JP7213491B2 - Ultrasound Image Construction Method, Ultrasound Image Construction Apparatus, Ultrasound Image Construction Program - Google Patents

Description

The present invention relates to a method, an apparatus, and a program for constructing an image of a living body's soft tissue, such as skin, or cultured cells, based on information obtained using ultrasound.

An ultrasonic B-mode echo image is a method widely used in the medical field, and many apparatuses for obtaining such an image have conventionally been proposed (see Patent Document 1). Briefly, an ultrasonic B-mode echo image is an image of a reflected signal train when ultrasonic waves incident on an object are reflected and returned. Assuming that the ultrasonic wave travels straight without scattering, reflection occurs due to the difference in the resistance value (specific acoustic impedance) where it travels, just like an electric signal. Therefore, if the distribution of the characteristic acoustic impedance is known, it becomes possible to estimate what kind of reflected signal train is returned. That is, if the acoustic physical property distribution is known, it is possible to estimate what kind of B-mode image will be observed. And vice versa.

However, for a non-uniform and thick (depth) target such as a biological tissue, the reflected waveform that is incident and returned is the result of the ultrasonic waves that have entered the target traveling in various ways after being scattered and absorbed. , and the result of multiple reflection. For this reason, it is considered difficult to convert the reflected waveform into an acoustic physical property such as a specific acoustic impedance, and this method has not been studied in the past. Furthermore, since the ultrasonic B-mode echo image tends to be disturbed by speckle noise caused by multiple reflections of ultrasonic waves inside the living tissue, it is not suitable for displaying the internal structure with high accuracy. There was also Therefore, in the conventional apparatus, measures such as inserting an acoustic filter are required, which causes problems such as complicating the configuration.

In addition, with a normal ultrasonic diagnostic apparatus that displays an ultrasonic B-mode echo image, although layer information inside a living tissue such as skin can be obtained to some extent, the obtained image is the reflection from the interface between layers with different specific acoustic impedances. is a statue. Therefore, such a reflected image is insufficient to grasp the internal structure of the living tissue, specifically, the difference in the characteristic acoustic impedance inside the living tissue. In other words, in the reflected image obtained by the conventional technique, it is intuitively easy to understand the position of the interface between the layers, but on the other hand, the characteristic acoustic impedance of the intermediate region surrounded by the interfaces is It was difficult to intuitively understand how things were going. Therefore, it is desired to construct an ultrasonic tomographic image of a very thin measurement object having a layered structure in a manner that facilitates intuitive understanding of the layered structure, based on information obtained using ultrasonic waves. was

In view of such circumstances, the inventors of the present application have already proposed an improved ultrasonic image construction device (see, for example, Patent Document 2). This apparatus includes a substrate having known acoustic properties, an ultrasonic transducer for transmitting and receiving ultrasonic waves through the substrate, computing means, image constructing means, and the like. In this apparatus, an object to be measured and a reference substance having known acoustic properties are placed in contact with a substrate having known acoustic properties. Then, in this state, an ultrasonic wave is transmitted, the ultrasonic wave is made incident on the object to be measured and the reference substance through the substrate, and the impulse response of the ultrasonic waveform is received from the object to be measured and the reference substance. Next, normalized impulse response information is obtained from the impulse response information of the ultrasonic waveform incident on the reference substance and the impulse response information of the ultrasonic waveform incident on the measurement object. Based on this normalized impulse response information, calculations are performed to estimate the acoustic physical property distribution in the depth direction (specifically, the characteristic acoustic impedance distribution) in consideration of the influence of multiple reflections. Then, image data of an acoustic physical property image is constructed based on the obtained acoustic physical property distribution in the depth direction, and a desired ultrasonic tomographic image is obtained.

JP 2006-271765 A Japanese Patent No. 6361001

However, the above apparatus adopts a method of sequentially estimating the characteristic acoustic impedance distribution in the direction of increasing depth along the depth direction, that is, in the direction from the front side to the back side of the object to be measured. For this reason, there is a drawback that the error in the estimated value of the characteristic acoustic impedance accumulates and expands as the depth increases, which is a negative factor in constructing a more accurate image. Moreover, in such a case, many streaks appear in the depth direction in the ultrasonic tomographic image, so it is difficult to say that the fine internal layer structure is intuitively understandable, and there is still room for improvement.

Cultured cells are also a type of very thin measurement object, and have fine structures such as nuclei and cytoskeleton inside them. However, there has been no proposal for a method capable of producing an ultrasonic tomographic image of the fine structure in a manner that is intuitively understandable.

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and its main purpose is to sensuously understand the fine internal structure of an ultrasonic tomographic image of a very thin measurement object having a fine internal structure. An object of the present invention is to provide an ultrasonic image construction method, an ultrasonic image construction apparatus, and an ultrasonic image construction program capable of constructing an image relatively easily and with high accuracy in an easy manner.

A further object of the present invention is to simply and accurately observe and evaluate the internal structure of cultured cells and the internal structure of soft tissues of a living body such as skin, based on information obtained using ultrasound. It is to construct an image that can be equivalent.

In order to solve the above problems, the inventors of the present application came up with the idea of appropriately correcting the estimated value of the specific acoustic impedance in the object to be measured, and conducted earnest studies. As a result, 1) a position different from the first reference substance existing in contact with the substrate like the measurement object (specifically, the opposite side of the measurement object that is not in contact with the substrate (deep side in the depth direction) ) is used in the correction calculation, or 2) when a predetermined condition is satisfied even if the second reference material does not exist at such a position. For example, if the specific acoustic impedance value (or the average of the estimated values) of a predetermined part in the measurement object is defined as the specific acoustic impedance value of the virtual reference part and used in the correction calculation, the deeper the depth, the more accumulated , it is possible to reduce the error in the estimated value of the characteristic acoustic impedance, which tends to expand, and to make it possible to more accurately estimate the characteristic acoustic impedance distribution in the depth direction. Based on these findings, the inventors of the present application have further pursued research, and have arrived at the solutions [1] to [15] listed below.

[1] transmitting ultrasonic waves in a state in which an object to be measured and a first reference substance are in contact with a substrate, and a second reference substance is in contact with the side of the object to be measured opposite to the substrate; a transmitting/receiving step of receiving an impulse response of an ultrasonic waveform from the measurement object, the first reference material, and the second reference material when ultrasonic waves are incident through the base; and an impulse of the ultrasonic waveform. an estimation step of sequentially estimating the intrinsic acoustic impedance in the measurement object and in the second reference material from the near side to the far side in the depth direction based on the normalized impulse response information obtained from the response information; The estimated value of the specific acoustic impedance of the object to be measured is obtained by replacing the estimated value of the specific acoustic impedance of the second reference material obtained in the estimation step with the actual value of the specific acoustic impedance of the second reference material. After correction, it has a correction step of estimating the characteristic acoustic impedance distribution in the depth direction, and an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. ultrasound image construction method.

[2] Ultrasonic waves are transmitted in a state in which the object to be measured and the first reference substance are in contact with a substrate, and when the ultrasonic waves are incident through the substrate, from the object to be measured and the first reference substance Based on the transmission/reception step of receiving the impulse response of the ultrasonic waveform and the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the specific acoustic impedance in the measurement object is measured in the depth direction on the front side an estimating step of sequentially estimating toward the far side from the measuring object, and the specific acoustic impedance value when a substance having a known specific acoustic impedance value is uniformly present in the layer direction at a specific depth in the measurement object, Alternatively, when the measurement object is a soft tissue of a living body, an average of estimated values of specific acoustic impedance at a specific depth in the measurement object is defined as a specific acoustic impedance value of the virtual reference site, and obtained in the estimation step. After correcting the estimated value of the specific acoustic impedance in the measurement object through a calculation that replaces the estimated value of the specific acoustic impedance at the specific depth in the measurement object with the specific acoustic impedance value of the virtual reference part, An ultrasonic image construction characterized by comprising a correction step of estimating a characteristic acoustic impedance distribution in the depth direction and an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. Method.

[3] In the correcting step, the actual value of the specific acoustic impedance of the second reference material or the value when replacing with the specific acoustic impedance value of the virtual reference part is maximized, and decreases toward the front side of the measurement object. 3. The ultrasonic image construction method according to means 1 or 2, wherein the estimated value of the intrinsic acoustic impedance in the object to be measured is corrected by adding or subtracting a correction value of .

