Optical measurement device and analysis method

Abstract

This optical measurement device comprises a light source, an ultrasonic wave source, an imaging device, a control device, and an analysis device. The control device causes the imaging device to image, during first to third imaging periods, signals of laser light that has passed through a region in a light scattering body, and controls imaging timings such that the interval between the first imaging period and the second imaging period and the interval between the second imaging period and the third imaging period are equal. The control device causes first laser light, second laser light, and third laser light to be respectively emitted from the light source during the first imaging period, the second imaging period, and the third imaging period, and causes ultrasonic waves to be generated from the ultrasonic wave source at the emission timing of the third laser light such that the ultrasonic waves arrive at a measurement location. The analysis device extracts modulated signal components by using a signal of the first laser light, a signal of the second laser light, and a signal of the third laser light, which have passed through the region in the light scattering body.

Description

Optical measurement device and analysis method

[0001] The present disclosure relates to an optical measurement device and an analysis method, and more particularly to a technique for improving the detection accuracy of light modulated by ultrasonic waves.

[0002] Many optical techniques have been developed as minimally invasive methods for measuring tissues in light-scattering bodies such as living organisms. For example, by irradiating light from outside the body and measuring the light that propagates through the body and is emitted, it is possible to obtain biological information such as morphological information and metabolic information (such as blood oxygen saturation) of the tissues inside the body. However, since tissues inside the body are light-scattering media, the light irradiated from outside the body is scattered by the tissues inside the body, resulting in poor spatial resolution and inability to measure deep tissues. Therefore, as shown in Wang, LV; Ku, G.; "Frequency-swept ultrasound-modulated optical tomography of scattering media," Optics Letters 23(12) 975-977 (1998) (Non-Patent Document 1) and Elson, Daniel S., et al. "Ultrasound-mediated optical tomography: a review of current methods," Interface Focus 1.4 632-648 (2011) (Non-Patent Document 2), an optical measurement device using ultrasound-modulated optical tomography (UOT) has been developed, which combines ultrasound that propagates with low scattering within a living body with light. UOT acquires biological information by measuring light modulated by ultrasound.

[0003] Japanese Patent No. 5672104 (Patent Document 1) and Sasakura Yu and Hisaka Maki, "Reflection-type ultrasonic modulated speckle optical measurement method," Biomedical Engineering, 45.4:235-241 (2007) (Non-Patent Document 3) disclose that a CCD camera is used to determine a change in a speckle pattern obtained when focused pulsed ultrasound is present at a specified depth, using a speckle pattern obtained when focused pulsed ultrasound is present on the surface of a sample as a reference, thereby obtaining information on a specified depth region.

[0004] The speckle pattern obtained when focused pulsed ultrasound is present at a predetermined depth contains not only signals derived from light modulated by ultrasound, but also noise that changes over time. In Patent Document 1 and Non-Patent Document 3, the influence of noise is reduced based on a speckle pattern obtained when there is no influence from pulsed ultrasound.

[0005] Patent No. 5672104

[0006] Wang, LV; Ku, G.; "Frequency-swept ultrasound-modulated optical tomography of scattering media," Optics Letters 23(12) 975-977 (1998). Elson, Daniel S., et al. "Ultrasound-mediated optical tomography: a review of current methods." Interface Focus 1.4 632-648 (2011). Sasakura, Y; Hisaka, M. "Reflection-type ultrasound-modulated speckle optical measurement method." Biomedical Engineering, 45.4:235-241 (2007).

[0007] In the methods disclosed in Patent Document 1 and Non-Patent Document 3, the time intervals at which the detection signal values ​​for which noise is to be reduced and the detection signal values ​​that are considered to be noise are obtained are different. Therefore, it can be difficult to remove from the detected signal the influence of noise that does not change constantly per unit time, such as noise caused by the irregular movement of particles.

[0008] The present disclosure has been made in consideration of the above circumstances, and its purpose is to improve the accuracy of extracting optical components modulated by ultrasonic waves from the acquired detection signal in an optical measurement device using ultrasonic modulated optical tomography.

[0009] An optical measurement device according to a first aspect of the present disclosure includes a light source, an ultrasound source, a detector, a control device, and an analysis device. The light source irradiates a light scattering medium with pulsed laser light. The ultrasound source emits ultrasound at a measurement position at a predetermined depth within the light scattering medium. The detector detects the laser light that has passed through a region within the light scattering medium that includes the measurement position. The control device controls the irradiation of the laser light and the emission of ultrasound. The analysis device extracts a modulated signal component modulated by ultrasound from the laser light detected by the detector. The control device sets the first imaging period, the second imaging period, and the third imaging period so that the interval between the first imaging period and the second imaging period is equal to the interval between the second imaging period and the third imaging period, and causes the detector to detect signals of the laser light that have passed through the region within the light scattering medium during the first imaging period, the second imaging period, and the third imaging period. The control device causes the light source to emit a first laser beam during a first imaging period, a second laser beam during a second imaging period, and a third laser beam during a third imaging period, and causes the ultrasound source to emit ultrasound so that the ultrasound reaches the measurement position at the timing of the emission of the third laser beam. The analysis device extracts a first signal component using signals of the first laser beam and the second laser beam that have passed through a region within the light scattering medium, extracts a second signal component using signals of the second laser beam and the third laser beam that have passed through a region within the light scattering medium, and extracts a modulated signal component from the first signal component and the second signal component.

