Ultrasonic device, head holder, and ultrasonic signal processing method

Abstract

The present invention discloses a technology that is for measuring brain function and that is appropriate for an infant or a moving subject who cannot be controlled easily during measurement. One embodiment of the present disclosure pertains to an ultrasonic device that comprises: multiple ultrasonic probes which receive / transmit ultrasonic signals from / to multiple brain areas via multiple head regions and which are so disposed as to correspond to the respective head regions; a control unit which controls the respective ultrasonic probes; and an image processing unit which, on the basis of measurement results acquired from the respective ultrasonic probes, generates brain function network information calculated from blood flow conditions between the respective brain areas.

Description

Technical Field

[0001] The present disclosure relates to an ultrasonic device, a head holder, and an ultrasonic signal processing method.

Background Art

[0002] The human brain forms the center of the nervous system and performs various functions such as motor regulation, sensation, autonomic regulation, language, emotion, and cognition. It is known that these functions can be realized by the cooperation of multiple brain regions in the brain. Therefore, brain functional network information indicating the inter-regional connection state of neural activities in the brain can be used for brain diagnosis and the like.

[0003] Several measurement methods for such brain functional network information have been proposed. For example, electroencephalogram measurement on the scalp, magnetoencephalogram measurement, optical topography measurement, functional magnetic resonance imaging measurement of the brain, and functional ultrasonic measurement of the brain can be mentioned. Electroencephalogram measurement on the scalp is a technique for measuring potential changes in the brain in milliseconds by electrodes installed on the scalp and mainly analyzing the activities in the cortical region. Magnetoencephalogram measurement is a technique for measuring magnetic field changes generated along with the electrical activities of the brain in milliseconds by a superconducting quantum interference device and mainly analyzing the brain activities in the cortical region. Optical topography measurement is a technique for transmitting and receiving near-infrared light by optical fibers installed on the scalp, measuring the cerebral hemodynamics accompanying neural activities, and mainly analyzing the brain activities in the cortical region. Functional magnetic resonance imaging measurement of the brain is a technique for measuring the cerebral hemodynamics accompanying neural activities by a magnetic resonance imaging device and analyzing the brain activities in the entire brain region. Functional ultrasonic measurement of the brain is a technique for measuring the cerebral hemodynamics accompanying neural activities by Doppler measurement of ultrasonic waves and analyzing the brain activities.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Literature

[0005]

Non-Patent Literature 1

Non-Patent Literature 2

Non-Patent Literature 3

Summary of the Invention

Problems to be Solved by the Invention

[0006] However, when using these measurement methods for subjects who are difficult to stay still during measurement, such as infants (defined here as up to 1 year old), or for subjects whose posture control is difficult, or for subjects who are in a moving state, several problems can be considered.

[0007] For example, although electroencephalogram (EEG) measurement on the scalp can directly capture the brain's electrical activity in milliseconds, it is mainly limited to measuring signals at a depth of about 10 mm from the brain surface. Also, in infant measurement, artifacts such as body movement and crying are likely to be mixed in, and it is often difficult to attach and maintain electrodes, so measurement during natural sleep or the use of sedatives is often necessary.

[0008] Also, magnetoencephalogram (MEG) measurement, like EEG measurement, can capture the brain's electrical activity in milliseconds, but it is difficult to measure deep in the brain, and the measurement device is large and expensive. Also, in infant measurement, artifacts such as body movement and crying are likely to be mixed in, and it is often necessary to measure during natural sleep or use sedatives.

[0009] Optical topography measurement is relatively less affected by body movement, but is limited to measuring signals at a depth of about 20 mm from the scalp, and also includes external information other than the brain.

[0010] Functional magnetic resonance imaging (fMRI) measurement can capture the activity of the entire brain, but the measurement device is large and expensive. Also, in infant measurement, artifacts such as body movement and crying are likely to be mixed in, and it is often necessary to measure during natural sleep or use sedatives. Furthermore, the noise generated during fMRI measurement reduces the connectivity of the brain network manifested in the resting state, affecting the accurate evaluation of the resting-state brain network.

[0011] Although transcranial Doppler ultrasound (TCD) is relatively less affected by body movement, ultrasound is highly attenuated and reflected in the skull. Therefore, TCD is limited to observing some brain regions using the fontanelle, which is a connective tissue membrane where skull ossification has not advanced in infants, or the temporal bone window where the skull is thin in adults as an acoustic window.

[0012] In view of the above problems, one object of the present disclosure is to provide a technique for measuring brain function suitable for infants and subjects in a moving state, for which control during measurement is difficult.

Means for Solving the Problems

[0013] One aspect of the present disclosure relates to an ultrasonic device, comprising: a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions; a head holder provided corresponding to each of the plurality of head regions and including the plurality of ultrasonic probes; a control unit that controls the plurality of ultrasonic probes; and an image processing unit that generates brain function network information calculated from the blood flow state between the plurality of brain regions based on measurement results obtained from the plurality of ultrasonic probes.

[0014] Another aspect of the present disclosure relates to a head holder having a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions, wherein the plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions.

[0015] Another aspect of the present disclosure relates to an ultrasonic signal processing method executed by a computer, comprising: obtaining measurement results from a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions; and generating brain function network information calculated from the blood flow state between the plurality of brain regions based on the measurement results, wherein the plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions.

Advantages of the Invention

[0016] According to the present disclosure, it is possible to provide a technique for measuring brain function suitable for infants and toddlers whose control during measurement is difficult and subjects in a moving state.

Brief Description of the Drawings

[0017]

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DETAILED DESCRIPTION OF THE INVENTION

[0018] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings.

