Optical measuring device and analysis method

Abstract

This optical measuring device comprises a light source, an ultrasound wave source, a detector, a control device, and an analysis device. The control device acquires a first speckle image and a second speckle image on the basis of outputs of a detector acquired in a first imaging period and a second imaging period, causes laser light to be emitted in the first imaging period and the second imaging period, and causes oscillation of ultrasound waves from the ultrasound wave source such that the ultrasound waves reach a measuring position. The analysis device calculates a first variation component indicating an amount of variation of speckle in a first region and a second variation component indicating an amount of variation of speckle in a second region between the first speckle image and the second speckle image, and extracts a modulated signal component from the first variation component and the second variation component.

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), optical measurement devices using ultrasound-modulated optical tomography (UOT) have 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. In Patent Document 1 and Non-Patent Document 3, the influence of noise in the speckle pattern obtained when ultrasound is focused at the measurement position is reduced based on a speckle pattern obtained without oscillating 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 difference between a speckle pattern obtained when ultrasonic waves are focused at the measurement position and a speckle pattern obtained without emitting ultrasonic waves is extracted as a signal component modulated by ultrasonic waves. However, since these speckle patterns are obtained at different times, measurement conditions change in addition to the presence or absence of ultrasonic waves. Therefore, the modulated signal component obtained by the above method may contain noise due to changes in measurement conditions, and it may be difficult to remove the effects of this noise from the detected signal.

[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 waves 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 timing of the irradiation of the laser light and the start and end of the oscillation of the ultrasound waves. The analysis device extracts a modulated signal component modulated by the ultrasound waves from the output of the detector. The control device acquires a first speckle image based on the output of the detector acquired during a first imaging period and a second speckle image based on the output of the detector acquired during a second imaging period, irradiates the laser light during the first imaging period and the second imaging period, and emits ultrasound waves from the ultrasound source so that the ultrasound waves reach the measurement position within the second imaging period. The analysis device calculates a first fluctuation component indicating the amount of fluctuation in the speckle in a first region and a second fluctuation component indicating the amount of fluctuation in the speckle in a second region different from the first region in the first speckle image and the second speckle image, and extracts a modulated signal component from the first fluctuation component and the second fluctuation component.

[0010] An analysis method according to a second aspect of the present disclosure is a method for analyzing a modulated signal component generated when laser light irradiated into a light scattering medium is modulated by ultrasound at a measurement position at a predetermined depth. A first speckle image is generated based on a detector output obtained by the detector detecting, during a first imaging period, the laser light that has passed through a region within the light scattering medium. A second speckle image is generated based on a detector output obtained by the detector detecting, during a second imaging period, the laser light that has passed through a region within the light scattering medium when ultrasound reaches the measurement position. The analysis method includes the steps of (a) acquiring the first speckle image and the second speckle image, (b) calculating, in the first speckle image and the second speckle image, a first fluctuation component indicating a fluctuation amount of speckles in the first region and a second fluctuation component indicating a fluctuation amount of speckles in a second region different from the first region, and (c) extracting a modulated signal component from the first fluctuation component and the second fluctuation component.

[0011] According to the optical measurement device 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.

[0012] 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 pulsed 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 the distribution of signal / background ratio in a speckle pattern; Fig. 4 is a diagram for explaining a method of extracting a signal component based on the signal / background ratio in a speckle pattern; Fig. 5 is a flowchart showing an analysis process of a modulated signal component according to an embodiment; Fig. 6 is a diagram for explaining a method of predicting the distribution of signal / background ratio.

[0013] 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.

[0014] [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 information 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 inside the observation object, and extracts signal components of the modulated light included in the speckle pattern using the analysis device 5. The speckle pattern in the embodiment corresponds to the image and laser light detection signal in the present disclosure.

[0015] 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.

[0016] 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.

[0017] 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.

[0018] The ultrasound source 2 is an ultrasound generator that emits ultrasound waves at a measurement position at a predetermined depth within the living organism 20. The ultrasound source 2 is provided with a concentrator 2a for focusing the emitted ultrasound waves at the measurement position within the living organism 20. The ultrasound waves are focused at a position where the ultrasound waves emitted from the multiple ultrasound transducers of the ultrasound source 2 are focused. 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 organism 20.

