Optical measurement device and analysis method

Abstract

The light measuring device is provided with a light source, an ultrasonic wave source, a photographing device, a control device, and an analysis device. The control device causes the photographing device to perform photographing to acquire a laser signal that passes through a region inside a light scattering body during a first to third photographing period, and controls a photographing timing so that an interval between the first photographing period and the second photographing period and an interval between the second photographing period and the third photographing period are equal. The control device causes the light source to irradiate a first laser during the first photographing period, a second laser during the second photographing period, and a third laser during the third photographing period, and causes the ultrasonic wave source to emit an ultrasonic wave at a timing of irradiation of the third laser so that the ultrasonic wave reaches a measurement position. The analysis device extracts a modulation signal component using a signal of the first laser, a signal of the second laser, and a signal of the third laser that pass through the region inside the light scattering body.

Description

Technical Field

[0001] This disclosure relates to optical measurement apparatus and analysis methods, and more specifically, to techniques for improving the detection accuracy of ultrasonically modulated light. Background Technology

[0002] As a method for minimally invasively measuring light-scattering tissues within organisms, many light-utilizing techniques have been developed. For example, by irradiating light from outside the body and measuring the light emitted after propagation within the organism, information about the organism's tissue morphology or metabolism (such as oxygen saturation in the blood) can be obtained. However, because tissues within organisms are light-scattering media, light irradiated from outside the body diffuses within the tissues, resulting in poor spatial resolution and an inability to measure deep tissues. Therefore, as Wang, LV; Ku, G., “Frequency-swept ultrasound-modulated optical tomography of scattering media,” Optics Letters, 23(12), 975-977 (1998) (Non-Patent Literature 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 Literature 2), optical measurement devices combining ultrasound waves propagating in a low-scattering manner within biological organisms and light have been developed. In UOT, biological information is obtained by measuring the ultrasound-modulated light.

[0003] Japanese Patent No. 5672104 (Patent Document 1) and Sasakura Yu; Himaka Masaki, “Reflective Ultrasonic Modulation Speckle Light Measurement Method”, Biomedical Engineering, 45.4:235-241 (2007) (Non-Patent Document 3) disclose a method that uses a CCD camera to measure the change in the speckle pattern obtained when the focused pulse ultrasonic wave is present on the sample surface, based on the speckle pattern obtained when the focused pulse ultrasonic wave is present at a predetermined depth, thereby obtaining information about the predetermined depth region.

[0004] The speckle pattern obtained when a focused pulsed ultrasound is present at a predetermined depth contains not only signals from ultrasound-modulated light but also noise that varies over time. Patent Document 1 and Non-Patent Document 3 mitigate the influence of noise based on speckle patterns obtained without the influence of the pulsed ultrasound.

[0005] Existing technical documents Patent documents Patent Document 1: Japanese Patent No. 5672104 Non-patent literature Non-patent literature 1: Wang, LV; Ku, G.; “Frequency-swept ultrasound-modulated optical tomography of scattering media”, Optics Letters, 23(12), 975-977 (1998). Non-patent literature 2: Elson, Daniel S. et al., “Ultrasound-mediated optical tomography: a review of current methods”, Interface Focus, 1.4, 632-648 (2011). Non-patent literature 3: Sasakura Yu; Himaka Masaki, “Reflective Ultrasonic Modulation Speckle Light Measurement Method”, Biomedical Engineering, 45.4:235-241 (2007). Summary of the Invention The technical problem that the invention aims to solve In the methods disclosed in Patent Document 1 and Non-Patent Document 3, the time interval for acquiring the detection signal value as the object of noise reduction and the detection signal value considered as noise are different. Therefore, for example, for noise whose change in unit time is not fixed, such as noise caused by the irregular movement of particles, it is sometimes difficult to eliminate its influence from the detected signal.

[0006] This disclosure was made in view of the above circumstances, and its purpose is to improve the accuracy of extracting the ultrasonically modulated light component from the acquired detection signal in an optical measurement apparatus utilizing ultrasonically modulated optical tomography.

[0007] Solution to the above technical problems According to the optical measurement apparatus of the first aspect of this disclosure, a light source, an ultrasonic source, a detector, a control device, and an analysis device are included. The light source irradiates a pulsed laser into a light scattering body. The ultrasonic source emits ultrasonic waves into a measurement position located at a predetermined depth within the light scattering body. The detector detects laser light passing through a region within the light scattering body including the measurement position. The control device controls the irradiation of the laser light and the emission of the ultrasonic waves. The analysis device extracts a modulated signal component modulated by the ultrasonic waves from the laser light detected by the detector. The control device sets a first shooting period, a second shooting period, and a third shooting period such that the interval between the first and second shooting periods and the interval between the second and third shooting periods are equal, and causes the detector to detect the signal of the laser light passing through the region within the light scattering body during the first, second, and third shooting periods. Furthermore, the control device causes the light source to irradiate a first laser light during the first shooting period, a second laser light during the second shooting period, and a third laser light during the third shooting period, and emits ultrasonic waves from the ultrasonic source at the irradiation time of the third laser light, so that the ultrasonic waves reach the measurement position. The analysis device uses the signals of the first and second lasers passing through the region of the light scattering body to extract the first signal component, uses the signals of the second and third lasers passing through the region of the light scattering body to extract the second signal component, and extracts the modulation signal component from the first and second signal components.

