JP5997384B2 - Biological light measurement device - Google Patents

Description

  The present invention relates to a technique for measuring an oxygenated state of a biological tissue or a hemodynamic change in the tissue, particularly in a biological optical measurement apparatus using visible light or near infrared light.

  A brain function measurement device (see Patent Document 1) using near-infrared spectroscopy (NIRS) is used as a medical and research instrument, or as an educational / rehabilitation effect, home health management, It can be used for market research such as merchandise monitors. Moreover, it can be used for tissue oxygen saturation measurement and oxygen metabolism measurement of muscle tissue by the same method. Furthermore, it can be used for general absorption spectroscopy equipment, such as sugar content measurement of fruits.

  On the other hand, in the conventional optical brain function measuring apparatus and tissue oxygen monitor in which the probe is installed on the head, the importance of considering the influence of the change in the amount of light absorption of the surface tissue has been reported (Non-Patent Document 2, 3), quantification of the signal contribution derived from the surface tissue is an issue. Furthermore, since the influence level of the surface layer signal changes depending on the skin-brain distance (brain depth), the acquisition of the tissue structure parameter is an important issue.

  As a method of separating the influence of the change in the light absorption amount of the surface tissue, the blood volume change in the surface tissue is measured by a short light source that transmits only the surface tissue and the probe arrangement of the distance between the detectors, and a long irradiation-detector distance ( A method of removing the influence of the surface structure by subtracting from the signal acquired by (SD distance) has been proposed. Alternatively, spatially resolved spectroscopy that quantifies the optical properties of the tissue after measuring multiple points with long irradiation, the distance between detectors, where the relative influence of the surface tissue can be ignored, and assuming the uniformity of the biological tissue. is there. However, since the magnitude of the effect on the surface layer varies depending on the optical path length of the surface layer portion, the method using only the signal waveform without considering the biological structure cannot accurately separate biological signals derived from the deep and shallow tissues. Such anatomy includes the optical constants and thickness of each layer of the head, and further varies depending on various conditions such as the SD distance, the subject (age, sex), and the measurement site. When anatomical information is assumed or known, NIRS measurement is performed using a probe arrangement with multiple SD distances using this information, and the SD distance dependence of the average effective optical path length in the surface layer and gray matter is determined. A method of separating NIRS signals into deep and shallow signals by modeling is disclosed (see Patent Document 2 and Non-Patent Document 4). On the other hand, when anatomical structure information is not assumed or unknown, a technique that enables measurement of oxygenation state or blood volume change in the deep part and shallow part using optimum analysis parameters in each condition is required. However, it has been difficult for the conventional method to easily determine such analysis parameters. Furthermore, in many cases, anatomical structure information cannot be used or is unknown in ordinary NIRS measurement, and it is desirable to use optimum values for each subject and each part without assuming anatomical structure information in advance. One method is to eliminate the influence of surface tissue by making the scalp close to ischemia using a tourniquet, but it is necessary to pressurize the scalp at the light irradiation position and the detection position. In the past, it has been difficult to perform such measurements efficiently and with good reproducibility.

  Non-Patent Document 4 describes a method for acquiring information on the SD distance dependency of the NIRS signal in a state in which the scalp is pressurized with a probe and the surface layer signal is suppressed. There is no description about the device for pressurizing. When the scalp is pressed through a probe, particularly in the case of manual operation, it is difficult to apply pressure stably in time, and there is a problem that a portion where compression is unnecessary is also pressed.

Japanese Unexamined Patent Publication No. 9-019408 PCT Publication WO / 2012/005303

A. Maki et al., “Spatial and temporal analysis of human motor activity using noninvasive NIR topography”, Medical Physics, Vol.22, No.12, pp.1997-2005 (1995). S. N. Davie and H. P. Grocott, 2012. “Impact of Extracranial Contamination on Regional Cerebral Oxygen Saturation: A Comparison of Three Cerebral Oximetry Technologies”. Anesthesiology 116, pp.834-840. P. Smielewski et al., “Clinical evaluation of near-infrared spectroscopy for testing cerebrovascular reactivity in patients with carotid artery disease”. Stroke 28, 331-338. T. Funane et al., “Quantitative evaluation of deep and shallow tissue layers' contribution to fNIRS signal using multi-distance optodes and independent component analysis”, NeuroImage (2013), http://dx.doi.org/10.1016/j .neuroimage.2013.02.026.

  In order to realize high-precision measurement even in measurement parts and subjects with different degrees of influence of surface tissue in a biological optical measurement device that measures oxygen saturation or hemodynamic change in deep tissue and shallow tissue, anatomical data And means for obtaining parameters, particularly parameters related to brain depth. In addition, a means for efficiently compressing the skin of the subject is provided.

  Furthermore, a means for calculating the absorption change contribution rate in the surface tissue depending on the anatomy is provided.

  The biological light measurement device of the present invention has a pressure measurement unit, a pressure receiving unit that receives pressure, and a pressurization unit that pressurizes the subject at the irradiation and detection position of light in the subject. The irradiation-detector distance dependence of the blood volume change derived from the deep part, which is the internal information of the subject, is calculated. Furthermore, using the dependency, the signal at the time of non-pressurization is separated into a deep part signal and a shallow part signal, and the contribution ratio of the shallow part signal is quantified.

  If an example of the biological light measuring device of the present invention is given, one or a plurality of light irradiation means for irradiating the subject with light, and a predetermined irradiation point on the subject is irradiated from the light irradiation means. One or a plurality of light detection means for detecting light propagating in the subject at a predetermined detection point on the subject, and an analysis unit for analyzing a signal obtained by the light detection means A pressure receiving unit for receiving an applied pressure, a pressure control unit for controlling the pressure applied to the pressure receiving unit, and the light receiving unit and the light detecting unit. A pressure unit that transmits the pressure received in step 1 to the surface tissue of the subject, a state confirmation unit for confirming the hemostatic state, ischemic state, or vascular occlusion state of the subject, and the analysis unit includes According to the analysis result and the state confirmation means A display unit that can display a result, and a storage unit that can store a result analyzed by the analysis unit and a result of the state confirmation unit, and the analysis unit applies a predetermined pressure to the pressure receiving unit. The information inside the subject is obtained from a signal at the time of pressurization obtained by calculating a signal obtained by the light detection means when the subject is pressurized at a predetermined pressure in the pressurizing unit. The non-addition obtained by calculating the signal acquired by the light detection means when no pressure is applied to the subject from the pressurizing unit or when the pressure is not applied, using information inside the subject. A deep signal mainly derived from a deep tissue and a shallow signal mainly derived from a shallow tissue, which are included in the pressure signal, are respectively obtained.

