 102 can be expressed by the following equation (11).

[0074]

[0075] Here, the component q(t0) of the reflection intensity q corresponds to the wave reflected from the interface between the resin film 102 and the biological tissue 100, as shown in Fig. 6. The component q(t1) corresponds to the wave reflected from the interface between the layer closest to the resin film 102 and the second closest layer of the biological tissue 100. The component q(t2) corresponds to the wave reflected from the interface between the layer second closest to the resin film 102 and the third closest layer of the biological tissue 100. In this way, the signal q corresponding to the wave reflected from the interface of each layer of the biological tissue 100 can be obtained.

[0076] Next, the acoustic impedance calculation unit 57 calculates the distribution of acoustic impedance along the direction of the axis of the ultrasonic beam 20 from the distribution of reflection intensity by the TDR method (FIG. 7, step S31).

[0077] Based on the acoustic impedance calculated by the acoustic impedance calculation unit 57 using the TDR method, the correction unit 56 corrects the distribution of reflection intensity that was the basis for calculating the acoustic impedance. Specifically, the correction unit 56 compares the distribution of acoustic impedance at a position among the multiple positions that corresponds to the culture solution 101 with the distribution of known acoustic impedance ( FIG. 7 , step S32), and if the two do not match ( FIG. 7 , step S32: No), corrects the reflection intensity so that the distribution of acoustic impedance at the position that corresponds to the culture solution 101 matches the known acoustic impedance of the culture solution 101 ( FIG. 7 , step S33), and then calculates the acoustic impedance distribution again ( FIG. 7 , step S31).

[0078] FIG. 8 is a diagram illustrating the correction of reflection intensity with reference to the acoustic impedance of the culture solution 101. The distribution of the known acoustic impedance of the culture solution 101 is shown by a solid line, and the distribution of the actually calculated acoustic impedance is shown by a dashed line. Comparing the two, the calculated acoustic impedance of the culture solution 101 appears lower than the known value. Therefore, the correction unit 56 multiplies the reflection intensity q obtained by the deconvolution process by a correction constant G so that the calculated acoustic impedance matches the known value. The degree to which the calculated acoustic impedance matches the known value can be kept within a certain percentage of the known acoustic impedance.

[0079] The correction method is not limited to multiplication by the correction constant G, and for example, a linear function (Az+B, where A and B are constants) or a nonlinear function (exp(-Az), where A is a constant) that changes depending on the time t, i.e., the distance (depth z) in the axial direction of the ultrasonic beam 20, can also be used.

[0080] Although the example in which the culture solution 101 is used as the reference member has been described, a reference member other than the culture solution 101 can be used as long as the acoustic impedance is known. For example, instead of the culture solution 101, the container 10 or the resin film 102 may be used as the reference member.

[0081] In this way, if, as a result of correcting the distribution of reflection intensity, the difference between the acoustic impedance corresponding to the culture solution 101 and the known acoustic impedance of the culture solution 101 falls within a certain range (FIG. 7, step S32: Yes), calculation of the acoustic impedance is performed for the next measurement position until calculations at all measurement positions are completed (FIG. 7, step S34).

[0082] If the calculation of the acoustic impedance has been completed at all measurement positions (FIG. 7, step S34: Yes), the dispersion suppression unit 58 performs dispersion suppression processing (FIG. 7, step S35), and the image generation unit 59 generates an image representing the distribution of the acoustic impedance (FIG. 7, step S36).

[0083] Here, the variance suppression process is a process for suppressing the influence of calculation of the distribution of acoustic impedance in the direction of the axis of the ultrasonic beam 20. In order to suppress the influence of calculation of the depth direction distribution of acoustic impedance, this variance suppression process is performed in a two-dimensional plane (for example, Frame i shown in FIG. 9 ) perpendicular to the direction of the axis of the ultrasonic beam 20 (depth z). Statistical processing such as averaging may be performed on adjacent planes in the depth direction to reduce the influence of calculation errors and noise in the depth direction.

[0084] The following methods can be used for variance suppression processing: (1) Total variation denoising This is a method that achieves both smoothing of images and signals and preservation of edges. It can smooth out sharp changes in edges of images and signals and suppress changes in smooth areas. Specifically, by minimizing local changes in images and signals (total variation), it is possible to remove noise and preserve edges, thereby making effective use of edge information of the measurement target.

[0085] (2) Wiener filter: A linear filter widely used in signal processing. It calculates optimal filter coefficients based on the characteristics of the noise and the original signal. Although it has limited edge preservation ability, it can restore the signal while minimizing noise by using the power spectral density of the noise and the signal, and the power spectral density of the signal.

[0086] (3) Median filter: A filtering method that replaces each pixel or sample of an image or signal with the median value of the surrounding area. Although bias errors may occur, it is less susceptible to noise and can remove outliers.

[0087] (4) Gaussian filter: A filter that calculates a weighted average of surrounding pixels or samples to smooth out noise. This results in blurring (smoothing) of the image.

[0088] (5) Bilateral filter: Taking into account the distance and color similarity of surrounding pixels and samples, a weighted average is calculated to remove noise while preserving edges.

[0089] 10A and 10B are visualizations of the measured acoustic impedance of biological tissue (cells). Fig. 10A is an image obtained without correction of reflection intensity or dispersion suppression processing, and Fig. 10B is an image obtained with correction of reflection intensity and dispersion suppression processing.

[0090] 11A and 11B show the acoustic impedance distributions of cross sections parallel to the y-z plane in Figures 10A and 10B, respectively, shifted by 3 μm in the x-axis direction. High-quality images are achieved by suppressing two-dimensional dispersion and matching the intensity of the reflected signal to the known signal intensity at the reference position.

