Ultrasonic image acquisition device and method

Abstract

An ultrasonic image acquisition device comprises: a beam operation unit (6) that shifts the irradiation position in the axial direction of an ultrasonic beam along the axial direction of the ultrasonic beam from a position at which the intensity of a reflected wave becomes maximum; a library creation unit (55) that performs processing for acquiring, as an index indicating the magnitude of the strain of a resin film 3, the time from the transmission time of the ultrasonic wave to the time at which the absolute value of the intensity of the reflected wave becomes maximum, for each position in the horizontal direction in a reference region, and creates a library in which the index and a reference waveform are associated, the reference waveform being the waveform of the reflected wave at the position where the index was acquired; and an acoustic impedance calculation unit (56) that calculates the acoustic impedance of the measurement object on the basis of the reference waveform and the waveform of the reflected wave in the region of the measurement object.

Description

Ultrasound image acquisition device and method

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

[0002] Observation of biological tissues has traditionally been performed using optical microscopes and electron microscopes. In recent years, ultrasonic microscopes with resolution equivalent to that of optical microscopes have been put to practical use, making it possible to observe biological tissues at the cellular level. When using ultrasonic microscopes, ultrasonic images such as sound velocity images and acoustic impedance images can be obtained from measured acoustic parameters such as tissue sound velocity and acoustic impedance.

[0003] Development of ultrasonic microscopes as diagnostic devices for biological tissues is progressing, and it is now possible to observe biological tissues with a resolution approaching that of optical microscopes. Optical microscopes use a staining method to distinguish between different chemical properties in biological tissues by changing their optical properties using chemicals. On the other hand, ultrasonic microscopes can distinguish between different physical properties, such as sound speed and acoustic impedance, without the use of chemicals or staining, which minimizes the impact on the subject and allows for non-invasive observation of biological tissues.

[0004] An ultrasonic imaging inspection device has been proposed that displays acoustic impedance images of cells using a pulsed excitation ultrasonic microscope (Non-Patent Document 1). The configuration of the ultrasonic imaging inspection device is shown in Figure 13. In this ultrasonic imaging inspection device, a reference member 101 is provided at the peripheral position of biological tissue 100 within the range scanned by ultrasonic waves, and ultrasonic waves are irradiated onto the biological tissue 100 and the reference member 101 via a resin film 3. In Figure 13, 102 denotes an ultrasonic beam irradiated from a transducer 1. In Figure 13, 4 denotes a scanning stage that moves the transducer 1 to change the position at which the ultrasonic beam is irradiated, and 103 denotes water, which is the ultrasonic propagation medium.

[0005] The relationship between the ultrasonic wave S0 irradiated to the reference member 101 at an angle perpendicular to its surface and the reflected wave Sr from the reference member 101 is expressed by the following equation (1): Sr=(Zs-Zr) / (Zs+Zr)S0 (1)

[0006] Zs is the acoustic impedance of the resin film 3, and Zr is the acoustic impedance of the reference member 101. The relationship between the ultrasonic wave S0 irradiated to the biological tissue 100 at an angle perpendicular to its surface and the reflected wave St from the biological tissue 100 satisfies the following equation (2): St = (Zs - Zt) / (Zs + Zt) S0 (2)

[0007] 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).

[0008]

[0009] In the ultrasonic imaging inspection device shown in Figure 13, a two-dimensional acoustic impedance image can be obtained by measuring the acoustic impedance Zt while moving the transducer 1 using the scanning stage 4. The acoustic impedance Zt is a parameter related to the stiffness of the biological tissue 100. The properties of the biological tissue 100 can be observed using the acoustic impedance image. Furthermore, a method has been proposed for estimating the acoustic impedance distribution in the depth direction using the acoustic impedance of the resin film 3 as a reference (Non-Patent Document 2).

[0010] However, since the resin film 3 has a thickness of only a few tens of micrometers, it is difficult to create a flat surface like an optical component. Therefore, even if the observation area of ​​the biological tissue 100 is a few tens of micrometers square, distortion and tilt exist in the resin film 3. In an ultrasound imaging inspection device, the ultrasonic beam is assumed to be a plane wave that propagates uniformly in the irradiation axis direction. However, in reality, the ultrasonic beam is focused by the acoustic lens 2 to irradiate a minute area, and the ultrasonic beam has a shape with a Gaussian distribution. The profile of a Gaussian beam is shown in Equations (4) to (8).

[0011]

[0012] In equations (4) to (8), λ is the wavelength of the ultrasonic beam, b is the confocal parameter, z Ｒ is the Rayleigh region, Z Ｒ is the Rayleigh radius, z is the axial distance, R(z) is the radius of curvature, ω(z) is the beam radius, θ is the beam divergence radius, ω ０ is the beam waist. The beam width of a Gaussian beam narrows toward the focal position and widens after passing through the focal position. Therefore, if the irradiation position of the ultrasonic beam is shifted due to distortion of the resin film 3, the beam spot will widen and the shape of the reflected wave will also change. If the acoustic impedance is calculated without taking into account such changes in the shape of the reflected wave, accurate acoustic impedance cannot be obtained.

[0013] FIG. 14 shows the relationship between the axial distance and the beam radius when the focal position is set to a distance of 0. FIG. 15 shows the relationship between the axial distance and the beam intensity when the focal position is set to a distance of 0. Here, the characteristics are shown for a transducer 1 having an ultrasonic center frequency of 320 MHz, a focal distance of 600 μm, and a beam waist of 2.5 μm. In FIGS. 14 and 15 , the more negative the distance value, the closer the transducer is, and the more positive the distance value, the farther the transducer is. As shown by the dashed line 200 in FIGS. 14 and 15 , the beam radius and beam intensity change nonlinearly with respect to the axial distance near the focal position, making it difficult to correct the shape of the reflected wave.

