Measuring device, measuring method, and program

Abstract

To provide a measuring device that can accurately measure information on an analyte by using light.SOLUTION: A measuring device (100) acquires information on an analyte (190), and has: an irradiation unit (110) that irradiates a specific area of the analyte with irradiation light; a detection unit (120) that receives emitted light emitted from the analyte when the specific area is irradiated with the irradiation light; and a processing unit (130) that processes a signal output from the detection unit. The processing unit causes the irradiation unit to form a wavefront of the irradiation light, while feeding back a first signal output by the detection unit when the detection unit receives the emitted light, and acquires information on the specific area by using a second signal output from the detection unit when the detection unit receives emitted light emitted from the analyte when the analyte is irradiated with irradiation light after the formation of the wavefront.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a measuring apparatus, a measuring method, and a program for measuring information of a subject using light.

Background Art

[0002] Patent Document 1 discloses a method and an apparatus for extracting parameters in blood, such as the amount of hemoglobin in blood and oxygen saturation, by measuring dynamic changes in blood flow in a living body using the dynamic light scattering method (DLS). Patent Document 2 discloses a measuring instrument for non-invasively measuring the scattering coefficient of a region including a blood vessel site and calculating the lipid concentration in blood from the scattering coefficient.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] According to the configurations disclosed in Patent Document 1 and Patent Document 2, a subject can be measured non-invasively and simply. However, since the wavefront of light is not shaped during measurement, it is difficult to accurately measure information such as minute changes in physiological parameters in a living body as information of the subject due to the influence of light scattering.

[0005] Therefore, an object of the present invention is to provide a measuring apparatus, a measuring method, and a program capable of accurately measuring information of a subject using light.

Means for Solving the Problems

[0006] As one aspect of the present invention, a measuring device includes an irradiation unit that irradiates irradiation light onto a specific region of a subject, a detection unit that receives emitted light emitted from the subject when the irradiation light is irradiated onto the specific region, and a processing unit that processes a signal output from the detection unit. The detection unit includes a first detection unit and a second detection unit that are arranged at different positions from each other. The processing unit The first forms the wavefront of the irradiation light on the irradiation unit based on the 1 first signal intensity and a second signal intensity output from the second detection unit by receiving the emitted light signal output from the detection unit, and of the shaped uses the second second 3 signal output from the detection unit upon receiving the emitted light emitted from the subject when the irradiation light is irradiated onto the subject to intensity acquire information regarding the specific region. and causes the irradiation unit to shape the wavefront so that a fourth signal intensity output from the first detection unit by receiving the emitted light emitted from the subject when the shaped wavefront irradiation light irradiates the subject is lower than the first signal intensity and the third signal intensity is higher than the second signal intensity.

[0007] Other objects and features of the present invention will be described in the following examples.

Advantages of the Invention

[0008] According to the present invention, it is possible to provide a measuring device, a measuring method, and a program capable of measuring information of a subject with high precision using light.

Brief Description of the Drawings

[0009]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Modes for Carrying Out the Invention

[0010] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

[0011] (First Embodiment) First, referring to FIG. 1, the measuring device in the first embodiment of the present invention will be described. FIG. 1 is a block diagram of a measuring device (subject information measuring device) 100 in this embodiment. The measuring device 100 in this embodiment can acquire (measure) information of a subject, and includes a light source 101, an irradiation unit 110, a detection unit 120, and a processing unit 130. The irradiation unit 110 irradiates a specific region of the subject 190 with the light emitted from the light source 101 as irradiation light 151. The detection unit 120 receives the emitted light 161, 162 emitted from the subject 190 when the irradiation light 151 is irradiated on the specific region of the subject 190. The processing unit 130 processes the signal output from the detection unit 120 and includes a control unit 131, a data acquisition unit 132, a signal processing unit 133, and a memory 134.

[0012] The light source 101 is, for example, a laser that emits continuous light (CW light: Continuous Wave light) with a wavelength in the range of 300 nm to 1200 nm and a constant intensity over time. For example, the wavelength can be selected according to the absorption spectrum of the item to be measured from water, fat, protein, oxyhemoglobin, deoxyhemoglobin, etc., which are the main components of the subject 190. Alternatively, when measuring the scattering coefficient, a wavelength avoiding the aforementioned absorption wavelength may be selected. However, depending on the purpose, the wavelength may be outside the aforementioned range, and the laser may emit light intensity-modulated at an arbitrary frequency or pulsed light. Also, it is desirable that the coherence length of the emitted light is sufficiently long (for example, several centimeters or more). Note that the light intensity irradiated on the subject 190 is adjusted within the intensity below the irradiable safety standard.

