Ultrasonic image generation method and apparatus, and signal processing method

Abstract

To generate a highly reliable and clear ultrasonic image by suppressing an occurrence of an arithmetic error caused by low frequency noise.SOLUTION: An ultrasonic image generation method includes each step of transmission / reception, first domain conversion, signal normalization, second domain conversion, estimation and image generation. In the first domain conversion step, a window function having an asymmetrical shape converging to zero with time and non-periodicity is applied (S152), thereby to cut out a necessary part of a waveform in a received signal from immediately before the necessary part, and to convert a target signal and a reference signal from a time domain to a frequency domain. In the signal normalization step, the target signal is deconvolved with the reference signal in the frequency domain (S154). In the second domain conversion step, the deconvolved target signal is converted from the frequency domain to the time domain to acquire a normalized impulse response signal (S154).SELECTED DRAWING: Figure 5

Description

Technical Field

[0001] The present invention relates to a method and apparatus for generating an ultrasonic image, and a signal processing method, by processing a reflected wave signal obtained when a focused beam of ultrasonic pulse waves is transmitted to an object.

Background Art

[0002] Conventionally, an ultrasonic image generation apparatus has been proposed that quantifies the state inside the skin or cells with acoustic physical property values such as acoustic impedance and displays the distribution as an image (for example, Patent Documents 1 and 2). This type of apparatus includes a substrate having known acoustic physical properties, an ultrasonic vibrator that transmits and receives ultrasonic waves through the substrate, arithmetic means, image construction means, and the like. In this apparatus, a measurement object and a reference substance having known acoustic physical properties are arranged in contact with a substrate having known acoustic physical properties. Then, ultrasonic waves are transmitted in this state, and the ultrasonic waves are made to enter the measurement object and the reference substance through the substrate, and the impulse responses of the ultrasonic wave waveforms from the measurement object and the reference substance are received. Next, normalized impulse response information is obtained from the impulse response information of the ultrasonic wave waveform incident on the reference substance and the impulse response information of the ultrasonic wave waveform incident on the measurement object. In the arithmetic processing for normalization, specifically, the reflected wave signals from the reference substance and the measurement object are subjected to Fourier transform, deconvolution is performed in the frequency domain, and then inverse Fourier transform is performed to return to the time domain again. Next, based on the normalized impulse response information, an arithmetic operation is performed to estimate the acoustic physical property distribution in the depth direction (specifically, the specific acoustic impedance distribution) considering the influence of multiple reflections. Then, based on the obtained acoustic physical property distribution in the depth direction, image data of an acoustic physical property image is constructed to obtain a desired ultrasonic tomographic image.

[0003] Incidentally, in the conventional device described above, the process of normalizing the reflected wave signal involves repeatedly converting the reflection coefficient into an intrinsic acoustic impedance value over time. The reflection coefficient contains low-frequency components. If any low-frequency noise is superimposed on it, the error propagates backward in the depth direction and accumulates, resulting in an even larger error. As a result, the estimation accuracy of the intrinsic acoustic impedance distribution in the depth direction decreases, causing distortion and blurring of the resulting ultrasonic image. To solve this problem, for example, Patent Document 3 proposes a method for correcting the estimation result of the intrinsic acoustic impedance distribution using a predetermined method.

[0004] In the invention described in Patent Document 3, specifically, when a substance having a known intrinsic acoustic impedance value is uniformly present throughout the layer direction at a specific depth within the object to be measured, that intrinsic acoustic impedance value is defined as the "intrinsic acoustic impedance value of the virtual reference site." Alternatively, when the object to be measured is living soft tissue, the average of the estimated values ​​of the intrinsic acoustic impedance at a specific depth within that object is defined as the "intrinsic acoustic impedance value of the virtual reference site." The estimated value of the intrinsic acoustic impedance within the object to be measured is then corrected through a calculation that replaces the estimated value of the intrinsic acoustic impedance at a specific depth within the object with the intrinsic acoustic impedance value of the virtual reference site. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2006-271765 [Patent Document 2] Patent No. 6361001 [Patent Document 3] Japanese Patent Publication No. 2020-190454 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] However, even with the correction processing of the conventional techniques described above, there were certain limitations to its effectiveness, and it was not always possible to obtain clear ultrasound images. In addition, the reliability of the obtained ultrasound images was not always high. Therefore, there was still a need for a method or apparatus that could generate highly reliable and clear ultrasound images that could reveal the fine layered structure of cells and tissues.

[0007] Furthermore, in the conventional techniques described above, when normalizing reflected wave signals, a Fourier transform is applied when extracting the necessary portion of the received signal and analyzing it in the frequency domain. At this time, it is necessary to multiply by a window function, which is a periodic function, to connect the wavefront and wavetail of the extracted waveform, but the frequency component of the window function remains as noise (the low-frequency noise mentioned above). This remaining low-frequency noise causes errors in the estimation calculation results, so it is desirable to suppress it as much as possible. However, no effective measures to suppress such low-frequency noise have yet been proposed.

[0008] The present invention has been made in view of the above-mentioned problems, and its objective is to provide an ultrasonic image generation method and apparatus that can suppress the occurrence of calculation errors caused by low-frequency noise and generate highly reliable and clear ultrasonic images. Another objective of the present invention is to provide a signal processing method that can accurately estimate the acoustic physical properties of a target material in the depth direction. [Means for solving the problem]

[0009] The inventors of this invention conducted diligent research to solve the above problems and came up with the idea of ​​reviewing the conversion method between the time and frequency domains in the normalization calculation processing of reflected wave signals. Further diligent research revealed that it is possible to effectively suppress the occurrence of calculation errors caused by low-frequency noise, leading to the invention of this invention. Means 1 to 8 for solving the above problems are shown below.

[0010] [1] A method for generating an ultrasonic image by processing a reflected wave signal obtained when a focused beam of ultrasonic pulse waves is transmitted to a target material while scanning the target material in a direction perpendicular to the depth direction of the target material, comprising: a transmit and receive step of transmitting ultrasonic pulses through a substrate while the target material and a reference material are in contact with the substrate and receiving a target signal from the target material and a reference signal from the reference material; and a process of cutting out a necessary portion of the waveform in the received signal from immediately before the necessary portion by applying an asymmetric and non-periodic window function that converges to zero over time, and then processing the target signal and the reference signal from the time domain An ultrasonic image generation method comprising: a first domain conversion step of converting to the frequency domain; a signal normalization step of deconvolving the target signal with the reference signal in the frequency domain; a second domain conversion step of obtaining a normalized impulse response signal by converting the deconvolved target signal from the frequency domain to the time domain; an estimation step of sequentially estimating the intrinsic acoustic impedance within the target material from the front to the back in the depth direction based on the normalized impulse response signal; and an image generation step of generating the ultrasonic image based on the estimation result of the intrinsic acoustic impedance.