[0014] 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

[0015] The present invention has been made to solve the above-mentioned problems, and aims to provide an ultrasonic image acquisition device and method that can eliminate the effects of changes in beam diameter and beam intensity due to distortion of the substrate.

[0016] The ultrasonic image acquisition device of the present invention includes a transducer configured to transmit and receive ultrasonic waves, an acoustic lens configured to focus an ultrasonic beam emitted from the transducer onto a measurement target on a substrate and irradiate the measurement target through the substrate, a beam manipulation unit configured to shift the axial irradiation position of the ultrasonic beam along the axial direction of the ultrasonic beam from a position where the intensity of the reflected wave from the measurement target is maximized, and then scan the entire region of the measurement target with the ultrasonic beam, and a reference region extractor configured to create a reflection intensity map that depicts the intensity of the reflected wave obtained by the scanning on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, and to extract a region where the measurement target is not present as a reference region based on the reflection intensity map. The acoustic impedance calculation device is characterized by comprising: an extraction unit; a library creation unit configured to perform a process of acquiring, for each horizontal position in the reference area, the time from the transmission time of the ultrasonic wave to the time when the absolute value of the intensity of the reflected wave is maximum as an index indicating the magnitude of strain in the substrate, and to create a library in which the index and the reference waveform are associated with each other by using the waveform of the reflected wave at the position where the index was acquired as a reference waveform; and a first acoustic impedance calculation unit configured to acquire from the library a reference waveform corresponding to the index for a position to be calculated in a region of the measurement object other than the reference area, and to calculate the acoustic impedance of the measurement object for each horizontal position in the region of the measurement object based on the waveform of the reflected wave at the position to be calculated and the reference waveform acquired from the library.

[0017] The ultrasonic image acquisition method of the present invention includes a first step of focusing an ultrasonic beam emitted from a transducer onto a measurement object on a substrate and irradiating the measurement object through the substrate; a second step of shifting an axial irradiation position of the ultrasonic beam along the axial direction of the ultrasonic beam from a position where the intensity of a reflected wave from the measurement object is maximum; a third step of scanning the entire region of the measurement object with the ultrasonic beam; a fourth step of creating a reflection intensity map in which the intensity of the reflected wave obtained by the scanning is plotted on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, and extracting a region where the measurement object is not present as a reference region based on the reflection intensity map; a fifth step of performing a process of obtaining, for each horizontal position in the reference area, the time from the time the wave is transmitted to the time when the absolute value of the intensity of the reflected wave is maximum, as an index indicating the magnitude of strain in the substrate, and using the waveform of the reflected wave at the position where the index is obtained as a reference waveform to create a library in which the index and the reference waveform correspond to each other; and a sixth step of obtaining, from the library, a reference waveform corresponding to the index for a position to be calculated in an area of ​​the measurement object other than the reference area, and calculating the acoustic impedance of the measurement object for each horizontal position in the area of ​​the measurement object based on the waveform of the reflected wave at the position to be calculated and the reference waveform obtained from the library.

[0018] According to the present invention, by providing a beam manipulation unit, a reference region extraction unit, a library creation unit, and a first acoustic impedance calculation unit, it is possible to eliminate the influence of changes in beam diameter and beam intensity due to distortion of the substrate.

[0019] FIG. 1 is a block diagram showing the configuration of an ultrasound imaging apparatus according to an embodiment of the present invention. FIG. 2 is a flowchart illustrating the operation of the ultrasound imaging apparatus according to an embodiment of the present invention. FIG. 3 is a flowchart illustrating the operation of the ultrasound imaging apparatus according to an embodiment of the present invention. FIG. 4 is a flowchart illustrating the operation of the ultrasound imaging apparatus according to an embodiment of the present invention. FIG. 5 is a diagram showing an example of the waveform of a reflected wave received by a transducer. FIG. 6 is a diagram showing an example of a reflection intensity map according to an embodiment of the present invention. FIG. 7 is a diagram visually explaining the concept of a library according to an embodiment of the present invention using the waveform of a reflected wave. FIG. 8 is a flowchart illustrating the operation of an acoustic impedance calculation unit according to an embodiment of the present invention. FIG. 9 is a diagram illustrating a method of calculating three-dimensional acoustic impedance according to an embodiment of the present invention. FIG. 10A is an acoustic impedance image of cardiomyocytes in the horizontal direction calculated by a conventional method. FIG. 10B is an acoustic impedance image of cardiomyocytes in the depth direction calculated by a conventional method. FIG. 11A is an acoustic impedance image of cardiomyocytes in the horizontal direction calculated by an embodiment of the present invention. FIG. 11B is an acoustic impedance image of cardiomyocytes in the depth direction calculated by an embodiment of the present invention. Fig. 12 is a block diagram showing an example of the configuration of a computer that realizes an ultrasound image acquisition apparatus according to an embodiment of the present invention. Fig. 13 is a diagram showing the configuration of a conventional ultrasound image acquisition apparatus. Fig. 14 is a diagram showing the relationship between axial distance and beam radius. Fig. 15 is a diagram showing the relationship between axial distance and beam intensity.

