JP2009232876A - Biopsy probe, and biopsy apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To accurately measure reference light intensity by stably making light incident to a living body. <P>SOLUTION: Caps 16 with a height of 0.5 mm, a diameter of 5 mm, and a durometer hardness of 90 are mounted on an optical part 15 and an optical fiber 13-3 for light reception. When an acoustic lens 141 is in contact with the living body 200, the optical part 15 and the optical fiber 13-3 for light reception are pushed into the living body 200. Thus, the light is stably made incident to the inner part of the living body 200, thereby accurately measuring the reference light intensity. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a living body inspection apparatus and a living body inspection probe that non-invasively measure the inside of a living body using light.

  There are various methods for diagnosing the inside of a living body. Optical measurement, which is one of them, has the advantage that there is no problem of exposure and the compound to be measured can be selected by selecting the wavelength. In addition, it is possible to reduce the size of the device and reduce the price, while other diagnostic devices are mainly used in medical institutions, but they can be commercialized with a view to use in homes and health institutions. It is being advanced.

  What has already been commercialized as a biological light measuring device is a blood oxygen saturation measuring device, a pulse wave meter (pulse meter), and an optical topography. These monitor the concentration of hemoglobin and oxygenated hemoglobin in the blood. An oxygen saturation measuring device and a pulse wave meter are used for state management during and after surgery, and monitor changes over time at one point such as a fingertip. Optical topography mainly maps hemoglobin in the brain and simply measures brain functions that have been conventionally measured by MRI or electric potential.

  Compared with X-ray, NMR (MRI), ultrasonic echo, and nuclear medicine (positron) devices that are currently established as medical diagnostic devices, the market for optical biometric devices is small. The technology itself has been known for thirty years ago, and the market for relevant products has yet to be formed despite the fact that both domestic and foreign countries have a biological boom.

  One cause of this is that the living body has strong scattering characteristics (see, for example, Non-Patent Document 1). Due to this scattering characteristic, it is difficult to specify a site inside the living body even if light incident from the skin acquires information inside the living body and is emitted from the skin. Therefore, the state of light propagating in the living body is simulated, and the average cross-sectional shape of the light path from when light enters the living body through diffuse reflection inside the living body and exits from the living body is “ It was analyzed to be “banana-like”. In living body light measurement, a method of limiting the arrival depth of light from the measurement position of diffuse reflected light based on the cross-sectional shape of the optical path is often used. This method is also adopted in the optical topography described above. By this method, for example, an apparatus for limiting the measurement site to the brain surface has been developed by arranging the light irradiator and the photodetector so that the measurement depth is the surface of the brain.

  By the way, in order to detect the state in the living body, the light absorption coefficient of the site of interest is used as an index. In order to obtain the absorption coefficient, the reference light intensity, which is the light intensity at the site where there is no absorber, is compared with the signal light intensity, which is the light intensity at the site of interest. Therefore, not only the signal light intensity but also the reference light intensity cannot be measured accurately to obtain the absorption coefficient accurately.

However, since the surface of the living body is a gentle curved surface, it is difficult to always keep the probe and the living body surface in close contact with each other. For this reason, there is a problem that the reference light intensity is not properly measured and the reference light intensity is not reproducible. If the reference light intensity is not reproducible, an absorption coefficient different from the true value is required. In an extreme case, there also arises a problem that an absorption coefficient cannot be obtained.
Biological information visualization technology, p. 121-128, Corona Physical properties of Tissue, FA Duck, 1990. JP-A-11-47120 Japanese National Patent Publication No. 11-507568

  As described above, the conventional biopsy apparatus has a problem that it is difficult to provide reproducibility to the measured reference light intensity because the surface of the living body is a curved surface.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a living body inspection apparatus and its probe capable of accurately measuring the reference light intensity by stably making light incident on the living body. is there.

  In order to achieve the above object, a biopsy probe according to the present invention is integrated with an ultrasonic probe for transmitting and receiving ultrasonic waves to and from the living body in contact with the surface of the living body, and the ultrasonic probe. The light irradiated end and the light incident end are in contact with the living body in a state where the ultrasonic probe is in contact with the living body, and the light diffused and reflected in the living body by irradiating light from the light emitting end. And an optical probe for making the light incident at the light incident end, and the light irradiation end and the light incident end of the optical probe protrude from the contact surface of the ultrasonic probe with respect to the living body surface, respectively. .

  The biopsy apparatus according to the present invention is integrated with an ultrasonic probe for transmitting and receiving ultrasonic waves to and from the living body in contact with the surface of the living body, and the ultrasonic probe, The light irradiation end and the light incident end are in contact with the living body in contact with the living body, the light irradiated from the light irradiation end and diffused and reflected in the living body at the light incident end. A biopsy probe including an optical probe for incidence; an image acquisition unit that transmits / receives ultrasonic waves to / from the living body using the ultrasonic probe; A light irradiation unit that irradiates light including a specific wavelength component that is an absorption wavelength band of the abnormal tissue of the living body from the light irradiation end, and receives light incident at the light incident end of the optical probe and detects its light intensity A light detection unit that An optical calculation unit that obtains an absorption coefficient of light of the abnormal region made of the abnormal tissue based on the light intensity detected by the light detection unit; and after the ultrasonic image is subjected to image processing based on the absorption coefficient of light Display means for displaying, wherein a light irradiation end and a light incident end of the optical probe protrude from a contact surface of the ultrasonic probe with respect to the living body surface, respectively.