[0019] In the following embodiments, an ultrasonic device is disclosed that analyzes the interaction between a plurality of brain regions of a subject by using automatic tracking using a head holder or a robotic arm provided with a plurality of ultrasonic probes corresponding to a plurality of head regions.

[0020] An ultrasonic device according to an embodiment of the present disclosure is suitable for, for example, infants, and the head holder has a plurality of ultrasonic probes provided corresponding to each position of a plurality of openings in the head peculiar to the infant period, that is, a plurality of fontanelles such as the anterior fontanelle and the posterior fontanelle. The ultrasonic device uses these plurality of openings as acoustic windows for ultrasonic waves, generates local brain images measured by each ultrasonic probe based on ultrasonic pulses transmitted and received between a plurality of brain regions of the infant, and constructs a wide-area brain image of the entire brain from the generated local brain images. Then, the ultrasonic device performs coordinate transformation of the wide-area brain image into a three-dimensional brain atlas, and generates brain function network information indicating the blood flow state between brain regions based on the correlation of the blood flow state between each brain region in the three-dimensional brain atlas.

[0021] By transmitting and measuring ultrasonic pulses alternately from a plurality of separated acoustic windows, it is possible to obtain brain functional network information between brain regions while suppressing local temperature rise of brain tissue due to the thermal effect of ultrasonic waves. In the conventional transcranial ultrasonic measurement method, a single hand-held ultrasonic probe was applied to the fontanelle or the temporal bone window to image the inside of the brain. On the other hand, according to an embodiment of the present disclosure, measurement and analysis based on the alternating control of a plurality of ultrasonic probes through a plurality of head regions are used. Compared with the conventional transcranial ultrasonic measurement, in infants, wide-area observation of the brain such as the cerebrum and the cerebellum can be automatically achieved. Further, by fixing the ultrasonic probe to a probe holder provided in a head holder such as a helmet, or fixing it to a robotic arm that can be automatically tracked based on a 4D image of the head shape by a stereo camera, the influence of the body movement of the subject can be suppressed. In infants, measurement during natural sleep used in other non-invasive measurement methods and simple and safe measurement can be performed without using a sedative. Thus, according to the present disclosure, it is possible to widely provide a subject with a functional network evaluation approach for grasping a wide area of the brain as a single entity.

[0022] [Ultrasonic device] First, with reference to FIGS. 1 to 16, an ultrasonic device 100 according to an embodiment of the present disclosure will be described. The ultrasonic device 100 according to this embodiment is preferably used for measuring the brain of an infant. However, the ultrasonic device according to the present disclosure is not limited to these infants, and may be used for measuring the brain of subjects of any type, regardless of gender, including children, adults, the elderly, or others. Here, an infant is defined as less than 1 year old, but the ultrasonic device according to the present disclosure is not limited to subjects of this age.

[0023] FIG. 1 is a schematic diagram showing the configuration of an ultrasonic device 100 according to an embodiment of the present disclosure. As shown in FIG. 1, the ultrasonic device 100 includes a plurality of ultrasonic probes 110, a head holder 120, a control unit 130, and an image processing unit 140.

[0024] A plurality of ultrasonic probes 110 transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions. Specifically, each ultrasonic probe 110 has a vibrator (piezoelectric element) that transmits an ultrasonic signal toward an object and receives a reflected signal from the object. For example, the ultrasonic probe 110 has a plurality of vibrators arranged in an array, and transmits an ultrasonic signal from each vibrator to the object, and transmits the measurement result measured by receiving the reflected signal from the object to the control unit 130. For example, as shown in FIG. 2, each ultrasonic probe 110 has N x pieces in the horizontal direction and N y pieces in the vertical direction, and may have (N x ×N y ) two-dimensionally arranged vibrators.

[0025] As shown in FIG. 1, the ultrasonic probe 110 may use a spherical diffusion wave in which the transmitted wave spreads with distance, and observe the inside of the brain over a wide area and in a short time using a narrow area of the foramen as an acoustic window. In order to form a spherical diffusion wave, a virtual point sound source is arranged behind the two-dimensionally arranged vibrators with respect to the ultrasonic transmission direction. The difference in the arrival time of the ultrasonic wave from the virtual point sound source to each vibrator is set as the delay time, and the control unit 130 transmits a drive signal to each vibrator of the ultrasonic probe 110. The control unit 130 and the image processing unit 140 integrally constitute a control device 150 for the ultrasonic probe 110, and the control device 150 and the ultrasonic probe 110 may be connected by wire or wirelessly as described in FIG. 1.

[0026] Note that the shape of the ultrasonic probe 110 may be any of a sector type, a convex type, a linear convex type, and a phased array type. In the example shown in FIG. 1, each ultrasonic probe 110 transmits a spherical diffusion wave, but the ultrasonic probe 110 of the present disclosure is not limited to this, and has any appropriate mechanism that constitutes a wavefront of an arbitrary shape, and uses this mechanism to transmit an ultrasonic signal having an arbitrary wavefront shape. For example, a two-dimensional or three-dimensional plane wave or a diffusion wave may be irradiated.

[0027] The head holder 120 includes a plurality of ultrasonic probes 110 corresponding to each of the plurality of head regions. For example, the head holder 120 may be a plurality of sets sized to cover the head of the subject, such as a helmet, a hat, a hood, etc., with a lower limit of 33 cm head circumference for newborns and an upper limit of 60 cm for adults. Specifically, the head holder 120 may be realized as a helmet having a two-layer structure with a hard resin on the outside and a soft sponge on the inside. By using a soft sponge material on the inside of the helmet, the head during wearing can be protected.