[0010] An optical measurement device according to a second aspect of the present disclosure includes a light source, an ultrasound source, a detector, a control device, and an analysis device. The light source irradiates a light scattering medium with pulsed laser light. The ultrasound source emits ultrasound at a measurement position at a predetermined depth within the light scattering medium. The detector detects the laser light that has passed through a region within the light scattering medium that includes the measurement position. The control device controls the irradiation of the laser light and the emission of ultrasound. The analysis device extracts a modulated signal component modulated by ultrasound from the laser light detected by the detector. The control device sets the first, second, third, and fourth imaging periods so that the interval between the first and second imaging periods is equal to the interval between the third and fourth imaging periods, and causes the detector to detect signals of the laser light that have passed through the region within the light scattering medium during the first, second, third, and fourth imaging periods. The control device causes the light source to irradiate the first laser light during the first imaging period, the second laser light during the second imaging period, the third laser light during the third imaging period, and the fourth laser light during the fourth imaging period, and oscillates ultrasonic waves so that the ultrasonic waves reach the measurement position at the timing of irradiation of the third laser light from the ultrasonic source. The analysis device extracts a first signal component using signals of the first laser light and the second laser light that have passed through a region within the light scattering medium, extracts a second signal component using signals of the third laser light and the fourth laser light that have passed through a region within the light scattering medium, and extracts a modulated signal component from the first signal component and the second signal component.

[0011] An analysis method according to a third aspect of the present disclosure is a method for analyzing modulated signal components generated when laser light irradiated into a light scattering medium is modulated by ultrasound at a measurement position at a predetermined depth, the analysis method comprising the steps of: (a) acquiring a detection signal of first laser light that has passed through a region within the light scattering medium, acquired during a first imaging period; (b) acquiring a detection signal of second laser light that has passed through a region within the light scattering medium, acquired during a second imaging period that is a predetermined interval from the first imaging period; (c) acquiring a detection signal of third laser light that has been irradiated when ultrasound reaches the measurement position and has passed through a region within the light scattering medium, acquired during a third imaging period that is a predetermined interval from the second imaging period; (d) extracting a first signal component using the detection signal of the first laser light and the detection signal of the second laser light; (e) extracting a second signal component using the detection signal of the second laser light and the detection signal of the third laser light; and (f) extracting a modulated signal component from the first signal component and the second signal component.

[0012] According to the optical measurement device and analysis method of the present disclosure, it is possible to improve the accuracy of extracting optical components modulated by ultrasonic waves from detection signals acquired by an optical measurement device using ultrasonic modulated optical tomography.

[0013] Fig. 1 is a schematic diagram of an optical measurement device according to an embodiment; Fig. 2 is a timing chart showing the imaging timing, the turn-on timing of a pulse laser, and the oscillation timing of ultrasonic waves of the optical measurement device according to an embodiment; Fig. 3 is a diagram showing an example of a speckle pattern obtained by the optical measurement device; Fig. 4 is a diagram showing an example of a signal component extracted from the speckle pattern; Fig. 5 is a flowchart showing an analysis process of a modulated signal component according to an embodiment; Fig. 6 is a timing chart showing the imaging timing, the turn-on timing of a pulse laser, and the oscillation timing of ultrasonic waves of the optical measurement device according to a modified example; Fig. 7 is a flowchart showing an analysis process of a modulated signal component according to a modified example.

[0014] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. Hereinafter, a living body will be exemplified as an observation target, but the present invention is not limited thereto and can be used for observing light scattering bodies. Note that the same or corresponding parts in the drawings will be assigned the same reference numerals, and their description will not be repeated.

[0015] [Optical Measurement Device] Fig. 1 is a diagram showing the configuration of an optical measurement device 10 according to an embodiment. Referring to Fig. 1, the optical measurement device 10 includes a laser source 1, an ultrasound source 2, a camera 3, a control device 4, and an analysis device 5. The optical measurement device 10 detects modulated light generated by irradiating a measurement area subjected to the action of ultrasound with laser light, and can acquire morphological and physiological information of the observation object. In practice, the optical measurement device 10 acquires, using the camera 3, an image of a speckle pattern, which is an aggregate of speckled particles (speckle grains) formed by multiple interference of a large number of light waves that are multiply scattered within the observation object, and extracts, using the analysis device 5, a signal component of the modulated light included in the speckle pattern. The speckle pattern in the embodiment corresponds to the laser light signal in this disclosure.

[0016] The optical measurement device according to this embodiment can be applied, for example, to an optical measurement device that performs minimally invasive optical measurement of a subject's brain activity using near-infrared spectroscopy (NIRS). Furthermore, the optical measurement device according to this embodiment can also be applied to a measurement device that measures blood oxygen saturation, in addition to optical measurement devices that measure brain activity using near-infrared spectroscopy. The oxygen saturation can be estimated, for example, using the relationship between the absorption spectra of oxygenated hemoglobin and reduced hemoglobin based on the results of measurements using lasers of different wavelengths.

[0017] The control device 4 and the analysis device 5 can be configured on a single computer (not shown), and external devices such as a memory and a printer can be connected as needed. The laser source 1, the ultrasound source 2, and the camera 3 can also be configured as an integrated device, and these and the control device 4 can be configured as an integrated device that can be worn by the subject.

[0018] The laser source 1 is a light source that irradiates the living body 20, which is the object of observation, with laser light, and is, for example, a semiconductor laser element. In this embodiment, the laser source 1 is controlled to generate pulsed laser light (pulsed laser light). The laser source 1 irradiates laser light in the near-infrared wavelength region (e.g., 780 nm, etc.), which has high transmittance through the living body 20. The laser light irradiated from the laser source 1 to the living body 20 is scattered by tissue within the living body 20 and reaches the measurement position, as shown in FIG. 1 . Furthermore, the laser source 1 can irradiate pulsed laser light of approximately several nanoseconds to several microseconds.