  According to the present invention, it is possible to provide a living body inspection apparatus and a living body inspection probe capable of stably entering light into a living body and accurately measuring a reference light intensity.

  Hereinafter, embodiments of a biopsy device and a biopsy probe according to the present invention will be described in detail with reference to the drawings.

  FIG. 1 is a block diagram showing a configuration of a biopsy apparatus according to an embodiment of the present invention. The biopsy probe 10 in FIG. 1 is an ultrasonic probe for transmitting and receiving ultrasonic waves to and from an optical probe composed of an optical fiber 11 for irradiating light and first and second optical fibers 12 and 13 for receiving light. A probe 14 (for example, 805AT manufactured by Toshiba Medical) is provided.

  The signal generator 20 drives near-infrared LDs (laser diodes) 30-1 and 30-2. By driving the signal generator 20, the near-infrared LD 30-1 outputs light having a wavelength of 760 nm, and the near-infrared LD 30-2 outputs light having a wavelength of 840 nm. That is, the wavelengths of light output from the near-infrared LDs 30-1 and 30-2 are set to a long wavelength and a short wavelength across 805 nm, which is an isosbestic point of oxyhemoglobin and hemoglobin. The outputs of the near infrared LDs 30-1 and 30-2 are 10 mW or 5 mW.

  The optical combiner / coupler 40 receives light from the near-infrared LDs 30-1 and 30-2 and outputs light of any wavelength to the optical fiber 11 for light irradiation. Further, the optical multiplexer / coupler 40 notifies the optical calculation unit 70 of which wavelength of light is being output to the optical fiber 11.

  Six optical fibers 11 for light irradiation are provided, and the living body 200 is irradiated with the output light of the optical multiplexer / coupler 40 from each light irradiation end. Each of these optical fibers 11 is made of quartz and has a diameter of 200 μm.

  Light for detecting the reference light intensity enters the light receiving first optical fiber 12 from the light incident end. The optical fiber 12 is made of quartz and has a diameter of 200 μm. The optical fiber 12 is connected to the light detection unit 50-1. Thereby, the light irradiated from the optical fiber 11 and diffusely reflected in the living body enters the optical fiber 12 and is received by the light detection unit 50-1.

  On the other hand, light for detecting signal light intensity enters the second optical fiber 13 for light reception from the light incident end. Nine of these optical fibers 13 are provided, all of which are made of polymer, and have a diameter of 1 mm. Each optical emission end of the optical fiber 13 is connected to the light detection units 50-2 to 50-10. Thereby, the light irradiated from the optical fiber 11 and diffusely reflected in the living body enters from the optical fiber 13 and is received by the light detection units 50-2 to 50-10.

  The light detection units 50-1 to 50-10 include a Si photodiode and a preamplifier. The light detection unit 50-1 receives incident light from the first optical fiber 12 for light reception and detects the light intensity. The light detection units 50-2 to 50-10 receive incident light from the second optical fiber 13 for light reception and detect the light intensity. The light detection units 50-1 to 50-10 supply the detected light intensity to the main amplifier 60 at a specified timing. The main amplifier 60 sequentially amplifies the received light intensity signal and supplies it to the light calculation unit 70.

  The light calculation unit 70 determines which light detection signal is supplied from which light detection unit based on the timing of receiving the light intensity signal. The light calculation unit 70 sets the light intensity signal supplied from the light detection unit 50-1 as the reference light intensity, and sets the light intensity supplied from the light detection units 50-2 to 50-10 as the signal light intensity. Then, the light calculation unit 70 compares the signal light intensity of the light having the same wavelength with the reference light intensity based on the information on the wavelength of the irradiation light notified from the optical multiplexing / combining unit 40 to determine the scattered light intensity. Calculate the distribution.

  The light calculation unit 70 includes a memory 71 in which a light absorption coefficient and a scattering coefficient for each substance and a scattered light intensity distribution theoretically obtained from them are recorded in advance. The light calculation unit 70 receives the ultrasonic image from the ultrasonic calculation unit 90 and, based on the ultrasonic image and the calculated scattered light intensity distribution, the theoretical scattered light intensity distribution that matches the scattered intensity distribution. Is retrieved from the memory 71. Then, an absorption coefficient and a substance showing the calculated scattered light intensity distribution are determined. The light calculation unit 70 supplies information regarding the obtained absorption coefficient to the ultrasonic calculation unit 90.

  The ultrasonic probe 14 is connected to an ultrasonic transmission / reception unit 80 including an ultrasonic transmission / reception element and an amplifier, and a drive signal for generating ultrasonic waves is supplied from the ultrasonic transmission / reception unit 80. The ultrasonic probe 14 receives a drive signal, and ultrasonically vibrates by a piezoelectric transducer to apply ultrasonic waves to the living body. Further, the ultrasonic probe 14 receives the ultrasonic wave reflected in the living body, and returns the echo signal to the ultrasonic transmitting / receiving unit 80. The ultrasonic transmission / reception unit 80 performs a delay addition process on the echo signal from the ultrasonic probe 14 and outputs the result to the ultrasonic calculation unit 90.