[0013] The light 150 emitted from the light source 101 is collimated and enters the wavefront shaping unit 111 of the irradiation unit 110. The wavefront shaping unit 111 is composed of a spatial light modulator (SLM). As the SLM, phase modulation is desirable, but amplitude modulation may also be used. Also, the wavefront shaping unit 111 may be either a transmissive or reflective SLM. Specifically, an LCOS (Liquid Crystal On Silicon), DMD (Digital Mirror Device), GLV (Grating Light Valve), etc. can be used as the SLM. Also, it is desirable that the SLM can be modulated as fast as possible (for example, several kHz or more).

[0014] The wavefront shaping unit 111 performs wavefront shaping processing (Wavefront Shaping: WFS) described later, and irradiates the subject 190 with the light having the shaped wavefront as the irradiation light 151. The wavefront shaping unit 111 performs phase modulation or amplitude modulation based on the base pattern to shape the wavefront of the irradiation light 151. At this time, the irradiation unit 110 may have an optical system for irradiating collimated light or focused light with an arbitrary beam size. Alternatively, the irradiation unit 110 may include an optical fiber, and irradiate the subject 190 with the light shaped by the wavefront shaping unit 111 via the optical fiber.

[0015] The emitted lights 161 and 162 that propagate inside the subject 190 and are emitted at different distances from the irradiation position on the surface of the subject 190 are received by the detector (first detector) 121 and the detector (second detector) 122 of the detection unit 120, respectively. The detection unit 120 may have an optical system for condensing the emitted lights 161 and 162 from the subject 190 onto the detectors 121 and 122. Alternatively, the emitted lights 161 and 162 may be respectively guided to the detectors 121 and 122 via optical fibers. The detectors 121 and 122 can use sensors such as photodetectors (PDs), avalanche photodiodes (APDs), and photomultiplier tubes (PMTs). Alternatively, two-dimensional array sensors such as CMOS and CCD can also be used. Note that it is desirable for the detectors 121 and 122 to respond at high speed (>1 MHz).

[0016] The light intensities received by the detectors 121 and 122 are converted into electrical signals, and the signals are passed to the data acquisition unit 132. The data acquisition unit 132 amplifies the signal with an amplifier circuit as necessary, and performs AD conversion on the amplified signal to generate a digital signal. The signal processing unit 133 performs various signal processes on the digital signal as necessary. The memory 134 appropriately stores measurement results, intermediate information during measurement, etc. Also stored in the memory 134 are measurement flows, measurement conditions, or parameters necessary for analysis, etc. The signal processing unit 133 appropriately accesses the memory 134 according to the process, and executes the process with reference to the necessary information.

[0017] The control unit 131 controls each module of the light source 101, the irradiation unit 110, the detection unit 120, and the processing unit (data acquisition unit 132, signal processing unit 133, and memory 134) of the measurement device 100 based on a measurement flow (measurement method) described later.

[0018] Next, with reference to FIG. 2, the propagation path of the irradiation light 151 emitted from the irradiation unit 110 until it propagates through the inside of the subject 190 and exits will be described. FIG. 2 is a schematic diagram of the propagation path of the irradiation light 151 emitted from the irradiation unit 110 until it propagates through the inside of the subject 190 and exits. The irradiation light 151 is affected by the scatterers 191 derived from cells and tissue structures inside the subject 190, and propagates inside the subject 190 while repeating scattering many times. Depending on the horizontal distance ρ from the light irradiation position where the irradiation light 151 enters the subject 190, the path through which the emitted light propagates inside the subject 190 is different. For example, at the emission position of the emitted light 161, it has a banana-shaped distribution with the spread shown in the propagation path 155. Similarly, at the emission position of the emitted light 162, it has a distribution like the propagation path 156.