[0011] [2] The ultrasonic image generation method according to means 1, characterized in that, in the first region conversion step, the position of the zero point of the window function is adjusted to set the position of the zero point to a flat portion that appears immediately in front of the reflected wave signal from the target material.

[0012] [3] The ultrasonic image generation method according to means 1 or 2, characterized in that, in the signal normalization step, coefficients that determine the characteristics of the window function are determined in order to suppress the noise signal appearing after the reflected wave signal from the target material to a predetermined level or less.

[0013] [4] The ultrasound image generation method according to means 3, characterized in that the target substance is living soft tissue or cultured cells.

[0014] [5] An apparatus for generating an ultrasonic image by processing a reflected wave signal obtained when a focused beam of ultrasonic pulse waves is transmitted to a target material while scanning the target material in a direction perpendicular to the depth direction of the target material, comprising: a transmitting and receiving means that transmits ultrasonic pulses through a substrate while the target material and a reference material are in contact with the substrate and receives a target signal from the target material and a reference signal from the reference material; and a process that applies a left-right asymmetric and non-periodic window function that converges to zero over time to cut out the necessary portion of the waveform in the received signal from immediately before the necessary portion, and then processes the target signal and the reference signal over time An ultrasonic image generating apparatus comprising: a first domain conversion means for converting from a domain to a frequency domain; a signal normalization means for deconvolving the target signal with the reference signal in the frequency domain; a second domain conversion means for obtaining a normalized impulse response signal by converting the deconvolved target signal from the frequency domain to the time domain; an estimation means for sequentially estimating the intrinsic acoustic impedance within the target material from the front to the back in the depth direction based on the normalized impulse response signal; and an image generating means for generating the ultrasonic image based on the estimation result of the intrinsic acoustic impedance.

[0015] [6] The ultrasonic image generating apparatus according to means 5, further comprising an automatic zero-point setting means for automatically adjusting and setting the position of the zero point of the window function, wherein the automatic zero-point setting means sets the position of the zero point to a flat portion that appears immediately in front of the reflected wave signal from the target material.

[0016] [7] The ultrasonic image generating apparatus according to means 5 or 6, further comprising an automatic coefficient determination means for automatically determining a coefficient that determines the characteristics of the window function, wherein the automatic coefficient determination means determines the coefficient to a value that suppresses a noise signal appearing after the reflected wave signal from the target material to a predetermined level or lower.

[0017] A signal processing method including: a first region conversion step of converting from a time domain to a frequency domain after performing a process of cutting out a necessary portion of a waveform in a received signal by applying a left-right asymmetric and aperiodic window function that converges to zero over time to a target signal from the target substance and a reference signal from the reference substance obtained by transmitting and receiving a pulse wave through the substrate with the target substance and the reference substance in contact with the substrate; a signal normalization step of deconvolving the target signal with the reference signal in the frequency domain; a second region conversion step of obtaining a normalized impulse response signal by converting the deconvolved target signal from the frequency domain to the time domain; and an estimation step of sequentially estimating acoustic property values in the target substance from the near side to the far side in the depth direction based on the normalized impulse response signal.

Advantages of the Invention

[0018] As described in detail above, according to the inventions described in the above means 1 to 7, it is possible to provide an ultrasonic image generation method and apparatus that suppress the occurrence of calculation errors due to low-frequency noise and generate a highly reliable and clear ultrasonic image. Further, according to the above means 8, it is possible to provide a signal processing method capable of accurately estimating acoustic property values in the depth direction of a target substance.

Brief Description of the Drawings

[0019] [Figure 1] Schematic configuration diagram showing an ultrasonic image generation apparatus according to an embodiment embodying the present invention. [Figure 2] Block diagram showing the electrical configuration of the ultrasonic image generation apparatus according to the embodiment. [Figure 3] Schematic diagram for explaining the arrangement relationship between the target substance and the reference substance. [Figure 4] Flowchart for explaining the arithmetic processing for generating an acoustic impedance image in the embodiment. [Figure 5] Flowchart for explaining the normalization processing of the reflected wave signal in FIG. 4. [Figure 6] Schematic diagram showing the waveform of the reflected wave signal in the time domain. [Figure 7] Schematic diagram for explaining the state when applying a window function to the waveform of the reflected wave signal in the time domain. [Figure 8] Schematic diagram showing the process of normalizing the target signal by deconvolution. [Figure 9] (a) is the uncorrected acoustic impedance image of cultured cells obtained by the conventional method, and (b) is the acoustic impedance image of cultured cells obtained by the method of the embodiment. [Figure 10] (a) to (c) are schematic diagrams for explaining the state when applying a window function of another embodiment to the waveform of the reflected wave signal in the time domain.

Embodiments for Carrying Out the Invention

[0020] Hereinafter, embodiments in which the ultrasonic image generation method and apparatus of the present invention are embodied will be described in detail based on FIGS. 1 to 9.

[0021] FIG. 1 is a schematic configuration diagram showing the ultrasonic image generation apparatus 1 of the present embodiment. As shown in FIG. 1, the ultrasonic image generation apparatus 1 of the present embodiment is an apparatus for observing cultured cells 8A using ultrasonic waves, and includes a pulse excitation type ultrasonic microscope 2 and a personal computer (PC) 3.

[0022] The pulse excitation type ultrasonic microscope 2 includes a microscope main body 5 having a stage 4 and an ultrasonic probe 6 installed below the stage 4. The ultrasonic probe 6 of the pulse excitation type ultrasonic microscope 2 is electrically connected to the PC 3.