[0019] The ultrasound emitted from the ultrasound source 2 may be continuous or pulsed. However, by using pulsed ultrasound as the ultrasound source 2, the length of the ultrasound in the propagation direction can be shortened, and the area where the ultrasound exists can be limited 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. Note that the distance to the measurement position is sufficiently short compared to the distance light travels per unit time, so the laser light reaches the measurement position approximately simultaneously with the irradiation of the pulsed laser light from the laser source 1. Therefore, the timing at which the laser source 1 emits the laser light and the timing at which the laser light reaches the measurement position can be considered to be approximately the same.

[0020] 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.

[0021] 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 where ultrasound is being emitted with pulsed laser light, and captures an image of the speckle pattern with the exposed image sensor 3a.

[0022] 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.

[0023] The light detected by camera 3 is a combination of laser light (signal) that has passed through the area where ultrasound is present and has been modulated by the ultrasound, and laser light (background) that has not passed through the area where ultrasound is present and has not been modulated by the ultrasound.

[0024] 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 wave source 2. The laser light is pulsed, and therefore 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 below.

[0025] 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.

[0026] [Comparative Example] Many optical techniques have been developed as minimally invasive methods for measuring tissues in living bodies. However, since light is multiple-scattered by living tissues, it can be difficult to measure deep tissues with high spatial resolution.

[0027] Therefore, an optical measurement technology using UOT has been developed that improves the spatial resolution of optical measurement by focusing ultrasonic waves, which are hardly scattered by biological tissue, into a specified area and measuring the modulated light due to the interaction between the ultrasonic waves and light.

[0028] An image of a speckle pattern is acquired by optical measurement using the UOT. To extract modulated signal components from the speckle pattern, which is the detection signal obtained by optical measurement, an analysis method is used that is based on the difference between an image obtained when ultrasonic waves are emitted and an image obtained when ultrasonic waves are not emitted.

[0029] However, the timing at which the image obtained without ultrasonic oscillation is captured is different from the timing at which the image obtained with ultrasonic oscillation is captured. Therefore, noise may occur due to changes in measurement conditions (e.g., body movement, changes in the state of internal tissues due to biological activity, and changes in laser mode) that occur between the time the two images are captured. This noise is difficult to remove simply by taking the difference between the two images, as in the above-mentioned analysis method.

[0030] [Optical measurement method according to the embodiment] Therefore, in the optical measurement device according to the present embodiment, the optical measurement device 10 extracts a first component and a second component that is more influenced by the laser light modulated by ultrasonic waves than the first component, based on the signal / background (SB) ratio from the difference between two images. Then, the second component is normalized by the first component to extract the modulated signal component.

[0031] In optical measurement, the difference between images acquired over two different time periods contains noise due to the difference in the timing at which the images were acquired. When a first component is extracted from a region with a relatively low SB ratio in the difference between the two images, the first component can be considered to correspond to the amount of fluctuation in the two images caused by noise. Furthermore, when a second component is extracted from a region with a relatively high SB ratio in the difference between the two images, the second component can be considered to correspond to the sum of the amount of fluctuation in the two images caused by ultrasonic modulation and the amount of fluctuation in the two images caused by noise. Because the noise affects each pixel of the two images approximately equally, the first and second components are equally affected by the noise. Therefore, by excluding the first component from the second component, the amount of fluctuation in the two images caused by ultrasonic modulation can be extracted. In other words, by using the optical measurement device according to this embodiment, the accuracy of extracting the modulation signal component from the results of measuring laser light can be improved.

[0032] First, the timing of photographing by the optical measurement device 10, the timing of irradiating the laser light, the timing of irradiating the ultrasonic wave, and the detection signals acquired as a result will be described. Fig. 2 is a timing chart showing the timing of photographing by the camera 3 of the optical measurement device 10 according to the embodiment, the timing of turning on the pulse laser, and the timing of emitting the ultrasonic wave.

[0033] <1. Setting the Capture Period> First, the user sets the capture 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 obtained image is an image in which the speckle patterns formed by the laser light received during the capture period are superimposed.

[0034] 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.

[0035] Two imaging periods are set. In Fig. 2, these correspond to a first imaging period and a second imaging period. After the end of each imaging period, the captured signals are read out, and a first speckle pattern and a second speckle pattern are acquired.