[0008] According to the optical measurement apparatus of the second aspect of this disclosure, a light source, an ultrasonic source, a detector, a control device, and an analysis device are included. The light source irradiates a pulsed laser beam into a light scattering body. The ultrasonic source emits ultrasonic waves into a measurement position located at a predetermined depth within the light scattering body. The detector detects laser beams passing through a region within the light scattering body including the measurement position. The control device controls the irradiation of the laser beam and the emission of the ultrasonic waves. The analysis device extracts a modulated signal component modulated by the ultrasonic waves from the laser beam detected by the detector. The control device sets a first shooting period, a second shooting period, a third shooting period, and a fourth shooting period such that the interval between the first and second shooting periods and the interval between the third and fourth shooting periods are equal, and causes the detector to detect the signal of the laser beam passing through the region within the light scattering body during the first, second, third, and fourth shooting periods. Furthermore, the control device causes the light source to irradiate a first laser beam during the first shooting period, a second laser beam during the second shooting period, a third laser beam during the third shooting period, and a fourth laser beam during the fourth shooting period, and emits ultrasonic waves from the ultrasonic source at the irradiation time of the third laser beam, so that the ultrasonic waves reach the measurement position. The analysis device uses the signals of the first and second lasers passing through the region of the light scattering body to extract the first signal component, uses the signals of the third and fourth lasers passing through the region of the light scattering body to extract the second signal component, and extracts the modulation signal component from the first and second signal components.

[0009] According to the analytical method of the third aspect of this disclosure, a method is provided for analyzing the modulation signal components generated by ultrasonic modulation of a laser irradiated onto a light scattering body at a measurement position located at a predetermined depth. The analytical method includes: (a) acquiring a detection signal of a first laser passing through a region within the light scattering body, acquired during a first shooting period; (b) acquiring a detection signal of a second laser passing through a region within the light scattering body, acquired during a second shooting period set at a predetermined interval from the first shooting period; (c) acquiring a detection signal of a third laser, acquired during a third shooting period set at a predetermined interval from the second shooting period, acquired when ultrasonic waves arrive at the measurement position and pass through a region within the light scattering body; (d) extracting a first signal component using the detection signals of the first and second lasers; (e) extracting a second signal component using the detection signals of the second and third lasers; and (f) extracting a modulation signal component from the first and second signal components.

[0010] Invention Effects According to the optical measurement apparatus and analysis method disclosed herein, the accuracy of extracting ultrasonically modulated light components from detection signals acquired by an optical measurement apparatus using ultrasonically modulated optical tomography can be improved. Attached Figure Description

[0011] 【 Figure 1 [Illustration] is a schematic diagram of an optical measurement device according to an embodiment.

[0012] 【 Figure 2 [This is a timing diagram showing the timing of the photo capture, the timing of the pulsed laser illumination, and the timing of the ultrasonic wave emission of the optical measurement device according to the embodiment.]

[0013] 【 Figure 3 The figure shown is an example of a speckle pattern obtained by an optical measuring device.

[0014] 【 Figure 4 The figure shown is an example of a signal component extracted from a speckle pattern.

[0015] 【 Figure 5 This is a flowchart illustrating the modulation signal component analysis process according to an embodiment.

[0016] 【 Figure 6 [This is a timing diagram showing the timing of the image capture, the timing of the pulsed laser illumination, and the timing of the ultrasonic wave emission of the optical measuring device according to a modified example.]

[0017] 【 Figure 7 The diagram above is a flowchart illustrating the analysis and processing of the modulated signal components according to a modified example. Detailed Implementation

[0018] The embodiments of this disclosure will now be described in detail with reference to the accompanying drawings. The description will use a living organism as an example, but the invention is not limited thereto and can also be used for the observation of light scattering bodies. Furthermore, the same or corresponding parts in the drawings are labeled with the same reference numerals, and their descriptions will not be repeated.

[0019] [Optical Measurement Device] Figure 1 This is a diagram showing the structure of the optical measuring device 10 according to an embodiment. (Refer to...) Figure 1 The optical measurement device 10 includes a laser source 1, an ultrasonic source 2, a camera 3, a control device 4, and an analysis device 5. The optical measurement device 10 can irradiate a measurement area subjected to ultrasonic waves with laser light and detect the generated modulated light, thereby acquiring morphological and physiological information of the observed object. Specifically, the optical measurement device 10 acquires an image of a speckle pattern through the camera 3. This speckle pattern is a collection of speckled particles (speckle spots) formed by the multiple interferences of multiple light waves scattered multiple times within the observed object. The analysis device 5 extracts the signal components of the modulated light contained in the speckle pattern. The speckle pattern in this embodiment corresponds to the laser signal in this disclosure.

[0020] The optical measurement device described in this embodiment can be applied, for example, to a device for minimally invasively measuring brain activity in a subject using near-infrared spectroscopy (NIRS). Furthermore, in addition to being applicable to devices for measuring brain activity using NIRS, the optical measurement device described in this embodiment can also be applied to devices for measuring blood oxygen saturation, etc. Oxygen saturation can be estimated, for example, based on results measured using lasers of different wavelengths, utilizing the relationship between the absorption spectra of oxyhemoglobin and deoxyhemoglobin.

[0021] The control device 4 and the analysis device 5 can be integrated onto a computer (not shown) and can be connected to external devices such as memory and printers as needed. Furthermore, the laser source 1, the ultrasonic source 2, and the camera 3 can be integrated into a single unit, and these components can also be integrated with the control device 4 so that it can be worn on the subject.

[0022] Laser source 1 is a light source that irradiates the biological object 20, which is the object of observation, with laser light; for example, it is a semiconductor laser element. In this embodiment, laser source 1 is controlled to generate pulsed laser light (pulsed laser). Laser source 1 irradiates the biological object 20 with laser light in the near-infrared wavelength region (e.g., 780 nm). Figure 1As shown, the laser light irradiated from the laser source 1 onto the organism 20 is scattered within the tissue of the organism 20 and reaches the measurement location. Furthermore, the laser source 1 is capable of irradiating pulsed laser light for approximately several nanoseconds to several microseconds.