[0023] Stage 4 of this embodiment is configured to be movable horizontally (i.e., in the X and Y directions) by manual operation by the user. A culture vessel 41 for positioning and contacting the target substance to be measured is fixed to this stage 4. The target substance here is cultured cells 8A, more specifically human glial cells, a type of adherent cell (see Figure 3). The glial cells are very thin, about a few μm thick. A support film 9 (substrate) is fixed to the center of the bottom of the culture vessel 41, on the upper side to which the cultured cells 8A adhere and are supported during culture. The support film 9, which has known acoustic properties, is a thin material that can transmit ultrasound and is made of a material harder than the target substance, the cultured cells 8A. When a material of such shape and hardness is used as a substrate, it becomes possible to reliably position the target substance, the cultured cells 8A, in close contact, and as a result, the intrinsic acoustic impedance distribution in the depth direction can be accurately estimated, which improves the accuracy of image reconstruction. In this embodiment, a polystyrene film with a thickness of 50 μm is used. Of course, it is also permissible to use film materials made from resins other than polystyrene.

[0024] As shown in Figure 3, the cultured cells 8A are completely immersed in the culture medium M within the culture vessel 41. Therefore, the culture medium M surrounds the cultured cells 8A, with contact with the upper surface of the support film 9 where the cultured cells 8A are positioned. The culture medium M has known acoustic properties different from those of the support film 9, and in this embodiment, it is positioned and used as reference material 10.

[0025] The ultrasonic probe 6 comprises a probe body 12 having a storage section 11 at its tip capable of storing an ultrasonic transmission medium W such as water, an ultrasonic transducer 13 (ultrasonic vibrator) positioned approximately in the center of the probe body 12, and an XY stage 14 for scanning the probe body 12 two-dimensionally along the planar direction of the stage 4. The storage section 11 of the probe body 12 is open at the top, and the ultrasonic probe 6 is installed below the stage 4 with the opening side of the storage section 11 facing upward.

[0026] The ultrasonic transducer 13 is composed of, for example, a thin-film piezoelectric element 16 made of zinc oxide and an acoustic lens 17 made of a sapphire rod. When pulsed, the ultrasonic transducer 13 irradiates the cultured cells 8A and the reference substance 10 (culture medium M) from the lower side of the support film 9 with ultrasound. The ultrasound emitted by the ultrasonic transducer 13 is focused in a conical shape via the ultrasonic transmission medium W in the storage unit 11 and focuses on the upper surface of the support film 9 (near the surface of the cultured cells 8A). In this embodiment, the ultrasonic transducer 13 has a diameter of 1 mm, a focal length of 0.6 mm, and a center frequency of 400 MHz.

[0027] Figure 2 is a block diagram showing the electrical configuration of the ultrasonic image generation device 1 of this embodiment.

[0028] As shown in Figure 2, the ultrasonic probe 6 comprises an ultrasonic transducer 13, an XY stage 14, a pulse generation circuit 21, a receiving circuit 22, a transmit / receive separation circuit 23, a detection circuit 24, an A / D conversion circuit 25, an encoder 26, and a controller 27.

[0029] The XY stage 14, as a scanning means, includes an X stage 14X and a Y stage 14Y for scanning the ultrasonic irradiation point in two dimensions, and also includes motors 28X and 28Y to drive the respective stages 14X and 14Y. Stepping motors or linear motors can be used as these motors 28X and 28Y.

[0030] A controller 27 is connected to each motor 28X and 28Y, and the motors 28X and 28Y are driven in response to the drive signal from the controller 27. By driving these motors 28X and 28Y, the X stage 14X is continuously scanned (continuous feed), and the Y stage 14Y is controlled to feed intermittently, thereby enabling high-speed scanning of the XY stage 14.

[0031] In this embodiment, an encoder 26 is provided corresponding to the X-stage 14X, and the scanning position of the X-stage 14X is detected by the encoder 26. Specifically, when the scanning range is divided into 300 x 300 measurement points (pixels), one scan in the X direction (horizontal direction) is divided into 300 sections. The position of each measurement point is then detected by the encoder 26 and input to the PC3. The PC3 generates a drive control signal in synchronization with the output of the encoder 26 and supplies this drive control signal to the controller 27. The controller 27 drives the motor 28X based on this drive control signal. The controller 27 also drives the motor 28Y when scanning one line in the X direction is completed based on the output signal of the encoder 26, moving the Y-stage 14Y by one pixel in the Y direction.

[0032] Furthermore, the controller 27 generates a trigger signal in synchronization with the drive control signal and supplies it to the pulse generation circuit 21. As a result, the pulse generation circuit 21 generates an excitation pulse at a timing synchronized with the trigger signal. This excitation pulse is supplied to the ultrasonic transducer 13 via the transmit / receive separation circuit 23, resulting in ultrasonic waves being emitted from the ultrasonic transducer 13.

[0033] The thin-film piezoelectric element 16 of the ultrasonic transducer 13 is an ultrasonic transducer that can both transmit and receive waves, and converts ultrasonic waves (reflected waves) reflected by cultured cells 8A and reference material 10 (culture medium M) into electrical signals. The signal of these reflected waves is then supplied to the receiving circuit 22 via the transmit / receive separation circuit 23. The receiving circuit 22 is configured to include a signal amplification circuit, which amplifies the signal of the reflected waves and outputs it to the detection circuit 24.

[0034] The detection circuit 24 is a circuit for detecting reflected wave signals from cultured cells 8A and reference substance 10 (culture medium M), and includes a gate circuit (not shown). In this embodiment, the detection circuit 24 extracts the reflected wave signals from cultured cells 8A and reference substance 10 (culture medium M) from the reflected wave signals received by the ultrasonic transducer 13. The reflected wave signals extracted by the detection circuit 24 are then supplied to the A / D conversion circuit 25, where they are A / D converted and then transferred to the PC 3.

[0035] PC3 comprises a CPU 31 (Central Processing Unit), an I / F circuit 32, memory 33, a storage device 34, an input device 35, and a display device 36, which are interconnected via a bus 37.

[0036] The CPU 31 executes control programs using the memory 33 and comprehensively controls the entire system. The control programs include a program for controlling two-dimensional scanning by the XY stage 14, a program for converting the data of the reflected signal sequence that forms the basis of the ultrasonic B-mode echo image into an intrinsic acoustic impedance image, and a program for displaying the intrinsic acoustic impedance image. In addition to the CPU 31, a separate DSP (Digital Signal Processor) may be provided to perform some of the signal processing that the CPU 31 performs.