[0020]

[0016] An embodiment of the present invention will now be described with reference to the drawings. Fig. 1 is a block diagram showing the configuration of an ultrasound imaging device according to an embodiment of the present invention. The ultrasound imaging device includes a transducer 1 for transmitting and receiving ultrasound, an acoustic lens 2 for focusing the ultrasound beam emitted from the transducer 1 and irradiating it onto biological tissue 100 to be measured, a resin film 3 (substrate) such as polystyrene for supporting the biological tissue 100, a scanning stage 4 capable of moving the transducer 1 in the axial direction of the ultrasound beam and in a horizontal direction perpendicular to the axial direction, and a processing device 5.

[0021] The processing device 5 comprises a transmitting unit 50 , a receiving unit 51 , a control unit 52 , a storage unit 53 , a reference region extracting unit 54 , a library creating unit 55 , and acoustic impedance calculating units 56 and 57 .

[0022] The scanning stage 4 may be a linear stage using a stepping motor or a piezo stage. The scanning stage 4 and the control unit 52 constitute a beam manipulation unit 6. Although not shown in FIG. 1 , distilled water is used as a propagation medium for ultrasonic waves between the bottom of the resin film 3 and the transducer 1.

[0023] First, referring to FIG. 2, a defocusing process will be described in which the irradiation position of the ultrasonic beam on the biological tissue 100 is slightly shifted along the axial direction of the ultrasonic beam from the position where the intensity of the reflected wave from the biological tissue 100 is maximum before acquiring an ultrasonic image.

[0024] The transmitter 50 supplies a driving transmission pulse to the transducer 1, causing the transducer 1 to transmit an ultrasonic pulse (step S100 in FIG. 2). The acoustic lens 2 focuses the ultrasonic beam emitted from the transducer 1 and irradiates it onto the biological tissue 100 through the resin film 3, and causes the reflected wave from the biological tissue 100 to enter the transducer 1.

[0025] The transducer 1 receives the reflected wave from the biological tissue 100. The receiving unit 51 stores the signal of the reflected wave output from the transducer 1 in the storage unit 53 (step S101 in FIG. 2).

[0026] The control unit 52 controls the scanning stage 4 to move the transducer 1 along the axial direction of the ultrasonic beam irradiated onto the biological tissue 100 (step S102 in FIG. 2). The control unit 52 adjusts the position of the transducer 1 so that the intensity of the reflected wave is maximized (step S103 in FIG. 2).

[0027] Next, the control unit 52 fixes the position of the transducer 1 in the axial direction of the ultrasonic beam by the processes of steps S102 and S103, and then controls the scanning stage 4 to move the transducer 1 in a direction perpendicular to the axial direction of the ultrasonic beam irradiated to the biological tissue 100. In this way, the entire area of ​​the biological tissue 100 is scanned with the ultrasonic beam (step S104 in FIG. 2). Hereinafter, the direction perpendicular to the axial direction of the ultrasonic beam irradiated to the biological tissue 100 will be referred to as the horizontal direction.

[0028] The control unit 52 acquires the time when the reflected wave has the maximum intensity while moving the transducer 1 (step S105 in FIG. 2). Fig. 5 is a diagram showing an example of the waveform of the reflected wave received by the transducer 1. In Fig. 5, the time when the transducer 1 transmits the ultrasonic wave is set to 0.

[0029] The control unit 52 determines the time from when the transducer 1 transmits the ultrasonic wave to the time tmax when the absolute value of the intensity of the reflected wave reaches a maximum as the propagation time of the ultrasonic wave, and calculates the distance between the transducer 1 and the reflection point of the ultrasonic wave by multiplying half of this propagation time by the known speed of sound (step S106 in Fig. 2). Although not clearly shown in Fig. 1, if there is a propagation medium such as water between the transducer 1 and the resin film 3 as in the conventional case, the known speed of sound of the ultrasonic wave passing through the propagation medium is used to calculate the distance.

[0030] The control unit 52 performs the processes of steps S105 and S106 for each horizontal position while moving the transducer 1. After completing scanning of the entire area of ​​the biological tissue 100 with the ultrasonic beam (YES in step S107 in FIG. 2), the control unit 52 determines the maximum value Dmax and minimum value Dmin of the distance calculated in step S106 (step S108 in FIG. 2).

[0031] The control unit 52 controls the scanning stage 4 to move the transducer 1 along the axial direction of the ultrasonic beam so that the beam radius (beam intensity) changes linearly over the distance range from the maximum value Dmax to the minimum value Dmin (step S109 in FIG. 2). At this time, it is desirable to move the transducer 1 in a direction away from the biological tissue 100.

[0032] Specifically, the relationship between the axial distance and the beam radius (beam intensity) when the focal position of the ultrasonic beam is at a distance of 0 is known, as shown in Figures 14 and 15. The above-mentioned maximum value Dmax corresponds to the position of distance 0 in Figures 14 and 15. Therefore, the control unit 52 may move the transducer 1 so that the range of distance from the maximum value Dmax to the minimum value Dmin falls within the distance range indicated by the dashed line 201 in Figures 14 and 15. At this time, it is desirable to fix the transducer 1 at a position where the movement amount of the transducer 1 from the position determined by the adjustment in steps S102 and S103 is minimal and where the beam radius (beam intensity) changes linearly with respect to the range of distance from the maximum value Dmax to the minimum value Dmin. In this way, the defocusing process is completed.