[0019] Comparing the two propagation paths 155 and 156, the propagation path 156 penetrates and propagates to a deeper region of the subject 190. That is, the larger the distance ρ between the irradiation position and the detection position, the more the detected emitted light is the light that has propagated to a deep position in the subject 190, and it becomes the light reflecting the optical characteristics of the deep position inside the subject 190. This propagation path can be estimated using the radiative transfer equation or the diffusion equation, which is a diffusion approximation thereof, based on the absorption coefficient and scattering coefficient, which are the optical characteristics of the subject 190. That is, by adjusting the distance ρ, it is possible to specify the propagation region of light in the depth direction inside the subject 190.

[0020] The detection unit 120 can arbitrarily set the detection positions (distance ρ) at which the detectors 121 and 122 receive light so that the emitted light from an arbitrary emission position can be measured on the surface of the subject 190. As shown in FIG. 2, the detector 121 detects the emitted light 161 that has propagated through a specific region near the surface layer of the subject 190 (the first region: a region that does not include blood vessels (non-vascular region)). On the other hand, the detector 122 sets the distance ρ so as to detect the emitted light 162 that has propagated to the blood vessel site 192 (the second region: a region that includes blood vessels (vascular region)), which is a relatively deep specific region of the subject 190.

[0021] Next, with reference to FIG. 3, the measurement method in this embodiment will be described. FIG. 3 is a flowchart of the measurement method in this embodiment. Each step in FIG. 3 is mainly executed by the irradiation unit 110, the detection unit 120, and the processing unit 130 of the measurement device 100.

[0022] First, in step S10, the processing unit 130 measures the emitted light 161 and performs WFS based on the signal intensity of the light that has propagated through the first region (non-vascular region). WFS shapes (optimizes) the wavefront (phase distribution or amplitude distribution) of the irradiation light 151 incident on the subject 190 such that the monitored feedback signal (first signal) is maximized or minimized. The processing in step S10 more specifically includes steps S11 and S12.

[0023] First, in step S11, the processing unit 130 measures the light intensity measured by the detector 121 as the feedback signal. This light intensity is the average value of the light intensity received by the detector 121 over a certain period of time. Subsequently, in step S12, the processing unit 130 performs wavefront shaping of the irradiation light 151 using the wavefront shaping unit 111. That is, the processing unit 130 shapes the wavefront of the irradiation light 151 in the irradiation unit 110 while feeding back the first signal (first feedback signal) obtained by receiving the emitted light 161 that has propagated through the non-vascular region (first region) and exited the subject 190 by the detection unit 120. The wavefront shaping can be performed based on a modulation pattern (basis pattern) such as an Hadamard basis displayed on the SLM (wavefront shaping unit 111).

[0024] Here, referring to FIG. 4, the modulation pattern will be described. FIG. 4 is a schematic diagram of the SLM (wavefront shaping unit 111) and the modulation pattern. The modulation pattern 113 is displayed on the SLM, and the light 150 emitted from the light source 101 is irradiated onto the modulation pattern 113. The white portion 114 of the modulation pattern 113 indicates a non-modulation region where phase modulation is not performed, and the gray portion 115 indicates a modulation region where phase modulation is performed. For the non-modulation region, in the modulation region, the phase is modulated with an arbitrary number of steps, and the irradiated light 151 modulated with that phase is irradiated onto the subject 190. Again, in step S11, the control unit 131 measures the feedback signal. Steps S11 and S12 are repeated for the number of steps, the phase when the feedback signal becomes maximum is searched for and set in the SLM (N = 1). Further, the processes of steps S11 and S12 are executed for an arbitrary number of modulation patterns N. After executing step S10 (the iterative process of steps S11 and S12) for N times of the number of patterns, the processing unit 130 ends the WFS for the first region. Note that FIG. 4 shows an example of a two-dimensional SLM and a two-dimensional modulation pattern 113, but a one-dimensional SLM and a one-dimensional modulation pattern may also be used.

[0025] After step S10 ends, the process proceeds to step S20. In step S20, the processing unit 130 irradiates the subject 190 with the irradiated light 151 shaped by the wavefront obtained in step S10 and executes DLS to acquire a first measurement signal (second signal). Specifically, the processing unit 130 measures the temporal change in the light intensity of the emitted light 161 when continuously irradiating the irradiated light (first irradiated light) 151 of the (optimized) wavefront shaped in step S10 using the detector 121. That is, the processing unit 130 irradiates the first irradiated light after wavefront shaping onto the subject 190 and measures (calculates) the second signal (correlation function g(τ)). The correlation function g(τ) is expressed as in the following formula (1).