[0023] The ultrasonic source 2 is an ultrasonic generator that emits ultrasonic waves to a measurement location at a predetermined depth within the organism 20. The ultrasonic source 2 is equipped with a focuser 2a to focus the emitted ultrasonic waves onto the measurement location within the organism 20. Within the focused area, the ultrasonic waves interact strongly with a laser, thereby generating modulated light. Therefore, by photodetecting the modulated light generated by this interaction, information about the measurement location within the organism 20 can be obtained.

[0024] The ultrasonic waves emitted from ultrasonic source 2 can be continuous or pulsed. However, by setting the ultrasonic waves emitted from ultrasonic source 2 to pulsed waves, the length of the ultrasonic wave's travel direction can be shortened, thereby limiting the area where the ultrasonic waves exist to the measurement location. Furthermore, when pulsed ultrasonic waves are emitted from ultrasonic source 2, a certain time (delay time) is required for the pulsed ultrasonic waves emitted from the surface of the biological body 20 to reach the measurement location. Therefore, it is necessary to control the timing of ultrasonic wave emission from ultrasonic source 2 so that the timing of the pulsed ultrasonic waves reaching the measurement location coincides with the timing of the pulsed laser emitted from laser source 1 reaching the measurement location. Strictly speaking, there is a deviation between the timing of laser irradiation and the timing of the laser reaching the measurement location, and the deviation is equal to the time required for the laser to travel from laser source 1 to the measurement location. However, since the distance from laser source 1 to the measurement location is sufficiently short than the distance light travels per unit time, the time required for the laser to travel from laser source 1 to the measurement location can be ignored. Therefore, it can be considered that the timing of laser source 1 irradiating the laser and the timing of the laser reaching the measurement location are essentially simultaneous.

[0025] Camera 3 includes an image sensor 3a that detects laser light from the measurement location and a lens 3b for imaging the image sensor 3a. In the optical measurement device 10, since it is necessary to image the speckle pattern, a single-element photodetector such as a photomultiplier tube is not used; instead, a multi-element photodetector, such as a CCD (Charge Coupled Device) sensor or a CMOS (Complementary Metal-Oxide-Semiconductor) sensor, i.e., the image sensor 3a, is used. By employing a CCD or CMOS sensor on the image sensor 3a, the manufacturing cost of the optical measurement device 10 can be reduced. The pixel size of the image sensor 3a is preferably smaller than the average size of the speckle spots to be imaged.

[0026] Generally, image sensors 3a, such as CCD sensors, have frame rates ranging from tens to hundreds of fps. In contrast, ultrasound frequencies reach several MHz, making it impossible for image sensors 3a to keep up with the changes in ultrasound. Therefore, in the optical measurement device 10, a pulsed laser is used to irradiate the tissue within the organism 20 irradiated by ultrasound using a stroboscopic imaging method, and the speckle pattern is captured by the image sensor 3a in the exposed state.

[0027] Alternatively, the exposure time of the image sensor 3a can be set to be longer than the ultrasonic cycle, and the acquired speckle pattern can be used for measurement. In this case, the pulse width of the laser is limited by the distance the ultrasonic wave travels within that time. If this pulse width is increased, the spatial resolution of the ultrasonic wave's travel direction may decrease; therefore, it is preferable to set it to less than a few microseconds.

[0028] The light detected by camera 3 is a mixture of laser light that is modulated by ultrasound as it passes through a region where ultrasound exists and laser light that is not modulated by ultrasound as it does not pass through a region where ultrasound exists.

[0029] Control device 4 controls the timing of laser irradiation from laser source 1 and the timing of ultrasonic wave emission from ultrasonic source 2. Since the laser is pulsed, it has a pulse width. Therefore, the laser irradiation timing is defined, for example, at the rising edge of the pulse. Of course, the laser irradiation timing can also be defined as at the midpoint of the pulse or at the falling edge of the pulse. Details regarding the timing of laser irradiation and ultrasonic wave emission will be described later. Control device 4 is, for example, a computer.

[0030] The analysis device 5 extracts the modulated signal component of the ultrasonic wave based on the detection signal of the laser detected by the camera 3. Details of the modulated signal component extraction method performed by the analysis device 5 will be described later. The analysis device 5 is, for example, a computer.

[0031] [Comparative Example] Many light-based methods have been developed as a means of measuring tissues in living organisms in a minimally invasive manner. However, because light is scattered multiple times by biological tissues, it is sometimes difficult to measure deep tissues with high spatial resolution.

[0032] Therefore, an optical measurement technique was developed to improve the spatial resolution of optical measurements using UOT. This technique focuses ultrasound waves that are hardly scattered by biological tissue onto a predetermined area and measures the modulated light through the interaction between the ultrasound waves and light.

[0033] Images of speckle patterns can be acquired through UOT-based optical measurements. The acquired speckle patterns contain not only signal components based on modulated light but also noise. When extracting the modulated signal components from the detection signal obtained as an optical measurement—that is, the speckle pattern—an analytical method can be used, for example, to remove noise components from the detection signal obtained when ultrasound is emitted, based on the detection signal obtained without ultrasound emission.

[0034] However, the above-mentioned analytical methods sometimes fail to adequately remove noise components, leading to a decrease in the extraction accuracy of the modulated signal components. Specifically, since the timing of obtaining the detection signal when no ultrasound is emitted differs from the timing of obtaining the detection signal when ultrasound is emitted, it is sometimes impossible to eliminate the influence of noise with different time averages between the two (such as noise caused by Brownian motion of scattering particles and noise caused by changes in the state of biological tissue).