[0036] 2. Setting the Laser Irradiation Timing The user sets the timing for emitting the first laser light and the timing for emitting the second laser light from the laser source 1. As shown in FIG. 2 , the first laser light is radiated during the first imaging period, and the second laser light is radiated during the second imaging period. Because the laser light has a pulse width, the timing for radiating the laser light 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 for radiating the laser light. Furthermore, because the laser light radiated by the laser source 1 is pulsed, there is a period during which the laser light is radiated, and this period (the period during which the laser drive signal is ON) is called the laser light irradiation time.

[0037] 3. Setting the Ultrasound Oscillation Timing Next, the user sets the timing for emitting ultrasound from the ultrasound source 2. Specifically, ultrasound is emitted from the ultrasound source 2 so that the ultrasound reaches the measurement position at the timing when the second laser light passes through the living body 20. The control device 4 transmits an ultrasound drive signal to the ultrasound source 2 at the timing for emitting ultrasound. As shown in FIG. 2 , this oscillation timing is the timing at which the ultrasound source 2 emits pulsed ultrasound before the ultrasound delay time from the irradiation timing of the second laser light.

[0038] The ultrasonic delay time can be calculated from the distance (depth) from the ultrasonic source 2 to the measurement position. Furthermore, since the ultrasonic waves emitted from 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. Furthermore, since the distance to the measurement position is sufficiently short compared to the distance traveled by light per unit time, it can be assumed that the timing at which the laser light is irradiated 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 propagate through the living body 20 by the ultrasonic delay time corresponds to the depth of the measurement position in the living body 20.

[0039] 4. Acquired Image 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, and the speckle pattern resulting from the second laser light corresponds to the second speckle pattern. In this specification, the speckle pattern corresponds to the signal and image of the laser light.

[0040] 5. Calculation of S / B Ratio Distribution The first speckle pattern is acquired under conditions where ultrasonic waves are not emitted. On the other hand, the second speckle pattern is acquired under conditions where ultrasonic waves are focused at the measurement position. That is, the first speckle pattern and the second speckle pattern are acquired under the same acquisition conditions except for whether ultrasonic waves are irradiated or not and the acquisition periods. Therefore, the difference between the first speckle pattern and the second speckle pattern corresponds to the sum of noise components and modulated signal components caused by the difference in the acquisition periods. Specifically, for example, the value obtained by subtracting the pixel value of each pixel of the first speckle pattern from the pixel value of each pixel of the corresponding second speckle pattern corresponds to the sum of noise components and modulated signal components generated during the acquisition interval. In this case, the difference between the first speckle pattern and the second speckle pattern is calculated as an image.

[0041] Generally, the fluctuation of the speckle pattern due to modulation by ultrasonic waves is often larger than the fluctuation of the speckle pattern due to noise. Therefore, a pixel having a large difference in pixel value between the first speckle pattern and the second speckle pattern is determined to be a pixel that is highly likely to be modulated by ultrasonic waves.

[0042] Fig. 3 is a diagram showing an example of the distribution of the SB ratio in a speckle pattern. In Fig. 3, regions with low pixel values ​​(dark regions) indicate regions with low SB ratios, and regions with high pixel values ​​(light regions) indicate regions with high SB ratios. In Fig. 3, regions with high pixel values ​​are regions in the speckle pattern that are susceptible to the influence of ultrasound. For example, region R1 has a low SB ratio, and region R2 has a high SB ratio.

[0043] The diagram shown in FIG. 3 is calculated, for example, by subtracting the pixel value of each pixel of the first speckle pattern from the pixel value of each pixel of the corresponding second speckle pattern.

[0044] The method for analyzing the degree of change in state between two speckle patterns is not limited to the above-described method of integrating the absolute value of the difference between pixel values ​​of corresponding pixels. For example, various general analytical methods for calculating image similarity, a method of integrating the square of the difference between pixel values ​​of corresponding pixels, and a method using normalized cross-correlation can be applied to analyze the degree of change in state between two speckle patterns. Furthermore, necessary preprocessing may be performed on the two speckle patterns to be analyzed before calculating the similarity. For example, a predetermined target region may be defined for the two speckle patterns, the speckle pattern contrast in each target region may be calculated, and the converted speckle pattern contrast image may be used by mapping the calculated contrast image.