[4] In the estimation step, it is assumed that lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. 4. The method according to any one of means 1 to 3, characterized in that calculation for estimating the characteristic acoustic impedance of the minute transmission line adjacent to the rear side thereof is performed based on the estimation result of the characteristic acoustic impedance of the minute transmission line. Ultrasound image construction method.

[5] The measurement object is a cultured cell, the first reference substance and the second reference substance are a culture medium for culturing the cultured cell, and the substrate contains the culture medium. 2. The method of claim 1 , wherein the ultrasonic image construction method is part of a culture vessel.

[6] The measurement object is skin as a soft tissue of a living body containing blood vessels extending in a direction substantially parallel to the tissue surface, and has a known specific acoustic impedance value at a specific depth within the measurement object. 3. The ultrasonic image constructing method according to claim 2 , wherein the characteristic acoustic impedance value when the substance exists uniformly in the layer direction is the characteristic acoustic impedance value of blood existing in the blood vessel. .

[7] When the measurement object is a soft tissue of a living body, the average of the estimated values of the specific acoustic impedance at a specific depth in the measurement object is the specific depth in the skin when the measurement object is the skin 3. The ultrasonic wave according to claim 2 , wherein the specific depth is set at a position deeper than the region in which the image data of the acoustic physical property image is constructed. Image construction method.

[8] ultrasonic waves in a state in which a substrate, an object to be measured and a first reference substance are in contact with the substrate, and a second reference substance is in contact with the side of the object to be measured opposite to the substrate; and receives impulse responses of ultrasonic waveforms from the measurement object, the first reference material, and the second reference material when ultrasonic waves are incident through the base; Based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the intrinsic acoustic impedance in the measurement object and in the second reference material is sequentially measured from the near side to the far side in the depth direction. Through a first calculation means for estimating and a calculation for replacing the estimated value of the specific acoustic impedance of the second reference material obtained by the first calculation means with the actual value of the specific acoustic impedance of the second reference material, the measurement object A second calculating means for estimating the characteristic acoustic impedance distribution in the depth direction after correcting the estimated value of the characteristic acoustic impedance in the second calculation means, and constructing image data of the acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. An ultrasound image construction device comprising: image construction means for:

[9] Ultrasonic waves are transmitted in a state in which a substrate, an object to be measured and a first reference substance are in contact with the substrate, and the object to be measured and the first reference substance when the ultrasonic waves are incident through the substrate. 1. An ultrasonic transducer that receives an impulse response of an ultrasonic waveform from a reference substance, and a specific acoustic impedance in the measurement object based on normalized impulse response information obtained from the impulse response information of the ultrasonic waveform and a first computing means for estimating sequentially from the front side to the back side in the depth direction, and a substance having a known specific acoustic impedance value at a specific depth in the measurement object is uniformly present in the layer direction defined as the intrinsic acoustic impedance value of the virtual reference site Then, through calculation for replacing the estimated value of the specific acoustic impedance at the specific depth in the measurement object obtained by the first calculation means with the specific acoustic impedance value of the virtual reference part, the specific acoustic impedance in the measurement object a second calculation means for estimating the characteristic acoustic impedance distribution in the depth direction after correcting the estimated value of; and an image constructing means for constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. An ultrasound image construction device comprising:

[10] The second calculating means maximizes the actual value of the specific acoustic impedance of the second reference material or the value when replacing it with the specific acoustic impedance value of the virtual reference part, and directs it toward the front side of the measurement object. 10. The ultrasonic image constructing apparatus according to means 8 or 9, wherein the estimated value of the intrinsic acoustic impedance in the object to be measured is corrected by adding or subtracting a correction value that becomes smaller as the correction value decreases.

[11] The first computing means assumes that lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. 11. The method according to any one of means 8 to 10, wherein calculation is performed for estimating the characteristic acoustic impedance of the minute transmission line adjacent to the back side based on the estimation result of the characteristic acoustic impedance of the minute transmission line on the side. The ultrasound image construction device described.

[12] The processor performs ultrasonic vibration in a state in which an object to be measured and a first reference substance are in contact with a substrate, and a second reference substance is in contact with the side of the object to be measured opposite to the substrate. ultrasonic wave is transmitted from the element, and the impulse response of the ultrasonic waveform from the measurement object, the first reference substance and the second reference substance when the ultrasonic wave is incident through the base is the ultrasonic vibration Based on the transmission/reception step of causing the child to receive and the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the characteristic acoustic impedance in the measurement object and in the second reference material is measured in the depth direction. Through an estimation step of sequentially estimating from the side to the back side, and an operation of replacing the estimated value of the specific acoustic impedance of the second reference material obtained in the estimation step with the actual value of the specific acoustic impedance of the second reference material a correction step of estimating a specific acoustic impedance distribution in the depth direction after correcting the estimated value of the specific acoustic impedance in the measurement object; and an image of an acoustic physical property image based on the specific acoustic impedance distribution in the depth direction. An ultrasound image construction program for performing an image construction step of constructing data.

[13] When the processor causes the ultrasonic transducer to transmit ultrasonic waves in a state in which the object to be measured and the first reference substance are in contact with the substrate, and the ultrasonic waves are incident through the substrate, the object to be measured a transmitting/receiving step of causing the ultrasonic transducer to receive impulse responses of ultrasonic waveforms from the object and the first reference material; and based on normalized impulse response information obtained from the impulse response information of the ultrasonic waveforms, an estimating step of sequentially estimating the intrinsic acoustic impedance within the object to be measured from the near side to the far side in the depth direction; The average of the specific acoustic impedance value when the measurement object exists uniformly or the estimated value of the specific acoustic impedance at a specific depth in the measurement object when the measurement object is a soft tissue of a living body is the virtual reference part defined as a specific acoustic impedance value, and through a calculation that replaces the estimated value of the specific acoustic impedance at the specific depth in the measurement object obtained in the estimation step with the specific acoustic impedance value of the virtual reference part, the measurement object A correcting step of estimating the characteristic acoustic impedance distribution in the depth direction after correcting the estimated value of the characteristic acoustic impedance in the image, and constructing image data of the acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. An ultrasound image construction program for performing the construction steps.

[14] In the correcting step, the actual value of the specific acoustic impedance of the second reference material or the value when replacing with the specific acoustic impedance value of the virtual reference part is maximized, and decreases toward the front side of the measurement object. 14. The program for constructing an ultrasonic image according to claim 12 or 13, wherein the estimated value of the characteristic acoustic impedance in the object to be measured is corrected by adding or subtracting a correction value of .

[15] In the estimating step, it is assumed that lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. 15. The method according to any one of claims 12 to 14, wherein calculation is performed for estimating the specific acoustic impedance of said micro-transmission channel adjacent on the far side based on the result of estimating the specific acoustic impedance of said micro-transmission channel. ultrasound image construction program.

According to the inventions described in the above means 1 to 15, an ultrasonic tomographic image of a very thin measurement object having a fine internal structure can be relatively easily obtained in a manner in which the fine internal structure can be intuitively understood. And it can be constructed with high accuracy. In addition, based on the information obtained using ultrasound, constructing an image that enables simple and accurate observation and evaluation of the internal structure of cultured cells and the internal structure of soft tissues of the living body such as the skin. can be done.

1 is a schematic configuration diagram showing an ultrasonic image constructing apparatus of a first embodiment embodying the present invention; FIG. FIG. 2 is a block diagram showing the electrical configuration of the ultrasonic image construction apparatus of the first embodiment; FIG. FIG. 4 is a schematic diagram showing an example of an ultrasonic scanning range accompanying movement of the XY stage; (a) is an explanatory diagram of acquisition of the reflected waveform from the measurement object when the measurement is actually performed, and (b) is an explanatory diagram of acquisition of the reflected waveform when the measurement object is regarded as a minute transmission path. . (a) is an explanatory diagram of acquisition of a reflected waveform from a reference substance when actually performing measurement, and (b) is an explanatory diagram of acquisition of a reflected waveform when the reference substance is regarded as a minute transmission path. FIG. 4 is a diagram conceptually showing how the characteristic impedance of each minute transmission path is estimated. FIG. 2 is a diagram conceptually showing the influence of multiple reflection; Schematic cross-sectional view showing the layered structure of human neck skin. 5 is a graph for explaining correction steps in the first embodiment; 4 is a flowchart for explaining arithmetic processing for constructing a specific acoustic impedance image in the first embodiment; It is for explaining the correction step in the ultrasonic image construction apparatus of the second embodiment embodying the present invention, (a) is a specific acoustic impedance image when the correction step is not performed, (b ) is the characteristic acoustic impedance image when the correction step is performed. FIG. 3 is a schematic block diagram showing an ultrasonic image constructing apparatus of a third embodiment embodying the present invention; A diagram schematically showing a cultured cell (glial cell), which is an object to be measured. FIG. 10 is a specific acoustic impedance image of cultured cells (glial cells) observed using the ultrasonic image construction apparatus of the third embodiment; FIG.