[0026]

Equation

[0027] In Equation (1), I(t) represents the light intensity at time t, τ represents the delay time, and < > represents the average, respectively. The calculation of the correlation function g(τ) may be performed using a hardware correlator. That is, the detection unit 120 includes a correlator, outputs the correlation function g(τ) from the output signal of the detector, and passes it to the data acquisition unit 132. Alternatively, the correlation function g(τ) may be calculated software-wise. For example, the light intensity I(t) received by the detection unit 120 is received by the data acquisition unit 132 and stored in the memory 134. Next, it is also possible for the signal processing unit 133 to read out the light intensity I(t) from the memory 134 and calculate the correlation function g(τ) by digital signal processing. FIG. 5 shows the measured correlation function g(τ), that is, an example of the measurement signal. In FIG. 5, the horizontal axis represents the delay time τ [s], and the vertical axis represents the correlation function g(τ), respectively. In the present embodiment, the correlation function 141 measured in step S20 is used as the first measurement signal (the second signal regarding the first region).

[0028] Subsequently, in steps S30 and S40, the processing unit 130 performs the same processing as in steps S10 and S20, respectively, on the detection position of the emitted light 162. More specifically, first in step S30, the processing unit 130 uses the light intensity of the emitted light 162 received by the detector 122 as a feedback signal and executes the WFS so that the feedback signal becomes maximum. As described above, the processing unit 130 measures the feedback signal using the detection unit 120 in step S31 and shapes the wavefront of the irradiation light 151 using the wavefront shaping unit 111 in step S32. That is, the processing unit 130 shapes the wavefront of the irradiation light 151 in the irradiation unit 110 while feeding back the first signal (the second feedback signal) obtained by receiving the emitted light 162 that has propagated through the second region (vascular region) and is emitted from the subject 190 by the detection unit 120. The control unit 131 repeats the iterative processing of steps S31 and S32 N times for the number of patterns, and optimizes the wavefront of the irradiation light 151 so that the intensity of the emitted light 162 that has propagated through the second region (vascular region) becomes maximum.

[0029] Here, constraints may be imposed so that the emitted light 162 selectively propagates through the second region. For example, in the WFS of step S32, after imposing constraints such that the light intensity of the emitted light 161 output from the detector 121 is minimized, the wavefront of the irradiation light 151 can be optimized such that the light intensity of the emitted light 162 output from the detector 122 is maximized. By the constraints, while suppressing the light propagating through the surface layer of the subject 190, the wavefront of the irradiation light 151 is optimized so that the signal intensity of the light that propagates to and is emitted from the deep blood vessel site 192 of the subject 190 becomes as large as possible. By this WFS, while specifying the propagation region, the S / N of the measurement feedback signal can be improved.

[0030] After step S30 ends, the process proceeds to step S40. In step S40, the processing unit 130 irradiates the subject 190 with the wavefront irradiation light 151 obtained in step S30, and performs DLS to obtain the correlation function g(τ) in the same manner as in step S20. That is, the processing unit 130 irradiates the subject 190 with the irradiation light (second irradiation light) 151 after wavefront shaping to measure the second signal. For example, in step S40, the correlation function 142 shown in FIG. 5 is measured. This is used as the second measurement signal (second signal regarding the second region). The measurement is completed above, and all the measured data is stored in the memory 134 from the data acquisition unit 132.

[0031] Subsequently, in step S50, the processing unit 130 compares and evaluates the first measurement signal measured in step S20 and the second measurement signal measured in step S40. That is, the processing unit 130 compares the second signal based on the first irradiation light and the second signal based on the second irradiation light to acquire information on the subject 190. The first measurement signal is the light that has propagated through the surface layer portion of the subject 190 as described above, and since there are almost no elements in which dynamic scattering changes, the temporal change in scattering is small. On the other hand, the second measurement signal includes the blood vessel site 192 and the scattering changes dynamically, so the temporal change in scattering is large.