[0045] <6. Extraction of Two Types of Signal Components> Based on the SB ratio distribution, a first component and a second component containing a larger amount of modulated signal components than the first component are extracted from the first speckle pattern and the second speckle pattern. Specifically, the optical measurement device 10 first acquires an image showing the fluctuations of the two speckle patterns by subtracting the pixel value of each pixel in the first speckle pattern from the pixel value of each corresponding pixel in the second speckle pattern. Next, based on the SB ratio distribution, the optical measurement device 10 determines regions in the image consisting of pixels with relatively low SB ratios and regions consisting of pixels with relatively high SB ratios. The optical measurement device 10 then extracts the first component from the region consisting of pixels with relatively low SB ratios and the second component from the region consisting of pixels with relatively high SB ratios. The first and second components are, for example, the sum, average, and median of the pixel values ​​of the pixels in each region.

[0046] 7. Extraction of Modulated Signal Component The modulated signal component is calculated by subtracting the first component from the second component, dividing the second component by the first component, or normalizing the second component by the first component using other processing methods.

[0047] In the above-described embodiment, the first and second components are extracted from two clearly separated regions, but the present invention is not limited to this, and the modulation signal component may be extracted by multiplying the values ​​calculated for each pixel of the changes in pixel values ​​in the two speckle patterns using the SB ratio as a coefficient. For example, the modulation signal component may be obtained by using the results of an analysis performed by weighting the coefficient in a region with a low SB ratio and the results of an analysis performed by weighting the coefficient in a region with a high SB ratio.

[0048] In the above-described embodiment, the images used to calculate the SB ratio distribution and the images used to extract the first and second components were the same, but different images may be used. That is, the SB ratio distribution may be calculated using an image acquired without oscillating ultrasound and an image acquired with ultrasound focused at a predetermined measurement position, and then the first and second components may be extracted from the different images using the SB ratio distribution. The SB ratio distribution calculated at a predetermined measurement position is the same at that measurement position, and can be applied to images that were not used to calculate the SB ratio.

[0049] 4 shows a different speckle pattern measured at the same measurement position as the second speckle pattern. In this case, the SB ratio distribution calculated in FIG. 3 can also be applied. That is, the SB ratio is low in region R1 and high in region R2.

[0050] [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 two speckle patterns 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.

[0051] In step S10, the optical measurement device 10 receives information on the first and second photographing periods, which are periods during which the camera 3 receives laser light, from the user.

[0052] In step S12, the optical measurement device 10 irradiates the living body 20 with the first laser light during the first imaging period.

[0053] In step S14, the optical measurement device 10 detects a first speckle pattern. In step S16, the optical measurement device 10 oscillates ultrasonic waves to the living body 20 at a predetermined timing. The predetermined timing is the timing at which the ultrasonic waves reach the measurement position of the living body 20 when the second laser light irradiated in step S18 passes through the living body 20.

[0054] In step S18, the optical measurement device 10 irradiates the living body 20 with the second laser light during the second imaging period.

[0055] In step S20, the optical measurement device 10 detects a second speckle pattern. In step S22, the optical measurement device 10 calculates the distribution of the SB ratio at the measurement position of the second speckle pattern based on the first speckle pattern and the second speckle pattern.

[0056] In step S24, the optical measurement device 10 calculates the difference between the pixel values ​​of each pixel of the first speckle pattern and the second speckle pattern, and generates an image showing the fluctuations of the two speckle patterns.

[0057] In step S26, the optical measurement device 10 extracts the first component from the region with a low SB ratio and the second component from the region with a high SB ratio in the image showing the fluctuations of the two speckle patterns generated in step S24 based on the distribution of the SB ratio calculated in step S22.

[0058] In step S28, the optical measurement device 10 calculates the modulated signal component based on the first component and the second component. Thereafter, the optical measurement device 10 ends the analysis processing subroutine and returns the processing to the main routine.

[0059] 5, the optical measurement device 10 irradiates the ultrasonic wave before irradiating the second laser light, but the ultrasonic wave may be irradiated before irradiating the first laser light, i.e., before step S12. In this case, the first speckle pattern contains a modulated signal component.

[0060] In the above-described analysis process, the first component and the second component including the modulated signal component are extracted from the fluctuation amounts of the two speckle patterns, and therefore both components are equally affected by noise. Therefore, by normalizing the second component based on the first component, the accuracy of extracting the optical component modulated by the ultrasound can be improved.