[First embodiment]
A first embodiment embodying an ultrasonic image constructing method and apparatus of the present invention will be described in detail below with reference to FIGS. 1 to 10. FIG.

FIG. 1 is a schematic configuration diagram showing an ultrasonic image constructing apparatus 1 of this embodiment. As shown in FIG. 1, an ultrasonic image constructing apparatus 1 of the present embodiment is an apparatus for observing, diagnosing, etc. skin 8 using ultrasonic waves, and includes a pulse excitation ultrasonic microscope 2 and a personal A computer (PC) 3 is provided.

A pulse excitation 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 ultrasonic microscope 2 is electrically connected to the PC3.

The stage 4 of this embodiment is configured to be movable in the horizontal direction (that is, the X direction and the Y direction) by a user's manual operation. A resin plate 9 is fixed to the stage 4 for placing an object to be measured in contact therewith. The object to be measured here is a living body's soft tissue (specifically, skin tissue; skin 8) containing blood vessels extending in a direction substantially parallel to the tissue surface. In this embodiment, the measurement or the like is performed by directly pressing the human skin 8 against the resin plate 9 . The resin plate 9 as a substrate having known acoustic properties is a plate-like member that can transmit ultrasonic waves, and is made of a material harder than the skin 8 that is the object to be measured. When a member having such a shape and hardness is used as a substrate, it becomes possible to securely place the skin 8, which is the object to be measured, in close contact with the body, and as a result, it becomes possible to accurately estimate the characteristic acoustic impedance distribution in the depth direction. As a result, the accuracy of image construction is improved. A polystyrene plate having a thickness of 1.4 mm is used in this embodiment. Of course, it is permissible to use a plate member made of a resin other than polystyrene.

A reference member 10 as a first reference substance is previously installed on the upper surface of the resin plate 9 on which the skin 8 is placed in contact. The reference member 10 has known acoustic properties different from those of the resin plate 9 . In this embodiment, for example, the reference member 10 is formed by adhering an acrylic resin (acrylic adhesive), but the present invention is, of course, not limited to this. The reference member 10 may be made of a material other than a resin material (for example, a glass material, a metal material, a ceramic material, etc.) as long as it can be brought into close contact with the reference member 10 . Alternatively, instead of installing such a reference member 10, for example, water or the like may be present so as to be in contact with the upper surface of the resin plate 9, and this may be used as the first reference substance. By previously setting the reference member 10 on the resin plate 9, the impulse response information of the ultrasonic waveform incident on the reference member 10 can be obtained accurately and stably without depending on changes in the environment in which the apparatus is placed. can be obtained.

The ultrasonic probe 6 includes a probe body 12 having a storage portion 11 capable of storing an ultrasonic transmission medium W such as water at its tip, and an ultrasonic transducer 13 (ultrasonic wave and an XY stage 14 for two-dimensionally scanning the probe body 12 along the surface direction of the stage 4 . The storage part 11 of the probe main 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 part 11 facing upward.

The ultrasonic transducer 13 is composed of, for example, a zinc oxide thin film piezoelectric element 16 and a sapphire rod acoustic lens 17 . The ultrasonic transducer 13 is pulse-excited to irradiate the skin 8 and the reference member 10 with ultrasonic waves from the lower surface side of the resin plate 9 . The ultrasonic waves emitted by the ultrasonic transducer 13 are converged into a conical shape via the ultrasonic transmission medium W of the reservoir 11 and focused on the upper surface of the resin plate 9 (near the surface of the skin 8). . In this embodiment, as the ultrasonic transducer 13, one with a diameter of 1.2 mm, a focal length of 1.5 mm, a center frequency of 80 MHz, and a bandwidth of 50 to 105 MHz (-6 dB) is used.

FIG. 2 is a block diagram showing the electrical configuration of the ultrasonic image constructing apparatus 1 of this embodiment.

As shown in FIG. 2, the ultrasonic probe 6 includes an ultrasonic transducer 13, an XY stage 14, a pulse generation circuit 21, a reception circuit 22, a transmission/reception separation circuit 23, a detection circuit 24, and an A/D conversion circuit 25. , an encoder 26 and a controller 27 .

The XY stage 14 as scanning means includes an X stage 14X and a Y stage 14Y for two-dimensionally scanning the irradiation point of the ultrasonic waves, and motors 28X and 28Y for driving the respective stages 14X and 14Y. I have. A stepping motor or a linear motor is used as these motors 28X and 28Y.

A controller 27 is connected to each of the motors 28X and 28Y, and the motors 28X and 28Y are driven in response to drive signals from the controller 27. FIG. By driving these motors 28X and 28Y, the X stage 14X is continuously scanned (continuously fed), and the Y stage 14Y is controlled to be intermittently fed, thereby enabling high-speed scanning of the XY stage 14. .

Further, 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. FIG. Specifically, when the scanning range is divided into 300×300 measurement points (pixels), one scanning in the X direction (horizontal direction) is divided into 300. Then, the position of each measuring point is detected by the encoder 26 and taken into the PC3. The PC 3 generates a drive control signal in synchronization with the output of the encoder 26 and supplies the drive control signal to the controller 27 . The controller 27 drives the motor 28X based on this drive control signal. Further, the controller 27 drives the motor 28Y based on the output signal of the encoder 26 when scanning of one line in the X direction is completed, and moves the Y stage 14Y by one pixel in the Y direction.

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. As a result of the excitation pulse being supplied to the ultrasonic transducer 13 via the transmission/reception wave separation circuit 23, the ultrasonic transducer 13 emits ultrasonic waves.

FIG. 3 shows an example of an ultrasonic scanning range R1 accompanying movement of the XY stage 14. As shown in FIG. In this example, a reference member 10 is provided so as to surround the area where the skin 8 is to be placed in contact. Scanning is then started from a position where the reference member 10 is located while the human skin 8 is pressed against the area. Then, as indicated by arrows, scanning is sequentially performed two-dimensionally along the surface of the skin 8 in the X and Y directions.

The thin-film piezoelectric element 16 of the ultrasonic transducer 13 is an ultrasonic transducer for transmitting and receiving waves, and converts ultrasonic waves (reflected waves) reflected by the skin 8 into electrical signals. A signal of the reflected wave is supplied to the receiving circuit 22 via the transmitting/receiving wave separating circuit 23 . The receiving circuit 22 includes a signal amplifying circuit, amplifies the signal of the reflected wave, and outputs the amplified signal to the detecting circuit 24 .

The detection circuit 24 is a circuit for detecting reflected wave signals from the skin 8 and includes a gate circuit (not shown). The detection circuit 24 of this embodiment extracts the reflected wave signal from the skin 8 and the reflected wave signal from the reference member 10 from the reflected wave signals received by the ultrasonic transducer 13 . Then, the reflected wave signal extracted by the detection circuit 24 is supplied to the A/D conversion circuit 25 to be A/D converted, and then transferred to the PC 3 .

The PC 3 includes a CPU 31 (central processing unit), an I/F circuit 32, a memory 33, a storage device 34, an input device 35, and a display device 36, which are interconnected via a bus 37.

The CPU 31 executes a control program using the memory 33 to centrally control 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 train that is the basis of the ultrasonic B-mode echo image into a specific acoustic impedance image, a specific acoustic Includes programs for displaying impedance images. In addition, for example, a DSP (Digital Signal Processor) may be provided separately from the CPU 31 to perform part of the signal processing performed by the CPU 31 there.

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 outputs control signals (driving control signals to the controller 27) to the ultrasonic probe 6, and transfers data from the ultrasonic probe 6 (data transferred from the A/D conversion circuit 25, etc.). It plays the role of inputting When transmitting and receiving signals to and from the ultrasonic probe 6, a wireless interface may be used without being limited to the physical interface as described above.

The display device 36 is, for example, a monitor display such as liquid crystal, plasma, or organic EL (electroluminescence). The display device 36 can be used regardless of color display or monochrome display, but color display is desirable. This display device 36 is used to display the characteristic acoustic impedance image of the surface layer of the skin 8 and to display input screens for various settings.

