Optical measurement device and analysis method

Abstract

The light measuring device has a light source, an ultrasonic wave source, a detector, a control device, and an analysis device. The control device acquires a first speckle image and a second speckle image based on outputs of the detector acquired during a first imaging period and a second imaging period, causes the laser to emit light during the first imaging period and the second imaging period, and causes the ultrasonic wave to be emitted from the ultrasonic wave source so that the ultrasonic wave reaches a measurement position. The analysis device calculates a first variation component representing an amount of variation of speckles in a first region and a second variation component representing an amount of variation of speckles in a second region in the first speckle image and the second speckle image, and extracts a modulation signal component from the first variation component and the second variation component.

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] In speckle patterns obtained when focused pulsed ultrasound is present at a predetermined depth, not only are signals from ultrasound-modulated light present, but also noise is included. In Patent Document 1 and Non-Patent Document 3, the influence of noise in speckle patterns obtained when ultrasound is focused at the measurement position is mitigated based on speckle patterns obtained without emitting 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 difference between a speckle pattern obtained when ultrasound is focused at the measurement position and a speckle pattern obtained without ultrasound emission is extracted as a signal component modulated by ultrasound. However, since these speckle patterns are acquired at different times, the measurement conditions change in addition to the presence or absence of ultrasound. Therefore, the modulated signal component obtained by the above method may contain noise caused by the change in measurement conditions, and it is sometimes difficult to eliminate the influence of this noise 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 the light scattering body at a measurement position located at a predetermined depth. The detector detects the laser light passing through a region within the light scattering body including the measurement position. The control device controls the timing of laser irradiation and the start and end of ultrasonic wave emission. The analysis device extracts a modulation signal component modulated by the ultrasonic wave from the detector output. The control device acquires a first speckle image based on the detector output acquired during a first shooting period, and acquires a second speckle image based on the detector output acquired during a second shooting period. During both the first and second shooting periods, the laser irradiates the light, and during the second shooting period, ultrasonic waves are emitted from the ultrasonic source, causing the ultrasonic waves to reach the measurement position. The analysis device calculates a first variation component representing the speckle variation in a first region and a second variation component representing the speckle variation in a second region different from the first region in the first and second speckle images, and extracts the modulation signal component from the first and second variation components.

[0008] According to the analytical method of the second aspect of this disclosure, a method is provided for analyzing the modulation signal components generated by ultrasonic modulation of a laser beam irradiated into a light scattering body at a measurement position located at a predetermined depth. A first speckle image is generated based on the detector output obtained by detecting the laser beam passing through a region within the light scattering body during a first imaging period. A second speckle image is generated based on the detector output obtained by detecting the laser beam passing through a region within the light scattering body during a second imaging period when the ultrasonic wave reaches the measurement position. The analytical method includes the following steps: (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 variation component representing the speckle variation in a first region and a second variation component representing the speckle variation in a second region different from the first region; and (c) extracting the modulation signal components from the first variation component and the second variation component.

[0009] Invention Effects According to the optical measurement apparatus of this disclosure, the accuracy of extracting ultrasonically modulated light components from the detection signal obtained by the optical measurement apparatus using ultrasonic modulation optical tomography can be improved. Attached Figure Description

[0010] 【 Figure 1 [Illustration] is a schematic diagram of an optical measurement device according to an embodiment.

[0011] 【 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.]

[0012] 【 Figure 3 The figure shown is an example of the signal / background ratio distribution in a speckle pattern.

[0013] 【 Figure 4 The figure is used to illustrate a method for extracting signal components based on the signal / background ratio in speckle patterns.

[0014] 【 Figure 5 This is a flowchart illustrating the analysis and processing of modulation signal components according to an embodiment.

[0015] 【 Figure 6 The figure is used to illustrate the method for predicting the signal / background ratio distribution. Detailed Implementation

[0016] 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.

[0017] [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 image and laser detection signal in this disclosure.

[0018] 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.

[0019] 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.

[0020] 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 1 As 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.