[0033] Next, the process of acquiring an ultrasound image will be described with reference to Figures 3 to 9. As described above, the transmitter 50 supplies a driving transmission pulse to the transducer 1, causing the transducer 1 to transmit an ultrasound pulse (step S200 in Figure 3). The transducer 1 receives a reflected wave from the biological tissue 100 (step S201 in Figure 3). The receiver 51 stores the waveform of the reflected wave output from the transducer 1 in the memory 53 (step S202 in Figure 3).

[0034] The control unit 52 controls the scanning stage 4 to move the transducer 1 in the horizontal direction (step S203 in FIG. 3). While the transducer 1 is being moved in this manner, the processes of steps S200 to S202 are performed for each horizontal position.

[0035] After scanning the entire area of ​​the biological tissue 100 with the ultrasound beam (YES in step S204 in FIG. 3 ), the reference region extraction unit 54 may interpolate the waveform of the reflected wave (step S205 in FIG. 3 ). If the sampling rate is insufficient (if the acquisition period of the reflected wave is long), it is not possible to acquire the reflected wave with sufficiently fine positional resolution. Therefore, the reference region extraction unit 54 may estimate the waveform of the reflected wave for horizontal positions where the reflected wave has not been measured using a model-based estimation method such as a Kalman filter or an interpolation method such as machine learning. However, the processing of step S205 is not essential to the present invention.

[0036] Next, the reference area extraction unit 54 acquires the maximum absolute value of the intensity of the waveform of the reflected wave stored in the storage unit 53 for each horizontal position (step S206 in FIG. 3). For horizontal positions where the maximum absolute value of the intensity cannot be acquired, the reference area extraction unit 54 may calculate the maximum value using a statistical method (step S207 in FIG. 3). However, the processing of step S207 is not essential to the present invention.

[0037] The reference region extraction unit 54 creates a reflection intensity map by plotting the maximum absolute values ​​of the intensity acquired in steps S206 and S207 on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasound beam irradiated onto the biological tissue 100 (step S208 in Figure 3). An example of a reflection intensity map is shown in Figure 6. The horizontal and vertical axes in Figure 6 indicate horizontal position. In the example of Figure 6, the maximum absolute value of the intensity of the waveform of the reflected wave is expressed by color, with whiter colors indicating higher intensity. Note that the waveform of the reflected wave may be Fourier transformed, and the reflection intensity map may be created by using the power spectrum in the same frequency band as the irradiated ultrasound as the intensity distribution.

[0038] The reference region extraction unit 54 extracts, as a reference region, a region where no biological tissue 100 is present, based on the generated reflection intensity map (step S209 in FIG. 3 . Specifically, the reference region extraction unit 54 extracts, as a reference region, a region on the reflection intensity map where the maximum absolute value of intensity is equal to or greater than a predetermined threshold. In the example in FIG. 6 , the reference region is designated A1, and the region corresponding to the biological tissue 100 is designated A2.

[0039] Next, the library creation unit 55 performs a process of acquiring, for each horizontal position in the reference area, the time from when the transducer 1 transmits the ultrasonic wave to when the absolute value of the intensity of the reflected wave is maximum (tmax in FIG. 5 ), as an index indicating the magnitude of strain in the resin film 3. Then, the library creation unit 55 uses the waveform of the reflected wave at the position where the index is acquired as a reference waveform, and creates a library in which the reference waveform at the position where the index is acquired is associated with the index (step S210 in FIG. 3 ).

[0040] The library creation method will be described with reference to Fig. 4. The library creation unit 55 acquires waveform data of reflected waves stored in the storage unit 53 for the reference region (step S300 in Fig. 4). The library creation unit 55 acquires indices from the acquired waveform data of reflected waves (step S301 in Fig. 4). The library creation unit 55 associates the reference waveform at the position where the indices were acquired with the indices and registers them in the library (step S302 in Fig. 4). The library creation unit 55 performs the processes of steps S300 to S302 for each horizontal position in the reference region until the entire reference region has been processed (YES in step S303 in Fig. 4).

[0041] To visually explain the concept of a library using the waveform of a reflected wave, the library associates an index with a reference waveform as shown in Figure 7. However, since the index values ​​that can be obtained from waveform data are discrete values, it is not possible to create a library for all possible ranges of index values.

[0042] Therefore, the library creation unit 55 performs statistical processing to estimate the reference waveform corresponding to the index value for which the reference waveform cannot be obtained within the predetermined index numerical range, and to remove noise from the reference waveform (step S304 in FIG. 4). The numerical range of the index to be registered in the library can be determined in advance, for example, based on the magnitude of strain that may occur in the resin film 3. This completes the creation of the library. The created library is stored in the storage unit 53.

[0043] The acoustic impedance calculation unit 56 calculates the acoustic impedance Zt of the biological tissue 100 for each horizontal position (step S211 in FIG. 3 ). Specifically, for a calculation target position in a region other than the reference region (region of the biological tissue 100), the acoustic impedance calculation unit 56 determines the maximum absolute value of the intensity of the waveform of the reflected wave as the intensity St of the reflected wave obtained from the interface between the resin film 3 and the biological tissue 100. Furthermore, for the calculation target position, the acoustic impedance calculation unit 56 obtains, as an index, the time from the time the transducer 1 transmits ultrasound to the time when the absolute value of the intensity of the reflected wave reaches a maximum, and obtains a reference waveform corresponding to this index from the library. The acoustic impedance calculation unit 56 determines the maximum absolute value of the intensity of the reference waveform obtained from the library as the intensity Sr of the reflected wave obtained from the interface between the resin film 3 and the reference member 101.