[0032] Therefore, as shown in FIG. 5, the correlation function of the first measurement signal has a long time τ until the correlation decays, and the correlation function of the second measurement signal decays in a relatively short time. Therefore, it is possible to use the first measurement signal with relatively stable results as reference data and measure the relative change in how much the second measurement signal has changed with respect to this. For example, as a method of comparing and evaluating these two signals, the respective correlation functions g(τ) may be fitted with an exponential function exp(−Γτ), the decay coefficient Γ may be calculated, and these may be compared. Let the decay coefficients of the first measurement signal and the second measurement signal be Γ1 and Γ2, respectively, and the time change of the ratio γ = Γ2 / Γ1 or the difference γ = Γ2−Γ1 may be monitored. Note that FIG. 5 shows the correlation function after normalization, but normalization is not necessary, and various analyses other than the decay coefficient can be performed on the measured correlation function for evaluation. It is also possible to compare the delay times until the correlation function decays to a certain value without performing fitting.

[0033] The above is the measurement flow of this embodiment. Note that pre-measurement may be performed to determine measurement conditions and measurement parameters before step S10. Based on the results of the pre-measurement, the detection positions ρ of the emitted lights 161 and 162, parameters related to the WFS, measurement conditions of the DLS, and the like may be determined.

[0034] Here, in this embodiment, DLS is used as a method for measuring information (physiological parameters of a living body) of the subject 190. As described above, in DLS, the temporal variation of scattered light is reflected in the correlation function. For example, that which gives dynamic variation to the scattered light such as blood flow and the variation in light intensity as an average bias component can be distinguished by the delay time τ or frequency analysis. The latter is, for example, an error component such as a system error on the light source or detection side, or light absorption without local temporal change of the subject 190. Therefore, by obtaining a measurement signal using DLS, it is possible to measure biological information robustly with less influence of error factors compared to simply measuring the light intensity. As physiological parameters of a living body, the correlation function changes depending on the scattering coefficient in blood, blood flow rate, and the like.

[0035] Therefore, by targeting the blood vessel site 192 and monitoring the change over time of the attenuation coefficient Γ2 of the second measurement signal, it is possible to monitor the change in the scattering characteristics in the blood. For example, if the scattering in the blood increases, the attenuation coefficient Γ2 will increase. Thus, by implementing the measurement flow shown in FIG. 3 using the measurement device 100 of this embodiment, it is possible to monitor changes in optical characteristics such as scattering in the blood. Also, by changing the wavelength of the light source 101, it is possible to measure other physiological parameters related to the blood, such as the amount of hemoglobin and oxygen saturation in the blood, from the DLS measurement results.

[0036] According to this embodiment, by applying WFS to maximize the feedback signal, scattered light that more reflects the optical characteristics of a specific region (the first region or the second region) inside the subject 190 can be measured with an improved S / N. Furthermore, when measuring the physiological parameters of the subject 190, instead of directly using the feedback signal, another signal, which is a correlation function based on DLS, is measured. The feedback signal varies depending on the measurement conditions of WFS, such as the number of patterns N. That is, since the feedback signal is an operable signal on the device side, this measurement result cannot be directly used as a signal for measuring biological information. Therefore, in this embodiment, another measurement signal that can utilize the effect of improving the feedback signal by WFS is obtained.

[0037] In addition, in the measurements of step S20 and step S40, if the effect of improving the S / N by WFS disappears, the WFS of step S10 and step S30 may be executed again, and then the measurements of step S20 and S40 may be executed again. For example, the feedback signal can be monitored in step S20 and step S40, and it can also be determined whether to re-execute WFS by comparing the feedback signal with a preset threshold. Also, as will be described in another embodiment below, the feedback signal can also use other signals.

[0038] In this embodiment, preferably, the processing unit 130 measures the measurement signal (second signal) based on a parameter related to the attenuation or delay time of the correlation function. Also preferably, the first detector (detector 121) receives the emitted light that has propagated through the first region (non-vascular region) as a specific region and is emitted from the subject, and the second detector (detector 122) receives the emitted light that has propagated through the second region (vascular region) as a specific region and is emitted from the subject.

[0039] In this embodiment, if the signal intensity of the emitted light 161 in step S11 is sufficient in terms of S / N, the process of step S10 may be omitted. In this case, the measurement is started from step S20. Also, in this embodiment, two detectors 121 and 122 are provided, but the number of detectors is not limited to two. When there is one detector, steps S10 and S20 may be omitted, and steps S30 and subsequent steps may be implemented to measure only the second measurement signal. In this case, in step S50, the comparison evaluation may not be performed and the result of the second measurement signal may be output. Also, three or more detectors may be arranged, the measurement regions of the subject 190 may be limited for each detector, the WFS may be executed for each of them to obtain measurement signals, and the results may be evaluated.