[0021] 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 for focusing the emitted ultrasonic waves at the measurement location within the organism 20. The ultrasonic waves are focused at the point where the focal points of the ultrasonic waves emitted from the plurality of ultrasonic transducers of the ultrasonic source 2 are aligned. Within the focused region, the ultrasonic waves strongly interact 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.

[0022] The ultrasonic waves emitted from ultrasonic source 2 can be either 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 the 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 light irradiated from laser source 1 reaching the measurement location. Moreover, since the distance to the measurement location is sufficiently short relative to the distance traveled by light per unit time, the laser light reaches the measurement location approximately simultaneously with the irradiation of the pulsed laser light from laser source 1. Therefore, it can be considered that the timing of the irradiation of the laser light from laser source 1 and the timing of the laser light reaching the measurement location are substantially simultaneous.

[0023] 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.

[0024] 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 that is emitting ultrasound using a stroboscopic imaging method, and the image sensor 3a, while in the exposed state, captures a speckle pattern.

[0025] 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.

[0026] The light detected by camera 3 is a mixture of laser light (signal) that has passed through an area where ultrasound exists and is modulated by ultrasound, and laser light (background) that has not passed through an area where ultrasound exists and is therefore not modulated by ultrasound.

[0027] 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 a pulsed laser, 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.

[0028] The analysis device 5 extracts the modulation signal component modulated by ultrasound based on the detection signal of the laser detected by the camera 3. Details of the modulation signal component extraction method performed by the analysis device 5 will be described later.

[0029] [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.

[0030] 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.

[0031] Images of speckle patterns can be acquired through UOT-based optical measurements. To extract modulation signal components from the speckle pattern, which is the detection signal acquired through optical measurements, an analysis method based on the difference between images acquired when ultrasound is emitted and images acquired when ultrasound is not emitted is used.

[0032] However, the timing of acquiring an image when ultrasound is not emitted differs from the timing of acquiring an image when ultrasound is emitted. Therefore, noise may be introduced due to changes in measurement conditions that occur between the acquisition of the two images (e.g., organismal movement, changes in the state of tissues associated with life activities, and changes in laser mode). As described in the analysis method above, this noise is difficult to eliminate simply by taking the difference between the two images.

[0033] [Optical measurement method according to the implementation method] Therefore, in the optical measurement apparatus according to this embodiment, the optical measurement apparatus 10 extracts a first component and a second component that is more affected by the ultrasonically modulated laser than the first component from the difference between two images based on the signal / background (SB) ratio. Then, the modulated signal component is extracted by normalizing the second component with the first component.

[0034] In optical measurement, the difference between images acquired at two different times contains noise caused by the different acquisition times. If a first component is extracted from the region with a relatively low SB ratio in the difference between the two images, the first component can be considered as the variation in the two images caused by noise. Conversely, if a second component is extracted from the region with a relatively high SB ratio in the difference between the two images, the second component can be considered as the sum of the variation in the two images originating from ultrasonic modulation and the variation in the two images caused by noise. Since the noise has a roughly equal effect on each pixel of the two images, the first and second components are affected by the noise to an equal degree. Therefore, by excluding the first component from the second component, the variation in the two images originating from ultrasonic modulation can be extracted. In other words, by using the optical measurement apparatus according to this embodiment, the accuracy of extracting the modulation signal component from the results obtained from measuring laser light can be improved.

[0035] First, the timing of the optical measurement device 10 taking 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 timing of the camera 3 of the optical measurement device 10 taking pictures, the timing of the pulsed laser lighting, and the timing of the ultrasonic wave emission according to the embodiment.

[0036] <1. Setup during filming> First, the user sets the shooting period for camera 3 to capture the speckle pattern. During the shooting period, camera 3 uses image sensor 3a, which is in an exposed state, to capture the speckle pattern. Therefore, the acquired image is obtained by superimposing the speckle patterns formed by the laser received during the shooting period.

[0037] 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.

[0038] The shooting schedule was set for two sessions. Figure 2 In the image, the first and second shooting periods are represented. After each shooting period, the acquired signals are read to obtain the first and second speckle patterns, respectively.