  According to the present invention, it is possible to easily determine in-vivo internal information, tissue structure information, or analysis parameters for accurately measuring an oxygenated state of a living tissue or a hemodynamic change in the tissue. In addition, the body tissue is compressed with good reproducibility and efficiency, and the surface tissue is in a state close to hemostasis or ischemia. You can get sex.

The figure which shows an example of the apparatus structure of the biological light measuring device of this invention. The flowchart showing the procedure of the measurement and analysis according to Example 1 of this invention. The flowchart which shows the procedure which acquires a subject internal information. The figure which shows the irradiation-detector (SD) distance dependence of the average effective optical path length of the skin and gray matter in a human head. The flowchart which shows the procedure which acquires the deep part signal and shallow part signal which are contained in the non-pressurization signal from the non-pressurization signal and the subject internal information. The figure which shows the probe cross section in the case of the arrangement | positioning which has several irradiation-detector distance. The figure which shows the structure of the holding | maintenance part which has a space | gap, and its periphery. Sectional drawing of the probe which has a circular pressurization part and a contact fixing | fixed part has a curvature. The figure which shows effective optical path length distribution of the skin part obtained by photon propagation simulation. The figure which shows the probe which has a pressurization area | region adjustment means. The flowchart for calculating an appropriate pressurization region and selecting an appropriate probe. The figure which shows the holding | maintenance part which has a pressing position guide means. (a) The figure which shows the cross section of the holding | maintenance part which has a pressure-receiving part with a recessed part, (b) The figure which shows the cross section of the holding | maintenance part which has a protrusion-like slip stopper. The figure which shows the holding | maintenance part which has a waveguide with a bending or a curve. (a) The figure which shows the cross section of the holding part which has a handle, (b) The figure which shows the cross section of the holding part which has a handle and an elastic mechanism. (a) The figure which shows the cross section of the holding part which has a pressurization mechanism, (b) The figure which shows the probe cross section when pressurizing with an air bag. The flowchart which shows the procedure which estimates the contribution rate of the light absorption in a surface layer component when the probe of normal SD distance arrangement | positioning (about 30 mm) is used. The figure which shows the cross section of the probe when the distance between the irradiation and detector (SD) is about 30 mm.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

In FIG. 1, an example of the apparatus structure of the biological light measuring device of this invention is shown. In a biological light measurement device capable of detecting light incident on a living body and detecting the light that is scattered / absorbed and propagated in the living body and emitted to the outside of the living body, the light is irradiated from one or a plurality of light sources 101 included in the apparatus main body 20. The light 30 is incident on the subject 10 through the waveguide 40 for propagating the light. The light 30 enters the subject 10 from the irradiation point 12, passes through and propagates through the subject 10, and then passes through the waveguide 40 from the detection point 13 at a position away from the irradiation point 12. It is detected by one or more photodetectors 102. The SD distance is defined by the distance between the irradiation point 12 and the detection point 13 as described above.
Here, the one or more light sources 101 are a semiconductor laser (LD), a light emitting diode (LED) or the like, and the one or more photodetectors are an avalanche photodiode (APD), a photodiode (PD), a photoelectron amplifier, or the like. A double tube (PMT) or the like may be used. The waveguide 40 may be any medium that can propagate the wavelength used, such as an optical fiber, glass, or light guide.

  The light source 101 is driven by the light source driving device 103, and the multiplication factor and gain of the one or more photodetectors 102 are controlled by the control / analysis unit 106. The control / analysis unit 106 also controls the light source driving device 103 and receives an input of conditions and the like from the input unit 107.

  An electric signal obtained by photoelectric conversion by the photodetector 102 is amplified by the amplifier 104, converted from analog to digital by the analog-digital converter 105, sent to the control / analysis unit 106, and processed. As a method of detecting a minute signal and separating a plurality of signals, a method of driving a plurality of light sources by an intensity modulation method, detecting a lock-in of a signal detected by a photodetector, and performing analog-digital conversion, or a light receiver There is a method of performing a lock-in process digitally after amplifying and analog-to-digital conversion of the signal from. Further, the present invention is not limited to this, and for example, a time division method for discriminating a plurality of lights by shifting the timing of irradiating a plurality of lights in time, or a spread spectrum modulation method can be used.

  Note that the light source 101 and the photodetector 102 may be integrated with the waveguide 40. For example, by installing light source elements such as LD and LED, and light detection elements such as PD and APD in the probe, there are effects such as reduction of light loss, downsizing of equipment, cost reduction, and reduction of power consumption. is there.

  The control / analysis unit 106 performs analysis based on the signal detected by the photodetector 102. Specifically, based on the digital signal received by the digital signal converted by the analog-digital converter 105, for example, based on the method described in Non-Patent Document 1, the detected light amount change or absorbance From the changes, oxygenated and deoxygenated hemoglobin changes (oxy-Hb, deoxy-Hb) are calculated. Here, the oxygenated and deoxygenated hemoglobin change is a value corresponding to a change amount of a product of the hemoglobin concentration and the effective optical path length. Alternatively, the amount of change in hemoglobin concentration may be calculated by substituting the effective optical path length.

  Here, the control / analysis unit 106 has been described on the assumption that the driving of the light source 101, the gain control of the photodetector 102, and the signal processing from the analog-digital converter 105 are all performed. And having the means for integrating them can also realize the same function.

  Further, the measurement data and the calculation result of the hemoglobin change are stored in the storage unit 108, and the measurement result can be displayed on the display unit 109 based on the analysis result and / or the stored data.

  Although the light transmitter 50 and the light receiver 60 are not shown in FIG. 1, the light transmitter 50 includes, for example, a waveguide 40 on the light source 101 side, and is installed in contact with or close to contact with the subject 10. The light receiver 60 includes, for example, the waveguide 40 on the light detector 102 side, and is placed in contact with or close to contact with the subject 10.