[0044] The acoustic impedance calculation unit 56 can calculate the acoustic impedance Zt of the biological tissue 100 by substituting the intensities St and Sr of the reflected waves into equation (3). The acoustic impedance Zs of the resin film 3 is a known value, and the acoustic impedance Zr of the reference member 101 such as water or a culture medium is also a known value.

[0045] In this way, the acoustic impedance Zt of the biological tissue 100 can be calculated for each horizontal position in the region of the biological tissue 100, and a two-dimensional acoustic impedance image can be generated. Note that the acoustic impedance of the reference region is the known acoustic impedance Zr of the reference member 101.

[0046] Next, the acoustic impedance calculation unit 57 calculates the acoustic impedance in the depth direction of the biological tissue 100 using the method reported in Non-Patent Document 2 (step S212 in FIG. 3). Fig. 8 is a flowchart explaining the operation of the acoustic impedance calculation unit 57. Fig. 9 is a diagram explaining a method for calculating three-dimensional acoustic impedance.

[0047] The biological tissue 100 is composed of a plurality of thin layers. Therefore, as can be seen from (a) of FIG. 9, the incident wave S ０On the other hand, the reflected wave includes reflections from the interfaces of multiple layers of the biological tissue 100. The acoustic impedance Zs of the resin film 3, which is the base material, is a known value. In this example, the acoustic impedance Zs of each layer of the biological tissue 100 shown in FIG. １ , Z ２ , ... Z ｉ－１ , Z ｉ (i is an integer of 2 or more) are calculated sequentially as follows:

[0048] First, the acoustic impedance calculation unit 57 acquires waveform data of the reflected wave stored in the storage unit 53 for the calculation target region (region of the biological tissue 100) other than the reference region (step S400 in FIG. 8 ). From the waveform of the acquired reflected wave, the acoustic impedance calculation unit 57 acquires, as an index, the time from the time when the transducer 1 transmits ultrasound to the time when the absolute value of the intensity of the reflected wave becomes maximum (step S401 in FIG. 8 ). Then, the acoustic impedance calculation unit 57 acquires reference waveform data corresponding to the index from the library (step S402 in FIG. 8 ).

[0049] Next, the acoustic impedance calculation unit 57 calculates a signal q obtained by performing a process of deconvolving the reference waveform obtained in step S402 with the reflected wave obtained in step S400 (step S403 in FIG. 8).

[0050] As shown in FIG. 9(c), the component q(t ０ ) corresponds to the reflected wave from the interface between the resin film 3 and the biological tissue 100. １ ) corresponds to the reflected wave from the interface between the layer closest to the resin film 3 and the second closest layer of the biological tissue 100. ２ ) corresponds to the reflected wave from the interface between the second closest layer and the third closest layer to the resin film 3 in the biological tissue 100. In this way, a signal q corresponding to the reflected wave from the interface of each layer of the biological tissue 100 can be obtained.

[0051] The acoustic impedance calculation unit 57 calculates the component q(t ０) and the known acoustic impedance Zs of the resin film 3, the acoustic impedance Z of the layer of the biological tissue 100 closest to the resin film 3 is calculated. １ is calculated by equation (9) (step S404 in FIG. 8).

[0052]

[0053] The acoustic impedance calculation unit 57 calculates the acoustic impedance Z １ and the acoustic impedance Zs of the resin film 3, the transmittance T when the ultrasound travels back and forth through each layer from the resin film 3 to the layer of the biological tissue 100 closest to the resin film 3 is calculated. ０ is calculated by equation (10) (step S405 in FIG. 8).

[0054]

[0055] The acoustic impedance calculation unit 57 calculates the component q(t １ ) and transmittance T ０ Based on this, the reflection coefficient Γ of the interface between the layer closest to the resin film 3 and the layer second closest to the resin film 3 in the biological tissue 100 is calculated. １ is calculated by equation (11) (step S406 in FIG. 8).

[0056]

[0057] Next, the acoustic impedance calculation unit 57 calculates the acoustic impedance Z of the layer of the biological tissue 100 closest to the resin film 3. １ and the reflection coefficient Γ １ Based on this, the acoustic impedance Z of the layer of the biological tissue 100 that is second closest to the resin film 3 is ２ is calculated by equation (12) (step S404).

[0058]

[0059] The acoustic impedance calculation unit 57 calculates the acoustic impedance Z １ , Z ２ Based on this, the transmittance T １ is calculated by equation (13) (step S405).

[0060]

[0061] The acoustic impedance calculation unit 57 calculates the component q(t ２ ) and transmittance T ０ , T １ Based on this, the reflection coefficient Γ of the interface between the layer second closest to the resin film 3 and the layer third closest to the resin film 3 in the biological tissue 100 is calculated. ２ is calculated by equation (14) (step S406).

[0062]

[0063] Similarly, the processes of steps S404 to S406 are performed for each interface of the layers of the biological tissue 100. The acoustic impedance Z of the layer of the biological tissue 100 closest to the resin film 3 is ｉ can be calculated as in equation (15).

[0064]

[0065] Gamma ｉ－１ is the reflection coefficient of the interface between the (i-1)th closest layer and the i-th closest layer to the resin film 3 in the biological tissue 100, Z ｉ－１ is the acoustic impedance of the (i-1)th layer of the biological tissue 100 closest to the resin film 3. The transmittance T ｉ－１ can be calculated as in equation (16).

[0066]

[0067] The reflection coefficient Γ of the interface between the layer of the biological tissue 100 closest to the resin film 3 and the layer of the biological tissue 100 closest to the resin film 3 is ｉ can be calculated as in equation (17).