[0028] The skull of an infant has an opening (gap) in the skull called the fontanelle. Specifically, as shown in FIG. 3, there are six fontanelles: the large fontanelle 120_A, the small fontanelle 120_B, the left anterior temporal fontanelle 120_C, the right anterior temporal fontanelle 120_D, the left posterior temporal fontanelle 120_E, and the right posterior temporal fontanelle 120_F. Also, there is a temporal bone window where the temporal bone is thin even after growth and ultrasonic waves can easily penetrate. The ultrasonic device 100 can measure the brain of the subject by using these head regions as acoustic windows of the ultrasonic probes 110_A to 110_F and transmitting and receiving ultrasonic signals to and from inside the brain. In this embodiment, the head holder 120 is configured to hold the ultrasonic probes 110_A to 110_F at positions corresponding to these six fontanelles. However, the head holder 120 according to the present disclosure is not limited to this, and may hold three or more, four or more, five or more, six ultrasonic probes 110 in two or more of the large fontanelle, small fontanelle, left anterior temporal fontanelle, right anterior temporal fontanelle, left posterior temporal fontanelle, right posterior temporal fontanelle, and temporal bone window head regions. On the other hand, in order to measure the entire brain of the subject, it is desirable to provide ultrasonic probes 110 in as many head regions as possible.

[0029] As shown in FIG. 4, each ultrasonic probe 110 may be connected to a probe holder 121 fixed to a head holder 120 such as a helmet. By being coupled to the probe holder 121, the coordinates and inclination of the ultrasonic probe 110 are fixed, which helps to accurately construct a wide-area brain image of the entire brain from the local brain images generated by each ultrasonic probe 110.

[0030] For example, as shown in FIG. 5, each ultrasonic probe 110 may be held by a probe holder 121 installed in a head holder 120. In the illustrated example, the probe holder 121 is attached to the head holder 120 at a position corresponding to the foramen magnum. Further, the ultrasonic probe 110 is arranged so as not to touch the subject's head by a stopper inside the probe holder 121. Although there are individual differences in the shape of the head, such individual differences can generally be accommodated by the combination of the head holder 120 and the probe holder 121. However, an adhesive silicon pad 122 may be attached between the probe holder 121 and the head so that the probe holder 121 fits tightly on the scalp. The inside of the silicon pad 122 is filled with an ultrasonic gel 123 warmed to human body temperature that has been sterilized, and the acoustic impedance of the gap between the ultrasonic probe 110 and the scalp is matched.

[0031] A plurality of types of head holders 120 and probe holders 121 may be prepared to accommodate the size and shape of the subject's head and the variations in the positions of the foramen magnum and the temporal bone window. Further, the head holder 120 may be configured so that each probe holder 121 can be arranged at various positions on the head and can be adjusted to various head sizes. This enables safe measurement of the subject's head while suppressing movement of the ultrasonic probe 110 due to the subject's body movement. If the head holder 120 does not conform to the shape of the subject's head, the ultrasonic probe 110 may be fixed with a rubber cap or the like. The cable connected to the ultrasonic probe 110 may be bundled into one as shown in FIG. 4 and connected to a probe socket.

[0032] The control unit 130 controls a plurality of ultrasonic probes 110. Specifically, the control unit 130 controls the operations of the respective ultrasonic probes 110 for ultrasonic measurement of an object such as one or more brain regions in the brain, and receives measurement results from the respective ultrasonic probes 110. Specifically, the control unit 130 may control the driving of the plurality of ultrasonic probes 110 so that the transmission and reception of ultrasonic signals by the respective ultrasonic probes 110 do not interfere with each other. For example, as shown in FIG. 6, ultrasonic probes 110_A to 110_F are respectively arranged at the Oizumi gate, Koizumi gate, left anterior temporal gate, right anterior temporal gate, left posterior temporal gate, and right posterior temporal gate 120_A to 120_F, and ultrasonic signals may be transmitted and received using these openings as acoustic windows.

[0033] In the head of a newborn, the positions of the respective ultrasonic probes are defined as follows. With reference to the line (A) on the scalp connecting the nasion and the inion in FIG. 3 and the line (B) on the scalp connecting the inter-aural foramina and passing through the vertex of the skull. The center of the ultrasonic probe corresponding to the Oizumi gate is arranged within ±5% of the length of A on the midline and within ±5% of the length of B on the perpendicular to A, centered at a position 13% of the length of A in front of the midpoint (vertex of the skull) of A. Also, with respect to the vertex of the skull, the ultrasonic probe corresponding to the Koizumi gate is arranged within ±5% of the length of A on the midline and within ±5% of the length of B on the perpendicular to A, centered at a position 40% of the length of A behind the vertex of the skull. Then, on the line on the scalp parallel to B and passing through a position 10% of the length of A in front of the vertex of the skull, the centers of the ultrasonic probes corresponding to the left and right anterior temporal gates are arranged within ±5% of the length of B on the parallel line to B and within ±5% of the length of A on the perpendicular to B, centered at positions 40% of the length of B on both sides of the intersection with A. Similarly, on the line on the scalp parallel to B and passing through a position 10% of the length of A behind the vertex of the skull, the centers of the ultrasonic probes corresponding to the left and right posterior temporal gates are arranged within ±5% of the length of B on the parallel line to B and within ±5% of the length of A on the perpendicular to B, centered at positions 45% of the length of B on both sides of the intersection with A. The head holder is provided with a probe holder corresponding to the above-mentioned vertex landmark and the above-mentioned ultrasonic probe coordinates, and by aligning the helmet landmark with the vertex of the skull, each ultrasonic probe automatically corresponds to the position of each gate.