[0019] The ultrasound source 2 is an ultrasound generator that emits ultrasound waves at a measurement position at a predetermined depth within the living body 20. The ultrasound source 2 is provided with a focuser 2a for focusing the emitted ultrasound waves at the measurement position within the living body 20. In the region where the ultrasound waves are focused, the ultrasound waves and laser light strongly interact with each other, generating modulated light. Therefore, by optically detecting the modulated light generated by this interaction, it is possible to obtain information about the measurement position within the living body 20.

[0020] The ultrasound emitted from the ultrasound source 2 may be continuous or pulsed. However, by using pulsed ultrasound, the length of the ultrasound in the propagation direction can be shortened, limiting the area where the ultrasound exists to the measurement position. Furthermore, when pulsed ultrasound is emitted from the ultrasound source 2, a delay time is required for the pulsed ultrasound emitted from the surface of the living body 20 to reach the measurement position. Therefore, it is necessary to control the timing of the ultrasound emission from the ultrasound source 2 so that the pulsed ultrasound reaches the measurement position in accordance with the timing of the pulsed laser light emitted from the laser source 1 reaching the measurement position. Strictly speaking, the timing of the laser light irradiation and the timing of the laser light arrival at the measurement position are offset by the time required for the laser light to travel from the laser source 1 to the measurement position. However, because the distance from the laser source 1 to the measurement position is sufficiently shorter than the distance light travels per unit time, the time required for the laser light to travel from the laser source 1 to the measurement position can be ignored. Therefore, the timing at which the laser source 1 irradiates the laser light and the timing at which the laser light arrives at the measurement position can be considered to be approximately the same.

[0021] The camera 3 includes an image sensor 3a that detects laser light from the measurement position and a lens 3b for forming an image on the image sensor 3a. Because the optical measurement device 10 needs to capture a speckle pattern, it uses the image sensor 3a, which is a multi-element photodetector, such as a CCD (Charge Coupled Device) sensor or a CMOS (Complementary Metal-Oxide-Semiconductor) sensor, rather than a single-element photodetector such as a photomultiplier tube. By using a CCD sensor or a CMOS sensor as the image sensor 3a, the manufacturing cost of the optical measurement device 10 can be reduced. It is preferable that the pixel size of the image sensor 3a be smaller than the average size of the speckle grains to be captured.

[0022] An image sensor 3a such as a CCD sensor generally has a frame rate of several tens to several hundred fps. In contrast, the frequency of ultrasound is as fast as several MHz, and the image sensor 3a cannot keep up with changes in the ultrasound. Therefore, the optical measurement device 10 uses stroboscopic photography to irradiate the tissue in the living body 20 that is being irradiated with ultrasound with pulsed laser light, and captures an image of the speckle pattern with the exposed image sensor 3a.

[0023] It is also possible to set the exposure time of the image sensor 3a longer than the period of the ultrasonic waves and use the acquired speckle pattern for measurement. In this case, the pulse time width of the laser light is limited by the distance the ultrasonic waves travel within that time. If the time width is extended, the spatial resolution in the direction of ultrasonic wave propagation may decrease, so it is preferable to set it to several microseconds or less.

[0024] The light detected by camera 3 is a combination of laser light that has passed through the area where ultrasound is present and been modulated by the ultrasound, and laser light that has not passed through the area where ultrasound is present and has not been modulated by the ultrasound.

[0025] The control device 4 controls the timing of emitting laser light from the laser source 1 and the timing of emitting ultrasonic waves from the ultrasonic source 2. Since the laser light is pulsed, it has a pulse width. Therefore, the timing of emitting laser light is defined as, for example, the timing of the rising edge of the pulse. Of course, the timing of emitting laser light may also be defined as, for example, the timing of the median value of the pulse or the timing of the falling edge of the pulse. The timing of emitting laser light and the timing of emitting ultrasonic waves will be described in detail later. The control device 4 is, for example, a computer.

[0026] The analysis device 5 extracts modulated signal components modulated by ultrasonic waves based on the detection signal of the laser light detected by the camera 3. The method of extracting modulated signal components executed by the analysis device 5 will be described in detail later. The analysis device 5 is, for example, a computer.

[0027] [Comparative Example] Many optical techniques have been developed as minimally invasive methods for measuring tissues in vivo. However, since light is multiple-scattered by biological tissues, it can be difficult to measure deep tissues with high spatial resolution.

[0028] Therefore, an optical measurement technology using UOT has been developed that improves the spatial resolution of optical measurement by focusing ultrasound waves, which are hardly scattered by biological tissue, into a specified area and measuring the light modulated by the interaction between the ultrasound waves and light.

[0029] An image of a speckle pattern is acquired by optical measurement using the UOT. The acquired speckle pattern contains not only signal components based on modulated light but also noise. When extracting modulated signal components from the speckle pattern, which is a detection signal obtained by optical measurement, an analysis method is used in which, for example, noise components are removed from a detection signal obtained when ultrasonic waves are oscillated, based on a detection signal obtained when ultrasonic waves are not oscillated.

[0030] However, the above-mentioned analysis method may not be able to sufficiently remove noise components, resulting in low extraction accuracy of modulated signal components. Specifically, since the timing at which the detection signal obtained when ultrasonic waves are not emitted is different from the timing at which the detection signal obtained when ultrasonic waves are emitted, it may not be possible to remove from the detection signal the influence of noise with different time averages occurring between these timings (for example, noise due to the Brownian motion of scattering particles and noise due to changes in the state of biological tissue).

[0031] [Optical measurement method according to the embodiment] Therefore, in the optical measurement device according to the present embodiment, the optical measurement device 10 acquires three speckle patterns acquired consecutively at equal time intervals. By finding the noise components occurring during the time intervals from the two speckle patterns, it is possible to improve the accuracy of extracting the noise components.

[0032] By using the optical measurement device according to this embodiment, the accuracy of extracting noise components whose change amount per unit time is not constant is improved, and by using these noise components, the accuracy of extracting modulated signal components can be improved.