[0035] [Optical measurement method according to the implementation method] Therefore, in the optical measurement apparatus according to this embodiment, the optical measurement apparatus 10 acquires three speckle patterns acquired consecutively at equal time intervals. By determining the noise component generated within this time interval from two speckle patterns, the extraction accuracy of the noise component can be improved.

[0036] By using the optical measurement device according to this embodiment, the accuracy of extracting noise components with variable changes per unit time can be improved, and the extraction accuracy of modulation signal components can be improved by utilizing these noise components.

[0037] First, the period during which the optical measurement device 10 takes pictures, the timing of laser irradiation, the timing of ultrasonic irradiation, and the detection signal obtained as a result will be explained. Figure 2 This is a timing diagram showing the period during which the camera 3 of the optical measurement device 10, according to the embodiment, takes pictures, the timing of pulsed laser illumination, and the timing of ultrasonic irradiation.

[0038] <1. Setup during filming> First, the user sets the period for camera 3 to capture the speckle pattern. During the capture period, camera 3 uses image sensor 3a, which is in an exposed state, to capture the speckle pattern. Therefore, the detection signal acquired by camera 3 is obtained by superimposing the speckle pattern formed by the laser received during the capture period.

[0039] In this embodiment, it is assumed that camera 3 is controlled to be in an exposed state throughout the entire shooting period, but it is also possible to control camera 3 to be in an exposed state only for a predetermined period during the shooting period. In this case, the predetermined period must include the period of laser illumination. Furthermore, camera 3 can also be in an exposed state during the time required for reading.

[0040] Set a period of three shooting sessions. Figure 2 The numbers correspond to the first, second, and third shooting periods. After each shooting period, the acquired signals are read to obtain the first, second, and third speckle patterns, respectively.

[0041] The shooting schedule was set so that the intervals between each shooting session were equal. That is, as shown in the image. Figure 2 As shown, the first shooting interval, from the start time of the first shooting period to the start time of the second shooting period, is set to be equal to the second shooting interval, from the start time of the second shooting period to the start time of the third shooting period. The shooting interval is, for example, 100ms.

[0042] <2. Setting the Timing of Laser Irradiation> The user sets the duration for irradiating the first, second, and third lasers from laser source 1. For example... Figure 2 As shown, the first laser irradiates during the first shooting period, the second laser irradiates during the second shooting period, and the third laser irradiates during the third shooting period. Since the lasers are pulse-width lasers, the laser irradiation timing is defined, for example, at the pulse rising edge. The control device 4 sends a laser drive signal to the laser source 1 in conjunction with the laser irradiation timing. Furthermore, since the laser source 1 irradiates a pulsed laser, there is a period during which the laser is irradiated; this period (the period during which the laser drive signal is in the on state) is called the pulse illumination time. Therefore, the irradiation of each type of laser needs to be completed within the corresponding shooting period.

[0043] <3. Setting the timing of ultrasonic wave emission> Next, the user sets the timing for emitting ultrasonic waves from ultrasonic source 2. Specifically, ultrasonic waves are emitted from ultrasonic source 2 at the irradiation time of the third laser, causing the ultrasonic waves to reach the measurement position. Control device 4 sends an ultrasonic drive signal to ultrasonic source 2 at the timing of ultrasonic wave emission. Figure 2 As shown, the emission timing is when the ultrasonic source 2 emits pulsed ultrasonic waves from the ultrasonic source 2 before the ultrasonic delay time of the third laser irradiation.

[0044] The ultrasonic delay time can be calculated based on the distance (depth) from the ultrasonic source 2 to the measurement position. Furthermore, since the ultrasonic waves emitted by the ultrasonic source 2 are pulsed, there exists a period of continuous ultrasonic wave emission; this period (the period during which the ultrasonic drive signal is in the conducting state) is also called the ultrasonic pulse width. Of course, the ultrasonic waves emitted by the ultrasonic source 2 are not limited to pulsed ultrasonic waves; they can also be continuous ultrasonic waves. In addition, strictly speaking, there is a deviation between the timing of laser irradiation and the timing of the laser reaching the measurement position; the deviation is equal to the time required for the laser to travel from the laser source 1 to the measurement position. However, since the distance from the laser source 1 to the measurement position is sufficiently short than the distance light travels per unit time, it can be assumed that the timing of laser irradiation and the timing of the laser reaching the measurement position are approximately simultaneous. Therefore, the distance calculated by multiplying the speed of ultrasonic wave propagation within the organism 20 by the ultrasonic delay time corresponds to the depth of the measurement position within the organism 20.

[0045] <4. Detected Signals> The irradiated laser light is scattered within the organism 20 and captured by camera 3 in the form of a speckle pattern. For example... Figure 2 As shown, the speckle pattern originating from the first laser corresponds to the first speckle pattern, the speckle pattern originating from the second laser corresponds to the second speckle pattern, and the speckle pattern originating from the third laser corresponds to the third speckle pattern.

[0046] <5. Extracting Modulation Signal Components from the Detected Signal> Both the first and second speckle patterns were acquired under conditions where no ultrasonic waves were emitted. That is, the acquisition conditions for the speckle patterns were the same, except for the different shooting periods. Therefore, the difference between the second and first speckle patterns (hereinafter referred to as the first signal component) corresponds to the noise component caused by the difference during the shooting period. Specifically, for example, the result of subtracting the pixel values ​​of the corresponding pixels in the first speckle pattern from the pixel values ​​of each pixel in the second speckle pattern corresponds to the noise component generated during the shooting interval. In this case, this noise component is calculated as part of the image.