  Furthermore, the living body optical measurement device of the present invention includes a pressure receiving portion 14 for receiving an applied pressure, a pressurizing portion 15 for transmitting the pressure received by the pressure receiving portion 14 to the subject 10, and the subject. The pressure sensor 16 for confirming the state of hemostasis or ischemia in 10 surface tissues is provided. The pressure control unit 11 includes means for efficiently applying pressure to the pressure receiving unit 14 and controlling the pressure to be applied. The pressurization control unit 11 may be manually controlled or automatically controlled by an electromagnetic method. The pressurization control unit may be detachable. Since the pressurization control unit is not necessary when performing measurement at the time of non-pressurization, the probe can be reduced in weight without changing the performance by removing the pressurization control unit. Reducing the weight of the probe reduces the burden on the subject.

  The control / analysis unit 106 applies a predetermined pressure to the pressure receiving unit 14 to calculate the signal obtained by the photodetector 102 when the subject 10 is pressurized by the pressurizing unit 15. Information on the inside of the subject is acquired from the pressure signal. At the time of applying pressure, the display unit 109 preferably displays pressure information at the time of measurement or notifies by sound. As a result, the operator can check whether the pressure is stably applied. At this time, if the pressure sensor 16 is installed inside the holding portion 17, it is possible to form a flat surface in which the unevenness of the pressurizing portion is reduced.

  In the following description, the holding unit 17 that contacts the subject 10, the light transmitter 50 and the light receiver 60 that are held by the holding unit 17, and components including peripheral components are called probes. The light transmitter 50 and the light receiver 60 may be the light source 101 and the photodetector 102, respectively. The pressure sensor 16 is installed on the surface or inside of the holding unit 17 or the probe, and measures the pressure between the pressurizing unit 15 and any one of the irradiation point 12 and the detection point 13. Here, the pressure sensor 16 is for the purpose of confirming the hemostatic state, ischemic state, or occlusion state of the blood vessel in the surface tissue of the subject 10 by measuring the pressurization state. It is only necessary that the parameters to be acquired can be acquired.

  In addition, although the method using the pressure sensor 16 was demonstrated here, by analyzing a frequency component using biological signals, such as a pulse oximeter and a laser Doppler blood flow meter, in addition to a pressure sensor, specifically, May be a method of confirming the hemostatic state, ischemic state, or vascular occlusion state in the surface tissue of the subject 10 by confirming that the pulse wave signal is small. Further, these methods may be used in combination with the pressure sensor 16. In this way, by separately acquiring biological signals having different measurement principles or independent, there is a possibility that the blood state can be measured with higher accuracy than in the case of measuring with only the pressure sensor.

  The flow of measurement and analysis according to the first embodiment will be described with reference to the flowchart shown in FIG. First, pressure is applied from the pressurization unit 15 to the subject 10 by applying pressure to the pressure receiving unit 14 by the pressurization control unit 11 (step S201). Next, a pressurization signal is acquired (step S202). In order to start acquiring the signal at the time of pressurization, it is necessary to confirm that the change in blood volume in the surface tissue is sufficiently suppressed. However, the visual (color lamp) or auditory means ( You may alert | report by alerting means, such as a sound. Next, subject internal information is acquired from the signal at the time of pressurization (step S203). Next, the pressure from the pressurizing unit is released (step S204). Further, a non-pressurization signal is acquired (step S205), and a deep signal and a shallow signal included in the non-pressurization signal are acquired from the non-pressurization signal and the subject internal information (step S206). ). Although not shown in the flowchart, when storing the data of the signal at the time of pressurization, by storing the pressure information measured by the pressure sensor 16, it is not necessary to acquire the signal at the time of pressurization in the next measurement. Thus, the burden on the subject 10 can be reduced, and the measurement can be advanced efficiently. Furthermore, it becomes possible to determine whether the pressure was sufficient at the time of later analysis, if necessary.

  In the procedure of FIG. 2, the case of acquiring the non-pressurization signal after acquiring the pressurization signal has been described. However, after the non-pressurization signal is acquired, the pressurization signal may be acquired. Since the signal at the time of pressurization is for the purpose of acquiring the internal information of the subject, that is, the structural parameter, if it has already been acquired, it may be determined that it is unnecessary to acquire the signal at the time of pressurization again. Furthermore, although the acquisition of the signal at the time of pressurization and the acquisition of the signal at the time of non-pressurization are described here as separate measurements, the pressure is released after acquiring the signal at the time of pressurization during one measurement, An unpressurized signal may be acquired. In that case, the signal derived from the surface tissue is expected to show a transient response at the time of change between the pressurized state and the non-pressurized state. Need to spend some time. For example, about 10 seconds is considered necessary. Even in the procedure of obtaining both the signal at the time of pressurization and the signal at the time of non-pressurization by this single measurement, the procedure of obtaining the signal at the time of pressurization and then obtaining the signal at the time of pressurization may be used.

The flow of acquiring the subject internal information will be described with reference to the flowchart shown in FIG. 3 (see Patent Document 2, Non-Patent Document 4, and Non-Patent Document 5). First, independent component analysis is applied to multi-distance measurement data (voltage or hemoglobin change converted from voltage data) measured during pressurization (step S301). Next, the signal contribution at each SD distance is calculated from the independent components and their weights (step S302). Next, for each independent component, the signal contribution is plotted against the SD distance, a linear regression line is calculated by the least square method, and the slope and x intercept of the regression line are calculated (step S303). Finally, a weighted averaging process based on signal contribution is performed on the x-intercept of each independent component to obtain subject internal information (Xi _gr ) (step S304).

  In step S301, the method using independent component analysis has been described as the signal separation method, but methods such as principal component analysis and factor analysis may be used. Further, without using a signal separation method, a method using a detected light amount or a representative amplitude of hemoglobin change may be used.

The subject internal information (Xi _gr ) obtained in step S304 is a value corresponding to the intercept of the SD distance axis in the SD distance-dependent line of the mean effective optical path length of the gray matter, and the photon reaches the gray matter ( Minimum SD distance for sensitivity to light absorption changes in gray matter). The subject internal information may be other parameters related to the subject head structure, such as a parameter depending on the thickness of each layer of the head tissue, a parameter proportional to the gray matter depth, and the like.