[0033] First, a description will be given of the period during which the optical measurement device 10 takes an image, the timing of irradiating the laser light, the timing of irradiating the ultrasonic wave, and the detection signal obtained as a result. Fig. 2 is a timing chart showing the period during which the camera 3 of the optical measurement device 10 takes an image, the timing of turning on the pulse laser, and the timing of irradiating the ultrasonic wave according to the embodiment.

[0034] <1. Setting the Capture Period> First, the user sets the period during which the speckle pattern is captured by the camera 3. During the capture period, the camera 3 captures the speckle pattern with the image sensor 3 a in an exposed state. Therefore, the detection signal acquired by the camera 3 is a superimposed speckle pattern formed by the laser light received during the capture period.

[0035] In this embodiment, it is assumed that the camera 3 is controlled so as to be constantly exposed to light throughout the shooting period, but the camera 3 may also be controlled so as to be exposed to light only during a predetermined period of the shooting period. In that case, the predetermined period must include a period during which the laser light is irradiated. The camera 3 may also be exposed to light during the readout period.

[0036] Three imaging periods are set. In Fig. 2, these correspond to a first imaging period, a second imaging period, and a third imaging period. After each imaging period ends, the captured signals are read out, and a first speckle pattern, a second speckle pattern, and a third speckle pattern are acquired.

[0037] The shooting periods are set so that the intervals between the shooting periods are equal. That is, as shown in Fig. 2, the first shooting interval, which is the interval between the start of the first shooting period and the start of the second shooting period, is set so that the second shooting interval, which is the interval between the start of the second shooting period and the start of the third shooting period, is equal. The shooting interval is, for example, 100 ms.

[0038] 2. Setting the Laser Irradiation Timing The user sets the times at which the first, second, and third laser beams are emitted from the laser source 1. As shown in FIG. 2 , the first laser beam is emitted during the first imaging period, the second laser beam is emitted during the second imaging period, and the third laser beam is emitted during the third imaging period. Because the laser beams have a pulse width, the timing of laser beam irradiation is defined, for example, as the timing of the rising edge of the pulse. The control device 4 transmits a laser drive signal to the laser source 1 in accordance with the timing of laser beam irradiation. Furthermore, because the laser beam emitted by the laser source 1 is pulsed, there is a period during which the laser beam is irradiated. This period (the period during which the laser drive signal is ON) is called the pulse lighting time. Therefore, the irradiation of each laser beam must be completed within the corresponding imaging period.

[0039] 3. Setting the Ultrasonic Wave Oscillation Timing Next, the user sets the timing at which ultrasonic waves are emitted from the ultrasonic wave source 2. Specifically, ultrasonic waves are emitted from the ultrasonic wave source 2 so that the ultrasonic waves reach the measurement position at the timing at which the third laser light is emitted. The control device 4 transmits an ultrasonic wave drive signal to the ultrasonic wave source 2 at the timing at which the ultrasonic waves are emitted. As shown in FIG. 2 , this oscillation timing is the timing at which the ultrasonic wave source 2 emits pulsed ultrasonic waves before the ultrasonic delay time from the timing at which the third laser light is emitted.

[0040] The ultrasonic delay time can be calculated from the distance (depth) from the ultrasonic source 2 to the measurement position. Because the ultrasonic waves emitted by the ultrasonic source 2 are pulsed, there is a period during which the ultrasonic waves continue to be emitted. This period (the period during which the ultrasonic drive signal is ON) is also referred to as the ultrasonic pulse width. Of course, the ultrasonic waves emitted by the ultrasonic source 2 are not limited to pulsed ultrasonic waves, but may be continuous ultrasonic waves. Strictly speaking, the timing at which the laser light is emitted and the timing at which the laser light reaches the measurement position are offset by the time it takes for the laser light to travel from the laser source 1 to the measurement position. However, because the distance from the laser source 1 to the measurement position is sufficiently shorter than the distance traveled by light per unit time, it can be assumed that the timing at which the laser light is emitted and the timing at which the laser light reaches the measurement position are approximately simultaneous. Therefore, the distance calculated by multiplying the speed at which the ultrasonic waves travel through the living body 20 by the ultrasonic delay time corresponds to the depth of the measurement position in the living body 20.

[0041] 4. Detected Signals The irradiated laser light is scattered in the living body 20 and acquired as a speckle pattern by the camera 3. As shown in Fig. 2 , the speckle pattern resulting from the first laser light corresponds to the first speckle pattern, the speckle pattern resulting from the second laser light corresponds to the second speckle pattern, and the speckle pattern resulting from the third laser light corresponds to the third speckle pattern.

[0042] 5. Extraction of Modulated Signal Component from Detection Signal Both the first speckle pattern and the second speckle pattern are acquired under conditions in which ultrasonic waves are not oscillated. That is, the speckle pattern acquisition conditions are the same except for the difference in the imaging period. Therefore, the difference between the second speckle pattern and the first speckle pattern (hereinafter referred to as the first signal component) corresponds to a noise component resulting from the difference in the imaging period. Specifically, for example, the noise component occurring during the imaging interval is calculated by subtracting the pixel value of each pixel of the first speckle pattern from the pixel value of each pixel of the second speckle pattern. In this case, the noise component is calculated as an image.

[0043] The second speckle pattern and the third speckle pattern are acquired under the same conditions, except for whether or not ultrasound is irradiated and for the different acquisition periods. Therefore, the difference between the third speckle pattern and the second speckle pattern (hereinafter referred to as the second signal component) corresponds to the sum of noise components and modulated signal components resulting from the difference in acquisition period. Specifically, for example, the value obtained by subtracting the pixel value of each pixel of the corresponding second speckle pattern from the pixel value of each pixel of the third speckle pattern corresponds to the sum of noise components and modulated signal components occurring during the acquisition interval. In this case, the sum of the noise components and modulated signal components is calculated as an image.