[0040] (Second Embodiment) Next, a second embodiment of the present invention will be described. The basic configuration of the measurement device of this embodiment is the same as that in FIG. 1, but the detection unit 120 has only one detector 121. Also, the measurement method of this embodiment is based on the flowchart shown in FIG. 3. In this embodiment, using one detector 121, two measurements are performed on the non-vascular region of the first region and the vascular region of the second region described in the first embodiment, and the two measurement results are compared and evaluated.

[0041] First, in step S10 of FIG. 3, the control unit 131 executes WFS for the purpose of measuring a first region near the surface layer of the subject 190. Also, as the feedback signal of WFS, a signal based on the correlation function g(τ) obtained by executing DLS is used. FIG. 6 is an explanatory diagram of the correlation function 143 obtained by measuring the temporal variation of the intensity of the emitted light 161 with the detector 121. In FIG. 6, the horizontal axis represents the delay time τ, and the vertical axis represents the correlation function g(τ). Here, only a part of the correlation function 143 may be used as the feedback signal. For example, the value of the correlation function at the time when the delay time τ1 has elapsed (feedback signal g(τ1)) may be used.

[0042] As shown in the flowchart of FIG. 3, in step S11, this feedback signal g(τ1) is monitored, and in step S12, the phase of the modulation pattern is changed, and again in step S11, the feedback signal is monitored. In order to execute the repetition of step S10 at high speed, it is desirable to shorten the acquisition time of the feedback signal. Therefore, the delay time τ1 is made as small as possible. On the other hand, for the second region where dynamic changes of the subject 190 are predicted, it may be set within a range where changes in the feedback signal value g(τ1) can be detected.

[0043] In S12, the control unit 131 monitors the feedback signal g(τ1) and shapes the wavefront of the irradiation light 151 so that the feedback signal g(τ1) increases or does not attenuate. That is, in step S10, it is optimized so that the light propagated while avoiding dynamic changes (for example, the blood vessel region in the second region) that affect the correlation function is detected by the detection unit 120. In other words, it is optimized so that the light mainly propagated through the non-vascular region of the first region and then emitted is measured.

[0044] Subsequently, in step S20, the control unit 131 irradiates the subject 190 with the irradiation light 151 having the wavefront obtained in step S10, and measures, as a measurement signal, a light intensity V1 (first measurement signal) different from the feedback signal g(τ1) with the detector 121.

[0045] Subsequently, in step S30, similar to step S20, the control unit 131 monitors the feedback signal g(τ1) and executes WFS. Specifically, in step S31, the control unit 131 acquires the feedback signal, and in step S32, it shapes the wavefront of the irradiation light 151 so that the feedback signal becomes smaller. That is, in step S30, the control unit 131 executes WFS so that the feedback signal g(τ1) becomes smaller (attenuates). Therefore, it is optimized so that the light propagated under the influence of dynamic changes in scattering due to blood flow or the like is detected by the detection unit 120. In other words, WFS is executed to measure the blood vessel region in the second region.

[0046] Subsequently, in step S40, the control unit 131 irradiates the subject 190 with the irradiation light 151 having the wavefront obtained in step S30 and measures the light intensity V2 (second measurement signal) as the measurement signal. In the measurement of step S40, the control unit 131 may execute the WFS of step S30 at any time and perform the measurement of step S40 while updating the wavefront of the irradiation light 151 at any time.

[0047] Subsequently, in step S50, the control unit 131 compares and evaluates the two measurement signals obtained in steps S20 and S40. As described in the first embodiment, the ratio or difference between the light intensities V1 and V2 may be evaluated. Alternatively, the measurement results may be analyzed based on models such as the transport equation or the diffusion equation, and the results may be evaluated. For example, when measuring with the absorption wavelength of a specific object such as hemoglobin in the blood as the irradiation light 151, it is also possible to evaluate the absorbance or the relative concentration of the object from the measurement signal.

[0048] In this embodiment, similar to the first embodiment, pre-measurement can be performed before step S10 to determine parameters such as measurement conditions in advance. In this embodiment, the detection position (distance ρ) shown in FIG. 2 may be fixed or variable. In the latter case, based on the results of the pre-measurement, the detection positions measured in steps S10, 20 and steps S30, 40 may be changed.