[0039] <2. Setting the Timing of Laser Irradiation> The user sets the timing for irradiating the first laser from laser source 1 and the timing for irradiating the second laser. For example... Figure 2 As shown, the first laser irradiates during the first shooting period, and the second laser irradiates during the second shooting period. Since it is a laser with a pulse width, the laser irradiation timing is defined, for example, at the rising edge of the pulse. 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 laser irradiation time.

[0040] <3. Setting the timing of ultrasonic wave emission> Next, the user sets the timing for emitting ultrasonic waves from the ultrasonic source 2. Specifically, ultrasonic waves are emitted from the ultrasonic source 2 when the second laser passes through the organism 20, causing the ultrasonic waves to reach the measurement position. The control device 4 sends an ultrasonic drive signal to the 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 second laser irradiation.

[0041] The ultrasonic delay time can be calculated based on the distance (depth) from the ultrasonic source 2 to the measurement location. Furthermore, since the ultrasonic waves emitted from 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. Moreover, since the distance to the measurement location is sufficiently short relative to the distance light travels per unit time, it can be assumed that the laser irradiation timing and the arrival timing of the laser at the measurement location 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 location within the organism 20.

[0042] <4. Acquired Images> 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, and the speckle pattern originating from the second laser corresponds to the second speckle pattern. In this specification, the speckle pattern corresponds to the laser signal and image.

[0043] <5. Calculation of SB ratio distribution> The first speckle pattern was acquired under conditions where no ultrasonic waves were emitted. On the other hand, the second speckle pattern was acquired under conditions where ultrasonic waves were focused at the measurement location. That is, the acquisition conditions for the first and second speckle patterns are the same, except for whether ultrasonic waves were emitted and the shooting period during acquisition. Therefore, the difference between the first and second speckle patterns corresponds to the superposition of noise components and modulation signal components caused by differences in the shooting period. Specifically, for example, the result obtained by 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 is equivalent to the superposition of noise components and modulation signal components generated during the shooting interval. In this case, the difference between the first and second speckle patterns is calculated as an image.

[0044] Here, the variation in speckle pattern caused by ultrasonic modulation is usually greater than the variation caused by noise. Therefore, pixels with a larger difference in pixel values ​​between the first and second speckle patterns are identified as pixels that tend to be strongly affected by ultrasonic modulation.

[0045] Figure 3 This is a diagram illustrating an example of the distribution of the SB ratio in a speckle pattern. Figure 3 In this context, areas with low pixel values ​​(darker colors) represent areas with low SB ratios, and areas with high pixel values ​​(lighter colors) represent areas with high SB ratios. Figure 3 In the speckle pattern, areas with high pixel values ​​are more susceptible to ultrasonic interference. For example, region R1 has a low SB ratio, while region R2 has a high SB ratio.

[0046] Figure 3 The diagram shown is, for example, calculated by subtracting the pixel values ​​of the corresponding pixels of the first speckle pattern from the pixel values ​​of each pixel of the second speckle pattern.

[0047] Furthermore, the method for analyzing the degree of state change between two speckle patterns is not limited to the method of accumulating the absolute value of the difference between corresponding pixel values ​​as described above. For example, various general analysis methods for calculating image similarity, methods for accumulating the square of the difference between corresponding pixel values, and methods using normalized cross-correlation can be applied to analyze the degree of state change between two speckle patterns. In addition, necessary preprocessing can be performed on the two speckle patterns as the objects of analysis before similarity calculation. For example, predetermined target regions can be set in the two speckle patterns, the contrast of the speckle patterns in each target region can be calculated, and a speckle pattern contrast image obtained by mapping can be used.