[0037] The I / F circuit 32 is an interface (specifically, a USB interface) for exchanging signals with the ultrasonic probe 6. The I / F circuit 32 plays the role of outputting control signals (drive control signals to the controller 27) to the ultrasonic probe 6 and inputting data transferred from the ultrasonic probe 6 (such as data transferred from the A / D conversion circuit 25). Note that when exchanging signals with the ultrasonic probe 6, the interface is not limited to the above physical interface, and a wireless interface may also be used.

[0038] The display device 36 is, for example, a monitor display such as a liquid crystal, plasma, or organic EL (electroluminescence) display. The display device 36 can be used for color or monochrome display, but color display is preferable. This display device 36 is used to display the intrinsic acoustic impedance image of cultured cells 8A and to display input screens for various settings.

[0039] The input device 35 is an input user interface such as a touch panel, mouse, keyboard, or pointing device, and is used for inputting requests, instructions, and parameters from the user.

[0040] The storage device 34 is a hard disk drive such as a magnetic disk drive or an optical disk drive, and stores various control programs and various data. The memory 33 includes RAM (random access memory) and ROM (read-only memory), and stores the reflected waveform of the reference member 10 and its intrinsic acoustic impedance, which have been acquired in advance for ultrasonic measurement. The CPU 31 transfers programs and data from the storage device 34 to the memory 33 according to instructions from the input device 35 and executes them sequentially. The programs executed by the CPU 31 may be programs stored on storage media such as memory cards, flexible disks, or optical disks, or programs downloaded via communication media, and are installed and used in the storage device 34 when they are executed.

[0041] Next, we will describe a method for generating an intrinsic acoustic impedance image from the reflected signal train that forms the basis of the ultrasonic B-mode echo image in the ultrasonic image generation device 1 of this embodiment.

[0042] In this ultrasonic image generation device 1, normalized impulse response information is obtained from the impulse response information of the ultrasonic waveform incident on the reference substance 10 (culture medium M) (see Sref in Figures 3 and 8) and the impulse response information of the ultrasonic waveform incident on the target substance, cultured cells 8A (see Stgt in Figures 3 and 8). Based on this normalized impulse response information, the acoustic property distribution in the depth direction is estimated, taking into account the effects of multiple reflections. Furthermore, in order to perform such estimation, in this embodiment, it is assumed that within the target substance, lossless minute transmission paths with different intrinsic acoustic impedances are connected in the depth direction, forming a collection of transmission paths. Then, the calculation process is sequentially repeated in which the intrinsic acoustic impedance of the minute transmission path adjacent to the near side is estimated based on the estimation result of the intrinsic acoustic impedance of the minute transmission path on the near side. Through this repeated calculation process, the acoustic property distribution in the depth direction of the transmission path (intrinsic acoustic impedance distribution in this case) is estimated. Such calculations are performed by the CPU 31 based on a predetermined algorithm stored in the memory 33.

[0043] This algorithm estimates the distribution of intrinsic acoustic impedance in the depth direction by using the reflected signal sequence that forms the basis of the ultrasonic B-mode echo image. This algorithm is based on the principles of time-domain reflectometry (TDR). This algorithm converts the reflected signal sequence that forms the basis of the ultrasonic B-mode echo image into an intrinsic acoustic impedance image in the depth direction through time-frequency analysis that takes into account multiple reflections within the target material. This algorithm is specifically described in, for example, Japanese Patent Publication No. 6361001, so its explanation is omitted here. The section on Fourier transform in Japanese Patent Publication No. 6361001 should be understood by replacing it with the method described later.

[0044] In the ultrasonic image generation apparatus 1 of this embodiment, the CPU 31 functions as a first region conversion means, a signal standardization means, a second region conversion means, and an estimation means.

[0045] The CPU 31, functioning as a first domain conversion means, performs a process to extract the necessary portion of the waveform in the received signal (i.e., the reflected wave signal of the received target signal and the reflected wave signal of the received reference signal) from immediately before the necessary portion. A predetermined window function is applied to this extraction. Specifically, each reflected wave signal is multiplied by the window function. In this case, the window function selected is an asymmetrical and non-periodic window function that converges to zero over time. Any function that satisfies the above conditions can be selected, but in this embodiment, an exponential function is used. After performing the extraction process by applying the window function, the CPU 31, functioning as a first domain conversion means, converts the target signal and the reference signal from the time domain to the frequency domain. In this embodiment, where an exponential function is used as the window function, the Laplace transform is used as the method for converting from the time domain to the frequency domain.

[0046] The CPU 31, which functions as a signal normalization means, performs a normalization operation by deconvolving the target signal by dividing it by a reference signal in the frequency domain.

[0047] The CPU 31, which functions as a second domain conversion means, obtains a normalized impulse response signal by converting the deconvoluted target signal from the frequency domain to the time domain. In this embodiment, where an exponential function is used as the window function, the inverse Laplace transform is used as the method for converting from the frequency domain to the time domain.

[0048] The CPU 31, which functions as an estimation means, sequentially estimates the intrinsic acoustic impedance within the target material and the reference material from the front to the back in the depth direction, based on the normalized impulse response signal.

[0049] Next, the calculation process performed by the CPU 31, which is the processor, to generate the intrinsic acoustic impedance image in the ultrasonic image generation device 1 of this embodiment will be explained using the flowcharts in Figures 4 and 5.

[0050] First, the ultrasonic probe 6 is placed on the underside of the support film 9 supporting the cultured cells 8A, and the ultrasonic probe 6 is made to perform initial operations in this state. That is, the controller 27 is activated based on instructions from the CPU 31 to drive the motors 28X and 28Y and move the XY stage 14. Then, the system is set up so that a focused beam of ultrasonic pulse waves can be irradiated at the position where the reference substance 10 (culture medium M) is located.

[0051] At this time, when an excitation pulse is supplied to the transducer 13 based on instructions from the CPU 31, a focused beam of ultrasonic pulse waves is irradiated onto the reference substance 10 (culture medium M). The reflected wave is then detected by the detection circuit 24 via the receiving circuit 22. Next, the CPU 31, acting as a means for acquiring the reflected wave, acquires the digital data converted by the A / D conversion circuit 25 via the I / F circuit 32. The CPU 31 stores this data in the memory 33 as data of the impulse response of the ultrasonic waveform from the reference substance 10 (culture medium M) (step S100).