  The ultrasonic calculation unit 90 generates an ultrasonic image from the echo signal subjected to the delay addition processing and the like by the ultrasonic transmission / reception unit 80. In addition, the ultrasonic calculation unit 90 performs image processing such as coloring based on information from the light calculation unit 70. By this image processing, substances having the same absorption coefficient are given the same color. The display 100 displays the image obtained by the ultrasonic calculation unit 90.

  FIG. 2 is a schematic diagram showing a plan view of the biopsy probe 10 according to one embodiment of the present invention. In FIG. 2, the biopsy probe 10 has a substantially convex shape, and a distal end portion (acoustic lens) 141 of the ultrasonic probe 14 is disposed in the longitudinal direction. An optical unit 15 is disposed substantially at the center of the biopsy probe 10. As shown in the enlarged view of FIG. 2, the optical unit 15 is arranged such that six optical fibers 11-1 to 11-6 for irradiating light surround the first optical fiber 12 for light reception. .

  The biopsy probe 10 includes five second optical fibers 13-1 to 13-5 for receiving light at positions divided into four equal parts on a semicircle having a radius of 10 mm with the optical unit 15 as the center. In addition, the biopsy probe 10 has four optical fibers 13-6 except for a part farthest from the acoustic lens 141 among the positions equally divided into four on a semicircle having a radius of 20 mm with the optical unit 15 as the center. To 13-9.

  A cap 16 made of Ultem (PEI) is attached to the tip of the optical unit 15 and the optical fibers 13-1 to 13-9. The outer diameter of the cap 16 is 5 mm, the height is 0.5 mm, and the durometer is 90. Note that the shape of the cap 16 is often circular, but may be, for example, a square or a hexagon (in the case of a square or a hexagon, the above-described diameter is a diagonal line). As an example of a living body, the durometer of the breast is about 20 to 40 (for example, see Non-Patent Document 2). The acoustic lens 141 has a durometer of 60.

  FIG. 3 is a cross-sectional view taken along the line A-A ′ in FIG. 2 of the biopsy probe 10 according to the embodiment of the present invention. In FIG. 3, the cross section of the biopsy probe 10 has a substantially rectangular shape. The acoustic lens 141 is connected to, for example, an ultrasonic transducer 142 in which a plurality of minute piezoelectric transducers are arranged in a two-dimensional band shape. The optical fiber 12 and the optical fibers 11-1 to 11-6 and the optical fiber 13-3 forming the optical unit 15 penetrate from the upper surface to the lower surface of the biopsy probe 10. The tip of the optical unit 15 and the optical fiber 13-3 has a cap 16, so that it is positioned 0.5 mm lower than the acoustic lens 141.

  Next, the height, diameter, and hardness of the cap 16 will be described in detail.

  First, a description will be given of problems in a process in which light enters an organism from an optical fiber (or a process in which light is received by the optical fiber) when the cap 16 is not attached to the light receiving end and the irradiation end as in the prior art. To do.

  When light irradiated from the end face of the optical fiber enters the surface of the living body, the amount of light decreases due to reflection due to unevenness on the surface and reflection due to a difference in refractive index. This is because the optical fiber is separated from the sample surface, and there is air between the optical fiber and the living body surface. When there is air between the optical fiber and the living body surface, the light passes through the boundary from the optical fiber to air and from the air to the living body surface twice.

  In the present invention, since ultrasonic measurement is performed at the same time, a biopsy probe is used while applying US jelly for matching ultrasonic waves to the interface. Even in this case, when the optical fiber is separated from the sample surface, the matching jelly enters between the optical fiber and the sample surface, and the incident state of light varies. As a result, the intensity of subcutaneous incident light from the optical fiber is not constant. In addition, there exists a well-known example which stabilizes an incident state by apply | coating a matching agent (liquid or jelly) to an interface (for example, refer patent document 1). However, the reproducibility of the adhesion state of the optical fiber is not improved by the matching agent alone depending on the surface condition and flexibility of the sample.

  Therefore, in the present invention, in order to make the structure where the optical fiber tip does not float from the surface when the acoustic lens 141 is in contact with the skin surface, a cap 16 is attached to the optical unit 15 and the fiber optic tip as shown in FIG. These positions protrude to some extent from the acoustic lens 141. In order to irradiate the living body with ultrasonic waves, it is necessary to press the acoustic lens 141 against the living body. By adopting this structure, the optical unit 15 and the tip of the optical fiber are pushed into the living body.

  A living body has a certain degree of flexibility, in other words, hardness, and is deformed by receiving an external force. The magnitude of this deformation is determined by the tip shape of the object to be pushed in, the pushing force (pressure), and the hardness. The state of the living tissue changes as the deformation of the living body increases. With the deformation of the living body, the physical constant of the living body changes. For example, when the skin is strongly pressed, the capillaries in the dermis layer are crushed and blood is not supplied, and the skin color becomes white. In such a state, the amount of hemoglobin decreases and the absorption intensity decreases. If the optical fiber is pushed too deep, the skin condition changes in this way.

  Further, in order to push the optical fiber to a certain depth of the living body, when the diameter of the tip of the optical fiber is increased, the load for pressing the measurement probe against the skin is increased. If it is assumed that the operator scans the entire measurement probe while pressing it against the skin, and the subject does not feel pain at that time, the force pressing the optical fiber against the skin cannot be increased too much. The force required to keep the optical fiber tip in contact is about 30 g weight, and the force for pushing the optical fiber is preferably 1 kg weight or less, more preferably 500 g weight or less.