[0047] The second and third speckle patterns were acquired under the same conditions, except for whether ultrasonic waves were used and the timing of the acquisition. Therefore, the difference between the third and second speckle patterns (hereinafter referred to as the second signal component) corresponds to the superposition of the noise component and the modulation signal component caused by the difference during the acquisition period. Specifically, for example, the result of subtracting the pixel values ​​of the corresponding pixels in the second speckle pattern from the pixel values ​​of each pixel in the third speckle pattern is equivalent to the superposition of the noise component and the modulation signal component generated within the acquisition interval. In this case, the superposition of the noise component and the modulation signal component is calculated as an image.

[0048] The noise components in the first and second signal components mentioned above are noise components generated within equal shooting intervals. These noise components are a collection of time-varying noises (e.g., noise caused by changes in light scattering paths due to Brownian motion of scattering particles and changes in the state of biological tissue). Individual noises have a significant impact on the speckle pattern within a small time frame, and this noise is not periodic. However, the effect of the superimposed signal of these noises on the speckle pattern can be considered to be of a fixed degree within a predetermined time interval (e.g., 10 μs). Therefore, the noise components in the first and second signal components acquired within equal shooting intervals can be considered to have approximately equal signal values.

[0049] Therefore, the modulation signal component can be extracted by subtracting the first signal component from the second signal component. Specifically, for example, the modulation signal component is extracted by subtracting the pixel value of the corresponding pixel of the second speckle pattern from the pixel value of each pixel of the third speckle pattern. In this case, the modulation signal component is calculated as an image.

[0050] [Example of Modulation Signal Component Extraction] Reference Figure 3 and Figure 4 Explain the method for extracting modulated signal components. Figure 3 The speckle pattern obtained when measuring an organism 20 by the light measurement device 10 is shown. Figure 4 The signal components extracted from the obtained speckle pattern are shown.

[0051] Figure 3 (a) corresponds to Figure 2 The first speckle pattern in the middle, Figure 3 (b) corresponds to Figure 2 The second speckle pattern in the middle, Figure 3 (c) corresponds to Figure 2 The third speckled pattern in the image.

[0052] Figure 4 (a) is the signal component calculated based on the first speckle pattern and the second speckle pattern. Specifically, it is the result obtained by subtracting the pixel value of each pixel in the first speckle pattern from the pixel value of each pixel in the second speckle pattern. Figure 4 The signal component shown in (a) corresponds to the noise component generated during the shooting interval.

[0053] Figure 4(b) is the signal component calculated based on the second and third speckle patterns. Specifically, it is the result obtained by subtracting the pixel value of each pixel in the second speckle pattern from the pixel value of each pixel in the third speckle pattern. Figure 4 The signal component shown in (b) corresponds to the signal component formed by adding the noise component generated during the shooting interval to the modulation signal component.

[0054] Figure 4 (c) is based on Figure 4 (a) and Figure 4 (b) The modulated signal components calculated. Specifically, it is the modulated signal components calculated by (b). Figure 4 (b) The pixel value of each pixel minus the corresponding pixel value. Figure 4 The result obtained from the pixel values ​​of each pixel in (a).

[0055] Figure 4 The signal component shown in (c) is from the detection signal containing the modulation signal component. Figure 3 The detection signal obtained by subtracting the signal obtained without ultrasonic irradiation from (c) Figure 3 (b) is then subtracted from the noise components obtained at equal time intervals. Figure 4 The result obtained from (a) is as follows. Therefore, this is the modulated signal component after removing the influence of noise components generated during the shooting interval.

[0056] [Analysis and processing flow of modulated signal components] Figure 5 This is a flowchart illustrating an example of the analytical processing performed to extract the modulation signal component from the speckle pattern measured by the optical measurement device 10. In one implementation example, Figure 5 The analysis processing subroutine is called and executed from the main program 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.

[0057] In step S10, the optical measurement device 10 receives information from the user regarding the periods during which the camera 3 receives the laser, namely the first shooting period, the second shooting period, and the third shooting period. This information is set such that the interval between the first and second shooting periods and the interval between the second and third shooting periods are equal.

[0058] In step S12, the photometry device 10 irradiates the organism 20 with a first laser during the first shooting period.

[0059] In step S14, the optical measurement device 10 detects the first signal. In this specification, the first signal corresponds to the detection signal of the first laser and the first speckle pattern.

[0060] In step S16, the light measurement device 10 irradiates the organism 20 with a second laser during the second imaging period.

[0061] In step S18, the optical measurement device 10 detects the second signal. In this specification, the second signal corresponds to the detection signal of the second laser and the second speckle pattern.

[0062] In step S20, the optical measuring device 10 emits ultrasonic waves at the organism 20 at a predetermined time. The predetermined time refers to the time when the third laser is irradiated in step S22, and the time when the ultrasonic waves reach the measurement position of the organism 20.

[0063] In step S22, the light measurement device 10 irradiates the organism 20 with a third laser during the third imaging period.

[0064] In step S24, the optical measurement device 10 detects the third signal. In this specification, the third signal corresponds to the detection signal of the third laser and the third speckle pattern.

[0065] 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.

[0066] 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.

[0067] In step S30, the optical measurement device 10 calculates the ultrasonically modulated signal component based on the first signal component calculated in step S26 and the second signal component calculated in step S28. Afterward, the optical measurement device 10 terminates the analysis processing subroutine and returns the processing to the main program.

[0068] In addition, Figure 5 In the described process, the ultrasonic wave is irradiated before the third laser, but it can also be irradiated before the first laser, i.e., before step S10. In this case, the first signal contains a modulation signal component.