[0052] Subsequently, based on instructions from the CPU 31, the controller 27 drives the motors 28X and 28Y, and two-dimensional scanning by the XY stage 14 begins. At this time, the CPU 31 moves the transducer 13 to the next measurement point (scanning point) (step S110) and acquires the coordinate data of the measurement point based on the output of the encoder 26 (step S120).

[0053] Then, based on instructions from the CPU 31, an excitation pulse is supplied to the transducer 13, and a focused beam of ultrasonic pulse waves is irradiated onto the cultured cells 8A. The reflected wave at a specific measurement point is detected by the detection circuit 24 via the receiving circuit 22. The CPU 31, acting as a means for acquiring the reflected wave, acquires the digital data converted by the A / D conversion circuit 25 via the I / F circuit 32. The CPU 31 stores the acquired data as data of the impulse response of the ultrasonic waveform from the cultured cells 8A (reflected wave signal data), associating it with coordinate data and storing it in the memory 33 (step S130).

[0054] Next, the CPU 31 determines whether processing at all measurement points has been completed and all image data has been acquired (step S140). If not all data has been acquired (step S130: NO), the CPU 31 returns to step S110, moves to the next measurement point, and then repeatedly executes the processing in steps S120 to S140. If all data has been acquired (step S140: YES), the CPU 31 proceeds to the next step S150.

[0055] In step S150, the CPU 31 performs a process to normalize the acquired reflected wave signal according to the procedure shown in the flowchart of Figure 5.

[0056] Specifically, in step S152, the above window function is applied to the reflected wave signal of the target signal and the reflected wave signal of the reference signal to extract the necessary portion. Figure 6 is a schematic diagram showing the waveform of the reflected wave signal S1 in the time domain. Figure 7 is a schematic diagram illustrating how the window function is applied to the waveform of the reflected wave signal S1 in the time domain. In the waveform shown in the figure, the first uneven waveform portion that appears is the reflected wave portion 51 (longitudinal wave) at the lower surface of the support film 9. The next uneven waveform portion that appears is the reflected wave portion 52 (longitudinal wave) at the upper surface of the support film 9 and the cultured cells 8A. The uneven waveform portion that appears further after is the reflected wave portion 53 in transverse wave conversion wave propagation (longitudinal wave → transverse wave → longitudinal wave) (i.e., the noise signal that appears after the reflected wave signal). On the other hand, no uneven waveform portion appears immediately before the reflected wave portion 52, and this portion is shown as a flat portion 54. Also, the area indicated by the square frame in Figure 7 is the portion that requires analysis (i.e., the necessary portion 55 of the waveform in the received signal). This rectangular frame region corresponds to a thickness of several micrometers in this embodiment. The curve 61 shown in Figure 7 represents an exponential function, which is a window function. In step S152, the necessary portion 55 is cut out from the flat portion 54 immediately before it so that it includes the upper surface of the support film 9 and the reflected wave portion 52 in the cultured cells 8A. That is, the zero point 56 of the window function is located in the flat portion 54. Subsequently, calculation processing is performed to convert the target signal and the reference signal from the time domain to the frequency domain (this concludes the first domain conversion step).

[0057] In the next step, S154, the target signal is deconvolved and normalized by dividing it by a reference signal in the frequency domain (signal normalization step). In the next step, S156, the deconvolved target signal is converted from the frequency domain to the time domain to obtain a normalized impulse response signal (second domain conversion step). After this, the CPU 31 proceeds to the next step, S160.

[0058] Next, the CPU 31, acting as a calculation means, uses the data of the normalized impulse response signal to perform calculations in the estimation step, which is based on the principle of the TDR method. The CPU 31 then estimates the intrinsic acoustic impedance distribution in the depth direction by sequentially estimating the intrinsic acoustic impedance in the depth direction at each measurement point in the cultured cell 8A from the front to the back in the depth direction, and stores the estimation result in the memory 33 (step S160).

[0059] Subsequently, the CPU 31, acting as an image generation means, performs image processing to generate a depth-direction intrinsic acoustic impedance image (ultrasound image) based on the estimation result of the intrinsic acoustic impedance distribution in the depth direction (step S170). Specifically, the CPU 31 performs color modulation processing based on the estimation result of the intrinsic acoustic impedance distribution, generates image data displayed in different colors according to the magnitude of the intrinsic acoustic impedance, and stores this image data in memory 33.

[0060] The CPU 31 then transfers this data to the display device 36 and displays an intrinsic acoustic impedance image along a predetermined straight line (step S180), after which the process shown in Figure 4 is terminated. Through this series of processes, an intrinsic acoustic impedance image is displayed, color-coded according to the magnitude of the intrinsic acoustic impedance in the cultured cells 8A.

[0061] Therefore, according to this embodiment, the following effects can be obtained.

[0062] (1) The ultrasonic image generation apparatus 1 of this embodiment includes a transmitting and receiving means, a first domain conversion means, a signal normalization means, a second domain conversion means, an estimation means, an image generation means, etc. The transducer 13, which is the transmitting and receiving means, transmits ultrasonic pulses through the support film 9 while the cultured cells 8A and the reference substance 10 are in contact with the support film 9. The transducer 13 then receives a target signal from the cultured cells 8A and a reference signal from the reference substance 10. The first domain conversion means applies an asymmetrical and non-periodic window function that converges to zero over time to extract the necessary portion of the waveform in the received signal from immediately before the necessary portion. After that, the first domain conversion means converts the target signal and the reference signal from the time domain to the frequency domain. The signal normalization means deconvolves the target signal with the reference signal in the frequency domain. The second domain conversion means obtains a normalized impulse response signal by converting the deconvolved target signal from the frequency domain to the time domain. The estimation means sequentially estimates the intrinsic acoustic impedance within the target material from the front to the back in the depth direction, based on a normalized impulse response signal. The image generation means generates an ultrasound image based on the estimated intrinsic acoustic impedance. Figure 9(a) shows the intrinsic acoustic impedance image G0 of cultured cell 8A obtained by a conventional method. On the other hand, Figure 9(b) shows the intrinsic acoustic impedance image G1 of cultured cell 8A obtained by the method of this embodiment. Clearly, the ultrasound image obtained by the latter is much clearer than that obtained by the former.