[0049] Also, as another example of this embodiment, autofluorescence of the subject 190 may be used. A wavelength in the range of 300 to 400 nm is used as the light source 101. For example, in steps S10 and S30 of FIG. 3, as the feedback signal of the WFS, light having a wavelength emitted by autofluorescence excited by the irradiation light 151 is received by the detector 121. The wavefront shaping unit 111 can shape the wavefront of the irradiation light 151 so that the fluorescence intensity received by the detector 121 increases. In the subsequent measurements of steps S20 and S40, based on DLS, the temporal variation of the light intensity of the autofluorescence may be measured to evaluate the correlation function. Here, in the processes of steps S10 and S30, in order to measure only fluorescence with the detector 121, the detection unit 120 may include an excitation light cut filter. Depending on the type of autofluorescence, there are some that can estimate the depth of the light emitting source inside the subject 190. For example, advanced glycation endproducts (AGEs), NADH, etc. may be used as the autofluorescence. The light source 101 is preferably a light source having a plurality of wavelengths in order to correspond to a plurality of phosphors and various measurement items.

[0050] Also, in the measurements of steps S20 and S40, it is also possible to receive with the detector 121 the light emitted at the wavelength of the excitation light, measure the temporal variation based on DLS, and evaluate the correlation function.

[0051] The measuring device in each embodiment is not limited to the configuration of the reflection arrangement as shown in FIG. 1, and may be a configuration of a transmission arrangement that detects the light transmitted through the subject from the light irradiated from the light source. Further, various combinations of the feedback signal (first signal) for executing WFS and the measurement signal (second signal) for acquiring information of the subject (physiological information of the living body) are conceivable and are not limited to the above-described respective embodiments. In each embodiment, as an effect of WFS, the improvement of S / N obtained as a result of scattering suppression and the effect of concentrating light on a more local region in the scattering medium are utilized for biological measurement. At this time, since the feedback signal used for WFS is operated and controlled on the measuring device side, in each embodiment, instead of directly using this feedback signal, another measurement signal affected by the effect of WFS is measured to acquire biological information.

[0052] As described above, the measuring device 100 of each embodiment is a measuring device that acquires information of a subject, and includes an irradiation unit 110, a detection unit 120, and a processing unit 130. The processing unit 130 shapes the wavefront of the irradiation light to the irradiation unit 110 while feeding back the first signal (feedback signal) output from the detection unit 120 by receiving the emitted light. Then, the processing unit 130 uses the second signal (measurement signal) output from the detection unit 120 by receiving the emitted light emitted from the subject when the irradiation light after wavefront shaping is irradiated on the subject, and acquires information regarding the specific region.

[0053] Preferably, the first signal or the second signal is the light intensity measured based on the distance between the irradiation position where the irradiation unit 110 irradiates the subject with irradiation light and the detection position where the detection unit 120 detects the emitted light. Alternatively, preferably, the first signal or the second signal is a signal based on a correlation function calculated by the dynamic light scattering method (DLS), or the fluorescence intensity emitted by autofluorescence. Also preferably, the processing unit 130 monitors the change in the information of the subject by comparing the second signals measured for at least two different first regions and second regions as the specific regions. More preferably, the irradiation unit 110 shapes the wavefront of the irradiation light so that the first signal obtained for the first region becomes small, and shapes the wavefront of the irradiation light so that the first signal obtained for the second region becomes large. Also preferably, the information of the subject is physiological information inside the living body, the first region is a non-vascular region of the living body, and the second region is a vascular region of the living body. Also preferably, the processing unit 130 uses the second signal regarding the non-vascular region as reference data and monitors the change in the second signal regarding the vascular region with respect to the reference data.

[0054] (Other embodiments) The present invention can also be realized by supplying a program that realizes one or more functions of the above-described embodiments to a system or device via a network or a storage medium, and causing one or more processors in the computer of the system or device to read and execute the program. It can also be realized by a circuit (for example, ASIC) that realizes one or more functions.

[0055] According to each embodiment, by suppressing scattering and limiting the measurement region in the living body as the subject, more local physiological parameters in the living body can be measured with good S / N. Therefore, according to each embodiment, it is possible to provide a measuring device, a measuring method, and a program capable of measuring information of a subject with high accuracy using light.