  Therefore, the depth to be pushed into the living body in order to bring the optical fiber into close contact should be given by this weighting and be in a range that does not change the optical constant of the skin. Further, if a small tip is used, only a certain local part may be deformed and the optical constant may be changed. Therefore, it is desirable to press the tip having a certain size vertically against the skin. Furthermore, when the optical fiber is pushed into the living body, the one with the higher hardness between the optical fiber tip and the living body deforms the other, and therefore the hardness of the optical fiber tip needs to be larger than that of the living body.

  The height and diameter of the cap 16 attached to the tip of the optical fiber were examined by experiment. At this time, Ultem having a durometer of 90 was used for the cap 16. The acoustic lens 141 has a durometer of 60, which is larger than the hardness of a living body. That is, since the hardness of the cap is larger than that of the living body, the living body can be deformed and pushed into the inside. In order to push the entire measurement probe vertically into the living body, it is most desirable that the hardness of the cap 16 matches the hardness of the acoustic lens 141. If the hardnesses do not match, it is desirable that the hardness of the cap 16 is higher than that of the acoustic lens 141.

  The experimental results show that the cap height that does not affect the optical constant is effective in the range of 0.5 mm to 1.5 mm, and more preferably in the range of 0.8 mm to 1.2 mm. It was. Moreover, it was shown that the diameter of the cap is effective at 5 mm or less at the largest portion, and is effective in the range of 1 mm to 5 mm in consideration of the thickness of the optical fiber (1 mm or less).

  Next, the light detection operation in the biopsy probe 10 shown in FIGS. 2 and 3 will be described in detail.

  The living body inspection apparatus detects the light intensity of diffusely reflected light that is diffusely reflected in the living body and irradiated outside the living body through a “banana-like” light path. The light carries the optical information of the substance on the path. For example, when light passes through a blood vessel and is absorbed by hemoglobin, the biopsy device can measure the blood state of the subject by obtaining an absorption coefficient from the detected light intensity.

  In order to read the optical information on the path, it is necessary to compare the light intensity after light absorption with the light intensity before light absorption, that is, the reference light intensity. Therefore, it is important for the biopsy device to correctly measure the reference light intensity. Since the target living body has various individual differences such as the position of the blood vessel, the color of the skin, and the skin condition, various cautions are required for measuring the reference light intensity. For example, assuming that there is a mole or bruise at the position where the reference light intensity is to be measured, or if a blood vessel passes under the skin, the position is measured despite the assumption that no absorber is present. The generated data has a problem that the signal level is lower than the original reference light intensity. In addition, when the reference light intensity is measured at a position where there is no absorber using a model sample, there is a problem that individual differences in skin color and skin condition are not considered.

  This problem is also observed in a detector arrangement method often used in a conventional measurement apparatus called a grid arrangement. In the grid arrangement, light sources (or elements that introduce light from an external light source) and detectors (or elements that transfer light to an external detection element) are alternately arranged at certain intervals. The measuring device measures information based on a measurement result of one light path connecting a pair of light source / detector pairs. This measurement information is assigned to the center position of the line connecting the light source and the detector. If an absorber other than the hemoglobin of interest, such as melanin (spot on the skin), is on the light path, the absorption of melanin (noise for this purpose) is added to the absorption of hemoglobin. Is measured so that the absorption of is increased. This result can be misinterpreted for the purpose of plotting only the state of hemoglobin.

In view of the above problems, the biopsy probe 10 according to the present invention has been developed.
The total thickness of the stratum corneum, which is the surface layer of the skin, and the epidermis is about 100 μm. For this reason, the light intensity entering below the surface layer varies depending on the color and state of the surface layer. The light that emerges on the surface after reaching 100 μm is detected at a distance of around 200 μm on average. In order to detect reflected light at the light incident end disposed at a distance of 200 μm from the light irradiation end, the optical fiber diameter needs to be 200 μm or less. However, when the optical fiber diameter is 200 μm or less, the amount of light incident on the living body is reduced and the SN ratio is deteriorated. In order to solve this problem, in the present invention, as shown in FIG. 2, six optical fibers 11-1 to 11-6 are arranged at a distance of 200 μm from the optical fiber 12 to increase the total amount of light introduced into the living body. Thereby, SN ratio can be increased.

  The depth at which the tumor occurs is inside the subcutaneous fat, and the light reaching this depth is emitted 5 mm or more away from the light incident position on average. Therefore, it is preferable to arrange the optical fiber on which the diffuse reflected light is incident at a distance of 5 mm or more from the optical unit 15. In order to make the SN ratio sufficiently large, the distance is preferably within 30 mm. Moreover, in order to detect efficiently the absorber in several depths, it is more preferable to use multiple detection distances. Furthermore, in order to improve the accuracy of obtaining the absorption coefficient when the attenuation of light by the absorber is small, it is further desirable to arrange a plurality of detectors for one distance. From the above, in the present invention, as shown in FIG. 2, the optical fibers 13-1 to 13-5 and the optical fibers 13-6 to 13-9 are arranged at a distance of 10 mm and 20 mm from the optical unit 15, respectively.