  In the procedure of FIG. 3, the method of extracting the x-intercept as the subject internal information has been described, but the slope of the regression line may be extracted as the internal information. The slope of the regression line represents amplitude information and depends on the task performed by the subject. By combining with the task information, it can be an effective database for knowing the characteristics of the task (effects on changes in cerebral blood volume and skin blood volume, etc.).

FIG. 4 is a diagram showing the irradiation-detector (SD) distance dependency of the average effective optical path length of skin and gray matter in the human head. The horizontal axis is the SD distance, and the vertical axis is the average effective optical path length or partial optical path length. According to FIG. 4, the average effective optical path length (74) in the skin does not change much at the SD distance of 10 to 40 mm, but the average effective optical path length (75) in gray matter increases linearly with the SD distance. To do. Therefore, as the SD distance increases, the gray matter-derived component in the NIRS measurement signal increases, but the skin-derived component is not expected to change. Further, the average distance of the gray matter effective optical path length is obtained by using the SD distance axis (70) as the intersection of the linear regression line (72) and the SD distance axis (70) obtained by linear regression using the data of the SD distance of 10 mm to 40 mm. An x-axis intercept (denoted Xi _gr ) (73) can be obtained. Here, the value is about 10 mm. This Xi _gr is an analysis parameter for brain and skin separation. By using this x-intercept according to the procedure of Patent Document 2 and the like, it is possible to separate the NIRS signal acquired by multi-distance measurement having a plurality of types of SD distances into a deep signal and a shallow signal.

  The bio-internal information obtained here is used as an analysis parameter for removing deep and shallow signals, but if already acquired, the acquired data stored in the storage unit 108 or the memory is read and the control / analysis unit 106 is read out. May be used. The SD contribution axis intercept 73 is necessary for the deep part contribution rate calculation formula, but since it differs depending on the measurement site in an individual or even in the same individual, it is analyzed that the optimum value for each subject and the measurement site is extracted from the memory. It is effective for improving the accuracy of results.

Next, the flow of acquiring the deep signal and the shallow signal included in the non-pressurization signal from the non-pressurization signal and the subject internal information will be described with reference to the flowchart shown in FIG. First, independent component analysis is applied to multi-distance measurement data (voltage data detected as a detected light quantity or hemoglobin change converted from voltage data) measured at the time of non-pressurization (step S501). Next, the signal contribution at each SD distance is calculated from the independent components and their weights (step S502). Next, for each independent component, the signal contribution is plotted against the SD distance, the linear regression line f (x) = a (x − Xi _ex ) is calculated by the least square method, and the slopes a and x of the straight line are calculated. An intercept (Xi _ex ) is calculated (step S503). Finally, the deep contribution rate of each independent component is calculated from Xi _gr and Xi _ex and the SD distance (x) for calculating the contribution rate (step S504). In step S504, when calculating the deep contribution ratio and the shallow contribution ratio of each independent component, for example, the expressions shown in Table 1 are used (see Non-Patent Document 4).

最後に、独立成分と深部、浅部各寄与率から、例えば数式１を用いて深部信号、浅部信号を再構成する（ステップＳ５０５）。

Finally, the deep signal and the shallow signal are reconstructed from the independent components and the respective contribution ratios of the deep part and the shallow part using, for example, Equation 1 (step S505).

ただし、ｒ_ｄｐ ^Ｃｉは独立成分iの深部寄与率、Ｗ_Ｃｉ ^Ｐｊは計測点mにおける独立成分iの重み、ｕ_Ｃｉは独立成分iの時系列データ、ΔＣＬは計測点mにおけるヘモグロビン（酸素化、もしくは脱酸素化）の深部信号である。浅部信号は、同様に浅部寄与率を用いる、もしくは元信号から深部信号を差し引く、等により求めることが可能である。

Where r _dp ^Ci is the depth contribution ratio of the independent component i, W _Ci ^Pj is the weight of the independent component i at the measurement point m, u _Ci is the time series data of the independent component i, and ΔCL is hemoglobin (oxygenation, (Or deoxygenation) deep signal. Similarly, the shallow portion signal can be obtained by using the shallow portion contribution ratio or subtracting the deep portion signal from the original signal.

  The shallow signal thus obtained is effective in examining the task dependency of the blood volume change in the surface tissue, and in examining the influence of individual differences on the blood volume change in the surface tissue. Further, by examining in advance the contribution of the shallow signal to the NIRS signal, there is an effect that an effective guideline can be obtained for data interpretation by a method other than the multi-distance arrangement.

  Next, a probe that realizes the above measurement will be described. FIG. 6 is a diagram showing a probe cross section in the case of an arrangement having a plurality of irradiation-detector distances (multi-distance arrangement) for performing measurement according to the first embodiment of the present invention.

  As described in Patent Document 2, it is effective to change the amount of light according to the SD distance in the multi-distance arrangement. The holding unit 17 for holding the light transmitter 50 and the light receiver 60 is installed so as to provide a gap 18 between the holding unit 17 and the subject 10. As the material of the holding portion 17, it is desirable to use hard rubber, plastic, or the like that hardly generates internal stress (not easily deformed). As a material of the surface constituting the gap 18, it is desirable to use the low reflector 19 that reflects little light. Once a photon that has exited space enters the tissue again and is detected by one of the photodetectors 102, the effective optical path moves to a shallower position, and the sensitivity to deep tissue is relatively reduced. Because. In order to prevent such a phenomenon, the material of only the inner wall portion of the gap 18 may be the low reflector 19 or the high absorber, or a coating process of these materials may be used.

  The gap 18 is effective in concentrating the pressure applied to the subject 10 from the pressurizing unit 15 directly below the pressurizing unit 15 or the probe. Furthermore, the space | gap 18 has a role as a space which escapes the biological tissue pressed and pressed by the pressurization part 15. FIG. Thereby, it is effective in efficiently transmitting the pressure 21 applied from the pressurization control unit 11 to the pressure receiving unit 14 from the pressurization unit 15 to the subject 10. That is, there is an effect that a larger pressure can be applied with a smaller force. When there is no gap 18, the applied pressure is dispersed and the applied pressure needs to be increased. The gap does not transmit the pressure and has an effect of limiting the pressurizing region. However, in order to realize the same effect, the pressure from the pressure receiving unit 14 may be replaced with a material that is difficult to transmit to the pressurizing unit 15.