[0063] Furthermore, with the apparatus 1 configured in this way, by applying a window function with different characteristics from the conventional Fourier transform window function (i.e., a periodic and symmetrical function), it becomes possible to almost completely eliminate the generation of low-frequency noise in the normalization calculation of reflected wave signals. In other words, the window function applied here does not have periodicity and has the characteristic of the wave tail converging to zero, so the wavefront and wave tail do not connect. As a result, the generation of intrinsic acoustic impedance estimation errors caused by low-frequency noise can be effectively suppressed. Therefore, it is possible to generate highly reliable and clear ultrasonic images.

[0064] Incidentally, using an exponential window results in different phase shifts for each frequency, causing distortion of the original waveform's frequency spectrum. However, this distortion is canceled out by dividing the reference signal by the frequency spectrum obtained by its Laplace transform and then performing an inverse Laplace transform. Furthermore, reflections from cultured cells 8A exist only at the heads of the exponential window. Therefore, the exponential window instantaneous spectral analysis becomes weighted towards the waveheads, and the distortion in the region where reflections from cultured cells 8A exist is significantly reduced. Thus, the normalization process of the reflected wave signal in this embodiment can be said to be the optimal processing method when targeting fine structures such as cultured cells 8A.

[0065] Here, we will describe the window function used in the normalization process of the reflected wave signal in this embodiment. Conventionally, when performing this type of processing, it is common knowledge among those skilled in the art to use a window function with a symmetrical shape, such as a Hanning window, while not using a window function with an asymmetrical shape, such as an exponential window. The reason why exponential windows are not generally used is as follows: In other words, the application of a window function is a simultaneous product in the time domain, which becomes a convolution integral in the frequency domain. Therefore, when performing frequency analysis, it is desirable for the amplitude to be highly sensitive and narrow bandwidth and the phase to be linear. Compared to a Hanning window, an exponential window has a low amplitude sensitivity and wide bandwidth, and the phase is nonlinear. In other words, an exponential window has the disadvantage of low frequency resolution and producing different phase shifts for each frequency. Consequently, exponential windows are not used in general frequency analysis.

[0066] The characteristics of an exponential window include its right-asymmetric shape, and the fact that when the entire waveform is frequency-analyzed, the weight of the forward part is large and the weight of the backward part is small. The conditions under which an exponential window exhibits a positive effect are listed below. The more of these conditions that are met simultaneously, the greater the positive effect (benefit) obtained. The ultrasonic image generation device 1 of this embodiment is composed of a pulse-excited ultrasonic microscope 2, and the ultrasonic microscope 2 satisfies the above conditions. The first is that the analysis is time → frequency → time (condition 1). In the case of time → frequency analysis, it is necessary to select a window function with small spectral distortion, so a symmetrical window such as a Hanning window is used (for example, filtering in the frequency domain). In the ultrasonic microscope 2, after deconvolution of the target signal and the reference signal is performed in the frequency domain, it is necessary to return to the time domain for image generation. Therefore, the ultrasonic microscope 2 satisfies condition 1. The second is that in the time waveform after calculation processing, the section of interest is at the beginning of the waveform (condition 2). When returned to the time domain, the signal waveform is corrected by the simultaneous time quotient of the signal waveform and the window function. At that time, the division occurs with smaller values ​​towards the rear, so the reliability is higher towards the front and lower towards the rear. As shown in Figure 7, ultrasonic microscope 2 is a reflection model in which the reflectance distribution is fine with respect to the transmission pulse width, and the area to be analyzed is in front of the signal waveform. Therefore, ultrasonic microscope 2 also satisfies condition 2. The third is that low-frequency noise is added to the entire waveform being analyzed in addition to the attenuated signal (condition 3). The instantaneous power of the attenuated signal is larger towards the front of the waveform and smaller towards the rear. When noise is superimposed across the entire waveform, the instantaneous SN is larger towards the front of the waveform and smaller towards the rear. Applying an exponential window gives greater weight to the front, so when analyzing the entire waveform, the part with a large SN can be analyzed as the main part. If the noise is sufficiently small, it reduces the signal, thus lowering the SN of the entire waveform. Since ultrasonic microscope 2 is driven by impulses, the transmitted waveform is an attenuated signal. In addition, there is the problem that low-frequency noise is added to the received waveform. Therefore, ultrasonic microscope 2 also satisfies condition 3. As described above, the conditions 1-3 under which the exponential window has a positive effect are limited, and ultrasonic microscope 2 satisfies these conditions 1-3.Since the effects are also observed in actual processing, it is clear that applying an exponential window yields benefits that outweigh the disadvantages.

[0067] (2) In the first region conversion step of the ultrasonic image generation method of this embodiment, for example, the user operates the input device 35 to adjust the position of the zero point 56 of the exponential window, which is a window function, thereby setting it to a flat portion 54 that appears immediately in front of the reflected wave signal S1 from the target material. If the zero point 56 were set to a non-flat location in the reflected wave signal S1, that is, a location where there are considerable irregularities in the signal waveform, it would become impossible to sufficiently remove low-frequency noise. Therefore, in this case, a decrease in the accuracy of the normalization calculation processing of the reflected wave signal S1 is unavoidable. In contrast, according to this embodiment, which adjusts the zero point position to an appropriate location, it becomes possible to sufficiently remove low-frequency noise and improve the accuracy of the normalization calculation processing of the reflected wave signal S1. Here, an example of user input operation will be given. First, the waveform of the reflected wave signal S1 from the target material, as shown in Figure 6, is displayed on the display screen of the display device 36. The user looks at the waveform display and determines the position of the flat portion 54 on the waveform, and moves the cursor to the flat portion 54. The zero point position is then set when the user clicks at the desired position on the flat portion 54. To make the flat portion 54 easier to understand, for example, text or an icon indicating the flat portion 54 may be displayed on the display screen. Alternatively, when the user moves the cursor, the display screen may be notified by text, an icon, a color change, or by sound when the cursor reaches the flat portion 54. Furthermore, as shown in Figure 7, a diagram schematically representing the support film 9 as the substrate and the target material may be displayed near the waveform of the reflected wave signal S1 to make the correspondence between their positions easier to understand.