[0068]

[0069] The acoustic impedance calculation unit 57 performs the processes of steps S404 to S406 for all components of the signal q shown in Fig. 9(c). After completing the processes for all components of the signal q (YES in step S407 in Fig. 8), the acoustic impedance calculation unit 57 determines whether or not the processes for the entire region of the calculation target (the entire region of the biological tissue 100) have been completed (step S408 in Fig. 8). If the processes have not been completed, the acoustic impedance calculation unit 57 returns to step S400.

[0070] In this way, by performing the process of FIG. 8 for each horizontal position in the region of the biological tissue 100, the acoustic impedance Z １ , Z ２ , ... Z ｉ－１ , Z ｉ It is possible to calculate the acoustic impedance image in the depth direction, and generate the acoustic impedance image in the depth direction. Note that the acoustic impedance in the depth direction of the reference region is the known acoustic impedance Zr of the reference member 101.

[0071] The library can also be created in Fourier space by capturing the reflected waves from the focal spot as a point spread function and filtering them using a deconvolution filter, Wiener filter, or Lucy-Richardson filter to remove the degradation of spatial resolution caused by shifting the focal spot.

[0072] Alternatively, an acoustic impedance image at the interface between the measurement target and the substrate may be obtained using a focal spot with high spatial resolution, and then correction may be performed based on an acoustic impedance image acquired by shifting the focal spot. Specifically, the low-frequency components of the spatial frequency of the acoustic impedance image obtained using a focal spot with high spatial resolution are considered to be dish noise. Therefore, the low-frequency components of this image are replaced with an acoustic impedance image acquired by shifting the focal spot. The high-frequency components of the spatial frequency of the acoustic impedance image obtained using a focal spot with high spatial resolution can be removed by image processing using a Gaussian filter or a median filter.

[0073] Fig. 10A is an acoustic impedance image of cardiomyocytes in the horizontal direction calculated using a conventional method, and Fig. 10B is an acoustic impedance image in the depth direction taken at line I-I in Fig. 10A. Fig. 11A is an acoustic impedance image of cardiomyocytes in the horizontal direction calculated using this embodiment, and Fig. 11B is an acoustic impedance image in the depth direction taken at line II-II in Fig. 11A. Reference numeral 300 in Figs. 10B and 11B indicates the resin film 3. In the examples of Figs. 10A, 10B, 11A, and 11B, acoustic impedance is represented by color, with whiter colors indicating higher acoustic impedance.

[0074] 10B, it is possible to confirm that the image is deficient and the spatial bias of the impedance is caused by distortion, tilt, or vibration of the resin film 3. On the other hand, according to this example, it is possible to confirm that the image that was deficient is visualized and the spatial bias of the acoustic impedance is eliminated.

[0075] It should be noted that a phased array transducer consisting of multiple transducer elements may be used instead of the general transducer 1. The focal position of the ultrasonic beam can be controlled by providing an appropriate delay to the transmission pulse supplied from the transmitting unit 50 to each transducer element. In this case, the phased array transducer and the transmitting unit 50 serve as a beam manipulation unit.

[0076] Furthermore, a beam steering mechanism such as a galvanometer mirror may be used instead of the scanning stage 4. The focal position of the ultrasonic beam can be controlled by changing the rotation angle and position of the beam steering mechanism that reflects the ultrasonic beam. In this case, the beam steering mechanism and the control unit 52 that controls the beam steering mechanism constitute the beam steering unit.

[0077] In this embodiment, no description is given of processing of the generated acoustic impedance image, but it goes without saying that appropriate processing such as image display, storage, data transmission, etc. may be performed as needed.

[0078] The processing device 5 described in this embodiment can be realized by a computer equipped with a CPU (Central Processing Unit), a storage device, and an interface, and a program that controls these hardware resources. An example of the configuration of this computer is shown in FIG.

[0079] The computer includes a CPU 500, a storage device 501, and an interface device (I / F) 502. The I / F 502 is connected to the transducer 1, a drive unit for the scanning stage 4, and the like. In such a computer, a program for realizing the ultrasonic image acquisition method of the present invention is stored in the storage device 501. The CPU 500 executes the processing described in this embodiment in accordance with the program stored in the storage device 501.

[0080] Some or all of the above embodiments can be described as, but are not limited to, the following supplementary notes.

[0081] (Supplementary Note 1) The ultrasonic image acquisition device of the present invention includes a transducer configured to transmit and receive ultrasonic waves, an acoustic lens configured to focus an ultrasonic beam emitted from the transducer onto a measurement target on a substrate and irradiate the measurement target through the substrate, a beam manipulation unit configured to shift an irradiation position in the axial direction of the ultrasonic beam from a position where the intensity of a reflected wave from the measurement target is maximized along the axial direction of the ultrasonic beam, and then scan the entire region of the measurement target with the ultrasonic beam, and a scanning unit configured to create a reflection intensity map on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, depicting the intensity of the reflected wave obtained by the scanning, and extracting a region where the measurement target is not present as a reference region based on the reflection intensity map. a library creation unit configured to perform a process of acquiring, for each horizontal position in the reference area, the time from the transmission time of the ultrasonic wave to the time when the absolute value of the intensity of the reflected wave is maximum, as an index indicating the magnitude of strain in the substrate, and to create a library in which the index and the reference waveform are associated with each other, using the waveform of the reflected wave at the position where the index was acquired as a reference waveform; and a first acoustic impedance calculation unit configured to acquire from the library a reference waveform corresponding to the index for a position to be calculated in a region of the measurement object other than the reference area, and to calculate the acoustic impedance of the measurement object for each horizontal position in the region of the measurement object based on the waveform of the reflected wave at the position to be calculated and the reference waveform acquired from the library.