The input device 35 is an input user interface such as a touch panel, mouse, keyboard, pointing device, etc., and is used to input requests, instructions, and parameters from the user.

The storage device 34 is a hard disk drive such as a magnetic disk device or an optical disk device, and stores various control programs and various data. The memory 33 includes a RAM (random access memory) and a ROM (read only memory), and stores the reflected waveform of the reference member 10 and its characteristic acoustic impedance 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 program executed by the CPU 31 may be a program stored in a storage medium such as a memory card, flexible disk, or optical disk, or a program downloaded via a communication medium. do.

Next, a method for constructing a specific acoustic impedance image from a reflected signal train that is the basis of an ultrasonic B-mode echo image in the ultrasonic image constructing apparatus 1 of this embodiment will be described.

In this ultrasonic image constructing apparatus 1, from the impulse response information of the ultrasonic waveform incident on the reference member 10, which is the first reference material, and the impulse response information of the ultrasonic waveform incident on the skin 8, which is the measurement object, the standard After obtaining normalized impulse response information, the acoustic physical property distribution in the depth direction is estimated based on the normalized impulse response information, taking into consideration the influence of multiple reflections. In order to perform such estimation, in the present embodiment, lossless minute transmission lines 51 having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. Assuming that, by sequentially repeating the process of estimating the characteristic acoustic impedance of the minute transmission line 51 adjacent to the back side based on the result of estimating the characteristic acoustic impedance of the minute transmission line 51 on the front side, the depth direction of the transmission line A calculation for estimating the acoustic physical property distribution (specific acoustic impedance distribution in this case) is performed. Such operations are performed based on predetermined algorithms stored in memory 33 .

This algorithm is an algorithm for estimating the distribution of the characteristic acoustic impedance in the depth direction by using the reflected signal train that is the basis of the ultrasonic B-mode echo image. This algorithm is based on the principle of the time domain reflectometry method (TDR method: Time Domain Reflectometry method), and considers multiple reflections inside the skin tissue. Through analysis in the time-frequency domain, ultrasound B This is an algorithm that transforms the reflected signal train, which is the basis of the mode echo image, into the characteristic acoustic impedance image in the depth direction. This will be described in detail below.

FIG. 4(a) is a diagram for explaining acquisition of the reflected waveform from the object to be measured when the measurement is actually performed, and FIG. FIG. 10 is a diagram for explaining acquisition of a reflected waveform in . FIG. 5(a) is a diagram for explaining acquisition of a reflected waveform from the first reference substance when actually performing measurement, and FIG. FIG. 10 is a diagram for explaining acquisition of a reflected waveform when

First, as shown in FIG. 4A, the ultrasonic transducer 13 is operated to transmit a focused ultrasonic beam having a sufficient depth of focus for the object to be measured through the resin plate 9 as a base. Then, a convergent beam of ultrasonic waves is made incident on the skin 8, which is an object to be measured, and a reflected waveform therefrom is acquired. The impulse response Γ ₀ (ω) at that time is represented by the following equation 1 from the incident wave S0 and the reflected wave S _tgt (ω) from the skin 8 using Fourier transform.

In this case, it is also necessary to acquire a reflected waveform from the reference member 10 having a known and uniform specific acoustic impedance and having a sufficient thickness compared to the object to be measured. A reflected wave S _ref (ω) from the reference member 10 is expressed by the following equation 2 using the specific acoustic impedance Z _ref of the reference member 10 and the specific acoustic impedance Z ₀ of the resin plate 9 .

Also, the impulse response Γ ₀ (ω) from the skin 8 which is the object to be measured is expressed by the following equation (3). However, since this impulse response Γ ₀ (ω) includes reflections generated from a plurality of interfaces deep within the tissue of the skin 8, the impulse response Γ ₀ (ω) has frequency characteristics. By the above formula, the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform incident on the first reference substance and the impulse response information of the ultrasonic waveform incident on the measurement object is obtained.

Here, FIG. 6 is a diagram _conceptually showing how the characteristic impedances Z ₁ , Z ₂ . . As shown in this figure, the characteristic _impedances Z ₁ , Z ₂ .

FIG. 7 is a diagram conceptually showing the influence of multiple reflections. The following equation 4 expresses g ₀ (t) obtained by inverse Fourier transforming the impulse response Γ ₀ (ω), the first term of which is not affected by multiple reflections (see FIG. 7). Therefore, the characteristic impedance Z1 of the minute transmission line 51 in contact with the resin plate 9 can be estimated from the value of the _first term as shown in the following equation (5).

The characteristic acoustic impedance Zx ₀ of the skin 8 in the frequency domain is expressed by the following Equation 6 using Γ ₀ .

Zx ₀ is also expressed by the following equation 7 using the impulse response Γ ₁ from the back.

Here, as represented by the following equations 8 and 9, γ is the propagation constant, α is the attenuation constant, β is the phase constant, and f is the frequency. It is assumed that the speed of sound in all microtransmission channels 51 is c=1600 (m/s).

Also, the distance .DELTA.l of each minute transmission path 51 is represented by the following equation 10, again assuming that the speed of sound is c=1600 (m/s). Δt corresponds to one sampling interval point of the reflected waveform from the skin 8 (Δt=2 (ns) in this embodiment).

Then, based on the above equation, the impulse response _Γ1 from the micro-transmission path 51 located further inside can be obtained (equation 11 below). That is, the value of Γ ₁ at the end point of Z ₁ can be estimated based on the values of Zx ₀ and Z ₁ .

The following equation 12 expresses g ₁ (t) obtained by inverse Fourier transforming the impulse response Γ ₁ (ω), the first term of which is not affected by multiple reflections. Therefore, from the value of the _first term, it is possible to estimate the characteristic impedance Z2 of the microtransmission line 51 adjacent to the microtransmission line 51 on the farther side, and similarly estimate _Zx1 and _Γ2 (ω). (Formulas 13, 14 and 15 below).

By repeating this process, the characteristic impedances (specific acoustic impedances) Z ₁ , Z ₂ . . . _Zn of each minute transmission line 51 can be estimated.

In the algorithm of this embodiment, after performing the estimation step as described above, the following predetermined correction step is further performed. That is, in this correction step, first, the intrinsic acoustic impedance value of the virtual reference site is defined. The object to be measured here is the skin 8 (skin tissue) (see FIG. 8). There are blood vessels 64 extending in a direction substantially parallel to the tissue surface. Since the specific acoustic impedance value of the blood 65 present in the blood vessel 64 is known (1.61 MNs/m ³ ), this value is used as the "specific acoustic impedance value of the virtual reference site" in this embodiment.

Next, the estimated value of the specific acoustic impedance at a specific depth (here, shallow subcutaneous tissue where transverse blood vessels exist) in the measurement object obtained in the estimation step is applied to the specific acoustic impedance value of the virtual reference site. Perform correction calculation to replace.

This correction calculation will be described in detail using the graph of FIG. In the graph, the vertical axis indicates the specific acoustic impedance, and the horizontal axis indicates time. Also, two curves C1 and C2 are drawn in the same graph. A curve C1 drawn with a solid line indicates the characteristic acoustic impedance curve C1 before correction, and a curve C2 drawn with a broken line indicates the characteristic acoustic impedance curve C2 after correction. Although these curves C1 and C2 overlap without difference in the left half region (that is, the region corresponding to the inside of the resin plate 9), they are different in the right half region (that is, the region corresponding to the inside of the skin 8). ing. In the present embodiment, the right side area of the curve C2 is positioned generally lower than the right side area of the curve C1.