[0044] The noise component of the first signal component and the noise component contained in the second signal component described above are both noise components generated at equal imaging intervals. These noise components are a collection of multiple noises that change over time (e.g., noise caused by changes in the light scattering path due to Brownian motion of scattering particles and changes in the state of biological tissue). The impact of each individual noise on the speckle pattern over a short period of time is significant, and the noise is not periodic. However, the impact of the signal resulting from the sum of these noises on the speckle pattern can be considered to be to a certain extent within a predetermined time interval (e.g., 10 μs). Therefore, the noise component of the first signal component and the noise component contained in the second signal component acquired at equal imaging intervals can be considered to have approximately equal signal values.

[0045] Therefore, the modulated signal component is extracted by subtracting the first signal component from the second signal component. Specifically, for example, the modulated signal component is extracted by subtracting the pixel value of each pixel of the corresponding second speckle pattern from the pixel value of each pixel of the third speckle pattern, and then subtracting the pixel value of each pixel of the corresponding first speckle pattern from the pixel value of each pixel of the second speckle pattern. In this case, the modulated signal component is calculated as an image.

[0046] [Example of Extraction of Modulated Signal Component] A method for extracting a modulated signal component will be described with reference to Fig. 3 and Fig. 4. Fig. 3 shows a speckle pattern obtained when measuring a living body 20 with the optical measurement device 10. Fig. 4 shows signal components extracted from the obtained speckle pattern.

[0047] 3(a) corresponds to the first speckle pattern in FIG. 2, FIG. 3(b) corresponds to the second speckle pattern in FIG. 2, and FIG. 3(c) corresponds to the third speckle pattern in FIG.

[0048] 4A shows signal components calculated based on the first speckle pattern and the second speckle pattern. Specifically, the signal components are calculated by subtracting the pixel values ​​of the corresponding pixels of the first speckle pattern from the pixel values ​​of the corresponding pixels of the second speckle pattern. The signal components shown in FIG. 4A correspond to noise components generated during the imaging interval.

[0049] 4B shows signal components calculated based on the second speckle pattern and the third speckle pattern. Specifically, the signal components are obtained by subtracting the pixel values ​​of the corresponding pixels of the second speckle pattern from the pixel values ​​of the corresponding pixels of the third speckle pattern. The signal components shown in FIG. 4B correspond to the sum of noise components and modulated signal components occurring during the imaging interval.

[0050] Fig. 4(c) shows the modulation signal component calculated based on Fig. 4(a) and Fig. 4(b). Specifically, it is the pixel value of each pixel in Fig. 4(b) minus the pixel value of each pixel in Fig. 4(a) corresponding to that pixel.

[0051] The signal component shown in Fig. 4(c) is obtained by subtracting the detection signal obtained without irradiating ultrasound (Fig. 3(b)) from the detection signal containing the modulated signal component (Fig. 3(c)), and then subtracting the noise component obtained at equal time intervals (Fig. 4(a)). Therefore, it is a modulated signal component from which the influence of the noise component occurring during the imaging interval has been removed.

[0052] [Flow of Analysis Processing of Modulated Signal Component] Fig. 5 is a diagram showing a flowchart of an example of analysis processing performed to extract modulated signal components from a speckle pattern obtained by measurement with the optical measurement device 10. In one implementation example, the analysis processing subroutine in Fig. 5 is called from the main routine and executed when the processor of the analysis device 5 executes a given program. In this sense, the analysis device 5 is an example of an image processing device.

[0053] In step S10, the optical measurement device 10 receives from the user information on the first, second, and third imaging periods, which are periods during which laser light is received by the camera 3. The interval between the first and second imaging periods and the interval between the second and third imaging periods are set to be equal.

[0054] In step S12, the optical measurement device 10 irradiates the living body 20 with the first laser light during the first imaging period.

[0055] In step S14, the optical measurement device 10 detects a first signal. In this specification, the first signal corresponds to a detection signal of the first laser light and a first speckle pattern.

[0056] In step S16, the optical measurement device 10 irradiates the living body 20 with the second laser light during the second imaging period.

[0057] In step S18, the optical measurement device 10 detects a second signal. In this specification, the second signal corresponds to a detection signal of the second laser light and a second speckle pattern.

[0058] In step S20, the optical measurement device 10 emits ultrasonic waves at a predetermined timing to the living body 20. The predetermined timing is the timing at which the ultrasonic waves reach the measurement position of the living body 20 at the timing at which the third laser light is irradiated in step S22.

[0059] In step S22, the optical measurement device 10 irradiates the living body 20 with the third laser light during the third imaging period.

[0060] In step S24, the optical measurement device 10 detects a third signal. In this specification, the third signal corresponds to a detection signal of the third laser light and a third speckle pattern.

[0061] In step S26, the optical measurement device 10 calculates the first signal component based on the first signal detected in step S14 and the second signal detected in step S18.

[0062] In step S28, the optical measurement device 10 calculates the second signal component based on the second signal detected in step S18 and the third signal detected in step S24.

[0063] In step S30, the optical measurement device 10 calculates the signal component modulated by the ultrasonic wave based on the first signal component calculated in step S26 and the second signal component calculated in step S28. Thereafter, the optical measurement device 10 ends the analysis processing subroutine and returns the processing to the main routine.

[0064] 5, ultrasonic waves are emitted before the irradiation of the third laser beam, but ultrasonic waves may be emitted before the irradiation of the first laser beam, i.e., before step S10. In this case, the first signal includes a modulated signal component.