[0069] In the above analysis, the three detection signals were acquired during an imaging period set at equal time intervals. Therefore, the difference between the first and second detected signals is caused by noise generated within that time interval. Thus, this can be considered to be of the same level as the noise contained in the difference between the third and second detected signals, which includes modulated signal components. That is, by performing the above analysis, the accuracy of noise extraction can be improved, and by using this noise, the measurement accuracy of the modulated signal components can be improved.

[0070] Furthermore, if the shooting interval is too long, the organism's state will fluctuate significantly, causing large changes in the speckle pattern within that interval, which can sometimes make the analysis of the modulated signal components extremely difficult. Therefore, the shooting interval is preferably less than 200 ms.

[0071] Furthermore, the first, second, and third shooting periods are preferably equal in length, but they do not necessarily have to be equal. For example, the lengths of the shooting periods can be unequal, unless the shortest shooting period is less than 90% of the longest shooting period, which is an extreme case of difference in length.

[0072] When the length of each shooting period is equal, the timing of laser irradiation within each shooting period is preferably consistent (e.g., irradiating the laser after a predetermined time has elapsed since the start of the shooting period), but the timing of irradiation is not restricted as long as each laser is irradiated within its corresponding shooting period.

[0073] (Modified example) The optical measurement device 10 can also extract the modulation signal component based on the first to fourth speckle patterns obtained from the laser irradiated during the first to fourth shooting periods. During the first to fourth shooting periods, if the interval between the start of the first shooting period and the start of the second shooting period is taken as the first shooting interval, and the interval between the start of the third shooting period and the start of the fourth shooting period is taken as the second shooting interval, then the first shooting interval and the second shooting interval are set to be equal. If this condition is met, shooting can be performed without limiting the interval between the second and third shooting periods.

[0074] The following describes the period during which the optical measuring device 10 takes pictures, the timing of laser irradiation, the timing of ultrasonic irradiation, and the detection signal obtained as a result in the modified example. Figure 6 This is a timing diagram showing the period during which the camera 3 of the optical measurement device 10, according to the embodiment, takes pictures, the timing of pulsed laser illumination, and the timing of ultrasonic irradiation.

[0075] The user sets the period during which camera 3 captures the speckle pattern. During the capture period, camera 3 uses image sensor 3a, which is in an exposed state, to capture the speckle pattern. Therefore, the detection signal is obtained by superimposing the speckle pattern formed by the laser received during the capture period.

[0076] Set a period of four shooting sessions. Figure 6 The numbers correspond to the first, second, third, and fourth shooting periods. After each shooting period, the acquired signals are read to obtain the first, second, third, and fourth speckle patterns, respectively.

[0077] The shooting schedule was set so that the intervals between each shooting session were equal. That is, as shown in the image. Figure 6As shown, the first shooting interval, from the start time of the first shooting period to the start time of the second shooting period, is set to be equal to the second shooting interval, from the start time of the third shooting period to the start time of the fourth shooting period. The shooting interval is, for example, 100ms.

[0078] like Figure 6 As shown, the first laser irradiates during the first shooting period, the second laser irradiates during the second shooting period, the third laser irradiates during the third shooting period, and the fourth laser irradiates during the fourth shooting period. Additionally, an ultrasonic wave is emitted at the moment the fourth laser irradiates, ensuring the ultrasonic wave reaches the measurement location.

[0079] Both the first and second speckle patterns were acquired under conditions where no ultrasonic waves were emitted. That is, the acquisition conditions for the speckle patterns were the same, except for the different shooting periods. Therefore, the difference between the second and first speckle patterns corresponds to the noise component caused by the difference in shooting periods.

[0080] The acquisition conditions for the third and fourth speckle patterns are the same, except for whether ultrasound was applied and the timing of the acquisition. Therefore, the difference between the fourth and third speckle patterns corresponds to the superposition of the noise component and the modulation signal component caused by the difference in the timing of the acquisition.

[0081] Here, since the first shooting interval is set to be equal to the second shooting interval, 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.

[0082] Therefore, the modulation signal component can be extracted by subtracting the noise component calculated based on the first and second speckle patterns from the sum of the noise component calculated based on the third and fourth speckle patterns and the modulation signal component.

[0083] [Analysis and processing flow of the modulation signal components involved in the variation example] Figure 7 This is a flowchart illustrating another example of the analytical processing performed to extract the modulation signal component from the speckle pattern measured by the optical measurement device 10. In one implementation example, Figure 7 The analysis and processing subroutine is called and executed from the main program when the processor of analysis device 5 executes a given program. Additionally, in Figure 7 In China, targeting and Figure 5 The flowcharts described herein have the same structure, use the same symbols, and will not be described in detail again.

[0084] In step S32, the optical measurement device 10 receives information from the user regarding the periods during which the camera 3 receives the laser, namely the first shooting period, the second shooting period, the third shooting period, and the fourth shooting period. This information is set such that the interval between the first and second shooting periods and the interval between the third and fourth shooting periods are equal.

[0085] In step S34, the light measurement device 10 irradiates the organism 20 with a fourth laser during the fourth imaging period.

[0086] In step S36, the optical measurement device 10 detects the fourth signal. In this specification, the fourth signal corresponds to the detection signal of the fourth laser and the fourth speckle pattern.

[0087] In step S38, the optical measurement device 10 calculates the second signal component based on the third signal detected in step S24 and the fourth signal detected in step S36.

[0088] In addition, Figure 7 In the described process, the ultrasonic wave is irradiated before the fourth laser, but it can also be irradiated before the third laser, i.e., before step S22. In this case, the third signal contains a modulation signal component.