Here, since the base resin plate 9 is made of polystyrene, its intrinsic acoustic impedance value Z(x) is known and constant (Z(0)=2.50 MNs/m ³ ). The area on the left side of the characteristic acoustic impedance curve C 1 is a portion that indicates the characteristic acoustic impedance value Z(x) of the resin plate 9 located near the ultrasonic transducer 13 . On the other hand, the skin 8 placed in contact with the resin plate 9 is softer than the polystyrene resin plate 9 . Therefore, the characteristic acoustic impedance value Z(x) sharply decreases across point A on the characteristic acoustic impedance curve C1. The area on the right side of the characteristic acoustic impedance curve C1 is the part showing the pre-correction estimated value of the characteristic acoustic impedance value Z(x) of the skin 8, which is much lower than 2.50 MNs/m ³ . In the curve C1, the right side of the point B (that is, the portion corresponding to the specific depth in the skin 8) is flat, and this portion is the pre-correction estimated value of the characteristic acoustic impedance value of the blood present in the blood vessel at the specific depth. It is the part that shows However, the estimated value contains an error and is presented as somewhat different from the actual value (1.80 MNs/m ³ in this example). Therefore, in order to replace the pre-correction estimated value of the specific acoustic impedance value of the blood 65 present in the blood vessel 64 at a specific depth with the specific acoustic impedance value (1.61 MNs/m ³ ) of the virtual reference site, 1.80 MNs/ A correction value of 0.19 ^MNs / ^m3 is subtracted from m3. As a result, the flat portion of the curve C1 moves downwards and forms part of the corrected specific acoustic impedance curve C2. Note that the point B on the curve C1 is moved to the point C on the curve C2.

Next, the area between point A and point B on the characteristic acoustic impedance curve C1 (that is, the area corresponding to the portion from the skin surface to the blood vessel) is corrected. At that time, a correction value is used in which the previous correction value of 0.19 MNs/m ³ is the maximum, and the correction value decreases toward the front side of the measurement object (that is, the skin surface). By subtracting this correction value, the estimated value of the specific acoustic impedance from the blood vessel to the skin surface is corrected. In other words, a correction value corresponding to the depth from the skin surface is set and subtracted from the estimated value. For example, when correcting the estimated value at a depth position that is half the specific depth, set a half value of 0.19 MNs/m ³ (that is, 0.095 MNs/m ³ ) as the correction value at that position. , subtract this from the estimate at that location. Also, when correcting the estimated value at a depth position of 1/4 of the specific depth, the value of 1/4 of 0.19 MNs/m ³ (that is, 0.0475 MNs/m ³ ) is used as the correction value at that position set and subtract this from the estimate at that location. Incidentally, the three downward arrows drawn in the graph of FIG. 9 visually indicate the difference in magnitude of the correction value at each depth.

Then, through the calculation of such a correction step, the estimated value of the specific acoustic impedance in the object to be measured is corrected, and then the distribution of the specific acoustic impedance in the depth direction is estimated. is converted into a characteristic acoustic impedance image.

Arithmetic processing executed by the CPU 31 as a processor in order to construct a specific acoustic impedance image in the ultrasonic image constructing apparatus 1 of the present embodiment will now be described with reference to the flowchart of FIG.

First, the human skin 8 (for example, neck skin 8 having relatively shallow thick blood vessels (cavitary veins, carotid arteries), etc.), which is the object to be measured, is pressed against the upper surface of the resin plate 9. Place in contact. In this state, first, the ultrasonic probe 6 is caused to perform an initial operation. That is, by operating the controller 27 based on instructions from the CPU 31, the motors 28X and 28Y are driven, and the XY stage 14 is moved so that ultrasonic waves are applied to the position where the reference member 10 is located.

Also at this time, when an excitation pulse is supplied to the transducer 13 based on an instruction from the CPU 31, as shown in FIG. passes through the receiving circuit 22 and is detected by the detecting circuit 24 . Then, the CPU 31 as reflected wave acquisition means acquires the digital data converted by the A/D conversion circuit 25 through the I/F circuit 32, and converts the data into an impulse response of the ultrasonic waveform from the reference member 10. It is stored in the memory 33 as data (step S100).

After that, the controller 27 drives the motors 28X and 28Y based on instructions from the CPU 31, and the XY stage 14 starts two-dimensional scanning. The CPU 31 acquires coordinate data of the measurement point based on the output of the encoder 26 (step S110).

Then, as shown in FIG. 4A, an excitation pulse is supplied to the transducer 13 based on an instruction from the CPU 31, so that the skin 8 is irradiated with an ultrasonic wave S _o and its reflected wave S _tgt (ω) passes through the receiving circuit 22 and is detected by the detecting circuit 24 . The CPU 31 as reflected wave acquisition means acquires the digital data converted by the A/D conversion circuit 25 via the I/F circuit 32, and coordinates the data as impulse response data of the ultrasonic waveform from the skin 8. It is stored in the memory 33 in association with the data (step S120).

Next, the CPU 31 as the first computing means uses the data of the normalized impulse response signal to perform the computation of the estimation step referring to the principle of the TDR method among the above algorithms. Then, the CPU 31 sequentially estimates the intrinsic acoustic impedance in the depth direction at the measurement points on the skin 8 from the near side to the far side in the depth direction by the calculation, and stores the estimation results in the memory 33 in association with the coordinate data. (Step S130).

Next, the CPU 31 as second computing means performs the computation of the correction step in the above algorithm. That is, after defining the specific acoustic impedance value of the virtual reference site, a calculation is performed to replace the estimated value of the specific acoustic impedance at a specific depth in the skin 8 with the specific acoustic impedance value of the virtual reference site. Correct the estimate of the intrinsic acoustic impedance of Then, the CPU 31 estimates the characteristic acoustic impedance distribution in the depth direction, associates the estimation result with the coordinate data, and stores it in the memory 33 (step S132).

After that, the CPU 31 as image constructing means performs image processing for constructing a specific acoustic impedance image (tomographic image) based on the estimation result of the specific acoustic impedance distribution in the depth direction (step S140). Specifically, the CPU 31 performs color modulation processing based on the estimated result of the characteristic acoustic impedance distribution, constructs image data displayed in different colors according to the magnitude of the characteristic acoustic impedance, and stores the image data in the memory 33. do.

Next, the CPU 31 determines whether the processing at all the measurement points has been completed and the image data has been acquired at all the measurement points (step S150). Here, if all the data has not been acquired (step S150: NO), CPU 31 returns to step S110 and repeats the processes of steps S110 to S140. When all the data have been acquired (step S150: YES), the CPU 31 proceeds to the next step S160.

Then, the CPU 31 transfers the data to the display device 36, displays a specific acoustic impedance image (tomographic image) on a predetermined straight line (step S160), and then terminates the processing of FIG. there is Through such a series of processes, a specific acoustic impedance image (tomographic image) is displayed that is color-coded according to the magnitude of the specific acoustic impedance of the skin 8 .

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

(1) In the ultrasonic image construction apparatus 1 of the present embodiment, the impulse response normalized from the impulse response information of the ultrasonic waveform incident on the reference member 10 and the impulse response information of the ultrasonic waveform incident on the skin 8 Information, ie device independent impulse response information, is obtained. Then, based on the normalized impulse response information, calculation (estimation step) for sequentially estimating the specific acoustic impedance in the skin 8 from the front side to the back side in the depth direction while considering the influence of multiple reflections. I am trying to do In addition to this, in the present embodiment, an operation of replacing the estimated value of the specific acoustic impedance at a specific depth in the skin 8 (here, the superficial subcutaneous tissue where the transverse blood vessel exists) with the specific acoustic impedance value of the virtual reference site. After correcting the estimated value of the specific acoustic impedance in the skin 8 through the skin 8, calculation (correction step) for estimating the specific acoustic impedance distribution in the depth direction is also performed. As a result, it is possible to reduce the error in the estimated value of the characteristic acoustic impedance, which tends to accumulate and expand as the depth increases, and it is possible to more accurately estimate the characteristic acoustic impedance distribution in the depth direction. In addition, in the conventional technique that does not perform the correction step, many streaks appear in the depth direction in the ultrasonic tomographic image, making it difficult to intuitively understand the fine layer structure. Streaks are reduced and color unevenness in the layer direction is reduced. Therefore, an ultrasonic tomographic image of the very thin skin 8 having a fine layer structure can be constructed relatively easily and with high precision as a specific acoustic impedance image whose layer structure is intuitively understandable. The specific acoustic impedance image obtained by this apparatus 1 is obtained by estimating the cross-sectional distribution (depth distribution) information of the mechanical properties for each layer without cutting the measurement object (that is, noninvasively). The image is color-coded for each absolute value of . Therefore, the layer structure of this image is intuitively easy to understand.