[0034] In one embodiment, the control unit 130 may control a plurality of ultrasonic probes 110 to alternately transmit and receive ultrasonic waves. Specifically, the control unit 130 may drive the ultrasonic probes 110_A to 110_F according to the transmission pattern of ultrasonic signals from the ultrasonic probes 110_A to 110_F as shown in FIG. 7.

[0035] In the illustrated example, the ultrasonic probe 110_A first performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the Oizumi gate 120_A for a predetermined period, and transmits the measurement result to the control unit 130.

[0036] Next, the ultrasonic probe 110_B performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the Koizumi gate 120_B for a predetermined period, and transmits the measurement result to the control unit 130.

[0037] Next, the ultrasonic probe 110_C performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the left anterior temporal gate 120_C for a predetermined period, and transmits the measurement result to the control unit 130.

[0038] Next, the ultrasonic probe 110_D performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the right anterior temporal gate 120_D for a predetermined period, and transmits the measurement result to the control unit 130.

[0039] Next, the ultrasonic probe 110_E performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the left posterior temporal gate 120_E for a predetermined period, and transmits the measurement result to the control unit 130.

[0040] Next, the ultrasonic probe 110_F performs ultrasonic measurement by transmitting and receiving ultrasonic signals with the brain through the right posterior temporal gate 120_F for a predetermined period, and transmits the measurement result to the control unit 130.

[0041] In this way, when all six ultrasonic probes 110_A to 110_F have completed ultrasonic measurement (N p = 6), as shown in FIG. 7, the ultrasonic measurement of the above-described ultrasonic probes 110_A to 110_F is further repeated. In the illustrated example, the transmission and reception pattern of ultrasonic signals by the above-described ultrasonic probes 110_A to 110_F is repeated 200 times (N r = 200). In this way, by alternately transmitting and measuring ultrasonic pulses from a plurality of separated acoustic windows, it is possible to obtain brain functional network information between brain regions while suppressing a local temperature rise of brain tissue due to the thermal effect of ultrasonic waves.

[0042] FIG. 8 shows the change in blood flow over time due to a nerve excitatory action in an example. As shown in FIG. 8, when a nerve excitatory action occurs, it is known that a change in the blood flow state in the brain caused by the nerve excitatory action appears with a time difference of several seconds as a vasomotor response. Therefore, the number of repetitions of the transmission and reception pattern of ultrasonic signals may be set corresponding to the period during which the vasomotor response can be observed.

[0043] However, the above-described transmission and reception pattern of ultrasonic signals is merely an example, and the transmission and reception pattern of ultrasonic signals by the ultrasonic probes 110_A to 110_F according to the present disclosure is not limited thereto. Also, it is not necessary to transmit ultrasonic signals having the same wavefront shape for all repetitions, and ultrasonic signals having different wavefront shapes may be transmitted for each repetition. Also, it is not necessary to transmit ultrasonic signals having the same wavefront shape for all the ultrasonic probes 110_A to 110_F, and ultrasonic signals having different wavefront shapes may be transmitted for each of the ultrasonic probes 110_A to 110_F.

[0044] When the control unit 130 receives a reflected wave as a measurement result from each of the ultrasonic probes 110_A to 110_F, the control unit 130 passes the acquired measurement result to the image processing unit 140.

[0045] The image processing unit 140 generates brain functional network information calculated from the blood flow state between a plurality of brain regions based on the measurement results obtained from the plurality of ultrasonic probes 110_A to 110_F. Specifically, the image processing unit 140 uses the measurement results obtained from each of the ultrasonic probes 110_A to 110_F to generate a local brain image indicating one or more brain regions measurable by the ultrasonic probes 110_A to 110_F based on the reflected waves of the transmitted ultrasonic signals.

[0046] For example, in the example shown in FIG. 9, the ultrasonic probe 110_A disposed at the Oizumi Gate 120_A is set to have virtual sound source coordinates as shown, for example, and acquires a local brain image of the brain region within the reach of the ultrasonic signal from the ultrasonic probe 110_A as shown. The ultrasonic probe 110_B disposed at the Koizumi Gate 120_B is set to have virtual sound source coordinates as shown, for example, and acquires a local brain image of the brain region within the reach of the ultrasonic signal from the ultrasonic probe 110_B as shown.

[0047] When generating the local brain images of each of the ultrasonic probes 110_A to 110_F, the image processing unit 140 synthesizes these local brain images to generate an image of the entire brain. For example, the image processing unit 140 may identify the overlapping portions of two local brain images as shown in FIG. 10A and synthesize the two local brain images by superimposing the overlapping portions. Similarly, the image processing unit 140 synthesizes the local brain images by superimposing the overlapping portions from the local brain images of each of the ultrasonic probes 110_A to 110_F to generate a wide-area brain image of the entire brain as shown in FIG. 10B. For example, the image processing unit 140 can reconstruct measurement data from a plurality of directions and obtain a wide-area brain ultrasonic image as shown in FIG. 10C.

[0048] When obtaining an image of the entire brain in this way, the image processing unit 140 may generate an image on the three-dimensional atlas coordinates representing a plurality of brain regions based on the brain image composed of the measurement results. For example, the transmission and reception pattern of the ultrasonic signals of the ultrasonic probes 110_A to 100_F is N rWhen repeated, as shown in FIG. 11, the image processing unit 140 can acquire a wide-area brain image of the entire brain from a plurality of local brain images provided from each ultrasonic probe 110, and can transform the wide-area brain image into a coordinate system of a standard brain image prepared in advance to acquire an image in the same space as the three-dimensional brain atlas.