[0089] In the modified example, the time interval between the second and third shooting periods is not limited. Therefore, for example, when there are multiple measurement locations, the total number of speckle patterns acquired can be reduced compared to the method using the three speckle patterns shown in the embodiment, by using the method shown in the modified example. For example, suppose signals are measured at three different measurement locations. In the processing method described in the embodiment, three speckle patterns need to be acquired at each measurement location to acquire the modulated signal components, requiring a total of nine speckle patterns. On the other hand, in the modified example, only two speckle patterns need to be acquired to calculate the noise signal, and then two speckle patterns are acquired at each measurement location, thus requiring only eight speckle patterns in total. Thus, by using the method shown in the modified example, the number of speckle patterns used can be reduced, thereby reducing the computational load.

[0090] [plan] Those skilled in the art will understand that the above-described exemplary embodiments are specific examples of the following solutions.

[0091] (Item 1) A light measurement apparatus according to one embodiment comprises: a light source that irradiates a pulsed laser into a light scattering body; an ultrasonic source that emits ultrasonic waves into the light scattering body at a measurement position located at a predetermined depth; a detector that detects the laser passing through a region within the light scattering body including the measurement position; a control device that controls the irradiation of the laser and the emission of the ultrasonic waves; and an analysis device that extracts a modulated signal component modulated by the ultrasonic waves from the laser detected by the detector, wherein the control device sets a first shooting period, a second shooting period, and a third shooting period such that the interval between the first shooting period and the second shooting period and the interval between the second shooting period and the third shooting period are equal; and the detector detects the laser passing through a region within the light scattering body including the measurement position. The signal of the laser passing through the region within the light scattering body during the first, second, and third shooting periods is detected; the light source is irradiated with the first laser during the first shooting period, the second laser during the second shooting period, and the third laser during the third shooting period; and the ultrasonic source emits the ultrasonic wave at the irradiation time of the third laser, so that the ultrasonic wave reaches the measurement position. The analysis device extracts a first signal component using the signals of the first and second lasers passing through the region within the light scattering body; extracts a second signal component using the signals of the second and third lasers passing through the region within the light scattering body; and extracts the modulation signal component from the first and second signal components.

[0092] According to the optical measurement device described in claim 1, the accuracy of extracting ultrasonically modulated light components from the detection signal obtained by the optical measurement device using ultrasonically modulated optical tomography can be improved.

[0093] (Item 2) In the optical measurement apparatus described in Item 1, the ultrasonic source can emit the ultrasonic waves to focus the ultrasonic waves at the measurement location.

[0094] According to the optical measurement device described in item 2, the light component modulated at the measurement position can be extracted, thereby improving the spatial resolution in optical measurement.

[0095] (Item 3) In the optical measurement device described in Item 1 or Item 2, the first laser, the second laser, and the third laser may be composed of multiple pulsed lasers.

[0096] According to the optical measurement device described in item 3, the intensity of the detection signal can be increased, thereby improving the accuracy of extracting the modulated signal components.

[0097] (Item 4) In any one of the optical measuring apparatuses in items 1 to 3, the ultrasonic source can emit pulsed ultrasonic waves.

[0098] According to the optical measurement device described in item 4, the length of the ultrasonic wave travel direction can be shortened, thereby limiting the area where the ultrasonic wave exists to the measurement position and improving the spatial resolution in optical measurement.

[0099] (Item 5) In any one of the optical measurement devices in items 1 to 4, the interval may be less than 200 ms.

[0100] According to the optical measurement device described in item 5, noise generated within 200 ms can be removed from the detection signal obtained by the optical measurement device using ultrasonic modulation optical tomography, thereby improving the accuracy of extracting the ultrasonically modulated light component.

[0101] (Item 6) In any one of the optical measurement apparatuses in items 1 to 5, the durations of the first shooting period, the second shooting period, and the third shooting period may be equal.

[0102] (Item 7) A light measurement apparatus according to one embodiment comprises: a light source for irradiating a pulsed laser into a light scattering body; an ultrasonic source for emitting ultrasonic waves at a measurement position located at a predetermined depth within the light scattering body; a detector for detecting the laser passing through a region within the light scattering body including the measurement position; a control device for controlling the irradiation of the laser and the emission of the ultrasonic waves; and an analysis device for extracting a modulated signal component modulated by the ultrasonic waves from the laser detected by the detector, wherein the control device sets a first shooting period, a second shooting period, a third shooting period, and a fourth shooting period such that the interval between the first shooting period and the second shooting period and the interval between the third shooting period and the fourth shooting period are equal; and the detector detects the laser passing through a region within the light scattering body including the measurement position; and the analysis device extracts a modulated signal component modulated by the ultrasonic waves from the laser detected by the detector. The signal of the laser passing through the region within the light scattering body during the second, third, and fourth shooting periods is detected; the light source is irradiated with the first laser during the first shooting period, the second laser during the second shooting period, the third laser during the third shooting period, and the fourth laser during the fourth shooting period; and the ultrasonic source emits the ultrasonic wave during the irradiation of the third laser, so that the ultrasonic wave reaches the measurement position. The analysis device extracts a first signal component using the signals of the first and second lasers passing through the region within the light scattering body; extracts a second signal component using the signals of the third and fourth lasers passing through the region within the light scattering body; and extracts the modulation signal component from the first and second signal components.

[0103] According to the optical measurement apparatus described in item 7, the accuracy of extracting the ultrasonically modulated light component from the detection signal obtained by the optical measurement apparatus using ultrasonically modulated optical tomography can be improved. Furthermore, measurements can be performed without being limited by the interval between the second and third shooting periods. Therefore, the user can flexibly set the shooting timing. Additionally, when measuring multiple measurement positions, the computational load can be reduced.