[0048] <6. Extraction of Two Signal Components> Based on the distribution of the SB ratio, a first component and a second component containing more modulation signal components compared to the first component are extracted from the first and second speckle patterns. Specifically, firstly, the optical measurement device 10 obtains an image representing the variation of the two speckle patterns by subtracting the pixel values ​​of the corresponding pixels of the first speckle pattern from the pixel values ​​of each pixel of the second speckle pattern. Next, based on the distribution of the SB ratio, the optical measurement device 10 determines in this image the regions composed of pixels with relatively low SB ratios and the regions composed of pixels with relatively high SB ratios. Then, the optical measurement device 10 extracts the first component from the regions composed of pixels with relatively low SB ratios and extracts the second component from the regions composed of pixels with relatively high SB ratios. The first and second components are, for example, the sum, average, and median values ​​of the pixel values ​​of the pixels in each region.

[0049] <7. Extraction of Modulation Signal Components> The modulated signal components are calculated by subtracting the first component from the second component, dividing the second component by the first component, or normalizing the second component with the first component using other processing methods.

[0050] Furthermore, although the first and second components were extracted from two clearly distinguished regions in the above embodiments, this is not a limitation. Alternatively, the results obtained by summing the pixel value changes in the two speckle patterns calculated at each pixel, using the SB ratio as a coefficient, can also be used to extract the modulation signal components. For example, the modulation signal components can be obtained by using the results obtained from weighted analysis of coefficients in regions with low SB ratios and the results obtained from weighted analysis of coefficients in regions with high SB ratios.

[0051] Furthermore, in the above embodiments, the images used to determine the SB ratio distribution are the same as those used to extract the first and second components, but different images can also be used. That is, after calculating the SB ratio distribution using images acquired without emitting ultrasound and images acquired with ultrasound focused at a predetermined measurement position, the first and second components can be extracted from different images using this SB ratio distribution. The SB ratio distribution determined at the predetermined measurement position is the same at that measurement position, and therefore can also be applied to images not used for calculating the SB ratio.

[0052] Figure 4 This is a diagram showing different speckle patterns measured at the same measurement location as the second speckle pattern. In this case, it can also be applied... Figure 3 The distribution of the SB ratio calculated in the data. That is, the SB ratio is low in region R1 and high in region R2.

[0053] [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 two speckle patterns 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.

[0054] In step S10, the optical measurement device 10 receives information from the user regarding the period during which the camera 3 receives the laser, namely the first shooting period and the second shooting period.

[0055] In step S12, the photometry device 10 irradiates the organism 20 with a first laser during the first shooting period.

[0056] In step S14, the optical measuring device 10 detects the first speckle pattern.

[0057] In step S16, the optical measuring device 10 emits ultrasonic waves at a predetermined time to the organism 20. The predetermined time refers to the moment when the ultrasonic waves reach the measuring position of the organism 20 after the second laser irradiated in step S18 has passed through the organism 20.

[0058] In step S18, the photometer 10 irradiates the organism 20 with a second laser during the second imaging period.

[0059] In step S20, the optical measuring device 10 detects the second speckle pattern.

[0060] 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.

[0061] In step S24, the optical measurement device 10 takes the difference in pixel values ​​of each pixel of the first speckle pattern and the second speckle pattern to generate an image representing the change of the two speckle patterns.

[0062] 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 representing the variation of the two speckle patterns generated in step S24, based on the distribution of the SB ratio calculated in step S22.

[0063] In step S28, the optical measurement device 10 calculates the modulation signal components based on the first component and the second component. Afterward, the optical measurement device 10 terminates the analysis processing subroutine and returns the processing to the main program.

[0064] In addition, Figure 5 In the described process, the optical measurement device 10 emits ultrasonic waves before irradiating the second laser, but it can also emit ultrasonic waves before irradiating the first laser, i.e., before step S12. In this case, the first speckle pattern contains a modulation signal component.

[0065] In the above analysis, since the first component and the second component, which contains the modulation signal, are extracted from the variations of the two speckle patterns, both components are affected by noise to an equal degree. Therefore, by normalizing the second component based on the first component, the accuracy of extracting the ultrasonically modulated light component can be improved.

[0066] (Modified example) In the above embodiments, the distribution of the SB ratio is calculated based on the measured image, but the optical measurement device 10 can also predict the distribution of the SB ratio through simulation and determine the regions with high SB ratio and low SB ratio in the speckle pattern difference.