[0049] More specifically, when the control unit 130 acquires the measurement results of each of the ultrasonic probes 110_A to 110_F, the image processing unit 140 performs analog-to-digital (AD) conversion on the received signals of each of the ultrasonic probes 110_A to 110_F of the acquired measurement results. Then, as shown in FIG. 9, the image processing unit 140 generates a local brain image of each ultrasonic probe 110 by using beamforming corresponding to the positions of the virtual sound sources of spherical diffusion wave formation. For example, in order to uniformly capture blood cells flowing in blood vessels running in various directions, N a virtual point sound source positions are set in a plane space, and the propagation direction of the spherical diffusion wave may be tilted three-dimensionally N a times. The images measured at the N a virtual point sound sources may be added and averaged, and the backscattering may be coherently added while suppressing the angle dependence of the blood vessel running in the brain.

[0050] At this time, the frame rate F of the image measurement using one ultrasonic probe 110 may follow Equation (1).

Equation

[0051] As described above, when N p (for example, N p is an integer from 2 to 6) ultrasonic probes 110 are sequentially driven and this sequential driving is repeated N r times, each of the ultrasonic probes 110_A to 110_F may add and average the received signals for the transmitted ultrasonic signals. The frame rate F of the image measurement at this time wIt may follow formula (2).

Number

[0052] With respect to the maximum frequency 0.3 Hz included in the hemodynamics accompanying neural excitation, the frame rate 1.42 Hz is a frame rate sufficiently higher than its Nyquist frequency 0.6 Hz. Therefore, it is possible to accurately detect the cerebral blood dynamics accompanying neural excitation. However, the present disclosure is not limited to this, and regardless of the number and arrangement of the elements of the vibrator of the ultrasonic probe 110 used for transmitting and receiving ultrasonic waves and the order of driving the ultrasonic probe 110, the frame rate F w is such that the number N of virtual point sound sources a , the number of repetitions N r and the number N of ultrasonic probes p may be adjusted.

[0053] For the signal value S measured using each ultrasonic probe 110, for example, the image processing unit 140 may apply a high-pass filter to emphasize the movement of blood cells and remove the clutter signal of the low-frequency component derived from the tissue. Then, the image processing unit 140 can obtain the cerebral blood flow value I by adding and averaging the signal value S according to formula (3).

Number

[0054] For the local brain images measured by each ultrasonic probe 110, the virtual sound source coordinates and the tilt angle of the ultrasonic probe 110 are known by selecting the head holder 120 used for the subject. The image processing unit 140 may arrange each local brain image in a lattice coordinate space by nearest neighbor search, as shown in Fig. 10A, and automatically superimpose these local brain images. For example, for the coordinates overlapping between the local brain images of each ultrasonic probe 110 in the lattice coordinate space, an arithmetic mean or a voxel value with a high signal-to-noise ratio is adopted, and the image processing unit 140 can generate a wide-area brain image of the entire brain from the local brain images by superimposing the overlapping parts.

[0055] In addition, in cases where the probe holder 121 is held by a rubber net or band, the virtual sound source coordinates may deviate from the expected position. For this reason, the image processor 140 may align the wide-area brain image with a standard brain template having a population-average brain shape of infants constructed by any imaging device such as MRI (Magnetic Resonance Imaging) or CT (Computed Tomography) by rigid or non-rigid image transformation, and perform coordinate transformation of the wide-area brain image to the standard brain template in the standard brain space.

[0056] The image processor 140 is r For a wide-area brain image obtained by repeating the measurement times, as shown in FIG. r / F w Four-dimensional time series image data 1-N of wide-area brain images R The image processing unit 140 may display the four-dimensional time-series image data thus obtained and three-dimensional image data obtained by adding these data on the time axis as a wide-area brain morphology, blood vessels, and blood flow change image on a display or the like.

[0057] Specifically, the image processing unit 140 performs coordinate transformation by rigid or non-rigid alignment on the standard brain template, applies the transformation information to the cerebral blood flow image with the same coordinates as the brain morphology, and converts the wide-area brain image into the standard brain coordinates. Next, the image processing unit 140 uses a three-dimensional brain atlas having the same coordinates as the standard brain coordinates to perform ROI (Region Of Interest) analysis on the ROI corresponding to each brain region, and obtains the signal change of each ROI. Finally, in order to evaluate the functional connectivity between brain regions, the image processing unit 140 extracts the components in the range of 0.01 to 0.1 Hz where there is fluctuation in the cerebral blood flow signal derived from neural activities such as neural excitation by a band-pass filter, and performs correlation analysis between two ROIs.

[0058] Then, the image processing unit 140 may display the correlation coefficient derived by the correlation analysis on the standard brain space as the strength of the connection between ROIs. For example, as shown in FIG. 12A, when the correlation coefficient between ROI1 and ROI2 is 0.3, the correlation coefficient between ROI1 and ROI3 is 0.4, and the correlation coefficient between ROI2 and ROI3 is 0.8, the image processing unit 140 may display on the display a three-dimensional brain space in which the brain function network information between ROI1, ROI2, and ROI3 as shown in FIG. 12B is superimposed.

[0059] Here, ROI i and ROI j at time point t n the cerebral blood flow values are respectively I i (t n ) and I j (t n ), then the functional connectivity FC i between ROI j and ROI ij can be derived from the Pearson correlation by Equation (4).