[0104] (Item 8) According to one method, an analysis method is used to analyze the modulation signal components generated by ultrasonic modulation of a laser irradiated into a light scattering body at a measurement position located at a predetermined depth. The analysis method includes the following steps: acquiring a detection signal of a first laser that passes through a region within the light scattering body during a first shooting period; acquiring a detection signal of a second laser that passes through a region within the light scattering body during a second shooting period set at a predetermined interval from the first shooting period; acquiring a detection signal of a third laser that irradiates a region within the light scattering body when the ultrasonic wave reaches the measurement position and passes through the region during a third shooting period set at the predetermined interval from the second shooting period; extracting a first signal component using the detection signals of the first and second lasers; extracting a second signal component using the detection signals of the second and third lasers; and extracting the modulation signal component from the first and second signal components.

[0105] According to the analytical method described in item 8, the accuracy of extracting ultrasonically modulated light components from detection signals obtained by an optical measurement device using ultrasonically modulated optical tomography can be improved.

[0106] The embodiments disclosed herein should be considered illustrative in all respects and not restrictive. The scope of this disclosure is defined not by the description of the embodiments above but by the scope of the claims, and is intended to include all modifications within the same sense and scope as the claims. Furthermore, the techniques in the embodiments are intended to be included herein, whether implemented individually or in combination with other techniques in the embodiments as needed.

[0107] Explanation of reference numerals in the attached figures 1 Laser source, 2 Ultrasonic source, 2a Focusing device, 3 Camera, 3a Image sensor, 3b Lens, 4 Control device, 5 Analysis device, 10 Optical measurement device, 20 Biological organism.

Claims

1. An optical measurement device, comprising: The light source irradiates pulsed laser light into the light-scattering body; An ultrasonic source emits ultrasonic waves toward a measurement position located at a predetermined depth within the light scattering body; A detector that detects the laser light passing through a region within the light scattering body, including the measurement location; A control device for controlling the irradiation of the laser and the emission of the ultrasonic waves; as well as The analysis device extracts the modulated signal components modulated by the ultrasonic waves from the laser detected by the detector. The control device Set a first shooting period, a second shooting period, and a third shooting period such that the interval between the first shooting period and the second shooting period is equal to the interval between the second shooting period and the third shooting period; The detector is configured to detect the signal of the laser passing through the region within the light scattering body during the first, second, and third shooting periods; The light source is used to irradiate the first laser during the first shooting period, the second laser during the second shooting period, and the third laser during the third shooting period; The ultrasonic source emits ultrasonic waves at the moment of irradiation by the third laser, so that the ultrasonic waves reach the measurement position. The analytical device The first signal component is extracted using the signals from the first laser and the second laser passing through the region within the light scattering body; The second signal component is extracted using the signals from the second and third lasers passing through the region within the light scattering body; The modulation signal component is extracted from the first signal component and the second signal component.

2. The optical measurement device as claimed in claim 1, wherein, The ultrasonic source emits the ultrasonic waves to focus them at the measurement location.

3. The optical measurement device as described in claim 1, wherein, The first laser, the second laser, and the third laser are composed of multiple pulsed lasers.

4. The optical measurement device as claimed in claim 1, wherein, The ultrasonic source is capable of emitting pulsed ultrasonic waves.

5. The optical measurement device as claimed in claim 1, wherein, The interval is less than 200ms.

6. The optical measurement device as claimed in claim 1, wherein, The durations of the first shooting period, the second shooting period, and the third shooting period are equal.

7. An optical measurement device, comprising: The light source irradiates pulsed laser light into the light-scattering body; An ultrasonic source emits ultrasonic waves toward a measurement position located at a predetermined depth within the light scattering body; A detector that detects the laser light passing through a region within the light scattering body, including the measurement location; A control device for controlling the irradiation of the laser and the emission of the ultrasonic waves; as well as The analysis device extracts the modulated signal components modulated by the ultrasonic waves from the laser detected by the detector. The control device Set a first shooting period, a second shooting period, a third shooting period, and a fourth shooting period, such that the interval between the first shooting period and the second shooting period is equal to the interval between the third shooting period and the fourth shooting period; The detector is configured to detect the signal of the laser passing through the region within the light scattering body during the first, second, third, and fourth shooting periods. The light source is used to irradiate the first laser during the first shooting period, the second laser during the second shooting period, the third laser during the third shooting period, and the fourth laser during the fourth shooting period. The ultrasonic source emits ultrasonic waves at the moment of irradiation by the third laser, so that the ultrasonic waves reach the measurement position. The analytical device The first signal component is extracted using the signals from the first laser and the second laser passing through the region within the light scattering body; The second signal component is extracted using the signals from the third and fourth lasers that pass through the region within the light scattering body; The modulation signal component is extracted from the first signal component and the second signal component.

8. An analytical method for analyzing the modulation signal components generated by ultrasonic modulation of laser light irradiated onto a light scattering body at a measurement position located at a predetermined depth, comprising the following steps: Acquire the detection signal of the first laser beam that passes through the region within the light scattering body during the first shooting period; Acquire the detection signal of the second laser that passes through the region within the light scattering body during a second shooting period set at a predetermined interval from the first shooting period; Acquire the detection signal of a third laser that is irradiated and passes through the region of the light scattering body when the ultrasonic wave reaches the measurement position during a third shooting period set at a predetermined interval from the second shooting period; The first signal component is extracted using the detection signal of the first laser and the detection signal of the second laser; The second signal component is extracted using the detection signal from the second laser and the detection signal from the third laser; and The modulation signal component is extracted from the first signal component and the second signal component.

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