JP2015224944A - Biological image acquisition device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biological image acquisition device capable of acquiring a high-resolution image that is improved infinitely compared with current cancer detection accuracy.SOLUTION: A biological image acquisition device comprises: a deformable mirror 20 into which input is observation light reflected or radiated by an inspection object tissue 10 via a lipid tissue 12 and which is made of individual regions where positional posture control of an inclination angle and a height direction is enabled; a wave surface reconfiguration calculation unit 32 for calculating the amount of control necessary for wave surface reconfiguration to perform positional posture control of the inclination angle and height direction of each individual region of the deformable mirror 20 so that the observation light reflected by the deformable mirror 20 is input into a wave surface sensor 30 and a component distorted by the lipid tissue 12 is compensated; and a light receiving unit 40 into which input is the observation light of the inspection object tissue 10, about the observation light, the component distorted by the lipid tissue 12 being compensated by performing wave surface reconfiguration of the deformable mirror 20 using the wave surface reconfiguration control amount.

Description

  The present invention relates to a biological image acquisition apparatus that can image a subcutaneous tissue with high resolution, which is suitable for, for example, examination of cancer cells in a living body.

When examining cancer cells in a living body, the cancer cells are often covered with subcutaneous tissue. Therefore, for example, in a biological image acquisition apparatus such as an endoscope, there is a difficulty in acquiring a high-resolution image due to disturbance of incident light caused by tissue in the living body.
On the other hand, for example, as shown in Non-Patent Document 1, laser mammography (Computed Tomographic Laser Mammography) has also been developed. However, there is a problem that the spatial resolution is not sufficient.
Non-Patent Document 2 reports that X-ray mammography is applied to the diagnosis of a living body, particularly breast cancer. Although it uses X-rays, it has excellent spatial resolution. However, human tissue is damaged by exposure to X-rays, so that it is necessary to reduce the amount of X-ray irradiation for detecting cancer tissues. there were.

  Here, “laser mammography” refers to a technique for determining the structure of the breast by solving the inverse problem after detecting the light after irradiating the breast in three dimensions with the laser as incident light. “X-ray mammography” refers to a technique for determining the structure of the breast by solving the inverse problem after detecting X-rays incident on the X-ray in three dimensions and then irradiating the breast in three dimensions. “Tomography” is a general term for a method for determining the structure of an affected area from information of detection light by solving an inverse problem, and many medical devices such as MRI use this method.

  Therefore, it is conceivable to improve the spatial resolution in the biological field by attaching an adaptive optics system to the biological image acquisition apparatus. However, in reality, there are examples in which the compensation optical system is attached to a living body image acquisition device and applied to improve the spatial resolution in the living body field, and there is an apparatus that optically corrects a crystalline lens for fundus examination, but it is not transparent. As far as the present inventor is aware, there is no example applied to the object to be measured.

JP 2006-6362 A JP 2013-7740 A

D. M. Richter, Jpn. Soc. Radiol. Tech. 59, 687-693 (2003) D. Floery et al. Investigative Radiology 40, 328-335 (2005)

  The present invention solves the above-described problems, and dramatically improves the current cancer detection accuracy by attaching a compensation optical system having a structure suitable for the biological image acquisition device to the biological image acquisition device. It is an object of the present invention to provide a biological image acquisition apparatus that can acquire a high-resolution image and can detect many cancers at an early stage.

  In order to achieve the above object, the living body image acquisition apparatus of the present invention can allow observation light reflected or emitted from the examination target tissue 10 to enter through the lipid tissue 12, as shown in FIGS. The deformable mirror 20 includes a deformable mirror 20 formed of individual regions whose position and orientation can be controlled in inclination angle and height direction, and a beam that branches the observation light reflected by the deformable mirror 20. The splitter 22, the wavefront sensor 30 that receives the observation light branched by the beam splitter 22, and the incident light of the wavefront sensor 30 are input for each pixel, and among the observation light of the examination target tissue 10, the lipid tissue A wavefront reconstruction calculating unit 32 for calculating a control amount necessary for wavefront reconstruction for performing position and orientation control in the tilt direction and height direction of each individual region of the deformable mirror 20 so as to compensate for the component distorted at 12; , Wavefront reconstruction calculation unit 32 The wavefront reconstruction control amount is sent to each corresponding region of the deformable mirror 20 to perform wavefront reconstruction of the deformable mirror 20, and the observation light of the tissue 10 to be examined that compensates for the distortion component in the lipid tissue 12 is obtained. The incident light receiving unit 40 is provided.