Equation

Equation

[0060] Based on the functional connectivity FC between brain regions of the whole brain thus obtained, the image processing unit 140 generates brain function network information. Specifically, the image processing unit 140 calculates the functional connectivity FC (i.e., the correlation coefficient) between each pair of ROIs for the number m of ROIs in the 3D brain atlas, and may generate an m×m adjacency matrix as shown in FIG. 13A for the number m of ROIs in the 3D brain atlas. That is, in the i-th row and j-th column (and the j-th row and i-th column) of the adjacency matrix, FC ij (=FC ji ) is input. Further, the image processing unit 140 may set the diagonal components of the adjacency matrix to 0, and use the adjacency matrix binarized by a predetermined threshold as shown in FIG. 13B as the object of network analysis.

[0061] In addition to the above-described brain function network information, the image processing unit 140 may also derive a brain function integration index and a brain function separation index. Specifically, for network analysis based on FIG. 13B, as shown in FIG. 14, the brain function network information may be expressed by a graph structure with ROIs as nodes and functional connectivity FC as links. In the graph, a set M of nodes, the degree k of each node i (the number of links connected to node i), the shortest path length d ij (the shortest distance between nodes i and j), the clustering coefficient c i (the value obtained by dividing the number of triangles with node i as one vertex and adjacent nodes connected to each other as vertices by the number of connection links with node i) and the like may be used.

[0062] The degree k of node i i is given by Equation (5) as the sum of the values a ij (0 or 1) in the i-th row of the binarized adjacency matrix A in the i-th row and j-th column. [Number]

[0063] Shortest path length d ij is the shortest path length between two nodes i and j and is given by Equation (6).

Equation

Equation

[0064] On the other hand, the clustering coefficient c i is calculated from the degree k i of node i and the number t i of triangles formed by node i and the nodes adjacent to it, and can be used as an index of functional separation of the network between brain regions.[[]]

Equation

Equation

[0065] The image processing unit 140 may apply such a network analysis method to the wide-area brain function activity data and display the derived network index together with the brain function network information on the display. Thereby, the user can quantitatively evaluate the functional separation and functional integration in the wide-area brain network of the subject.[[]]

[0066] In the ultrasonic device 100 shown in FIG. 1, a plurality of ultrasonic probes 110 are provided in a head holder 120 that is attached to the head of a subject such as a newborn, corresponding to each of a plurality of head regions. However, the present disclosure is not limited to this, and may be implemented by other configurations capable of transmitting and receiving ultrasonic signals to and from a plurality of head regions of the subject.

[0067] FIG. 15 is a schematic diagram showing an ultrasonic device according to another embodiment of the present disclosure. As shown in FIG. 15, the ultrasonic device 100A includes a camera 110A, a robotic arm 120A, a control unit 130A, and an image processing unit 140A. That is, the ultrasonic device 100A uses the camera 100A and the robotic arm 120A instead of the head holder 120 of the ultrasonic device 100 described above. Further, in the illustrated embodiment, the ultrasonic device 100A includes the camera 110A and the robotic arm 120A, but the present disclosure is not limited thereto. For example, the camera 110A and / or the robotic arm 120A may be used as an external device of the ultrasonic device 100A and may be controlled by the ultrasonic device 100A via, for example, a wired or wireless connection.

[0068] The camera 110A images a plurality of head regions. Specifically, the camera 110A may be realized by a stereo camera or the like, image the head of the subject, and acquire 4D measurement data of the surface shape of the head of the subject. Further, for example, the camera 110A may be capable of controlling an optical system such as a lens to follow a plurality of head regions corresponding to the movement of the subject under the control of the control unit 130A.

[0069] The robotic arm 120A has an ultrasonic probe 121A at the tip of the arm or the like. Each ultrasonic probe 121A transmits an ultrasonic signal toward the object and receives a reflected signal from the object, similar to the ultrasonic probe 110 described above. The robotic arm 120A identifies and tracks a plurality of head regions of the subject based on the image of the subject's head captured by the camera 100A under the control of the control unit 130A, and transmits an ultrasonic signal toward the plurality of head regions of the subject by the ultrasonic probe 121A and receives a reflected signal from these head regions. Typically, a plurality of robotic arms 120A can be provided in the ultrasonic device 100A to transmit and receive ultrasonic signals to and from a plurality of head regions.

[0070] The control unit 130A controls the camera 110A and the robotic arm 120A. Specifically, the control unit 130A controls the movement of the robotic arm 120A based on the image of the head region of the subject captured by the camera 110A so that an ultrasonic signal can be transmitted and received between the head region to be examined and the ultrasonic probe 121A. For example, the control unit 130A may control the movement of the robotic arm 120A so that the ultrasonic probe 121A can follow the head region during the transmission and reception of the ultrasonic signal. When the control unit 130A obtains measurement results from the ultrasonic probes 121A of the plurality of robotic arms 120A, the control unit 130A passes the obtained measurement results to the image processing unit 140A. The image processing unit 140A performs the same image processing as the image processing unit 140 described above on the obtained measurement results to generate brain function network information.

[0071] For example, the robotic arm 120A operates based on the three-dimensional shape of the infant's nipple area acquired from the camera 110A. First, from the acquired three-dimensional head shape, the position on the head where the ultrasonic probe is to be placed and the angle at which the ultrasonic probe is to be applied can be estimated by image processing and / or point cloud data processing. The control unit 130 controls the robotic arm 120A so that the ultrasonic probe 121A is placed on a predetermined head region based on the estimated position and angle information. Further, the control unit 130A may track the movement of the infant's head using the three-dimensional information obtained in real time from the camera 110A, and control the position and angle of the robotic arm 120A so that the relative positional relationship between the ultrasonic probe 121A and the head always remains the same. Note that the camera 110A may be another camera as long as it can acquire three-dimensional shape information in real time. In addition to tracking the movement of the head by the camera 110A, the robotic arm 120A equipped with each ultrasonic probe 121A may automatically adjust the position and angle of the ultrasonic probe 121A so that the field of view and contrast of the brain image data of the infant measured by each ultrasonic probe 121A are maximized.