[0067] Figure 6The results of an optical simulation of the scattering and absorption of laser light incident from laser source 1 into the head tissue are shown. Figure 6 It is an image that schematically shows a cross-section of the internal structure of the head tissue.

[0068] like Figure 6 As shown, the user defines the internal structure of the head tissues. The head tissues consist 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 tissue's scattering and absorption coefficients. Furthermore, the thickness of each tissue was determined using measured values ​​based on magnetic resonance imaging.

[0069] The user decides which area within the head tissue to measure. This area is where the ultrasound waves are focused and corresponds to the measurement location. Let's assume the focused area is a cylinder with a diameter of 10mm and a height of 10mm. The focused area corresponds to the resolution in the measurement.

[0070] Figure 6 The diagram shows the predicted path of the laser emitted from laser source 1. After incident on the head, the laser emitted from laser source 1 undergoes scattering and absorption in various tissues. A portion of the laser passes through the area focused by the ultrasound and is captured by camera 3. A portion of the laser emitted from laser source 1 does not pass through the area focused by the ultrasound and is captured by camera 3. The remaining laser is not captured by camera 3.

[0071] The speckle pattern acquired by camera 3 can be predicted based on the predicted laser path. The distribution of the SB ratio can be predicted based on the difference between the predicted speckle pattern obtained when the ultrasound is focused on the measurement position and the predicted speckle pattern obtained without ultrasound.

[0072] For example, the first speckle pattern and the second speckle pattern in the above embodiments can be obtained, and the first component and the second component can be extracted based on the distribution of the predicted SB ratio by simulation.

[0073] By implementing simulation-based prediction of the SB ratio distribution, the first and second components of the obtained speckle pattern can be extracted without analyzing the distribution of the SB ratio based on measured values.

[0074] Based on the aforementioned optical measurement device, a first component and a second component containing the modulation signal are extracted from the variations in two speckle patterns acquired at different times. These components are affected by noise to an equal degree. Therefore, by normalizing the second component based on the first component, the accuracy of extracting the ultrasonically modulated optical component can be improved.

[0075] Furthermore, as a variation, by using simulation to calculate the distribution of the SB ratio, the distribution of the SB ratio can be determined independently of the measurement data. Therefore, for example, the distribution of the SB ratio can be determined without being affected by the variations caused by noise in the two speckle patterns.

[0076] [plan] Those skilled in the art will understand that the above-described exemplary embodiments are specific examples of the following solutions.

[0077] (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 beam passing through a region within the light scattering body including the measurement position; a control device that controls the timing of the irradiation of the laser beam and the start and end of the ultrasonic wave emission; and an analysis device that extracts a modulated signal component modulated by the ultrasonic wave from the output of the detector, wherein the control device obtains a first scattering signal based on the output of the detector acquired during a first imaging period. A second speckle image is obtained based on the output of the detector acquired during a second capture. During both the first and second captures, the laser is applied, and during the second capture, the ultrasonic wave is emitted from the ultrasonic source so that the ultrasonic wave reaches the measurement position. The analysis device calculates a first variation component representing the speckle variation in a first region and a second variation component representing the speckle variation in a second region different from the first region in the first and second speckle images, and extracts the modulation signal component from the first and second variation components.

[0078] According to the optical measurement device described in claim 1, it is possible to improve the accuracy of extracting the ultrasonically modulated optical component from the detection signal obtained by the optical measurement device using ultrasonically modulated optical tomography.

[0079] (Item 2) In the optical measurement apparatus described in Item 1, the analysis apparatus may determine the first region and the second region based on: the output of the detector obtained when the laser passes through the light scattering body and the state in which the ultrasonic wave reaches the measurement position, and the output of the detector obtained when the laser passes through the light scattering body and the state in which the ultrasonic wave does not reach the measurement position.

[0080] According to the optical measurement device described in item 2, the distribution of the SB ratio is calculated based on the measured value, and the region for extracting the first component and the second component is determined based on the distribution of the SB ratio.

[0081] (Item 3) In the optical measurement device described in Item 1, the analysis device can determine the first region and the second region based on a simulation model within the light scattering body.