Here, in an ultrasonic B-mode echo image generally obtained by a normal ultrasonic diagnostic apparatus, although layer information inside a living tissue such as the skin 8 can be obtained, the obtained image has a difference of more than a certain amount in intrinsic acoustic impedance. It is a reflected image from the interface between the layers. That is, when the difference in specific acoustic impedance becomes small to some extent, even if an interface exists, it is not detected histologically, making it extremely difficult to form an image that reflects the structure. In other words, a general reflected image is insufficient for grasping the fine internal structure of the living tissue and the reflected image (difference in specific acoustic impedance) inside the living tissue reflecting the fine layered structure. On the other hand, according to this ultrasonic image construction device 1, the layer structure of the skin 8 based on the mechanical property distribution, which could not be detected at all by the conventional B-mode ultrasonic waves, can be clearly visualized with sufficient resolution. It became possible to capture it as a tomogram. In addition, such a clear tomographic image could not be obtained with other noninvasive visualization devices (optical coherence tomography (OCT), in vivo confocal microscope, etc.), so this ultrasonic image construction device 1 The significance of being embodied is great. As described above, according to the ultrasonic image construction apparatus 1 of the present embodiment, the state of the skin 8 (the state regarding the mechanical properties of each layer of the skin 8) can be easily and noninvasively evaluated.

(2) In the ultrasonic image construction apparatus 1 of the present embodiment, through analysis in the time-frequency domain considering multiple reflections inside the skin tissue, the reflected signal train that is the basis of the ultrasonic B-mode echo image is obtained in the depth direction. A method of converting to a characteristic acoustic impedance image is adopted. Therefore, the predetermined calculation can be performed relatively easily. Further, in this embodiment, using the algorithm described above, the process of estimating the specific acoustic impedance of the minute transmission line 51 adjacent to the rear side based on the result of estimating the characteristic acoustic impedance of the minute transmission line 51 on the front side is sequentially repeated. By doing so, a calculation for estimating the characteristic acoustic impedance distribution in the depth direction of the transmission path is performed. Therefore, according to this calculation, the influence of multiple reflections can be minimized, and the characteristic acoustic impedance distribution in the depth direction can be accurately estimated.

[Second embodiment]
A second embodiment embodying the ultrasonic image constructing method and apparatus of the present invention will now be described in detail with reference to FIG. It should be noted that the same member numbers are assigned to the configurations that are common to the first embodiment, and detailed description thereof will be omitted.

In the ultrasonic image constructing apparatus 1 of the present embodiment, the correction step is performed after the predetermined estimation step, and then the image constructing step is performed. 10, etc.). However, in the correction step of the first embodiment, the characteristic acoustic impedance value (1.61 MNs/m ³ ) of the blood 65 present in the blood vessel 64 extending in a direction substantially parallel to the skin tissue surface is defined as the “virtual reference site However, here, focusing on the fact that the object to be measured is the soft tissue of a living body, the average of the estimated values of the specific acoustic impedance at a specific depth is taken as the "specific acoustic impedance value of the virtual reference site value”. In this embodiment, an average value (for example, 1.65 MNs/m ³ ) of the estimated values of the intrinsic acoustic impedance of the tissue at a depth of about 350 μm from the surface of the skin tissue is obtained and used. This is because the soft tissues of a living body do not contain hard parts such as bones or ^cartilage and have little variation in ^hardness . This is based on the idea that it is suitable for selection as a virtual reference site because the value does not deviate greatly. For soft tissue excluding fat, the specific acoustic impedance is approximately within the range of 1.60 MNs/m ³ to 1.70 MNs/m ³ .

In this case, the specific depth in the skin 8 is preferably set to a position deeper than the region where the image data of the specific acoustic impedance image is constructed. In this embodiment, for example, since the image construction region is set to a position about 300 μm deep from the surface of the skin tissue, the specific depth for obtaining the average of the estimated values of the specific acoustic impedance of the tissue is a position 50 μm deeper than that. and By doing so, the specific acoustic impedance image at a specific depth is intentionally not displayed, so that the image does not look unnatural.

Here, FIG. 11(a) is the characteristic acoustic impedance image obtained by constructing the image without performing the correction step, and (b) is the characteristic acoustic impedance image obtained by constructing the image after performing the correction step. It is an impedance image. In the former, many streaks appear in the depth direction, making it difficult to understand the layer structure. On the other hand, in the latter, since the streaks are somewhat eliminated, the color tends to be more uniform in the layer direction, making the layer structure easier to understand.

Therefore, the ultrasonic image construction apparatus 1 of this embodiment described above can also achieve the same effects as the ultrasonic image construction apparatus 1 of the first embodiment. That is, it is possible to construct an ultrasonic tomographic image of the very thin skin 8 having a fine layer structure relatively easily and with high accuracy in a manner in which the layer structure is intuitively understandable. Also, based on the information obtained using ultrasound, it is possible to construct an image that allows easy and accurate observation and evaluation of the fine layer structure of the skin 8 . In particular, according to this embodiment, there is no appropriate virtual reference site (for example, relatively thick blood vessels such as cervical veins and arteries) in the inner layer of the measurement site as in the first embodiment. can also correct the estimate of the intrinsic acoustic impedance. Therefore, it is possible to observe and evaluate not only the neck region but also various regions (for example, cheeks).

[Third embodiment]
A third embodiment embodying the ultrasonic image constructing method and apparatus of the present invention will be described in detail below with reference to FIGS. 12 to 14. FIG. It should be noted that the same member numbers are assigned to the configurations that are common to the first embodiment, and detailed description thereof will be omitted.

FIG. 12 is a schematic configuration diagram showing the ultrasonic image constructing apparatus 101 of this embodiment. As shown in FIG. 12, this ultrasonic image construction device 101 is a device for observing cultured cells 8A using ultrasonic waves, and includes a pulse excitation ultrasonic microscope 2 and a personal computer (PC) 3. and

A culture container 102 containing a culture medium M for culturing cultured cells 8A, which are objects to be measured, is installed on the stage 4 . Here, human glial cells 8A, which are a type of adherent cells, are used as the cultured cells 8A. The thickness of the glial cell 8A is very thin, approximately several μm. At the center of the bottom of the culture container 102, a resin plate 9 is fixed on the upper surface side to which the cultured cells 8A are adhered and supported during culture. The resin plate 9 as a substrate having known acoustic properties is a plate-like member that can transmit ultrasonic waves, and is made of a material harder than the cultured cells 8A that are the objects to be measured.

It should be noted that the cultured cells 8A exist in the culture container 102 in a state of being completely immersed in the culture medium M. Therefore, the culture medium M is present not only in contact with the upper surface of the resin plate 9 on which the cultured cells 8A are arranged, but also in contact with the side of the cultured cells 8A opposite to the resin plate 9. It can be understood that The culture medium M has known acoustic properties different from those of the resin plate 9, and is used as the first reference material and the second reference member in this embodiment. For the convenience of the following description, the culture solution existing in contact with the resin plate 9 (that is, the culture solution that is the first reference substance) is denoted by M1, and the cultured cell 8A is attached to the side opposite to the resin plate 9. The existing culture medium (ie the culture medium which is the second reference substance) is marked with M2 to distinguish it.

Next, a method for constructing a specific acoustic impedance image from a reflected signal train that is the basis of an ultrasonic B-mode echo image in the ultrasonic image constructing apparatus 101 of this embodiment will be described.

In this ultrasonic image construction apparatus 101, the cultured cells 8A that are the objects to be measured and the culture solution M1 that is the first reference substance are in contact with the resin plate 9 that is the base, and the resin plate 9 in the cultured cells 8A is Ultrasonic waves are transmitted while the culture medium M2, which is the second reference substance, is in contact with the opposite side. Then, impulse responses of ultrasonic waveforms from the cultured cells 8A, the culture solution M1 as the first reference substance, and the culture solution M2 as the second reference substance when ultrasonic waves are incident through the resin plate 9 are received respectively. (transmission/reception step).

Next, normalized impulse response information is obtained from the impulse response information of the ultrasonic waveforms incident on the culture solutions M1 and M2 and the impulse response information of the ultrasonic waveforms incident on the cultured cells 8A, and the normalized impulse response information is obtained. Based on the impulse response information, the characteristic acoustic impedance in the cultured cells 8A and in the culture medium M2, which is the second reference member, is sequentially estimated from the near side to the far side in the depth direction (estimating step). In this step, an operation is performed to estimate the characteristic acoustic impedance distribution in the depth direction in consideration of the influence of multiple reflections, but this has been explained in detail in the first embodiment, so its explanation is omitted. Note that this calculation is executed based on a predetermined algorithm stored in the memory 33 .