[0061] (Modification) In the above-described embodiment, the distribution of the SB ratio is calculated from an actually measured image, but the optical measurement device 10 may predict the distribution of the SB ratio by simulation and determine the areas with high SB ratio and areas with low SB ratio in the difference of the speckle pattern.

[0062] Fig. 6 shows the results of an optical simulation of scattering and absorption of laser light incident from the laser source 1 inside head tissue. Fig. 6 is an image that schematically shows a cross section inside head tissue.

[0063] As shown in Figure 6, the user sets the internal structure of the head tissue. The head tissue consists of the scalp, skull, cerebrospinal fluid, gray matter, and white matter. The scattering and absorption of laser light incident on each tissue region are determined by the scattering coefficient and absorption coefficient of the tissue. The thickness of each tissue is measured using magnetic resonance images.

[0064] The user decides which region of the head tissue to measure. This region is the region where the ultrasound waves are focused and corresponds to the measurement position. The region where the ultrasound waves are focused is assumed to be a cylinder with a diameter of 10 mm and a height of 10 mm. The region where the ultrasound waves are focused corresponds to the resolution of the measurement.

[0065] 6 shows the predicted path of laser light emitted from laser source 1. After entering the head, the laser light emitted from laser source 1 is scattered and absorbed by each tissue, and some of the laser light passes through the region where the ultrasound is focused and is captured by camera 3. Some of the laser light emitted from laser source 1 does not pass through the region where the ultrasound is focused and is captured by camera 3. The remaining laser light is not captured by camera 3.

[0066] The speckle pattern obtained by the camera 3 can be predicted from the predicted path of the laser light. The distribution of the SB ratio can be predicted from the difference between the speckle pattern predicted to be obtained when ultrasonic waves are focused on the measurement position and the speckle pattern predicted to be obtained when there is no ultrasonic wave.

[0067] For example, the first speckle pattern and the second speckle pattern in the above-described embodiment can be acquired, and the first component and the second component can be extracted based on the distribution of the SB ratio predicted by simulation.

[0068] By predicting the distribution of the SB ratio through simulation, the first and second components of the obtained speckle pattern can be extracted without analyzing the distribution of the SB ratio based on actual measurements.

[0069] According to the optical measurement device described above, a first component and a second component including a modulated signal component are extracted from the fluctuation amounts of two speckle patterns acquired at different times. These components are equally affected by noise. Therefore, by normalizing the second component based on the first component, the accuracy of extracting the optical component modulated by ultrasound can be improved.

[0070] Furthermore, as shown as a modified example, the distribution of the SB ratio can be determined independently of the measurement data by calculating the distribution of the SB ratio through simulation, which makes it possible to determine the distribution of the SB ratio without being influenced by fluctuations in the two speckle patterns that are caused by the influence of noise, for example.

[0071] Aspects It will be understood by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0072] (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 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 timing of the irradiation of the laser light and the start and end of the oscillation of the ultrasonic waves, and an analysis device that extracts a modulated signal component modulated by the ultrasonic waves from an output of the detector, and the control device acquires a first speckle image based on the output of the detector acquired in a first imaging period, and The analyzer may acquire a second speckle image based on the acquired output of the detector, irradiate the laser light during the first shooting period and the second shooting period, and generate the ultrasonic waves from the ultrasonic source during the second shooting period so that the ultrasonic waves reach the measurement position, and calculate, in the first speckle image and the second speckle image, a first fluctuation component indicating the amount of fluctuation in the speckles in a first region and a second fluctuation component indicating the amount of fluctuation in the speckles in a second region different from the first region, and extract the modulated signal component from the first fluctuation component and the second fluctuation component.

[0073] 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.

[0074] (Clause 2) In the optical measurement device described in paragraph 1, the analysis device may determine the first region and the second region based on the output of the detector obtained when the ultrasonic waves reach the measurement position when the laser light passes through the light scattering body, and the output of the detector obtained when the ultrasonic waves do not reach the measurement position when the laser light passes through the light scattering body.

[0075] According to the optical measurement device described in paragraph 2, the distribution of the SB ratio is calculated based on the actual measurement values, and the region from which the first component and the second component are extracted is determined based on the distribution of the SB ratio.

[0076] (Clause 3) In the optical measurement device described in clause 1, the analysis device may determine regions from which the first region and the second region are extracted based on a simulation model of the inside of the light scattering medium.