  The holding unit 17 checks whether the subject can be pressurized with a predetermined pressure, that is, confirms the hemostatic state, ischemic state, or vascular occlusion state in the surface tissue of the subject 10. As a means, a pressure sensor 16 is installed. Since the temporal change of the pressure applied to the subject 10 via the pressurizing unit 15 affects the NIRS signal, it is necessary to always monitor it. The pressure sensor 16 is preferably installed inside the probe. Since the pressure sensor 16 is not installed on the surface of the pressurizing unit 15, the planarity of the living tissue contact portion can be maintained. Therefore, there is an effect that pressure can be uniformly applied to the subject 10.

  Confirmation that the pressure is sufficient, the hemostatic state, ischemic state, or occlusion state of the blood vessel in the surface tissue of the subject 10 may be confirmed by the absence of heartbeat (pulse). As for the pulsation of the heartbeat, the presence or absence of the pulsation of the NIRS waveform may be visually checked, the output value of the pressure sensor, or an optical measurement system installed in the immediate vicinity of the NIRS probe may be used. The optical measurement system here may be based on a technique such as a pulse oximeter or a photoelectric volume pulse wave measuring device (photoplethysmography). From the measurement result by the optical measurement system, the pressure is determined based on the presence or absence of a pulsation (pulse wave) component. That is, when there is no pulsation (pulse wave) component, it is determined that the blood flow of the surface tissue is sufficiently suppressed to an extent that does not affect the NIRS signal. In addition, you may make it alert | report the result by alerting | reporting means, such as visual (color lamp) or an auditory means (sound). Further, a visual signal (color lamp) is used to acquire the signal at the time of pressurization in the flowchart of FIG. 2 (step S202), and to inform the end of the acquisition of the internal information of the subject from the signal at the time of pressurization (step S203) ) Or informing means such as auditory means (sound). Thereby, when pressurizing manually, the timing which stops pressurization can be known, and there is an effect that unnecessary pressurization can be prevented.

  Further, as a means for confirming the hemostatic state, a configuration in which one detector is added and one 5 mm measurement point is added may be used. Furthermore, this measurement point with an SD distance of 5 mm can be used for evaluation of separation performance after separation of brain and skin-derived signals. In addition, when the skin blood flow is assumed to be uniform in the measurement range of interest, the measurement point with an SD distance of 5 mm can be used as a reference signal for analysis for separating skin blood flow components.

  In FIG. 6, the pressure receiving unit 14 receives a pressure from the outside and transmits the pressure to the subject 10 via the pressurizing unit 15. However, as a pressurization control unit, the pressure receiving unit 14 has a pressure in the holding unit 17 or the probe. By having the generating means, it may be configured to include the pressure receiving portion inside.

  The above can be used for any NIRS device such as a brain oxygen monitor, a tissue oxygen monitor device, and an optical brain function measuring device such as optical topography.

  The pressurizing area at the time of pressurization is arranged so as to surround the irradiation point or the detection point at the time of installation on the subject. A circle having a radius of 5 mm, preferably a circle having a radius of 10 mm, centering on the center point of each of the irradiation point and the detection point is configured. If a circle with a radius of 5 mm is used, the pressurizing portion 15 may have a relatively small area, and there is an effect that the surface blood immediately below the probe can be suppressed to some extent. When the radius is 10 mm, it is necessary to increase the pressure applied to the pressure receiving portion 14 during pressurization, but this has a more remarkable effect in suppressing blood changes in the surface tissue. However, enlarging the pressurizing region requires the application pressure to be increased in order to transmit the predetermined pressure to the subject 10, and is not a practical means especially when assuming that the pressurization is performed manually. It is important to find the minimum applied pressure that can sufficiently suppress the surface tissue-derived signal by using information from the pressure sensor 16 or the like.

  FIG. 7 is a diagram illustrating a configuration of a holding unit having a gap and a surrounding area. The upper figure shows the cross section AA and the lower figure shows the cross section BB. In the structure for transmitting the pressure received from the pressure receiving unit 14 to the living body from the pressurizing unit 15, a contact fixing unit 24 is provided around the space 18. The pressurizing unit 15 includes a light source 101 and a light detector 102. For the purpose of applying a uniform pressure to the periphery of the light source 101 and the detector 102, the light source 101 and the detector 102 transmit pressure. Although it is desirable to be configured, a configuration that does not transmit pressure may be used. Since the living body contact portion 24 is provided with the living body contact portion 24 in addition to the pressurizing portion 15 and has the gap 18, the living body contact portion is configured to be difficult to apply pressure. The gap 18 is effective for concentrating the pressure on the pressurizing unit 15 and reducing the force applied to the pressure receiving unit. When the light source 101 and the detector 102 are configured to transmit pressure to the subject 10, for example, an optical fiber bundle curved and bent in an L shape is used as the waveguide 40, and the periphery of the fiber is made of metal or plastic. This can be realized by covering with a covering and further integrating with the covering and the holding portion 17. Alternatively, it is possible to transmit the pressure to the subject 10 via the housing of the optical element by arranging the elements of the light source and the photodetector in contact with the holding unit and transmitting the pressure applied to the pressure receiving unit. is there.

  FIG. 8 is a cross-sectional view of a probe having a circular pressure part and a contact fixing part having a curvature. By making it circular, it is possible to uniformly pressurize the periphery of the irradiation point 12 and the detection point 13 located directly below the light source 101 and the photodetector 102, and it is possible to uniformly press the surface tissue at a site where compression is required. effective. In addition, pain due to non-uniform pressure can be reduced. Furthermore, by combining with the biological contact portion 25 having a curvature and the holding band 26, it is possible to prevent local pressure application to the surface of the living body due to the pressure 21 applied from the pressure control unit 11 to the pressure receiving unit 14. . For example, the pressurizing portion is flat, and the living body contact portion located below the place where the holding band 26 is connected has a curvature that matches the curved surface of the living body surface. In the living body contact portion 25 having a curvature, the pressure is dispersed. The material constituting the biological contact portion 25 having a curvature may be an elastic body such as a rubber material or plastic. In addition, although it was set as the structure which provides the space | gap 18 between the light source 101 and the photodetector 102 here, and between both the photodetectors 102 here, without providing the space | gap between these, between the biological contact part 24 and a pressurization part. A configuration having a gap or a member that hardly transmits pressure may be used.