[0065] In the above-described analysis process, the three detection signals are acquired during an imaging period set at equal time intervals. Therefore, the difference between the first detected signal and the second detected signal is due to noise occurring during that time interval. Therefore, the noise contained in the difference between the second detected signal and the third detected signal, which includes a modulated signal component, can be considered to be of the same level as the noise contained in the difference. In other words, by performing the above-described analysis process, the accuracy of noise extraction can be improved, and by using that noise, the accuracy of measuring the modulated signal component can be improved.

[0066] However, if the imaging interval is too long, the state of the living body may fluctuate significantly, causing the speckle pattern to change significantly during the imaging interval, making it extremely difficult to analyze the modulated signal component. Therefore, it is preferable to set the imaging interval to 200 ms or less.

[0067] Furthermore, although it is preferable that the first, second, and third shooting periods have the same time length, they do not necessarily have to be the same time length. For example, the lengths of the shooting periods do not have to be equal as long as they are not extremely different, such as when the shortest shooting period is 90% or less of the longest shooting period.

[0068] When the length of each shooting period is equal, it is preferable that the timing of irradiating the laser light in each shooting period is the same (for example, the laser light is irradiated after a predetermined time has elapsed since the start of the shooting period), but the timing of irradiation of each laser light is not limited as long as it is irradiated within the corresponding shooting period.

[0069] (Modification) The optical measurement device 10 may extract modulated signal components based on first to fourth speckle patterns obtained from the laser light irradiated in the first to fourth imaging periods. Among the first to fourth imaging periods, the interval between the start point of the first imaging period and the start point of the second imaging period is defined as the first imaging interval, and the interval between the start point of the third imaging period and the start point of the fourth imaging period is defined as the second imaging interval. The first imaging interval and the second imaging interval are set to be equal. If this condition is satisfied, imaging can be performed without limiting the interval between the second imaging period and the third imaging period.

[0070] The period during which the optical measurement device 10 in the modified example takes an image, the timing of irradiating the laser light, the timing of irradiating the ultrasonic wave, and the detection signal obtained as a result will be described. Fig. 6 is a timing chart showing the period during which the camera 3 of the optical measurement device 10 takes an image, the timing of turning on the pulse laser, and the timing of irradiating the ultrasonic wave according to the embodiment.

[0071] The user sets the period during which the speckle pattern is captured by the camera 3. During the capturing period, the camera 3 captures the speckle pattern with the image sensor 3 a in an exposed state. Therefore, the detection signal is a superposition of speckle patterns formed by the laser light received during the capturing period.

[0072] Four imaging periods are set. In Fig. 6, these correspond to the first imaging period, the second imaging period, the third imaging period, and the fourth imaging period. After each imaging period ends, the captured signals are read out, and a first speckle pattern, a second speckle pattern, a third speckle pattern, and a fourth speckle pattern are acquired.

[0073] The shooting periods are set so that the intervals between the shooting periods are equal. That is, as shown in Fig. 6, the first shooting interval, which is the interval between the start of the first shooting period and the start of the second shooting period, is set so that the second shooting interval, which is the interval between the start of the third shooting period and the start of the fourth shooting period, is equal. The shooting interval is, for example, 100 ms.

[0074] 6, the first laser light is emitted during the first imaging period, the second laser light is emitted during the second imaging period, the third laser light is emitted during the third imaging period, and the fourth laser light is emitted during the fourth imaging period. Furthermore, the ultrasonic waves are oscillated so that the ultrasonic waves reach the measurement position at the timing when the fourth laser light is emitted.

[0075] Both the first speckle pattern and the second speckle pattern were acquired under conditions in which ultrasonic waves were not emitted. That is, the speckle pattern acquisition conditions were the same except for the different imaging periods. Therefore, the difference between the second speckle pattern and the first speckle pattern corresponds to noise components resulting from the difference in imaging periods.

[0076] The third speckle pattern and the fourth speckle pattern were acquired under the same conditions, except for whether or not ultrasound was irradiated and the acquisition period. Therefore, the difference between the fourth speckle pattern and the third speckle pattern corresponds to the sum of noise components and modulated signal components resulting from the difference in acquisition period.

[0077] Here, since the first photographing interval and the second photographing interval are set to be equal, the noise component contained in the difference between the fourth speckle pattern and the third speckle pattern is approximately equal to the difference between the second speckle pattern and the first speckle pattern.

[0078] Therefore, the modulated signal component can be extracted by subtracting the noise component calculated based on the first speckle pattern and the second speckle pattern from the sum of the noise component and the modulated signal component calculated based on the third speckle pattern and the fourth speckle pattern.

[0079] [Flow of analysis processing of modulated signal components according to a modified example] Fig. 7 is a diagram showing a flowchart of an example of analysis processing performed to extract modulated signal components from a speckle pattern obtained by measurement by the optical measurement device 10. In one implementation example, the analysis processing subroutine in Fig. 7 is called from the main routine and executed when the processor of the analysis device 5 executes a given program. Note that in Fig. 7, the same components as those in the flowchart described in Fig. 5 are assigned the same reference numerals, and detailed description thereof will not be repeated.

[0080] In step S32, the optical measurement device 10 receives from the user information on the first, second, third, and fourth imaging periods, which are periods during which laser light is received by the camera 3. The interval between the first and second imaging periods and the interval between the third and fourth imaging periods are set to be equal.

[0081] In step S34, the optical measurement device 10 irradiates the living body 20 with the fourth laser light during the fourth imaging period.

[0082] In step S36, the optical measurement device 10 detects a fourth signal. In this specification, the fourth signal corresponds to a detection signal of the fourth laser light and a fourth speckle pattern.

[0083] In step S38, the optical measurement device 10 calculates the second signal component based on the third signal detected in step S18 and the fourth signal detected in step S36.

[0084] 7, ultrasonic waves are emitted before the irradiation of the fourth laser beam, but ultrasonic waves may be emitted before the irradiation of the third laser beam, i.e., before step S22. In this case, the third signal includes a modulated signal component.