In the ultrasonic image constructing apparatus 101 of the present embodiment, the correction step is performed after the estimation step, and then the image constructing step is performed. 10, etc.). However, in the correction step of this embodiment, the following correction steps that are different from those in the first embodiment are performed. That is, here, correction calculation is performed to replace the "estimated value" with the "actual value" for the specific acoustic impedance of the second reference substance (culture medium M2) obtained in the estimation step. Assuming that the "actual value" of the culture solution M2 is, for example, 1.55 MNs/m3 ^, and the "estimated value" that is likely to contain an error is, for example, 1.80 MNs/m3 ^, from that value The "actual value" is corrected by subtracting a correction value of 0.25 ^MNs /m3. As a result, the flat part of the characteristic acoustic impedance curve C1 before correction shown in the graph of FIG. 9 shown in the previous embodiment moves downward, forming part of the corrected characteristic acoustic impedance curve C2. become a thing. Note that the point B on the curve C1 is moved to the point C on the curve C2.

Next, the area between points A and B on the characteristic acoustic impedance curve C1 is corrected. At that time, the correction value is set to a maximum value of 0.25 MNs/m ³ , which is the previous correction value, and a correction value that decreases toward the front side of the measurement object (that is, the side of the cultured cell 8A that is in contact with the resin plate 9) is used. . By subtracting this correction value from the "estimated value", the "estimated value" from the interface between the culture fluid M2 and the cultured cells 8A to the interface between the cultured cells 8A and the resin plate 9 is corrected.

Then, through the calculation of such a correction step, the estimated value of the specific acoustic impedance in the object to be measured is corrected, and then the distribution of the specific acoustic impedance in the depth direction is estimated. is converted into a characteristic acoustic impedance image.

Therefore, the ultrasonic image construction apparatus 101 of this embodiment described above can also achieve the same effects as the ultrasonic image construction apparatus 1 of the first embodiment. That is, it is possible to construct an ultrasonic tomographic image of the very thin cultured cells 8A having fine internal structures relatively easily and with high precision in a manner in which the fine internal structures are intuitively understandable. Also, based on the information obtained using ultrasonic waves, it is possible to construct an image that allows easy and accurate observation and evaluation of the internal structure of the cultured cells 8A.

FIG. 13 is a diagram schematically showing glial cells 8A. The glial cell 8A has a nucleus 112 and a pseudopodia 114 formed by polymerization of a cytoskeleton 113 (actin filaments). In addition, the pseudopodia 114 can be seen on the traveling direction side of the migrating glial cells 8A. FIG. 14 is an ultrasonic tomographic image of glial cells 8A observed using this ultrasonic image constructing apparatus 101. FIG. According to this, it was found that there are high and low specific acoustic impedance points inside the glial cells 8A. Referring to the schematic diagram of FIG. 13, it was inferred that the sites with high specific acoustic impedance, ie, relatively hard sites, were pseudopodia 114 containing many cytoskeleton 113 . Also, it was presumed that the portion with low specific acoustic impedance, ie, the relatively soft portion, was the nucleus. According to such an ultrasonic image constructing apparatus 101 of this embodiment, not only the internal structure of the cultured cell 8A can be observed, but also the movement of the cultured cell 8A can be observed.

Each embodiment of the present invention may be modified as follows.

In the ultrasonic image constructing apparatus 1 of the first and second embodiments, arithmetic processing is performed using the reflected wave from the reference member 10 as the reference waveform, but the present invention is not limited to this. The reference waveform may be a reflected wave from a portion of the upper surface of the resin plate 9 that is not in contact with the skin 8. For example, a portion ( Specifically, a reflected wave from the surface of the resin plate 9 located outside the reference member 10 may be used. In other words, the reflected wave from the interface between the resin plate 9 and the air layer may be used as the reference waveform.

In the ultrasonic image constructing apparatus 1 of the first and second embodiments, ultrasonic waves are emitted using the inverted ultrasonic microscope 2 that emits ultrasonic waves from below, but ultrasonic waves are emitted from above. An upright ultrasonic microscope may be used.

- In the above-described first and second embodiments, the ultrasonic image construction apparatus 1 is used for the purpose of evaluating the condition of relatively healthy skin 8 that is basically disease-free. Not limited. For example, the ultrasonic image construction device 1 may be used for the purpose of early detection of skin abnormalities associated with diseases such as skin cancer.

In the ultrasonic image construction apparatus 1 of the first and second embodiments, the measurement object was the skin 8 of the human neck, but the skin 8 in other parts other than the neck (such as cheeks) is of course good. Moreover, the object to be measured may not be the skin 8, but may of course be internal organs, muscles, brains, teeth, nails, surface layers of bones, and the like. In addition, in the ultrasonic image construction apparatus 101 of the third embodiment, the object to be measured was human glial cells, but any cultured cells of any species can be used as long as they are adherent cells. . Furthermore, the object to be measured does not necessarily have to be a living tissue or living organism, and may be a non-living organism (for example, a coating film). In other words, the ultrasonic image construction apparatus 1, 101 of the present invention is not limited to the medical field, beauty field, and cosmetic field, but can also be used in the industrial field, for example.

The ultrasonic image constructing apparatuses 1 and 101 of the above-described embodiments both have scanning means for relatively scanning the measurement object with the ultrasonic transducer 13 in two-dimensional directions. Scanning means may be provided for relatively scanning the acoustic wave transducer 13 only in one-dimensional direction. Further, since the scanning means is not an essential component, it may of course be omitted. In this case, the size and cost of the apparatus can be reduced.

In the ultrasonic image constructing apparatuses 1 and 101 of the above-described embodiments, the characteristic acoustic impedance image is constructed based on the estimation result of the characteristic acoustic impedance distribution in the depth direction, but the present invention is not limited to this. For example, a sound velocity distribution in the depth direction may be estimated, and a sound velocity image may be constructed based on the result.

In the ultrasonic image constructing apparatuses 1 and 101 of the above-described embodiments, a specific acoustic impedance image is constructed from the reflected signal train that is the basis of the ultrasonic B-mode echo image, and the image is displayed on the display device 36. Of course, not only the characteristic acoustic impedance image but also the ultrasonic B-mode echo image may be displayed. Further, by incorporating the algorithm of the above-described embodiment into a general-purpose ultrasonic diagnostic apparatus that displays an ultrasonic B-mode echo image, the apparatus may be operated as the ultrasonic image constructing apparatus 1 or 101 .

・In the above embodiment, a method of converting a reflected signal train, which is the basis of an ultrasonic B-mode echo image, into a specific acoustic impedance image in the depth direction through analysis in the time-frequency domain that considers multiple reflections within the measurement object. was adopted, but is not limited to this. As a method for estimating the distribution of the characteristic acoustic impedance from the reflected waveform, for example, a method is adopted in which all reflection paths, including multiple reflections inside the transmission path, are assumed and the response is analyzed at any time on the time axis. You may Even with this method, it is possible to obtain the same estimation result of the characteristic acoustic impedance distribution as with the method of the above embodiment.

In the above embodiment, an analysis method that considers multiple reflections within the object to be measured is used to convert the reflected signal train, which is the basis of the ultrasonic B-mode echo image, into the characteristic acoustic impedance image in the depth direction. It is not limited to this. For example, when the influence of multiple reflections is considered to be small, such as soft tissue of a living body, an analysis method that does not consider multiple reflections within the measurement object may be employed.

Reference Signs List 1, 101: Ultrasonic image construction device 8: Soft tissue (skin) of a living body as an object to be measured
8A... Cultured cells (glial cells) as measurement objects
9 Resin plate as base 10 Reference member as first reference material 13 Ultrasonic transducer as ultrasonic transducer 31 First calculation means, second calculation means, image constructing means, CPU as processor
51 Microtransmission channel 64 Blood vessel 65 Blood M1 Culture medium M2 as first reference material Culture medium Γ ₀ , Γ ₁ as second reference material Impulse response

Claims (15)