[0068] In the embodiment described above, the user performs the zero-point position adjustment themselves. However, as in the ultrasonic image generating device 1 of Modified Example 1, an automatic zero-point setting means may be provided to automatically adjust and set the position of the zero point 56 of the window function. The automatic zero-point setting means may also be configured to set the position of the zero point 56 to a flat portion 54 that appears immediately in front of the reflected wave portion 52 in the reflected wave signal S1 from the target substance. There are no particular limitations on the method for finding the flat portion 54 in the reflected wave signal S1. For example, the amplitude of the reflected wave signal S1 is calculated along the time axis to first find the reflected wave portion 52 on the upper surface of the support film 9 and the cultured cells 8A. Next, it is calculated whether the amplitude of the waveform immediately in front of this reflected wave portion 52 falls within a predetermined range based on a horizontal baseline. If there is a region that falls within the predetermined range, it is defined as the flat portion 54, and an arbitrary position within that range is set as the zero point 56. In this case, the point within the above range that is closest to the baseline value and closest to the reflected wave portion 52 may be set as the zero point 56. Alternatively, the system may be configured to present the user with multiple candidates for the zero point 56 and encourage the user to make a final selection. The configuration of Modified Example 1 reduces the burden on the user, thus improving convenience. Furthermore, it becomes easier to adjust the zero point to an appropriate position, which in turn improves the accuracy of the normalization calculation process of the reflected wave signal S1, and consequently improves the reliability and clarity of the ultrasound image.

[0069] (3) In the signal normalization step of the ultrasonic image generation method of this embodiment, for example, the user operates the input device 35 to determine a coefficient that determines the characteristics of the exponential function which is a window function, thereby suppressing the noise signal that appears after the reflected wave signal S1 from the target material (i.e., the reflected wave portion 53 in the transverse wave conversion wave propagation shown in Figure 7) to a predetermined level or less. A predetermined level or less means, for example, that it is 1 / 5 or less of the amplitude of the original waveform, and preferably 1 / 10 or less. In this embodiment, "exponential function" refers to a function with respect to a given base e and the exponent x as the variable, and the "coefficient" therein refers to the coefficient a that is multiplied by the exponent x. That is, the window function applied in this embodiment is, for example, "y=e ax The function is represented by , and since the window function converges to zero over time, the coefficient a is a negative number. According to this embodiment, a suitable exponential window can be applied by setting an appropriate coefficient a. Therefore, it becomes possible to sufficiently remove low-frequency noise and improve the accuracy of the normalization calculation processing of the reflected wave signal S1. Here, an example of user input operation will be given. First, the waveform of the reflected wave signal S1 from the target material, as shown in Figure 6, is displayed on the display screen of the display device 36. The user can look at the waveform display and confirm that there is a reflected wave portion 53 on the waveform. Next, the user performs an operation to input the coefficient a of the exponential function. In this case, the signal waveform when the exponential window is applied is displayed. The user looks at this signal waveform, adjusts the coefficient a and then decides on the desired value. To make the effect of coefficient a easier to understand, for example, a number or characters indicating the degree of the effect may be displayed near the reflected wave portion 53 on the display screen.

[0070] In the embodiment described above, the user sets the coefficient a that determines the characteristics of the exponential function. However, as in the ultrasonic image generation device 1 of Modified Example 2, the device may be further equipped with an automatic coefficient determination means that automatically determines the coefficient a. In this case, for example, the device may be configured to automatically set the value of the coefficient a when the coefficient a of the exponential function, which is a window function, is changed, by comparing the waveforms. Alternatively, multiple waveforms when the coefficient a of the exponential function is changed may be displayed, and the user may select from among them. The configuration of Modified Example 2 reduces the burden on the user, thus improving convenience. In addition, it becomes easier to apply an appropriate window function, which in turn improves the accuracy of the normalization calculation processing of the reflected wave signal S1, and consequently improves the reliability and clarity of the ultrasonic image.

[0071] Furthermore, each embodiment of the present invention may be modified as follows.

[0072] • In the ultrasonic image generation device 1 of the above embodiment, the reflected wave from the culture medium M was used as a reference waveform for calculation processing, but the device is not limited to this. For example, a reference member (reference substance) may be provided on the upper surface of the support film 9 at a location where the cultured cells 8A are not in contact, and the reflected wave from there may be used as a reference waveform for calculation processing.

[0073] In the ultrasonic image generation apparatus 1 of the above embodiment, ultrasonic irradiation was performed using an inverted ultrasonic microscope 2 that irradiates ultrasonic waves from below, but an upright ultrasonic microscope that irradiates ultrasonic waves from above may also be used.

[0074] In the ultrasonic image generating apparatus 1 of the above embodiment, the target substance was cultured cells 8A such as glial cells, but it is not limited to this, and cultured cells 8A other than glial cells may also be used. Furthermore, the cultured cells do not need to be single cells, and can be cell aggregates such as organoids composed of multiple cells. Moreover, the cultured cells are not limited to those derived from humans, but can be of any species. The target substance in the present invention is not limited to cultured cells 8A, and may be soft tissue isolated or not isolated from a living organism (e.g., skin, internal organs, muscles, brain, fat, etc.), or hard tissue such as teeth, nails, or bones. Furthermore, the target substance does not necessarily have to be living tissue or an organism, but may be non-living (e.g., a coating film, etc.). In other words, the present invention is not limited to the medical, beauty, and cosmetics fields, but can be widely applied in industrial fields such as measurement, aerospace, etc.

[0075] The ultrasonic image generating apparatus 1 of the above embodiment was equipped with scanning means for mechanically scanning the ultrasonic transducer 13 in two directions along the planar direction with respect to the target material to move the scanning point. Alternatively, the apparatus may be equipped with scanning means for mechanically scanning the ultrasonic transducer 13 in only one direction along the planar direction to move the scanning point. Furthermore, instead of mechanical scanning means, scanning means for electronically scanning the scanning point to move it may be used.

[0076] In the ultrasonic image generation device 1 of the above embodiment, an exponential function was used as a window function that is asymmetrical and non-periodic, converging to zero over time. However, other functions may be used as long as they satisfy the above conditions. For example, a downward-sloping straight line as shown in Figure 10(a), in other words, a linear function such as y = -ax + b (where a and b are positive numbers), may be used as a window function. Alternatively, a part of a sinusoidal curve as shown in Figure 10(b), in other words, a cosine function such as y = (cos(x) + 1) / 2 (where 0° ≤ x < 180°), may be used as a window function. Furthermore, as shown in Figure 10(c), a function of a curve approximating the envelope of the reflected wave portion 52 in the upper surface of the support film 9 and the cultured cells 8A may be obtained, and this function may be used as is or with an appropriate adjustment of the time constant, as a window function. Other options include, for example, y = (x + a) -2 Functions like +b, or y=(x+a) -3 It is also possible to use functions such as +b as window functions (where a and b are positive numbers).