  FIG. 9 is a diagram showing an effective optical path length distribution in the scalp obtained by photon propagation simulation. The effective optical path length is expressed in shades. The darker the color, the greater the effective optical path length. Assuming the head structure (each tissue thickness, absorption coefficient, scattering coefficient), after calculating the photon path by the photon propagation simulation, the 100 photon paths are weighted and averaged according to the detected light quantity, and the surface layer This is a calculation of the effective optical path length in each voxel (2 mm × 2 mm × 3 mm (skin thickness)) located in the tissue. The diameter of the irradiation / detection point was assumed to be 1.5 mm. It can be seen that the distribution of the surface layer tissue (scalp) optical path length is concentrated around the irradiation point 12 and the detection point 13 and in a straight line connecting the irradiation point 12 and the detection point 13. In particular, it is concentrated in a circle with a radius of 5 mm centered on the irradiation point 12 and the detection point 13. Therefore, if this region is pressurized, it is possible to effectively suppress changes in blood volume in the surface tissue that contribute to changes in the detection light. In practice, it is effective to compress a blood vessel for flowing blood flowing into this region, so it is important to simultaneously compress the region around this region. Therefore, in actuality, the radius may be set to about 10 to 15 mm in consideration of the stability when the pressure unit is fixed. Since the thickness of the scalp varies from subject to subject and from site to site, the optimal pressure area varies depending on conditions. If the burden at the time of pressurization is not taken into consideration, it is considered that pressing a sufficiently wide range is effective in suppressing the blood volume of the surface tissue. As described above, by using the photon propagation simulation result on the assumption of the head structure and the optical characteristic distribution, it is possible to determine a region where pressurization can be performed efficiently with a minimum. By creating a simulation model of the head structure using the results of MRI, X-ray CT, etc., it is possible to determine the optimum pressure region for each subject. Note that the shape of the pressurizing unit 15 is not limited to a circle, and it is more effective that the shape preferably covers the shape of the effective optical path length distribution. That is, the pressurizing unit 15 is configured to include a region that covers a predetermined ratio (for example, 95%) or more of the total effective optical path length in the surface tissue in the distribution of the effective optical path length in the surface tissue of the detection light. That's fine.

  FIG. 10 is a view showing a probe having a pressurizing region adjusting means 28. Since the optimal pressurization region varies depending on the subject, the measurement site, and the possible pressurization range, it is effective to adjust the pressurization region according to the conditions. Here, a probe having a pressurizing region adjusting means will be described. The pressurizing region adjusting means 28 is for adjusting the area of the pressurizing unit 15 that is a region for transmitting the pressure 21 applied from the pressurizing control unit 11 to the pressure receiving unit 14 to the surface of the living body. For example, it is a member that can be attached to and detached from the probe (or the holding portion 17), and may be any member that can be inserted into a groove installed in the inner wall of the holding means constituting the gap 18. When the member is inserted into the probe, the area of the pressure unit 15 can be increased. With this configuration, it is possible to easily adjust the pressurization region, and the probe can be configured according to various conditions (examinee, measurement site, possible pressurization range). There is an effect that it is possible to reduce the trouble of exchanging probes with different parts. Furthermore, since the effective optical path changes according to the SD distance, the appropriate pressure area changes, so even when measuring multiple SD distances, the pressure area can be changed according to the SD distance. .

  Next, a flow of calculating an appropriate pressure region and selecting an appropriate probe will be described with reference to the flowchart shown in FIG. First, head structure data is acquired from an MRI, an X-ray CT image, probe position information, a database, etc. (step S1101). Next, an absorption coefficient and a scattering coefficient are assumed with reference to documents and the like (step S1102). Next, the photon propagation path is calculated by the photon propagation simulation using the scattering coefficient and the absorption coefficient according to the algorithm (step S1103). For example, a Monte Carlo simulation or a method of solving a light diffusion equation by a finite element method may be used. Next, the effective optical path length distribution in the surface tissue is calculated in consideration of the absorption coefficient distribution (step S1104). Next, the ratio to the total detected power (and the margin of the pressurizing area) is set (step S1105). The margin here is a certain margin width from a region including a predetermined ratio with respect to the total detection power. By giving a margin width and designating a wider range as the pressurization region, it becomes possible to sufficiently compress the blood vessel under the region necessary for pressurization. Next, a pressurization area is calculated (step S1106). Next, the pressure area is adjusted using the pressure area adjusting means 28 (step S1107). The procedure from step S1101 to step S1106 described above may be performed by the control / analysis unit 106 or may be performed offline by the user.

  FIG. 12 is a diagram showing a holding unit having a pressed position guide means. The holding unit 17 that holds the light transmitter 50 and the light receiver 60 includes a pressing position guide unit 80. The pressed position guide means 80 is displayed at a place where pressure can be applied to the subject 10 from the pressurizing unit 15 most effectively. For example, it is arranged at the midpoint between the light transmitter 50 and the light receiver 60 set to an SD distance of about 30 mm. Although the pressure receiving unit 14 is not shown in the drawing, it is in the same position as the position of the pressed position guide means 80 here. As a result, when pressure is applied manually, it serves as a guide for the location of pressing, so there is an effect that measurement can be performed easily with good reproducibility.

  Next, an example of the structure of the pressing part when the pressure is applied manually will be described. FIG. 13A is a view showing a cross section of a holding portion having a pressure receiving portion with a recess. The holding portion 17 that holds the light transmitter 50 and the light receiver 60 includes a pressure receiving portion 81 having a recess. Since the holding portion 17 has a concave portion in the pressure receiving portion 14, it becomes effective to concentrate manual pressure on the pressure receiving portion 14 while serving as a tactile guide. FIG. 13B is a view showing a cross section of the holding portion having the protrusion-like slip stopper. By providing the non-slip 82 that serves as a guide for the pressing position, the pressure can be more stably applied manually. At this time, the pressure receiving unit 81 having the concave portion also serves as the pressure control unit 11, and thus the pressure control unit 11 may not be provided separately.