  In addition, an attempt to remove the influence of noise by arranging a plurality of detectors in a row is already a well-known example, and Israel's Cypro Medical has proposed a device in which sensors are arranged on the circumference (for example, , See Patent Document 2). The purpose of this device is to reduce the influence of noise by measuring a plurality of signals at points equidistant from the center by arranging sensors on the circumference and taking this average. However, since the living body is not uniform, there is a risk of distorting the signal by simply taking an average operation. Therefore, it is desirable to obtain the absorption coefficient from the detected intensity at each position calculated based on the ultrasonic image without mechanically averaging the signals of the detectors at the same distance.

  By the way, since the light source that has been positioned at the center in the past is in a ring shape, the distance from the optical fibers 11-1 to 11-6 to the optical fibers 13-1 to 13-9 is shifted by a maximum of twice the diameter of the optical fiber 11. Arise. When the influence of the deviation of ± 200 μm on the reflected light intensity and its path at the nearest 5 mm among the above-mentioned distances was estimated by Monte Carlo simulation, it was found that it was smaller than the detected noise level. Therefore, it was confirmed that there is no adverse effect such as distorting the signal by increasing the light amount by using the light source as a ring shape.

  FIG. 4 is a schematic diagram showing a state of light detection in the biopsy probe 10 according to the embodiment of the present invention. Although not shown in FIG. 4, the acoustic lens 141 is used in contact with the skin. At this time, the cap 16 attached to the optical unit 15 and the optical fiber 13 is pushed into the skin. As shown in FIG. 4, the light irradiated from the optical fiber 11 enters the skin, diffuses while repeating scattering in the living body, and is emitted from the skin again as diffuse reflected light through a “banana-like” light path. The “banana-like” light path passes through the deepest position between the entrance position and the exit position. Light diffusely reflected only by the surface layer portion of the living body enters the optical fiber 12. Further, light that has been diffusely reflected by the subcutaneous fat through the surface layer portion is incident on the optical fiber 13.

  Hereinafter, embodiments of the biopsy device having the above configuration will be described in detail.

Example 1
The following model samples were prepared as measurement targets for evaluating the device performance.

  As the model sample, a silicone resin is used as a base material, and a scatterer (10% fat sphere dispersion, product name: Intralipid) and an absorber (pigment) are dispersed and then cured. The optical constants (scattering coefficient and absorption coefficient) of this block were the same as fat. The durometer after curing of the block was 48. As the absorbent on the surface of the sample, an absorption film 1 (thickness 100 μm, 10 cm square) with an absorption strength (absorbance Abs) 0.5 and an absorption film 2 (thickness 100 μm, 10 cm square) with an absorption strength 1 are used. It was. The absorbance Abs is a natural logarithm of the ratio of the amount of incident light to the amount of emitted light.

The following three types of samples were prepared using the block, the absorption film 1 and the absorption film 2.
Sample 1: Block only and no absorption film.
Sample 2: The absorbent film 1 is placed on the upper surface of the block, and the four sides are bonded with an adhesive tape.
Sample 3: The absorption film 2 is placed on the upper surface of the block, and the four sides are bonded with an adhesive tape.

  Ultrasonic jelly was selected by selecting a position free from dirt and scratches on the block or film surface, and the biopsy probe 10 was slowly brought closer to the samples 1 to 3 from above. In this embodiment, the height at which the acoustic lens 141 first contacts the sample surface is 0 mm, and a positive displacement is taken downward.

  In this embodiment, light with wavelengths of 760 nm and 840 nm are output from the near infrared LDs 30-1 and 30-2 at an output of 10 mW. The optical combiner / coupler 40 receives both lights and outputs only light having a wavelength of 760 nm to the optical fibers 11-1 to 11-6. The optical fibers 11-1 to 11-6 installed in the optical unit 15 irradiate the samples 1 to 3 with this light. When the height is 0 mm, the light irradiation end and the optical fibers 13-1 to 13-9 are pushed into the sample by 0.5 mm from the acoustic lens 141, that is, the cap 16.

  When the sample 1 is irradiated with light, the light diffusely reflected in the block is incident on the optical fiber 12 and the optical fibers 13-1 to 13-9 of the optical unit 15. In addition, when the samples 2 and 3 are irradiated with light, the light diffusely reflected by the absorption films 1 and 2 adhered to the surfaces of the samples 2 and 3 enters the optical fiber 12 and is diffusely reflected within the block. The incident light enters the optical fibers 13-1 to 13-9.

  The light detection unit 50-1 receives light incident from the optical fiber 12 with an integration time of 1 second, and detects the light intensity. The light detection units 50-2 to 50-10 receive light incident from the optical fibers 13-1 to 13-9 with an integration time of 1 second and detect the light intensity. The light detection units 50-1 to 50-10 supply light intensity signals to the light calculation unit 70 in order from the light detection unit 50-1. The light calculation unit 70 sets the light intensity signal received from the light detection unit 50-1 as the reference light intensity, and sets the light intensity signals received from the light detection units 50-2 to 50-10 as the signal light intensity. Then, the light calculation unit 70 calculates the absorption intensity of the sample from the obtained reference light intensity and signal light intensity.

  In Samples 1 to 3, the light intensity was measured by the light detection units 50-1 to 50-10 in increments of 0.5 mm from 0 mm in height. In each measurement, the light intensity was measured five times, and the variation in the light intensity in the five measurements was 1% or less.