[0072] Autism spectrum disorder, which is one of the developmental disorders, is characterized by communication disorders, reduced language ability, and repetitive behaviors as its main symptoms (diagnostic criteria by the American Psychiatric Association; DSM-V, 2013). As for the brain network of autism spectrum disorder, strong local connections are characteristic as shown by research using MRI (Belmonte, J Neurosci 2004). The maternal immune activation model used in preclinical developmental disorder research has been widely used in the study of the pathogenesis of autism as a phenotype of autism with reduced sociality and increased repetitive behaviors (Choi, Science 2016). By measuring the brain network using ultrasound in this autism model, an excessive brain network in a wide area of the brain including the deep brain, similar to that of autism patients, was observed, and as a result of the network analysis, the clustering coefficient for evaluating local connectivity was larger than that of the healthy model (Figure 16). From this, in this disclosure for evaluating the wide-area brain network using ultrasound, as one of its embodiments, it is conceivable to apply the characteristics of the brain network of infants with developmental disorders to an inspection method using network indices.

[0073] [Ultrasonic signal processing] Next, with reference to FIG. 17, ultrasonic signal processing according to an embodiment of the present disclosure will be described. The ultrasonic signal processing is executed by the ultrasonic device 100 described above, and more specifically, it may be realized by one or more processors of the ultrasonic device 100 executing one or more programs or instructions stored in one or more memories.

[0074] FIG. 17 is a flowchart showing ultrasonic signal processing according to an embodiment of the present disclosure.

[0075] As shown in FIG. 17, in step S101, the ultrasonic device 100 transmits and receives ultrasonic signals to and from a brain region in the brain through an acoustic window of the subject's head using the ultrasonic probe 110. In this embodiment, the ultrasonic probe 110 is disposed in the head holder 120 corresponding to each of a plurality of head regions of the infant. For example, the head regions used as the acoustic windows of the ultrasonic probe 110 may include two or more of the great fontanelle, small fontanelle, anterior temporal fontanelle, and posterior temporal fontanelle that open on the head of the infant. When the infant wears the head holder 120, a probe holder 121 for holding each ultrasonic probe 110 is provided in the head holder 120 so that the ultrasonic probe 110 is disposed in these head regions. Each ultrasonic probe 110 transmits an ultrasonic signal into the subject's brain from the acoustic window as the disposed opening and receives the reflected ultrasonic signal. The ultrasonic device 100 may control the transmission and reception pattern of the ultrasonic signal by each ultrasonic probe 110, such as alternately driving a plurality of ultrasonic probes 110. Each ultrasonic probe 110 can obtain a measurement result regarding the brain region near the opening based on the difference between the transmission time and the reception time of the transmitted and received ultrasonic signal.

[0076] In step S102, the ultrasonic device 100 obtains the measurement results from each ultrasonic probe 110. Specifically, the ultrasonic device 100 obtains the measurement results of the brain region near the arrangement position from each ultrasonic probe 110 and generates a local brain image based on the measurement results from each ultrasonic probe 110. The blood flow state of one or more brain regions is shown in the local brain image.

[0077] In step S103, the ultrasonic device 100 estimates the blood flow state between a plurality of brain regions in the brain from the measurement results. Specifically, the ultrasonic device 100 may identify an overlapping portion between a local brain image acquired from each ultrasonic probe 110 and a local brain image acquired from an adjacent ultrasonic probe 110, and synthesize these adjacent local brain images by superimposing the identified overlapping portion. The ultrasonic device 100 repeats the synthesis of the local brain images based on this overlapping portion for all the local brain images to generate a wide-area brain image of the entire brain. Then, the ultrasonic device 100 estimates the change in the blood flow state of each brain region as a vasomotor response to neural excitation, and performs a correlation analysis on the blood flow states between the brain regions. For example, when the correlation coefficient calculated for brain regions A and B is equal to or greater than a predetermined threshold, it may be determined that brain regions A and B are functionally connected. On the other hand, when the correlation coefficient calculated for brain regions A and B is less than the predetermined threshold, it may be determined that brain regions A and B are not functionally connected.

[0078] In step S104, the ultrasonic device 100 can determine the presence or absence of the above-described functional connectivity for each pair of brain regions, and acquire brain functional network information between the brain regions as a graph structure based on the determination result.

[0079] According to the above-described embodiment, since the cerebral hemodynamics associated with neural excitation is observed as in functional magnetic resonance imaging of the brain, brain activity and brain functional network analysis are possible. And it becomes possible to widely provide an approach for functional network evaluation that grasps the entire wide area of the brain as one entity even to infants. As a result, early diagnosis of developmental disorders suspected of brain activity and brain functional network abnormalities, understanding of the developing brain, and furthermore, wide-ranging applications such as neuromarketing industries such as the development of toys for infants can be expected.

[0080] As described above, the embodiments of the present disclosure have been described in detail, but the present disclosure is not limited to the above-described specific embodiments, and various modifications and changes are possible within the scope of the gist of the present disclosure described in the claims.