[0082] (Supplementary Note 2) The ultrasound image acquisition device described in Supplementary Note 1 further includes a second acoustic impedance calculation unit configured to: acquire from the library a reference waveform corresponding to the index for a position of a calculation target in the region of the measurement target; calculate a signal obtained by performing a process of deconvolving the reference waveform acquired from the library with a waveform of a reflected wave at the position of the calculation target; and calculate an acoustic impedance in the depth direction of the measurement target at the position of the calculation target based on this signal.

[0083] (Supplementary Note 3) In the ultrasonic image acquisition device described in Supplementary Note 1, the beam manipulation unit adjusts the axial irradiation position of the ultrasonic beam so that the intensity of the reflected wave from the measurement object is maximized, then scans the entire area of ​​the measurement object with the ultrasonic beam, defines the time from the transmission time of the ultrasonic wave to the time when the intensity of the reflected wave is maximized as the propagation time of the ultrasonic wave, calculates the distance between the transducer and the reflection point of the ultrasonic wave based on the propagation time for each horizontal position in the entire scanned area, and shifts the axial irradiation position of the ultrasonic beam along the axial direction so that the diameter of the ultrasonic beam changes linearly over the range of distance from the maximum value to the minimum value of the distance.

[0084] (Supplementary Note 4) In the ultrasonic image acquisition device described in Supplementary Note 1, the first acoustic impedance calculation unit calculates the acoustic impedance of the measurement object based on a reference waveform acquired from the library, a waveform of a reflected wave at the position of the calculation object, the known acoustic impedance of the substrate, and the known acoustic impedance of a reference member arranged to cover the measurement object.

[0085] (Supplementary Note 5) The ultrasonic image acquisition method of the present invention includes a first step of focusing an ultrasonic beam emitted from a transducer onto a measurement object on a substrate and irradiating the measurement object through the substrate; a second step of shifting the axial irradiation position of the ultrasonic beam along the axial direction of the ultrasonic beam from a position where the intensity of the reflected wave from the measurement object is maximum; a third step of scanning the entire region of the measurement object with the ultrasonic beam; and a fourth step of creating a reflection intensity map on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, depicting the intensity of the reflected wave obtained by the scanning, and extracting a region where the measurement object is not present as a reference region based on the reflection intensity map. a fifth step of performing a process of obtaining, for each horizontal position in the reference area, the time from the transmission time of the ultrasonic wave to the time when the absolute value of the intensity of the reflected wave is maximum, as an index indicating the magnitude of strain in the substrate, and using the waveform of the reflected wave at the position where the index was obtained as a reference waveform, creating a library in which the index and the reference waveform correspond to each other; and a sixth step of obtaining, from the library, a reference waveform corresponding to the index for a position to be calculated in a region of the measurement object other than the reference area, and calculating the acoustic impedance of the measurement object for each horizontal position in the region of the measurement object based on the waveform of the reflected wave at the position to be calculated and the reference waveform obtained from the library.

[0086] (Supplementary Note 6) The ultrasound image acquisition method described in Supplementary Note 5 further includes a seventh step of acquiring from the library a reference waveform corresponding to the index for the position of a calculation target in the region of the measurement target, calculating a signal by performing a process of deconvolving the reference waveform acquired from the library with the waveform of a reflected wave at the position of the calculation target, and calculating an acoustic impedance in the depth direction of the measurement target at the position of the calculation target based on this signal.

[0087] (Supplementary Note 7) In the ultrasonic image acquisition method described in Supplementary Note 5, the second step includes a step of: adjusting the axial irradiation position of the ultrasonic beam so that the intensity of the reflected wave from the measurement object is maximized; scanning the entire area of ​​the measurement object with the ultrasonic beam; defining the time from the transmission time of the ultrasonic beam to the time when the intensity of the reflected wave is maximized as the propagation time of the ultrasonic beam; calculating the distance between the transducer and the reflection point of the ultrasonic beam based on the propagation time for each horizontal position in the entire scanned area; and shifting the axial irradiation position of the ultrasonic beam along the axial direction so that the diameter of the ultrasonic beam changes linearly within a distance range from the maximum value to the minimum value of the distance.

[0088] (Appendix 8) In the ultrasonic image acquisition method described in Appendix 5, the sixth step includes a step of calculating the acoustic impedance of the measurement object based on a reference waveform acquired from the library, a waveform of a reflected wave at the position of the calculation object, a known acoustic impedance of the substrate, and a known acoustic impedance of a reference member arranged on the substrate so as to cover the measurement object.

[0089] The present invention can be applied to techniques for generating ultrasound images.

[0090] 1...transducer, 2...acoustic lens, 3...resin film, 4...scanning stage, 5...processing device, 6...beam manipulation unit, 50...transmitting unit, 51...receiving unit, 52...control unit, 53...storage unit, 54...reference area extraction unit, 55...library creation unit, 56, 57...acoustic impedance calculation unit.