  When the height was set from 0 mm to 1 mm, the light intensity values in Samples 1 to 3 were constant values in each sample regardless of the set height. Moreover, the absorption intensity of the absorption film 2 calculated for the sample 3 was 1.8 to 2.2 times the absorption intensity of the absorption film 1 calculated for the sample 2. Since the absorption intensity of the absorption film 2 in the prepared sample is twice the absorption intensity of the absorption film 1, the difference in absorption intensity from 1.8 times to 2.2 times calculated in this example is calculated accuracy. It can be seen that the value is sufficiently high.

  When the height was set to −0.5 mm (the state where the tip of the cap 16 was in close contact with the sample surface), the light intensity measured with the sample 1 was highly dispersed. In some cases, the light intensity should increase due to absorption. In this case, the absorption is negative and the measurement accuracy is low. Moreover, in the measurement with respect to the samples 2 and 3, extremely strong light intensity was observed, and a result depending on the absorption intensity of the absorption films 1 and 2 was not obtained. This can be interpreted as that the light irradiated to the samples 2 and 3 was strongly regularly reflected due to the high smoothness on the surfaces of the absorption films 1 and 2. That is, the light intensity detected when the tip of the cap 16 is in contact with the sample and the acoustic lens 141 is lifted from the sample is irradiated from the optical fibers 11-1 to 11-6, not the subcutaneous incident light intensity. It is the light intensity itself.

  That is, in the first embodiment, when the cap 16 having a height of 0.5 mm and a diameter of 5 mm is attached to the light irradiation end and the light receiving end, the light irradiation end can be appropriately pushed into the sample, and the irradiated light Indicates that almost all of is incident on the sample.

(Example 2)
In Example 2, the height and diameter of the cap 16 were changed using the samples 1 to 3 used in Example 1. The cap 16 used was a cap 16-1 having a height of 1 mm and a diameter of 2.5 mm, a cap 16-2 having a height of 1 mm and a diameter of 5 mm, and a cap 16-3 having a height of 1.5 mm and a diameter of 2.5 mm. The cap 16-4 has a height of 1.5 mm and a diameter of 5 mm. As in Example 1, the height at which the acoustic lens 141 first contacts the sample surface is 0 mm, and a positive displacement is taken downward. Then, the biopsy probe 10 was lowered in steps of 0.5 mm, and the light intensity was measured.

  When the measurement of the light intensity was repeated using Samples 1 to 3, in the state where the tips of the optical fibers 11-1 to 11-6, which are light irradiation ends, were pushed into the sample from 0.5 mm to 1.5 mm, The reflected light intensity could be measured with a stability within 1%. On the other hand, when the tips of the optical fibers 11-1 to 11-6 were pushed into the sample by 2 mm or more, the reflected light intensity was reduced and the stability was also deteriorated from 3%. This is interpreted as an influence on the optical constants of Samples 1 to 3 because the deformation of Samples 1 to 3 due to indentation is excessive.

  That is, Example 2 shows that when the height of the cap 16 is appropriate, the light intensity can be stably measured.

(Example 3)
The following model samples were prepared as measurement targets for evaluating the device performance. In this embodiment, it is assumed that the measurement target is a tumor.

  As the model sample, a silicone resin is used as a base material, and a scatterer (10% fat sphere dispersion, product name: Intralipid) and an absorber (pigment) are dispersed and then cured. The optical constant (scattering coefficient / absorption coefficient) of this block was the same as that of fat. The durometer after curing of the block was 48. And the groove | channel of the depth of 8 mm was produced by the square of 3 mm on the block surface.

Assuming hemoglobin and oxygenated hemoglobin as a tumor (determining whether or not the tumor is malignant by the ratio of hemoglobin), an aqueous solution 1 of a dye whose absorption spectrum matches that of hemoglobin, and an aqueous solution of a dye whose absorption spectrum matches that of oxyhemoglobin 2 were prepared. And the aqueous solution which mixed the aqueous solution 1 and the aqueous solution 2 with the following ratio was inject | poured into the above-mentioned groove | channel, paying attention so that air might not remain.
Tumor model 1: 10 in aqueous solution 1 and 0 in aqueous solution 2.
Tumor model 2: aqueous solution 1 is 7, aqueous solution 2 is 3.
Tumor model 3: aqueous solution 1 is 5, aqueous solution 2 is 5.
Tumor model 4: aqueous solution 1 is 3, aqueous solution 2 is 7.
Tumor model 5: aqueous solution 1 is 0, aqueous solution 2 is 10.

  A thin plate obtained by slicing the block to a thickness of 5 mm was prepared, and the thin plate was carefully placed on the block in which the tumor models 1 to 5 were injected into the groove so that an air layer was not formed. FIG. 5 is a schematic diagram illustrating a sample in the third embodiment.

  In this embodiment, light with wavelengths of 760 nm and 840 nm are output from the near-infrared LDs 30-1 and 30-2 at an output of 5 mW. The optical combiner / coupler 40 received both lights, and each laser beam was incident on the optical fibers 11-1 to 11-6 alternately by a rotating chopper. At this time, the optical multiplexer / coupler 40 notifies the optical calculation unit 70 of which frequency light is output to the optical fibers 11-1 to 11-6. Note that the measurement systems such as the light detection units 50-1 to 50-10 were the same as those in Example 1.