  FIG. 14 is a diagram illustrating a holding unit having a bent or curved waveguide. The light transmitter 50 and the light receiver 60 held in the holding unit 17 have a waveguide 41 having a bend or a curve. When the pressure 21 is applied, the light transmitter 50 and the light receiver 60 have an effect of reducing physical and spatial obstacles and transmitting the pressure efficiently. That is, there is an effect of eliminating spatial interference with the pressurization control unit 11. Furthermore, when the light transmitter 50 and the light receiver 60 are configured by an optical fiber or the like, the possibility that the light transmitter 50 and the light receiver 60 break due to contact during manual pressure application is reduced. Furthermore, there is an effect that it is easy to apply pressure when the pressure is manually applied to the pressure receiving portion 14. In order to obtain the same effect, an optical element such as a light source element and a detector element may be arranged directly in a positional relationship close to contact with the subject.

  FIG. 15A is a view showing a cross section of a holding portion having a handle. A handle 22 is connected to the holding unit 17 as the pressurization control unit 11 for applying pressure to the pressure receiving unit 14. By having the handle 22, there is an effect that it is easier to apply pressure manually, especially when the holding portion 17 is small. Further, since the pressure receiving portion 14 when manually applying pressure is also fixed at the connection position of the handle, there is an effect that the pressure can be applied to the target position. The handle 22 may be removable.

  FIG. 15B is a view showing a cross section of the holding portion having the handle and the elastic mechanism. The probe module including the pressure receiving unit 14 and the pressurizing unit 15 is fixed to the subject 10 by the holding unit 17 via the elastic mechanism 29. At this time, by attaching the handle 22 as the pressurizing control unit 11 to the pressure receiving unit 14 on the probe module so as not to interfere with the holding unit 17, the handle 22 can be moved even when the holding unit 17 has the elastic mechanism 29. The pressure can be directly applied to the pressure receiving unit 14 via the pressure sensor 14. With this configuration, a predetermined pressure can be efficiently applied from the pressurization unit 15 to the subject 10 when acquiring a signal during pressurization, and the elastic mechanism 29 improves probe mounting when acquiring a signal during non-pressurization, and This has the effect of contributing to prevention of excessive pressure.

  FIG. 16A is a view showing a cross section of the holding portion 17 having a pressurizing mechanism. The pressure mechanism 23 applies pressure to the pressure receiving unit 14. The pressurizing mechanism 23 may be mechanical, electromagnetic, hydraulic, or the like. In particular, a gas or liquid pressure may be used, or an elastic body may be pressed against the subject 10 by pressing the pressurizing portion by screwing. Or the structure which adjusts the pressure just under the said member by screwing a bolt-shaped member in the belt wound around a head may be sufficient. The pressurizing mechanism 23 may be fixed to the subject 10, and thereby, a configuration may be adopted in which pressure is effectively applied to the contact portion of the subject 10 with the pressurizing unit 15. The pressurizing mechanism 23 may be removable.

  FIG. 16B is a diagram showing a cross section of the probe when the pressure receiving portion 14 is pressurized with an air bag. An air bag 27 is used as a pressurizing mechanism. As the air bladder 27 expands, pressure is applied to the pressure receiving portion 14. Then, the pressure applied to the pressure receiving unit 14 is transmitted to the surface of the living body via the pressurizing unit 15. By controlling the air pressure of the air bag by electromagnetic means, it is possible to adjust the pressure applied to the surface of the living body with high accuracy and good reproducibility. Thereby, it becomes possible to pressurize a living body surface with high reproducibility using automatic control, and it becomes possible to solve the subject that a pressurization pressure may change with the date of measurement or an individual so far. Further, when the applied pressure is controlled by the air pressure from an external pump and the air pressure is measured and monitored by an external device, a configuration in which the pressure sensor is not provided in the holding unit 17 is possible.

  When the pressurizing mechanism 23 is configured to be automatically controlled, it is possible to automatically compress the subject 10 and further control the pressure applied from the pressurizing unit 15. The storage unit 108 stores and stores the pressure information, the measurement data, and the internal structure information in which the surface blood flow is sufficiently suppressed for each subject and for each part, so that the same subject can measure again. In doing so, automatic compression can be efficiently performed by reading the corresponding pressure information and internal structure information from the storage unit 108. Alternatively, when it is not necessary to remeasure the internal structure information, it is possible to omit the measurement during pressurization.

  At the time of automatic compression using the pressurizing mechanism 23, the surface layer is sufficiently obtained by using a means for confirming the hemostatic state, ischemic state, or occlusion state of the blood vessel in the surface tissue of the subject 10 such as the pressure sensor 16. The pressure can be automatically adjusted to suppress the influence of blood flow in the tissue.

  Although the probe arrangement having a plurality of irradiation-detector (SD) distances has been described above, an example of an application example in the case of the arrangement of one SD distance will be described. The flow of estimating the absorption contribution of the surface layer component when using the probe with the normal SD distance arrangement according to the second embodiment will be described with reference to the flowchart shown in FIG. Here, the normal SD distance arrangement refers to, for example, a probe arrangement with a light source-detector distance of 30 mm.

  First, by applying a pressure 21 to the pressure receiving unit 14, a pressure is applied from the pressurizing unit 15 to the subject 10, and a pressurization signal is acquired (step S1701). Next, the pressure from the pressurizing unit 15 is released, and a non-pressurization signal is acquired (step S1702). Next, the absorption contribution ratio of the surface layer component is calculated (step S1703).

  A probe for realizing measurement according to the above procedure will be described below. FIG. 18 is a diagram showing a cross section of the probe when the irradiation-detector (SD) distance is about 30 mm. The light transmitter 50 and the light receiver 60 are held by the holding unit 17, and light is incident on the subject 10 to detect the light (light path distribution: 31) that has propagated through the subject 10. The holding part 17 has a gap 18, and a low reflector 19 is disposed on the inner wall of the gap 18. The pressure 21 applied from the pressurization control unit 11 to the pressure receiving unit 14 is transmitted from the pressurization unit 15 to the subject 10 via the holding unit 17. The pressure applied to the subject 10 is detected by the pressure sensor 16. As the pressurization method, the method described in Embodiment 1 may be used.

  Since the light detected by the light receiver 60 is attenuated in both the surface tissue and the deep tissue, the absorption by the blood or the like in the surface tissue is reduced by the pressure on the surface tissue of the subject 10. Thereby, the absorption contribution rate by the blood of a surface layer component can be estimated. By quantifying the absorption contribution ratio of the surface layer component by blood, for example, there is an effect that it can be used to select a measurement point having a small influence of the surface layer component in NIRS measurement.