[0085] In the modified example, the time interval between the second and third imaging periods is not limited. Therefore, for example, when there are multiple measurement positions, using the method shown in the modified example can reduce the total number of speckle patterns to be acquired compared to the method using three speckle patterns shown in the example. For example, assume a case where signals are measured at three different measurement positions. The processing method described in the embodiment requires three speckle patterns at each measurement position to acquire the modulated signal component, for a total of nine speckle patterns. On the other hand, in the modified example, two speckle patterns are acquired to calculate the noise signal, and two speckle patterns are acquired at each measurement position, for a total of eight speckle patterns. In this way, using the method shown in the modified example can reduce the number of speckle patterns used and the amount of calculation.

[0086] Aspects It will be understood by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0087] (Item 1) An optical measurement device according to one aspect includes a light source that irradiates a light scattering medium with pulsed laser light, an ultrasound source that oscillates ultrasound at a measurement position at a predetermined depth within the light scattering medium, a detector that detects the laser light that has passed through a region within the light scattering medium that includes the measurement position, a control device that controls the irradiation of the laser light and the oscillation of the ultrasound, and an analysis device that extracts a modulated signal component modulated by the ultrasound from the laser light detected by the detector, wherein the control device sets the first imaging period, the second imaging period, and the third imaging period so that an interval between a first imaging period and a second imaging period and an interval between the second imaging period and a third imaging period are equal, and The analysis device may detect a signal of the laser light that has passed through a region within the light scattering body during the third imaging period, irradiate a first laser light from the light source during the first imaging period, a second laser light during the second imaging period, and a third laser light during the third imaging period, and oscillate the ultrasound from the ultrasound source at the timing of irradiating the third laser light so that the ultrasound reaches the measurement position, and the analysis device may extract a first signal component using the signals of the first laser light and the second laser light that have passed through the region within the light scattering body, extract a second signal component using the signals of the second laser light and the third laser light that have passed through the region within the light scattering body, and extract the modulated signal component from the first signal component and the second signal component.

[0088] According to the optical measurement device described in paragraph 1, it is possible to improve the accuracy of extracting the optical component modulated by the ultrasonic wave from the detection signal acquired by the optical measurement device using ultrasonic modulated optical tomography.

[0089] (Item 2) In the optical measurement device described in item 1, the ultrasonic wave source may emit the ultrasonic waves so that the ultrasonic waves are focused at the measurement position.

[0090] According to the optical measurement device described in paragraph 2, it is possible to extract the modulated light component at the measurement position, and it is possible to improve the spatial resolution in optical measurement.

[0091] (Clause 3) In the optical measurement device described in clause 1 or 2, the first laser light, the second laser light, and the third laser light may be configured by a plurality of pulsed laser lights.

[0092] According to the optical measurement device described in the third aspect, the intensity of the detection signal can be increased, and the precision with which the modulated signal component is extracted can be improved.

[0093] (4) In the optical measurement device described in any one of paragraphs 1 to 3, the ultrasonic wave source may be capable of emitting the ultrasonic waves in pulse form.

[0094] According to the optical measurement device described in paragraph 4, the length of the ultrasonic wave in the propagation direction can be shortened and the area where the ultrasonic wave exists can be limited to the measurement position, thereby improving the spatial resolution in optical measurement.

[0095] (Item 5) In the optical measurement device described in any one of items 1 to 4, the interval may be 200 ms or less.

[0096] According to the optical measurement device described in paragraph 5, noise occurring within 200 ms or less can be removed from the detection signal acquired by the optical measurement device using ultrasonic modulated optical tomography, thereby improving the accuracy of extracting the optical component modulated by ultrasonic waves.

[0097] (Item 6) In the optical measurement device described in any one of Items 1 to 5, the first photographing period, the second photographing period, and the third photographing period may have the same time length.

[0098] (Clause 7) An optical measurement device according to one aspect includes a light source that irradiates a light scattering medium with pulsed laser light, an ultrasonic source that oscillates ultrasonic waves at a measurement position at a predetermined depth within the light scattering medium, a detector that detects the laser light that has passed through a region within the light scattering medium that includes the measurement position, a control device that controls the irradiation of the laser light and the oscillation of the ultrasonic waves, and an analysis device that extracts a modulated signal component modulated by the ultrasonic waves from the laser light detected by the detector, wherein the control device sets the first imaging period, the second imaging period, the third imaging period, and the fourth imaging period so that an interval between a first imaging period and a second imaging period is equal to an interval between a third imaging period and a fourth imaging period, and The signal of the laser light that has passed through a region within the light scattering body during four photographing periods is detected, a first laser light is irradiated from the light source during the first photographing period, a second laser light is irradiated during the second photographing period, a third laser light is irradiated during the third photographing period, and a fourth laser light is irradiated during the fourth photographing period, and ultrasonic waves are oscillated from the ultrasonic source at the timing of irradiating the third laser light so that the ultrasonic waves reach the measurement position, and the analysis device may extract a first signal component using the signal of the first laser light and the signal of the second laser light that have passed through the region within the light scattering body, extract a second signal component using the signal of the third laser light and the signal of the fourth laser light that have passed through the region within the light scattering body, and extract the modulated signal component from the first signal component and the second signal component.

[0099] According to the optical measurement device described in paragraph 7, it is possible to improve the accuracy of extracting optical components modulated by ultrasonic waves from detection signals acquired by an optical measurement device using ultrasonic modulated optical tomography. Furthermore, measurement can be performed without being limited by the interval between the second and third imaging periods. Therefore, the user can flexibly set the imaging timing. Furthermore, when measuring multiple measurement positions, the amount of calculation can be reduced.