  In the present embodiment, first, the biopsy probe 10 is pressed against a portion of the sample where there is no groove, and the reflected light intensity of two wavelengths is measured for each of the light detection units 50-1 to 50-10. At this time, the reflected light intensity of the light incident on the optical fiber 12 is set as the reference light intensity. Next, as shown in FIG. 6, the biopsy probe 10 is arranged so that the optical unit 15 is aligned with the center of the groove, and the reflected light intensity is measured. At this time, the reflected light intensity of the light incident on the optical fibers 13-1 to 13-9 is set as the signal light intensity. The above measurement is repeated for the sample into which any one of the tumor models 1 to 5 is injected, and the absorption intensity is obtained from the obtained signal light intensity and reference light intensity. Then, the distribution of the scattered light intensity of the absorber is calculated by comparing the absorption intensity itself and the total hemoglobin amount and oxygen saturation value calculated from the absorption intensity with the reference value, and the composition of the absorber is determined. To do.

  Next, the distribution of scattered light intensity obtained by measurement is compared with the distribution of scattered light intensity obtained by simulation. In the simulation, first, near-infrared absorption spectra of the tumor models 1 to 5 are measured by FT-NIR (Fourier transform type near-infrared spectrometer), and absorbances at 760 nm and 840 nm are obtained. Based on this absorbance, the theoretical value of the absorption coefficient is calculated using the optical path length of the tumor model in the groove. Then, assign the fat optical constant to the part corresponding to fat, assign the theoretical value of the calculated absorption coefficient to the part corresponding to the absorber, and perform the simulation by the finite element method to calculate the scattered light intensity distribution To do.

  The measurement result coincided with the scattered light intensity distribution calculated by simulation. Therefore, it can be interpreted that the composition of the tumor model in the sample can be determined by measuring the light intensity.

  That is, Example 3 shows that when the cap 16 is attached to the light irradiation end and the light receiving end, the biopsy device can measure the absorption intensity for each absorber.

  As described above, the biopsy probe 10 according to the present embodiment includes the cap 16 for pushing the light irradiation end and the light incident end into the living body. Thereby, the biopsy probe 10 can stably enter the light emitted from the optical fibers 11-1 to 11-6 into the living body.

  The biopsy probe 10 according to the present embodiment includes, as the optical unit 15, an optical fiber 12 for receiving light and optical fibers 11-1 to 11-6 for light irradiation located 200 μm away from the optical fiber 12. And the optical fibers 13-1 to 13-5 for light reception are arranged at a position 10 mm from the optical unit 15, and the optical fibers 13-6 to 13-9 are arranged at a position 20 mm. Thereby, the biopsy probe 10 can make only the light irradiated from the optical fibers 11-1 to 11-6 to the optical fiber 12 and diffusely reflected by the surface layer portion of the living body enter the optical fiber 12. On the other hand, the biopsy probe 10 can make light diffusely reflected by subcutaneous fat enter the optical fibers 13-1 to 13-9. Further, in this configuration, when the cap 16 is attached to the optical unit 15, the light emitted from the optical fibers 11-1 to 11-6 is stably incident on the living body. It becomes possible to accurately enter diffusely reflected light.

  The biopsy apparatus according to the present embodiment uses the light intensity detected from the light incident on the optical fiber 12 as the reference light intensity, and the light intensity detected from the light incident on the optical fibers 13-1 to 13-9 as a signal. The light intensity. The living body inspection apparatus calculates the scattered light intensity distribution in the living body based on the detected reference light intensity and signal light intensity. As a result, the biopsy apparatus according to the present invention can accurately measure the reference light intensity and the signal light intensity even when there are individual differences in the surface layer of the living body, and therefore calculates the scattered light intensity distribution with high accuracy. It becomes possible.

  Therefore, according to the present invention, it is possible to solve the conventional problem that the signal becomes small because the value of the reference light intensity is not appropriate in the device that detects the in-vivo information with light without exposure risk. That is, it is possible to provide a biopsy device and a biopsy probe capable of providing data that can withstand analysis by improving the reproducibility of the detected signal and considering individual differences.

  In the living body inspection probe 10 in the above embodiment, the example in which the light irradiation end and the light incident end are optical fibers has been described. However, other optical components (for example, lenses) may be used.

  In the biopsy probe 10 in the above embodiment, the example in which the near-infrared LD outputs laser light has been described. However, the present invention is not limited to the near-infrared LD, and a semiconductor laser, a solid-state laser, a gas laser, or the like. The light emitting element may be used.

  Moreover, in the probe 10 for living body inspection in the said embodiment, although the optical detection part demonstrated the example which detects light intensity with Si photodiode, it is not restricted to Si photodiode, Photosensitive elements, such as a phototransistor, or A photomultiplier tube may be used.

  Moreover, although the example which arrange | positions the six optical fibers 11-1 to 11-6 around the optical fiber 12 was demonstrated in the probe 10 for biopsy in the said embodiment, the optical fiber for light irradiation is limited to six. There is nothing.

  Furthermore, the present invention is not limited to the above-described embodiments as they are, and can be embodied by modifying the constituent elements without departing from the scope of the invention in the implementation stage. In addition, various inventions can be formed by appropriately combining a plurality of components disclosed in the embodiment. For example, some components may be deleted from all the components shown in the embodiment.