[0077] According to the optical measurement device described in paragraph 3, the distribution of the SB ratio is calculated based on a simulation, and the region from which the first component and the second component are extracted is determined based on the distribution of the SB ratio.

[0078] (4) In the optical measurement device described in any one of the preceding paragraphs 1 to 3, the ultrasonic source may focus the ultrasonic waves at the measurement position by aligning the focus of the ultrasonic waves generated from a plurality of ultrasonic vibration sources at the measurement position.

[0079] According to the optical measurement device described in item 4, it is possible to extract the light component modulated at the measurement position, and it is possible to improve the spatial resolution in optical measurement.

[0080] (Item 5) In the optical measurement device described in items 1 to 4, the laser light may be composed of a plurality of pulsed laser lights.

[0081] According to the optical measurement device described in the fifth aspect, the intensity of the detection signal can be increased, and the precision with which the modulated signal component is extracted can be improved.

[0082] (Item 6) In the optical measurement device described in any one of items 1 to 5, the ultrasonic wave source may be capable of emitting the ultrasonic wave in a pulsed form.

[0083] According to the optical measurement device described in paragraph 6, 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.

[0084] (Item 7) An analysis method according to one aspect is a method for analyzing a modulated signal component generated when laser light irradiated into a light scattering medium is modulated by ultrasound at a measurement position at a predetermined depth, wherein a first speckle image is generated based on an output of a detector obtained by the detector detecting the laser light that has passed through a region within the light scattering medium during a first imaging period, and a second speckle image is generated based on an output of the detector obtained by the detector detecting the laser light that has passed through a region within the light scattering medium during a second imaging period when the ultrasound reaches the measurement position, and may include the steps of acquiring the first speckle image and the second speckle image, calculating a first fluctuation component indicative of a fluctuation amount of speckles in a first region and a second fluctuation component indicative of a fluctuation amount of speckles in a second region different from the first region, in the first speckle image and the second speckle image, and extracting the modulated signal component from the first fluctuation component and the second fluctuation component.

[0085] According to the analysis method described in Section 7, 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.

[0086] 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.

[0087] 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 timing of the irradiation of the laser light and the start and end of the oscillation of the ultrasonic waves, The system includes an analysis device that extracts a modulated signal component modulated by the ultrasound from the output of the detector, The control device is A first speckle image is acquired based on the output of the detector acquired during the first imaging period, and a second speckle image is acquired based on the output of the detector acquired during the second imaging period. The laser light is irradiated during the first and second imaging periods. During the second imaging period, the ultrasonic waves are emitted from the ultrasonic source so that they reach the measurement position. The aforementioned analysis device is In the first speckle image and the second speckle image, a first variation component representing the amount of speckle variation in the first region and a second variation component representing the amount of speckle variation in the second region, which is different from the first region, are calculated. An optical measuring device for extracting the modulated signal component from the first and second fluctuating components.

2. The optical measurement device according to claim 1, wherein the analysis device determines the first region and the second region based on the output of the detector obtained when the ultrasonic waves reach the measurement position as the laser light passes through the light scatterer, and the output of the detector obtained when the ultrasonic waves do not reach the measurement position as the laser light passes through the light scatterer.

3. The optical measurement device according to claim 1, wherein the analysis device determines the first region and the second region based on a simulation model of the light scattering body.

4. The ultrasonic source includes a plurality of ultrasonic transducers, The optical measuring device according to claim 1, wherein the ultrasonic source focuses the ultrasonic waves emitted from the plurality of ultrasonic transducers at the measurement position by aligning the focus of the ultrasonic waves at the measurement position.

5. The optical measuring device according to claim 1, wherein the laser light includes a plurality of pulsed laser beams.

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

7. 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 first speckle image is generated based on the output of the detector, which is obtained by the detector detecting the laser light that has passed through the region within the light scatterer during the first imaging period. When the ultrasonic waves reach the measurement position, the second speckle image is generated based on the output of the detector obtained by the detector detecting the laser light that has passed through the region within the light scatterer during the second imaging period. The steps include acquiring the first speckle image and the second speckle image, The steps include calculating a first variation component representing the amount of speckle variation in a first region and a second variation component representing the amount of speckle variation in a second region different from the first region, in the first speckle image and the second speckle image. An analysis method comprising the step of extracting the modulated signal component from the first variation component and the second variation component.