[0082] According to the optical measurement device described in item 3, the distribution of the SB ratio is calculated based on simulation, and the regions for extracting the first component and the second component are determined based on the distribution of the SB ratio.

[0083] (Item 4) In any one of items 1 to 3, the ultrasonic source can focus the ultrasonic waves emitted from a plurality of ultrasonic vibrations onto the measurement position, thereby focusing the ultrasonic waves at the measurement position.

[0084] According to the optical measurement device described in item 4, the light component modulated at the measurement position can be extracted, thereby improving the spatial resolution in optical measurement.

[0085] (Item 5) In any one of items 1 to 4, the laser may be composed of a plurality of pulsed lasers.

[0086] According to the optical measurement device described in item 5, the intensity of the detection signal can be increased, thereby improving the accuracy of extracting the modulated signal components.

[0087] (Item 6) In any one of the optical measuring apparatuses in items 1 to 5, the ultrasonic source can emit pulsed ultrasonic waves.

[0088] According to the optical measurement device described in item 6, 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.

[0089] (Item 7) According to one method, a method for analyzing the modulation signal components generated by ultrasonic modulation of laser light irradiated into a light scattering body at a measurement position located at a predetermined depth, wherein a first speckle image is generated based on the output of the detector obtained by the detector detecting the laser light passing through a region within the light scattering body during a first imaging period, and a second speckle image is generated based on the output of the detector obtained by the detector detecting the laser light passing through a region within the light scattering body during a second imaging period when the ultrasonic wave reaches the measurement position. The analysis method includes the following steps: acquiring the first speckle image and the second speckle image; calculating a first variation component representing the speckle variation in a first region and a second variation component representing the speckle variation in a second region different from the first region in the first and second speckle images; and extracting the modulation signal components from the first variation component and the second variation component.

[0090] According to the analytical method described in item 7, 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.

[0091] 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 in 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.

[0092] 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; The control device controls the timing of the laser irradiation and the start and end of the ultrasonic wave emission; and The analysis device extracts the modulated signal components modulated by the ultrasonic waves from the output of the detector. The control device A first speckle image is obtained based on the detector output acquired during the first image capture, and a second speckle image is obtained based on the detector output acquired during the second image capture. The laser is applied during both the first and second shooting periods. During the second imaging period, the ultrasonic wave is emitted from the ultrasonic source, causing the ultrasonic wave to reach the measurement location. The analytical device In the first speckle image and the second speckle image, a first variation component representing the speckle variation in the first region and a second variation component representing the speckle variation in the second region, which is different from the first region, are calculated. The modulation signal components are then extracted from the first variation component and the second variation component.

2. The optical measurement device as claimed in claim 1, wherein, The analysis device determines the first region and the second region based on: the output of the detector obtained when the laser passes through the light scattering body and the state where the ultrasonic wave reaches the measurement position, and the output of the detector obtained when the laser passes through the light scattering body and the state where the ultrasonic wave does not reach the measurement position.

3. The optical measurement device as described in claim 1, wherein, The analysis device determines the first region and the second region based on a simulation model within the light scattering body.

4. The optical measurement device as claimed in claim 1, wherein, The ultrasonic source focuses the ultrasonic waves emitted from a plurality of ultrasonic transducers onto the measurement location, thereby focusing the ultrasonic waves at the measurement location.

5. The optical measurement device as claimed in claim 1, wherein, The laser is composed of multiple pulsed laser beams.

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

7. 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, wherein... A first speckle image is generated based on the detector output obtained by detecting the laser light passing through the region within the light scattering body during the first image capture. A second speckle image is generated based on the detector's output, obtained by detecting the laser light passing through the region within the light scattering body during the second imaging period when the ultrasonic wave reaches the measurement position. The analytical method includes the following steps: Acquire the first speckle image and the second speckle image; In the first speckle image and the second speckle image, a first variation component representing the speckle variation in the first region and a second variation component representing the speckle variation in the second region, which is different from the first region, are calculated. as well as The modulation signal components are extracted from the first variation component and the second variation component.

Images