[0081] Furthermore, the following additional remarks are disclosed regarding the above description. (Appendix 1) An ultrasonic device comprising: a plurality of ultrasonic probes disposed corresponding to each of the plurality of head regions for transmitting and receiving ultrasonic waves between a plurality of brain regions via the plurality of head regions; a control unit for controlling the plurality of ultrasonic probes; and an image processing unit for generating brain function network information calculated from the blood flow state between the plurality of brain regions based on measurement results obtained from the plurality of ultrasonic probes. (Appendix 2) The ultrasonic device according to Appendix 1, further comprising a head holder including the plurality of ultrasonic probes. (Appendix 3) a camera for imaging the plurality of head regions; and a plurality of robotic arms including the plurality of ultrasonic probes, The ultrasonic device according to Appendix 1, further comprising the same. (Appendix 4) The ultrasonic device according to Appendix 3, wherein the control unit controls the movement of the plurality of robotic arms to follow the plurality of head regions based on images of the plurality of head regions captured. (Appendix 5) The ultrasonic device according to any one of Appendices 1 to 4, wherein the plurality of head regions includes two or more of the Oizumi Gate, Koizumi Gate, left anterior temporal gate, right anterior temporal gate, left posterior temporal gate, right posterior temporal gate, and temporal bone window. (Appendix 6) The ultrasonic device according to any one of Appendices 1 to 5, wherein the control unit controls the plurality of ultrasonic probes to transmit and receive ultrasonic waves alternately. (Appendix 7) The ultrasonic device according to any one of Appendices 1 to 6, wherein the ultrasonic probe includes a mechanism for forming a wavefront of an arbitrary shape, and uses the mechanism to transmit the ultrasonic wave. (Appendix 8) The ultrasonic device according to any one of Appendices 1 to 7, wherein the image processing unit represents the plurality of brain regions based on a brain image composed of the measurement results, and generates an image on three-dimensional atlas coordinates. (Appendix 9) The ultrasonic apparatus according to any one of Appendices 1 to 8, wherein the image processing unit generates the brain function network information based on a correlation in a temporal change of brain blood flow signal intensity between the plurality of brain regions. (Appendix 10) The ultrasonic apparatus according to any one of Appendices 1 to 9, wherein the brain function network information is expressed as a graph structure. (Appendix 11) Having a plurality of ultrasonic probes for transmitting and receiving ultrasonic waves between a plurality of brain regions via a plurality of head regions, The plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions, a head holder. (Appendix 12) A step of obtaining measurement results from a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions, A step of generating brain function network information calculated from a blood flow state between the plurality of brain regions based on the measurement results, and having, The plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions, an ultrasonic signal processing method executed by a computer.

Explanation of Signs

[0082] 100, 100A Ultrasonic apparatus 110, 121A Ultrasonic probe 110A Camera 120 Head holder 120A Robot arm 121 Probe holder 122 Silicon pad 123 Ultrasonic gel 130, 130A Control unit 140, 140A Image processing unit 150 Control device

Claims

1. a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions, and are arranged corresponding to each of the plurality of head regions; a control unit that controls the plurality of ultrasonic probes; an image processing unit that generates brain function network information calculated from a blood flow state of four-dimensional time-series data acquired by repeated measurement based on measurement results acquired from the plurality of ultrasonic probes; characterized by comprising; The control unit controls alternating ultrasonic wave transmission by the plurality of ultrasonic probes so as to ensure a frame rate equal to or higher than the Nyquist frequency with respect to the maximum frequency included in the hemodynamic response associated with neural excitation. An ultrasonic device.

2. The ultrasonic device according to claim 1, further comprising a head holder including the plurality of ultrasonic probes.

3. a stereo camera that images the plurality of head regions; a plurality of robotic arms including the plurality of ultrasonic probes; The ultrasonic device according to claim 1, further comprising.

4. The control unit controls the movement of the plurality of robotic arms to follow the plurality of head regions based on images of the plurality of head regions captured. The ultrasonic device according to claim 3.

5. The plurality of head regions include three or more of the Oizumi gate, Koizumi gate, left anterior temporal gate, right anterior temporal gate, left posterior temporal gate, right posterior temporal gate, and temporal bone window. The ultrasonic device according to claim 1.

6. The plurality of ultrasonic probes are arranged at three or more of the Oizumi gate, Koizumi gate, left anterior temporal gate, right anterior temporal gate, left posterior temporal gate, and right posterior temporal gate. The ultrasonic device according to claim 1.

7. The ultrasonic probe includes a mechanism that forms a wavefront of an arbitrary shape, and transmits the ultrasonic wave using the mechanism. The ultrasonic device according to claim 1.

8. The image processing unit generates an image on three-dimensional atlas coordinates representing the plurality of brain regions based on a brain image composed of the measurement results. The ultrasonic device according to claim 1.

9. The image processing unit generates the brain function network information based on a correlation in a temporal change of a brain blood flow signal intensity between the plurality of brain regions. The ultrasonic device according to claim 1.

10. The brain function network information is expressed as a graph structure. The ultrasonic device according to claim 1.

11. having a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions; The plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions, and each ultrasonic probe is a head holder that alternately transmits ultrasonic waves so as to ensure a frame rate equal to or higher than the Nyquist frequency with respect to the maximum frequency included in the hemodynamics accompanying neural excitation.

12. A step of obtaining measurement results from a plurality of ultrasonic probes that transmit and receive ultrasonic waves between a plurality of brain regions via a plurality of head regions; A step of generating brain function network information calculated from the blood flow state between the plurality of brain regions based on the measurement results; comprising: The plurality of ultrasonic probes are disposed corresponding to each of the plurality of head regions, and each ultrasonic probe is an ultrasonic signal processing method executed by a computer that alternately transmits ultrasonic waves so as to ensure a frame rate equal to or higher than the Nyquist frequency with respect to the maximum frequency included in the hemodynamics accompanying neural excitation.

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