[0091] As described above, according to the acoustic characteristic measuring device and method of the present embodiment, a more accurate acoustic impedance image can be obtained using the acoustic impedance and its distribution within the measurement object.

[0092] (Additional Notes) The following additional notes are further disclosed in relation to the above-described embodiment.

[0093] (Supplementary Note 1) An acoustic characteristic measurement method comprising the steps of: irradiating an ultrasonic beam through a substrate to a measurement target and a reference member placed on the substrate at a plurality of positions within a predetermined measurement area, and receiving reflected waves; calculating a distribution of reflection intensities along the direction of the ultrasonic beam at the plurality of positions by performing a deconvolution operation on the reflected waves with the incident waves; calculating a distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensities; correcting the distribution of reflection intensities by comparing the acoustic impedance corresponding to the reference member with a known acoustic impedance; performing a process to suppress variance in the calculated acoustic impedance distribution at each of the plurality of positions in a plane perpendicular to the direction of the ultrasonic beam; and visualizing the variance-suppressed acoustic impedance distribution at the plurality of positions to generate an acoustic impedance image.

[0094] (Supplementary Note 2) The acoustic characteristic measurement method according to Supplementary Note 1, wherein the reference member is either a container that holds the measurement object or a medium surrounding the measurement object.

[0095] (Supplementary Note 3) In the acoustic characteristic measurement method described in Supplementary Note 1 or 2, the step of correcting the distribution of reflection intensity comprises performing the correction using a correction coefficient calculated based on the difference between the acoustic impedance corresponding to the reference member and the known acoustic impedance of the reference member, the correction coefficient being a coefficient for matching the acoustic impedance corresponding to the reference member to the known acoustic impedance of the reference member.

[0096] (Supplementary Note 4) An acoustic property measuring device comprising: a transducer configured to irradiate an ultrasonic beam through a substrate to a measurement target and a reference member placed on the substrate at a plurality of positions within a predetermined measurement area and receive reflected waves; a reflection intensity calculation unit configured to calculate a distribution of reflection intensity along the direction of the ultrasonic beam at the plurality of positions by performing a deconvolution operation on the reflected wave with the incident wave; an acoustic impedance calculation unit configured to calculate a distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensity; a correction unit configured to correct the distribution of reflection intensity by comparing an acoustic impedance corresponding to the reference member with a known acoustic impedance; a variance suppression unit configured to perform a process to suppress variance in the acoustic impedance distribution calculated at each of the plurality of positions in a plane orthogonal to the direction of the ultrasonic beam; and an image generation unit configured to generate an acoustic impedance image by visualizing the variance-suppressed acoustic impedance distribution at the plurality of positions.

[0097] The present invention can be applied to an acoustic characteristic measuring method and apparatus for obtaining an acoustic impedance image of a measurement target such as biological tissue by using ultrasonic waves.

[0098] 10...container, 2...acoustic lens, 20...ultrasonic beam, 3...transducer, 4...scanning stage, 5...processing unit, 6...display unit, 50...transmitting unit, 51...receiving unit, 52...control unit, 53...memory unit, 55...iterative intensity calculation unit, 56...correction unit, 57...acoustic impedance, 58...dispersion suppression unit, 59...image generation unit.

Claims

1. A method for measuring acoustic characteristics, comprising: a step of irradiating an ultrasonic beam through a substrate at a plurality of positions within a predetermined measurement area with respect to a measurement target and a reference member placed on the substrate, and receiving reflected waves; a step of deconvolving the reflected waves with the incident waves to calculate a distribution of reflection intensity along the direction of the ultrasonic beam at the plurality of positions; a step of calculating a distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensity; a step of correcting the distribution of reflection intensity by comparing the acoustic impedance corresponding to the reference member with a known acoustic impedance; a step of performing processing to suppress variance in the calculated acoustic impedance distribution at each of the plurality of positions in a plane perpendicular to the direction of the ultrasonic beam; and a step of visualizing the variance-suppressed acoustic impedance distribution at the plurality of positions to generate an acoustic impedance image.

2. An acoustic characteristic measuring method according to claim 1, wherein the reference member is either a container that holds the object to be measured or a medium surrounding the object to be measured.

3. An acoustic characteristic measurement method according to claim 1 or 2, wherein the step of correcting the distribution of reflection intensity comprises performing the correction using a correction coefficient calculated based on the difference between the acoustic impedance corresponding to the reference member and the known acoustic impedance of the reference member, the correction coefficient being a coefficient for matching the acoustic impedance corresponding to the reference member to the known acoustic impedance of the reference member.

4. An acoustic property measuring device comprising: a transducer configured to irradiate an ultrasonic beam through a substrate to a measurement target and a reference member placed on the substrate at a plurality of positions within a predetermined measurement area and receive reflected waves; a reflection intensity calculation unit configured to perform a deconvolution operation on the reflected wave with the incident wave to calculate a distribution of reflection intensity along the direction of the ultrasonic beam at the plurality of positions; an acoustic impedance calculation unit configured to calculate a distribution of acoustic impedance along the direction of the ultrasonic beam from the distribution of reflection intensity; a correction unit configured to correct the distribution of reflection intensity by comparing the acoustic impedance corresponding to the reference member with a known acoustic impedance; a variance suppression unit configured to perform processing to suppress variance in the acoustic impedance distribution calculated at each of the plurality of positions in a plane perpendicular to the direction of the ultrasonic beam; and an image generation unit configured to generate an acoustic impedance image by visualizing the variance-suppressed distribution of acoustic impedance at the plurality of positions.

Images