The block diagram which shows the function structure of one Embodiment of the biopsy apparatus which concerns on this invention. The schematic diagram which shows the structure of the measurement probe of the biopsy apparatus shown by FIG. Sectional drawing of the measurement probe shown by FIG. The schematic diagram of the optical detection in the measurement probe of the said embodiment. The schematic diagram which shows the sample in Example 3 of the said embodiment. The schematic diagram which shows the positional relationship of the measurement probe and sample in Example 3 of the said embodiment.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Measurement probe, 11, 11-1 to 11-6 ... Optical fiber for light irradiation, 12 ... Optical fiber for light reception, 13, 13-1 to 13-9 ... Optical fiber for light reception, 14 ... Ultrasonic probe, 141 ... Acoustic lens DESCRIPTION OF SYMBOLS 142 ... Ultrasonic transducer, 15 ... Optical part, 16 ... Cap, 20 ... Signal generation part, 30-1, 30-2 ... Near-infrared LD, 40 ... Optical multiplexing and coupling part, 50-1-50- DESCRIPTION OF SYMBOLS 10 ... Light detection part, 60 ... Main amplifier, 70 ... Light calculating part, 71 ... Memory, 80 ... Ultrasonic transmission / reception part, 90 ... Ultrasonic calculating part, 100 ... Display, 200 ... Living body.

Claims (10)

An ultrasonic probe for transmitting and receiving ultrasonic waves to and from the living body while being in contact with the surface of the living body;
The light irradiation end and the light incident end are in contact with the living body with the ultrasonic probe being in contact with the living body, and the living body is irradiated with light from the light irradiation end. An optical probe for entering the light diffusely reflected in the body at the light incident end;
A light inspection end of the optical probe and a light incident end protrude from a contact surface of the ultrasonic probe with respect to the surface of the living body, respectively. A projecting portion for projecting the light irradiation end and the light incident end from the living body surface of the ultrasonic probe;
The protruding portion protrudes from 0.5 mm to 1.5 mm with respect to the contact surface of the ultrasonic probe with the living body,
The width of the protrusion is 1 mm to 5 mm,
The biopsy probe according to claim 1, wherein the protrusion has a hardness higher than that of the living body. The biopsy probe according to claim 2, wherein the hardness of the protruding portion is equal to or higher than the hardness of a contact surface of the ultrasonic probe with the living body. The optical probe is
A light irradiation means disposed at the light irradiation end for irradiating light;
A first light incident means that is disposed at the light incident end and that makes the light incident on the surface layer portion including the epidermis and stratum corneum in the living body diffusely reflected;
2. The probe for biopsy according to claim 1, further comprising: a second light incident unit that is disposed at the light incident end and that makes the light diffused and reflected at a position deeper than the surface layer portion. . A plurality of the light irradiation means are installed in a range of 100 μm to 300 μm from the first light incident means,
5. The probe for biopsy according to claim 4, wherein a plurality of the second light incident means are installed in a range of 5 mm to 30 mm from the first light incident means. An ultrasonic probe for transmitting and receiving ultrasonic waves to and from the living body while being in contact with the surface of the living body, and the ultrasonic probe are integrated with the ultrasonic probe, and the ultrasonic probe is in contact with the living body and in contact with the living body. A living body inspection provided with a light irradiation end and a light incident end in contact with each other, and an optical probe for irradiating light from the light irradiation end and diffused and reflected in the living body at the light incident end Probe for,
An image acquisition unit for acquiring ultrasonic images in the living body by transmitting and receiving ultrasonic waves to and from the living body by the ultrasonic probe;
A light irradiation unit that irradiates light including a specific wavelength component that is an absorption wavelength band of the abnormal tissue of the living body from a light irradiation end of the optical probe;
A light detection unit that receives light incident at a light incident end of the optical probe and detects its light intensity;
A light calculation unit that obtains an absorption coefficient of light of the abnormal site composed of the abnormal tissue based on the light intensity detected by the light detection unit;
Display means for displaying the ultrasonic image after image processing based on the light absorption coefficient;
The living body inspection apparatus, wherein the light irradiation end and the light incident end of the optical probe protrude from a contact surface of the ultrasonic probe with respect to the living body surface, respectively. A projecting portion for projecting the light irradiation end and the light incident end from the living body surface of the ultrasonic probe;
The protruding portion protrudes from 0.5 mm to 1.5 mm with respect to the contact surface of the ultrasonic probe with the living body,
The width of the protrusion is 1 mm to 5 mm,
The biopsy apparatus according to claim 6, wherein the protrusion has a hardness greater than that of the living body. The biopsy device according to claim 7, wherein the hardness of the protruding portion is equal to or higher than the hardness of the contact surface of the ultrasonic probe with the living body. The optical probe is
A light irradiation means disposed at the light irradiation end for irradiating light;
A first light incident means that is disposed at the light incident end and that makes the light incident on the surface layer portion including the epidermis and stratum corneum in the living body diffusely reflected;
A second light incident means that is disposed at the light incident end and that makes the light diffusely reflected at a position deeper than the surface layer portion, and
The light detection unit is
A first photodetector for receiving the light incident by the first light incident means and detecting the light intensity;
A second photodetector for receiving the light incident by the second light incident means and detecting the light intensity thereof;
The light calculation unit uses the light intensity detected by the first photodetector as a reference light intensity and the light intensity detected by the second photodetector as a signal light intensity. The biological examination apparatus according to claim 6, wherein the absorption coefficient is obtained using light intensity. A plurality of the light irradiation means are arranged in a range of 100 μm to 300 μm from the first light incident means,
The biological examination apparatus according to claim 9, wherein a plurality of the second light incident means are arranged in a range of 5 mm to 30 mm from the first light incident means.

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