[0056] As described above, the preferred embodiments of the present invention have been described, but the present invention is not limited to these embodiments, and various modifications and changes are possible within the scope of the gist.

[0057] For example, although each embodiment has described a measuring device and a measuring method for measuring physiological information in a living body as information of a subject, the present invention is not limited thereto and is also applicable to the measurement of information of other subjects.

Description of Reference Numerals

[0058] 100 Measuring device 110 Irradiation unit 120 Detection unit 130 Processing unit

Claims

1. An irradiation unit that irradiates irradiation light onto a specific region of a subject; A detection unit that receives emitted light emitted from the subject when the irradiation light irradiates the specific region; A processing unit that processes a signal output from the detection unit, The detection unit includes a first detection unit and a second detection unit arranged at different positions, The processing unit, Based on a first signal intensity output from the first detection unit by receiving the emitted light and a second signal intensity output from the second detection unit by receiving the emitted light, the wavefront of the irradiation light is shaped on the irradiation unit, Using a third signal intensity output from the second detection unit by receiving the emitted light when the irradiated light of the shaped wavefront irradiates the subject, information regarding the specific region is acquired, A measuring device, characterized in that the wavefront is shaped on the irradiation unit such that a fourth signal intensity output from the first detection unit by receiving the emitted light when the irradiated light of the shaped wavefront irradiates the subject is lower than the first signal intensity and the third signal intensity is higher than the second signal intensity.

2. The first signal intensity or the second signal intensity is a signal intensity based on the light intensity of the backscattered light of the irradiation light, The third signal intensity is a signal intensity based on a correlation signal calculated by a dynamic light scattering method of the irradiation light or a signal intensity based on fluorescence intensity based on luminescence by a fluorescent dye, according to the measuring device described in Claim 1.

3. The measuring device according to Claim 1 or 2, characterized in that the first detection unit is arranged at a position closer to the irradiation unit than the second detection unit.

4. The measuring device according to any one of Claims 1 to 3, characterized in that the processing unit shapes the wavefront of the irradiation light on the irradiation unit such that the first signal intensity becomes maximum or minimum.

5. The irradiation unit has a spatial light modulator, and shapes the wavefront of the irradiation light by performing phase modulation or amplitude modulation on the spatial light modulator based on a base pattern, and the measuring apparatus according to any one of claims 1 to 4.

6. The information of the subject is physiological information inside the living body, The first detection unit is disposed at a position where the emitted light scattered from a non-vascular region near the surface of the living body and emitted is dominant in the first signal intensity, The second detection unit is disposed at a position where the emitted light scattered from a vascular region deeper than the non-vascular region of the living body and emitted is dominant in the second signal intensity, and the measuring apparatus according to any one of claims 1 to 5.

7. The processing unit measures the third signal intensity based on a parameter related to the attenuation or delay time of the correlation function, and the measuring apparatus according to any one of claims 1 to 6.

8. The processing unit acquires the information of the subject by comparing the third signal intensity and the fourth signal intensity, and the measuring apparatus according to any one of claims 1 to 7.

9. A measuring method for acquiring information of a subject, An irradiation step of irradiating the specific region of the subject with irradiation light, A detection step of receiving the emitted light emitted from the subject by the irradiation of the irradiation light by a detection unit including a first detection unit and a second detection unit disposed at different positions, And a processing step of processing a signal output by receiving the emitted light, The detection step includes a first detection step and a second detection step, In the processing step, the wavefront of the irradiation light is shaped based on the first signal intensity output from the first detection unit in the first detection step by receiving the emitted light, and the second signal intensity output from the second detection unit in the first detection step. In the processing step, information regarding the specific region is acquired by using the third signal intensity output from the second detection unit in the second detection step by receiving the emitted light emitted from the subject when the irradiation light of the shaped wavefront is irradiated onto the subject. A measurement method, characterized in that in the irradiation step, the wavefront is shaped such that the fourth signal intensity output from the first detection unit in the second detection step by receiving the emitted light emitted from the subject when the irradiation light of the shaped wavefront is irradiated onto the subject is lower than the first signal intensity, and the third signal intensity is higher than the second signal intensity.

10. A program, characterized in that the computer executes the measurement method according to Claim 9.

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