An ultrasonic wave is transmitted in a state in which an object to be measured and a first reference substance are in contact with a substrate, and a second reference substance is in contact with the side of the object to be measured opposite to the substrate, and the substrate is a transmitting/receiving step of receiving impulse responses of ultrasonic waveforms from the measurement object, the first reference material, and the second reference material when ultrasonic waves are incident through the
Based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the intrinsic acoustic impedance in the measurement object and in the second reference material is sequentially measured from the near side to the far side in the depth direction. an estimation step to estimate;
The estimated value of the specific acoustic impedance of the object to be measured is obtained by replacing the estimated value of the specific acoustic impedance of the second reference material obtained in the estimation step with the actual value of the specific acoustic impedance of the second reference material. a correction step of estimating the characteristic acoustic impedance distribution in the depth direction after correction;
and an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. Ultrasonic waves from the measurement object and the first reference substance when the ultrasonic waves are transmitted while the measurement object and the first reference substance are in contact with the substrate, and the ultrasonic waves are incident through the substrate. a transmitting/receiving step of receiving an impulse response of the waveform;
an estimation step of sequentially estimating the intrinsic acoustic impedance in the measurement object from the near side to the far side in the depth direction based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform;
A specific acoustic impedance value when a substance having a known specific acoustic impedance value exists uniformly in the layer direction at a specific depth in the measurement object, or when the measurement object is a soft tissue of a living body The average of the estimated values of the specific acoustic impedance at a specific depth in the measurement object is defined as the specific acoustic impedance value of the virtual reference part, and the specific acoustic impedance at the specific depth in the measurement object obtained in the estimation step a correcting step of estimating a specific acoustic impedance distribution in the depth direction after correcting the estimated value of the specific acoustic impedance in the measurement object through a calculation that replaces the estimated value of the impedance with the specific acoustic impedance value of the virtual reference part; ,
and an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. In the correction step, the correction value is set such that the actual value of the specific acoustic impedance of the second reference material or the value when replacing with the specific acoustic impedance value of the virtual reference portion is maximized, and the correction value decreases toward the front side of the measurement object. 3. The method of constructing an ultrasound image according to claim 1, wherein the estimated value of the intrinsic acoustic impedance within the object is corrected by adding or subtracting . In the estimating step, it is assumed that lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. 4. The ultrasonic wave according to any one of claims 1 to 3, wherein an operation for estimating the specific acoustic impedance of said micro-transmission channel adjacent to the back side thereof is performed based on the result of estimating the specific acoustic impedance of the channel. Image construction method. The object to be measured is a cultured cell,
The first reference substance and the second reference substance are culture solutions for culturing the cultured cells,
2. The method of constructing an ultrasonic image according to claim 1 , wherein the substrate is a part of a culture vessel containing the culture medium. The object to be measured is the skin as a soft tissue of a living body containing blood vessels extending in a direction substantially parallel to the tissue surface,
When a substance having a known specific acoustic impedance value exists uniformly in the layer direction at a specific depth in the measurement object, the specific acoustic impedance value is the specific acoustic impedance value of blood present in the blood vessel. 3. The method of constructing an ultrasound image according to claim 2 , wherein: When the measurement object is the soft tissue of a living body, the average of the estimated values of the specific acoustic impedance at the specific depth in the measurement object is the specific acoustic impedance at the specific depth in the skin when the measurement object is the skin. is the average of the impedance estimates,
3. The ultrasonic image constructing method according to claim 2 , wherein the specific depth is set to a position deeper than a region in which the image data of the acoustic physical property image is constructed. a substrate;
An ultrasonic wave is transmitted in a state in which an object to be measured and a first reference substance are in contact with the base, and a second reference substance is in contact with the side of the object to be measured opposite to the base, and the base is an ultrasonic transducer that receives impulse responses of ultrasonic waveforms from the measurement object, the first reference material, and the second reference material when ultrasonic waves are incident via
Based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the intrinsic acoustic impedance in the measurement object and in the second reference material is sequentially measured from the near side to the far side in the depth direction. a first computing means for estimating;
Estimated value of specific acoustic impedance in the object to be measured through calculation of replacing the estimated value of specific acoustic impedance of the second reference material obtained by the first calculating means with the actual value of specific acoustic impedance of the second reference material. a second computing means for estimating the characteristic acoustic impedance distribution in the depth direction after correcting the
An ultrasonic image constructing apparatus, comprising: image constructing means for constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. a substrate;
Ultrasonic waves are transmitted while the object to be measured and the first reference substance are in contact with the substrate, and the ultrasonic waves from the object to be measured and the first reference substance when the ultrasonic waves are incident through the substrate an ultrasonic transducer that receives an impulse response of a sound wave waveform;
a first computing means for sequentially estimating the intrinsic acoustic impedance in the object to be measured from the near side to the far side in the depth direction based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform; ,
A specific acoustic impedance value when a substance having a known specific acoustic impedance value exists uniformly in the layer direction at a specific depth in the measurement object, or when the measurement object is a soft tissue of a living body defined as the intrinsic acoustic impedance value of the virtual reference part, and the intrinsic acoustic impedance at the specific depth in the measurement object obtained by the first computing means A second method for estimating a specific acoustic impedance distribution in the depth direction after correcting the estimated value of the specific acoustic impedance in the measurement object through a calculation for replacing the estimated value of the acoustic impedance with the specific acoustic impedance value of the virtual reference part. computing means;
An ultrasonic image constructing apparatus, comprising: image constructing means for constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. The second computing means maximizes the actual value of the specific acoustic impedance of the second reference material or the value when replacing with the specific acoustic impedance value of the virtual reference part, and decreases toward the front side of the measurement object. 10. The ultrasonic image construction apparatus according to claim 8 or 9, wherein the estimated value of the intrinsic acoustic impedance within the measurement object is corrected by adding or subtracting a correction value. The first computing means assumes that in the object to be measured, lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines, and the front side of the 11. The method according to any one of claims 8 to 10, wherein calculation is performed for estimating the specific acoustic impedance of said micro-transmission channel adjacent on the far side based on the result of estimating the specific acoustic impedance of the micro-transmission channel. Ultrasound imaging equipment. to the processor,
An ultrasonic wave is transmitted to an ultrasonic transducer in a state in which an object to be measured and a first reference substance are in contact with a substrate, and a second reference substance is in contact with the side of the object to be measured opposite to the substrate. and a transmitting/receiving step of causing the ultrasonic transducer to receive an impulse response of an ultrasonic waveform from the object to be measured, the first reference substance, and the second reference substance when ultrasonic waves are incident through the substrate. When,
Based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform, the intrinsic acoustic impedance in the measurement object and in the second reference material is sequentially measured from the near side to the far side in the depth direction. an estimation step to estimate;
The estimated value of the specific acoustic impedance of the object to be measured is obtained by replacing the estimated value of the specific acoustic impedance of the second reference material obtained in the estimation step with the actual value of the specific acoustic impedance of the second reference material. a correction step of estimating the characteristic acoustic impedance distribution in the depth direction after correction;
An ultrasonic image construction program for executing an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. to the processor,
The object to be measured and the first reference when the object to be measured and the first reference substance exist in contact with the substrate and the ultrasonic wave is transmitted through the ultrasonic transducer and the ultrasonic wave is incident through the substrate. a transmitting/receiving step of causing the ultrasonic transducer to receive an impulse response of an ultrasonic waveform from a substance;
an estimation step of sequentially estimating the intrinsic acoustic impedance in the measurement object from the near side to the far side in the depth direction based on the normalized impulse response information obtained from the impulse response information of the ultrasonic waveform;
A specific acoustic impedance value when a substance having a known specific acoustic impedance value exists uniformly in the layer direction at a specific depth in the measurement object, or when the measurement object is a soft tissue of a living body The average of the estimated values of the specific acoustic impedance at a specific depth in the measurement object is defined as the specific acoustic impedance value of the virtual reference part, and the specific acoustic impedance at the specific depth in the measurement object obtained in the estimation step a correcting step of estimating a specific acoustic impedance distribution in the depth direction after correcting the estimated value of the specific acoustic impedance in the measurement object through a calculation that replaces the estimated value of the impedance with the specific acoustic impedance value of the virtual reference part; ,
An ultrasonic image construction program for executing an image construction step of constructing image data of an acoustic physical property image based on the characteristic acoustic impedance distribution in the depth direction. In the correction step, the correction value is set such that the actual value of the specific acoustic impedance of the second reference material or the value when replacing with the specific acoustic impedance value of the virtual reference portion is maximized, and the correction value decreases toward the front side of the measurement object. 14. The ultrasonic image construction program according to claim 12 or 13, wherein the estimated value of the intrinsic acoustic impedance in the object to be measured is corrected by adding or subtracting . In the estimating step, it is assumed that lossless minute transmission lines having different characteristic acoustic impedances are connected in the depth direction to form a collection of transmission lines in the object to be measured. 15. The ultrasonic wave according to any one of claims 12 to 14, wherein an operation is performed for estimating the specific acoustic impedance of said micro-transmission channel adjacent on the far side based on the result of estimating the specific acoustic impedance of the channel. Image construction program.

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