Claims

1. A transducer configured to transmit and receive ultrasonic waves; an acoustic lens configured to focus an ultrasonic beam emitted from the transducer onto a measurement target on a substrate and irradiate the measurement target through the substrate; a beam manipulation unit configured to shift an axial irradiation position of the ultrasonic beam along the axial direction of the ultrasonic beam from a position where the intensity of the reflected wave from the measurement target is maximum, and then scan the entire region of the measurement target with the ultrasonic beam; a reference region extraction unit configured to create a reflection intensity map in which the intensity of the reflected wave obtained by the scanning is plotted on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, and to extract a region where the measurement target is not present as a reference region based on the reflection intensity map; a library creation unit configured to perform a process of obtaining, for each horizontal position in the reference region, the time from the transmission time of the ultrasonic wave to the time when the absolute value of the intensity of the reflected wave is maximum as an index indicating the magnitude of distortion of the substrate, and to create a library in which the index and the reference waveform are associated with each other, using the waveform of the reflected wave at the position where the index was obtained as a reference waveform; and a first acoustic impedance calculation unit configured to obtain, from the library, a reference waveform corresponding to the index for a position of a calculation target in a region of the measurement target other than the reference region, and to calculate the acoustic impedance of the measurement target for each horizontal position in the region of the measurement target based on the waveform of a reflected wave at the position of the calculation target and the reference waveform obtained from the library.

2. An ultrasonic image acquisition device as described in claim 1, further comprising a second acoustic impedance calculation unit configured to obtain a reference waveform corresponding to the index for the position of the calculation target in the area of ​​the measurement target from the library, calculate a signal by performing a process of deconvolving the reference waveform obtained from the library with the waveform of the reflected wave at the position of the calculation target, and calculate the acoustic impedance in the depth direction of the measurement target at the position of the calculation target based on this signal.

3. An ultrasonic image acquisition device as described in claim 1, characterized in that the beam manipulation unit adjusts the axial irradiation position of the ultrasonic beam so that the intensity of the reflected wave from the object to be measured is maximized, then scans the entire area of ​​the object to be measured with the ultrasonic beam, defines the time from the transmission time of the ultrasonic beam to the time when the intensity of the reflected wave is maximized as the propagation time of the ultrasonic beam, and calculates the distance between the transducer and the reflection point of the ultrasonic beam based on the propagation time for each horizontal position in the entire scanned area, and shifts the axial irradiation position of the ultrasonic beam along the axial direction so that the diameter of the ultrasonic beam changes linearly over the range of distance from the maximum value to the minimum value of the distance.

4. An ultrasonic image acquisition device as described in claim 1, characterized in that the first acoustic impedance calculation unit calculates the acoustic impedance of the measurement object based on a reference waveform acquired from the library, a waveform of a reflected wave at the position of the calculation object, a known acoustic impedance of the base material, and a known acoustic impedance of a reference member arranged to cover the measurement object.

5. A first step of focusing an ultrasonic beam emitted from a transducer onto a measurement target on a substrate and irradiating the measurement target through the substrate; a second step of shifting an axial irradiation position of the ultrasonic beam along the axial direction of the ultrasonic beam from a position where the intensity of the reflected wave from the measurement target is maximum; a third step of scanning the entire area of ​​the measurement target with the ultrasonic beam; a fourth step of creating a reflection intensity map in which the intensity of the reflected wave obtained by the scanning is plotted on a two-dimensional plane corresponding to a horizontal plane perpendicular to the axial direction of the ultrasonic beam, and extracting an area where the measurement target is not present as a reference area based on the reflection intensity map; and a fifth step of performing a process of obtaining the time from the transmission time of the ultrasonic wave to the time when the absolute value of the intensity of the reflected wave is maximum as an index indicating the magnitude of distortion of the substrate for each horizontal position in the reference area, and using the waveform of the reflected wave at the position where the index was obtained as a reference waveform, creating a library in which the index and the reference waveform are associated with each other. and a sixth step of obtaining from the library a reference waveform corresponding to the index for a position of a calculation target in a region of the measurement target other than the reference region, and calculating the acoustic impedance of the measurement target for each horizontal position in the region of the measurement target based on the waveform of a reflected wave at the position of the calculation target and the reference waveform obtained from the library.

6. An ultrasonic image acquisition method as claimed in claim 5, further comprising a seventh step of obtaining from the library a reference waveform corresponding to the index for the position of the calculation target in the region of the measurement target, calculating a signal by performing a process of deconvolving the reference waveform obtained from the library with the waveform of the reflected wave at the position of the calculation target, and calculating the acoustic impedance in the depth direction of the measurement target at the position of the calculation target based on this signal.

7. An ultrasonic image acquisition method as described in claim 5, characterized in that the second step includes a step of adjusting the axial irradiation position of the ultrasonic beam so that the intensity of the reflected wave from the object to be measured is maximized, scanning the entire area of ​​the object to be measured with the ultrasonic beam, determining the time from the transmission time of the ultrasonic beam to the time when the intensity of the reflected wave is maximized as the propagation time of the ultrasonic beam, and calculating the distance between the transducer and the reflection point of the ultrasonic beam based on the propagation time for each horizontal position in the entire scanned area, and shifting the axial irradiation position of the ultrasonic beam along the axial direction so that the diameter of the ultrasonic beam changes linearly over the range of distance from the maximum value to the minimum value of the distance.

8. An ultrasonic image acquisition method as described in claim 5, characterized in that the sixth step includes a step of calculating the acoustic impedance of the measurement object based on a reference waveform acquired from the library, a waveform of a reflected wave at the position of the calculation object, a known acoustic impedance of the substrate, and a known acoustic impedance of a reference member arranged on the substrate to cover the measurement object.

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