[0100] (Item 8) An analysis method according to one aspect is a method for analyzing modulated signal components generated when laser light irradiated into a light scattering body is modulated by ultrasound at a measurement position at a predetermined depth, and may include the steps of: acquiring a detection signal of first laser light that has passed through a region within the light scattering body, acquired during a first imaging period; acquiring a detection signal of second laser light that has passed through a region within the light scattering body, acquired during a second imaging period that is provided at a predetermined interval from the first imaging period; acquiring a detection signal of third laser light that has been irradiated when the ultrasound reaches the measurement position and has passed through a region within the light scattering body, acquired during a third imaging period that is provided at the predetermined interval from the second imaging period; extracting a first signal component using the detection signal of the first laser light and the detection signal of the second laser light; extracting a second signal component using the detection signal of the second laser light and the detection signal of the third laser light; and extracting the modulated signal component from the first signal component and the second signal component.

[0101] According to the analysis method described in Section 8, it is possible to improve the accuracy of extracting the optical component modulated by ultrasonic waves from the detection signal acquired by the optical measurement device using ultrasonic modulated optical tomography.

[0102] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present disclosure is defined by the claims, not by the description of the above-described embodiments, and is intended to include all modifications within the meaning and scope of the claims. Furthermore, it is intended that each technique in the embodiments can be implemented alone or, if necessary, in combination with other techniques in the embodiments to the extent possible.

[0103] 1 Laser source, 2 Ultrasound source, 2a Focuser, 3 Camera, 3a Image sensor, 3b Lens, 4 Control device, 5 Analysis device, 10 Optical measurement device, 20 Living body.

Claims

1. A light source that irradiates pulsed laser light into a light scattering body, An ultrasonic source that emits ultrasonic waves at a measurement position at a predetermined depth within the light scattering body, A detector for detecting the laser light that has passed through the region within the light scatterer including the measurement position, A control device that controls the irradiation of the laser light and the oscillation of the ultrasonic waves, The system includes an analysis device that extracts a modulated signal component modulated by the ultrasound from the laser light detected by the detector, The control device is The first, second, and third shooting periods are set such that the interval between the first and second shooting periods is equal to the interval between the second and third shooting periods. The detector is made to detect the signal of the laser light that has passed through the region within the light scatterer during the first imaging period, the second imaging period, and the third imaging period. The first laser beam is emitted from the light source during the first imaging period, the second laser beam during the second imaging period, and the third laser beam during the third imaging period. The ultrasonic source is made to emit ultrasonic waves such that the ultrasonic waves reach the measurement position at the timing of irradiation of the third laser beam. The aforementioned analysis device is A first signal component is extracted using the signals of the first laser beam and the second laser beam that have passed through the region within the light scatterer. The second signal component is extracted using the signals of the second laser beam and the third laser beam that have passed through the region within the light scatterer. An optical measuring device for extracting the modulated signal component from the first signal component and the second signal component.

2. The optical measuring device according to claim 1, wherein the ultrasonic source emits ultrasonic waves such that the ultrasonic waves are focused at the measurement position.

3. The optical measuring device according to claim 1, wherein the first laser beam, the second laser beam, and the third laser beam include a plurality of pulsed laser beams.

4. The optical measuring device according to claim 1, wherein the ultrasonic source is capable of emitting pulsed ultrasonic waves.

5. The optical measuring device according to claim 1, wherein the interval is 200 ms or less.

6. The optical measuring device according to claim 1, wherein the temporal lengths of the first imaging period, the second imaging period, and the third imaging period are equal.

7. A light source that irradiates pulsed laser light into a light scattering body, An ultrasonic source that emits ultrasonic waves at a measurement position at a predetermined depth within the light scattering body, A detector for detecting the laser light that has passed through the region within the light scatterer including the measurement position, A control device that controls the irradiation of the laser light and the oscillation of the ultrasonic waves, The system includes an analysis device that extracts a modulated signal component modulated by the ultrasound from the laser light detected by the detector, The control device is The first, second, third, and fourth shooting periods are set such that the interval between the first and second shooting periods is equal to the interval between the third and fourth shooting periods. The detector is made to detect the signal of the laser light that has passed through the region within the light scattering body during the first imaging period, the second imaging period, the third imaging period, and the fourth imaging period. The first laser beam is emitted from the light source during the first imaging period, the second laser beam during the second imaging period, the third laser beam during the third imaging period, and the fourth laser beam during the fourth imaging period. The ultrasonic source is made to emit ultrasonic waves such that the ultrasonic waves reach the measurement position at the timing of irradiation of the third laser beam. The aforementioned analysis device is A first signal component is extracted using the signals of the first laser beam and the second laser beam that have passed through the region within the light scatterer. The second signal component is extracted using the signals of the third laser beam and the fourth laser beam that have passed through the region within the light scatterer. An optical measuring device for extracting the modulated signal component from the first signal component and the second signal component.

8. A method for analyzing modulated signal components generated when laser light irradiated into a light scatterer is modulated by ultrasound at a measurement position at a predetermined depth, A step of acquiring the detection signal of the first laser light that passed through the region within the light scatterer, which was acquired during the first imaging period, The steps include acquiring a detection signal of the second laser light that has passed through the region within the light scatterer, which is acquired during a second imaging period set at a predetermined interval from the first imaging period, The steps include acquiring a detection signal of a third laser beam that was irradiated when the ultrasonic waves reached the measurement position and passed through a region within the light scatterer, which was acquired during a third imaging period set at a predetermined interval from the second imaging period, A step of extracting a first signal component using the detection signal of the first laser beam and the detection signal of the second laser beam, A step of extracting a second signal component using the detection signal of the second laser beam and the detection signal of the third laser beam, An analysis method comprising the step of extracting the modulated signal component from the first signal component and the second signal component.