[0077] • In the ultrasonic image generation device 1 of the above embodiment, an intrinsic acoustic impedance image was generated based on the estimation result of the intrinsic acoustic impedance distribution in the depth direction, but the device is not limited to this. For example, the sound velocity distribution in the depth direction may be estimated, and a sound velocity image may be generated based on the result.

[0078] In the above embodiment of the ultrasound image generation device 1, a characteristic acoustic impedance image is generated from the reflected signal sequence that forms the basis of the ultrasound B-mode echo image and displayed on the display device 36. However, it is also possible to display not only the characteristic acoustic impedance image but also the ultrasound B-mode echo image. Furthermore, the signal normalization algorithm of the above embodiment may be incorporated into a general-purpose ultrasound diagnostic device that displays ultrasound B-mode echo images, thereby enabling it to operate as the ultrasound image generation device 1.

[0079] In the above embodiment, the present invention was embodied with reference to reflected wave signals when transmitting and receiving using ultrasonic pulse waves, but it may also be applied to reflected wave signals when transmitting and receiving using electromagnetic waves of different frequency bands. For example, it may be applied to reflected wave signals when transmitting and receiving using gigahertz pulse waves, terahertz pulse waves, or even light wave pulse waves with shorter wavelengths than those, and the acoustic properties of the object in the depth direction may be estimated by performing the same signal processing as in the embodiment. In this case, the estimated acoustic properties may of course be other than the intrinsic acoustic impedance. [Explanation of symbols]

[0080] 1… Ultrasonic imaging device 8A...Cultured cells as target substances 9…Support film as a substrate 10...Reference substance 13. Transducers as a means of transmission and reception 31...CPU as a first domain conversion means, signal standardization means, second domain conversion means, estimation means, image generation means, automatic zero point setting means, and automatic coefficient determination means. 53...Longitudinal wave as a noise signal; transverse wave; longitudinal wave conversion portion 54... Flat section 55...The necessary part of the waveform 56... Zeros of window functions M…Culture solution S1…Reflected wave signal

Claims

1. A method for generating an ultrasonic image by processing the reflected wave signal obtained when a focused beam of ultrasonic pulse waves is transmitted to a target material while scanning the target material in a direction perpendicular to the depth direction of the target material, A transmission and reception step in which an ultrasonic pulse is transmitted through the substrate while the target material and the reference material are in contact with the substrate, and a target signal from the target material and a reference signal from the reference material are received, A first domain conversion step involves applying an asymmetrical and non-periodic window function that converges to zero over time to extract the necessary portion of the waveform in the received signal from immediately before the necessary portion, and then converting the target signal and the reference signal from the time domain to the frequency domain. A signal normalization step of deconvolving the target signal with the reference signal in the frequency domain, A second domain conversion step involves converting the deconvolved target signal from the frequency domain to the time domain to obtain a normalized impulse response signal. An estimation step in which the intrinsic acoustic impedance within the target material is sequentially estimated from the front to the back in the depth direction based on the normalized impulse response signal, Based on the estimation result of the intrinsic acoustic impedance, an image generation step is performed to generate the ultrasonic image. An ultrasound image generation method including [details omitted].

2. The ultrasonic image generation method according to claim 1, characterized in that, in the first region conversion step, the position of the zero point of the window function is adjusted to set the position of the zero point to a flat portion that appears immediately in front of the reflected wave signal from the target material.

3. The ultrasonic image generation method according to claim 1 or 2, characterized in that the signal normalization step involves determining coefficients that determine the characteristics of the window function in order to suppress noise signals appearing after the reflected wave signal from the target material to a predetermined level or lower.

4. The method for generating an ultrasound image according to claim 3, characterized in that the target substance is soft tissue or cultured cells of a living organism.

5. An ultrasonic image is generated by processing the reflected wave signal obtained when a focused beam of ultrasonic pulse waves is transmitted to a target material while scanning the target material in a direction perpendicular to the depth direction of the target material, A transmitting and receiving means that transmits ultrasonic pulses through a substrate while the target material and reference material are in contact with the substrate, and receives a target signal from the target material and a reference signal from the reference material, A first domain conversion means that applies an asymmetrical and non-periodic window function that converges to zero over time to extract the necessary portion of the waveform in the received signal from immediately before the necessary portion, and then converts the target signal and the reference signal from the time domain to the frequency domain. A signal normalization means for deconvolving the target signal with the reference signal in the frequency domain, A second domain conversion means for obtaining a normalized impulse response signal by converting the deconvolved target signal from the frequency domain to the time domain, An estimation means for sequentially estimating the intrinsic acoustic impedance within the target material from the front to the back in the depth direction based on the standardized impulse response signal, Based on the estimation result of the intrinsic acoustic impedance, an image generation means generates the ultrasonic image. An ultrasonic imaging device equipped with [specific features / equipment].

6. The system further includes an automatic zero-point setting means for automatically adjusting and setting the position of the zeros of the window function, The automatic zero-point setting means sets the position of the zero point to a flat portion that appears immediately in front of the reflected wave signal from the target material. The ultrasonic image generating apparatus according to claim 5, characterized in that...

7. The system further includes an automatic coefficient determination means for automatically determining the coefficients that determine the characteristics of the window function, The coefficient automatic determination means determines the coefficient to a value that suppresses the noise signal appearing after the reflected wave signal from the target material to a predetermined level or lower. An ultrasonic image generating apparatus according to claim 5 or 6, characterized by the above.

8. A first domain conversion step involves converting the time domain to the frequency domain, after applying a window function that is asymmetrical and non-periodic, converging to zero over time, to the target signal from the target material and the reference signal from the reference material obtained by transmitting and receiving pulse waves through the substrate while the target material and reference material are in contact with the substrate, and then cutting out the necessary portion of the waveform in the received signal from immediately before the necessary portion, and then converting it from the time domain to the frequency domain. A signal normalization step of deconvolving the target signal with the reference signal in the frequency domain, A second domain conversion step involves converting the deconvolved target signal from the frequency domain to the time domain to obtain a normalized impulse response signal. An estimation step in which the acoustic properties within the target material are sequentially estimated from the front to the back in the depth direction based on the normalized impulse response signal, A signal processing method that includes [a specific component].

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