  In accordance with the present invention, as a medical and research device, or for confirming educational effects / rehabilitation effects, home health management, market research such as product monitoring, etc., tissue oxygen saturation measurement and muscle oxygen metabolism measurement by similar methods Used as a means to improve spatial resolution in biological measurement devices that can be used for radiology, especially devices that use probes with multiple irradiation-detector distances (SD distances) to separate surface and deep components, etc. it can.

10: Subject 11: Pressurization control unit 12: Irradiation point 13: Detection point 14: Pressure receiving unit 15: Pressurization unit 16: Pressure sensor 17: Holding unit 18: Air gap 19: Low reflector 20: Device main body 21: Pressure 22: Handle 23: Pressurizing mechanism 24: Biological contact part 25: Biological contact part 26 having curvature: Holding band 27: Air bag 28: Pressurizing area adjusting means 29: Elastic mechanism 30: Light 31: Optical path distribution 40: Waveguide 41: Curved or curved waveguide 50: Light transmitter 60: Light receiver 70: SD distance axis 71: Average effective optical path length 72: Primary regression line 73: SD distance axis (X axis) intercept 74: Skin average Effective optical path length 75: Gray matter average effective optical path length 80: Pressing position guide means 81: Pressure receiving part 82 having a concave part: Non-slip 101: Light source 102: Light detector 103: Light source driving device 104: Amplifier 105: Analog-digital conversion Vessel 106 Control and analysis unit 107: input unit 108: storage unit 109: display unit

Claims (15)

One or more light irradiation means for irradiating the subject with light;
One or a plurality of light detection means for detecting, at a predetermined detection point on the subject, light that has been irradiated from the light irradiation means to a predetermined irradiation point on the subject and propagated through the subject. When,
An analysis unit for analyzing a signal obtained by the light detection means;
A pressure receiving portion for receiving an applied pressure;
A pressure controller for controlling the pressure applied to the pressure receiver;
A pressure unit that is provided around the light irradiation unit and the light detection unit, and transmits the pressure received by the pressure receiving unit to the surface tissue of the subject;
A state confirmation means for confirming the hemostatic state, ischemic state, or vascular occlusion state of the subject;
A display unit capable of displaying a result of analysis by the analysis unit and a result of the state confirmation unit;
A storage unit capable of storing a result analyzed by the analysis unit and a result of the state confirmation unit;
The analysis unit
At the time of pressurization obtained by calculating a signal acquired by the light detection means when the subject is pressurized at the pressurization unit by a predetermined pressure by applying a predetermined pressure to the pressure receiving unit. From the signal, obtain information inside the subject,
Non-pressurization obtained by calculating a signal acquired by the light detection means when no pressure is applied to the subject from the pressurizing unit or when no pressure is applied using information inside the subject. The deep signal mainly derived from the deep tissue and the shallow signal mainly derived from the shallow tissue included in the time signal are respectively acquired.
A biological light measurement device characterized by that. The biological light measurement device according to claim 1,
Holding means for fixing the light irradiating means and the light detecting means in contact with and fixed to the subject;
The holding means is contacted and fixed to the subject so as to have a gap between the subject and a material that is difficult to transmit the pressure from the pressure receiving unit to the pressurizing unit.
A biological light measurement device characterized by that. The biological light measurement device according to claim 1 or 2,
The biological light measurement device, wherein the pressurization control unit is an air bag whose pressure can be adjusted. The biological light measurement device according to claim 1 or 2,
The biological light measurement device according to claim 1, wherein the pressurization control unit is a handle for applying pressure to the pressure receiving unit. In the living body light measuring device according to any one of claims 1 to 4,
The light irradiation means and the light detection means are arranged so that an irradiation-detection distance (SD distance) that is a distance between the irradiation point and the detection point is two or more types. Biological light measurement device. In the living body light measuring device according to any one of claims 1 to 5,
The state confirmation unit is a pressure measurement unit that is installed on the surface or inside of the holding unit and measures the pressure between the pressurizing unit and any of the irradiation point and the detection point. A biological light measurement device. In the living body light measuring device according to any one of claims 1 to 5,
The state confirmation means is means for confirming a hemostatic state, an ischemic state, or a blood vessel occlusion state in a surface tissue of the subject by analyzing a frequency component of a biological signal of the subject. A biological light measuring device characterized by the above. The biological light measurement device according to claim 7,
A biological optical measurement device comprising visual or audible notification means for notifying a measurement operator of the state based on the hemostatic state, ischemic state, or vascular occlusion state . In the living body light measuring device according to any one of claims 1 to 5,
The living body light measurement apparatus according to claim 1, wherein the state confirmation means is measurement data having an irradiation point-detection point distance of 10 mm or less, more preferably 5 mm or less. In the living body light measuring device according to any one of claims 1 to 9,
The pressurizing unit is configured to include a circle with a radius of 5 mm, preferably a circle with a radius of 10 mm, centered on each of the center points of the irradiation point and the detection point when installed on the subject. A biological light measurement device. In the living body light measuring device according to any one of claims 1 to 10,
The biological light measurement apparatus according to claim 1, wherein the information inside the subject is related to irradiation-detector distance dependency of a blood volume change derived from a deep tissue of the subject. In the living body light measuring device according to any one of claims 1 to 11,
It said having a pressure area adjusting means for changing the area of the pressure, BIOLOGICAL light measuring device you wherein a. The biological light measurement device according to any one of claims 4 to 12,
A probe module including the pressure receiving unit and the pressurizing unit is elastically fixed to the holding unit through an elastic mechanism, and the handle as the pressurizing control unit or the pressurizing control unit includes the holding unit. The living body light measuring device is installed in the pressure receiving part on the probe module so as not to interfere with the living body. In the biological light measurement device according to any one of claims 2 to 13,
The biological light measurement device according to claim 1, wherein the pressure receiving unit or the pressurization control unit is a recess provided on a surface of the holding unit. In the living body light measuring device according to any one of claims 2 to 14,
The living body light measurement apparatus according to claim 1, wherein the holding means has a curvature matched to an installation surface of the subject.

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