In the living body image acquisition apparatus of the present invention, preferably, each individual region of the deformable mirror 20 has a telescopic actuator that moves in the height direction provided for each individual region, and the deformable mirror 20 has each individual region. The surface mirror layers may be connected to each other in a continuous state.
In the biological image acquisition device of the present invention, preferably, the individual region of the deformable mirror 20 has a range in which the height direction can be controlled in position and orientation is at least one quarter of the wavelength included in the observation light and less than half a wavelength. It is good to be. At one quarter wavelength, the observation light is amplified by interference. At half wavelength, the observation light is attenuated by interference. Therefore, if the wavelength included in the observation light is not less than one quarter of the wavelength and not more than half, the range in which the position and orientation can be controlled in the height direction is the minimum range.
In the biological image acquisition device of the present invention, preferably, the shape of each individual region of the deformable mirror 20 is larger than the single cell shape of the tissue to be examined and smaller than twice the maximum length of the cell shape. It may have a shape. If the shape of each individual region of the deformable mirror 20 is smaller than the single cell shape of the tissue to be examined, the single cell shape of the tissue to be examined is divided into a plurality of individual regions, which is not preferable. When the shape of each individual region of the deformable mirror 20 is larger than twice the maximum length of the cell shape, optical compensation of a single individual region is applied to a plurality of cell shapes, so that image distortion compensation is performed. Is not possible with a single cell shape unit.

  According to the living body image acquisition apparatus of the present invention, by applying to an optical tissue examination such as cancer detection of a living body, an image of a tissue of interest under a lipid, which has been difficult until now, is acquired with higher resolution. It becomes possible.

It is an optical system conceptual diagram in the biological image acquisition apparatus of this invention. It is a figure explaining the optical characteristic of a wavefront sensor, and is a reference image. It is a figure explaining the optical characteristic of a wavefront sensor, and is a test image. It is a figure explaining the optical characteristic of a wavefront sensor, and is the result of having measured the difference of a reference image and a test image for every pixel. It is a figure explaining the optical characteristic of a wavefront sensor, and is a contour-line display of the shift for every pixel. It is a figure explaining the optical characteristic of a wavefront sensor, and is a shift direction and shift amount display for each pixel. It is a figure which shows the example of calculation of the quantity which should correct | amend the displacement in a separate area | region of a deformable mirror, and a displacement. Step 1 is shown in the flowchart explaining the details of the wavefront reconstruction calculation. Step 2 is shown in the flowchart illustrating the details of the wavefront reconstruction calculation. In the flowchart explaining the details of the wavefront reconstruction calculation, substep 1 is shown. In the flowchart explaining the details of the wavefront reconstruction calculation, sub-step 2 is shown. It is explanatory drawing of one Example which combines a wave front sensor and a deformable mirror, and compensates the image distorted by lipid tissue, (A) has shown the distorted image, (B) has shown the image after compensation. It is an optical system implementation figure which shows embodiment in the biometric image acquisition apparatus of this invention. It is a figure which shows an example of the analysis result in the wavefront sensor of the image distorted with soybean oil. It is explanatory drawing of one Example which combines a wave front sensor and a deformable mirror, and compensates the image distorted with soybean oil, (A) has shown the distorted image, (B) has shown the image after compensation. It is a figure which shows an example of the wave front for every pixel compensated with the deformable mirror.

Definitions of scientific and technical terms used in the present specification are as follows.
The “microlens array” is an optical element for two-dimensionally arranging lenses having a diameter of about several μm and acquiring an image from each lens with a CCD camera.
The “deformable mirror” is also called a deformable mirror. It is also called a wavefront compensator with an emphasis on functional aspects, and “Wavefront Corrector” is also used in English. The deformable mirror is an optical element for correcting light incident on the entire mirror in units of pixels by mechanically driving a reflecting mirror of about several μm and independently driving each mirror.
The “scattering body” has “Turbulent Media” written in English, and changes the traveling direction of the light by scattering the light.

“Wavefront sensor” is written in English as “Wavefront Sensor”, and has the capability of detecting the phase of the light that arrives for each pixel.
“Object” has “Object” in English, and is a target on which, for example, a test pattern for verifying the performance of the biological image acquisition device is drawn. In an actual biological image acquisition device, the target part corresponds to an affected part of a patient.

“Spherical wave” means that the light emitted from the laser has a flat wavefront, but when the light is irradiated to the scatterer, each scatterer becomes a new wave source and is emitted as spherical light. It is shown that.
The “frame rate” is the reciprocal of the time required to acquire one screen, and is the number of screens that can be acquired per unit time.
The “wavefront sensor” is a CCD camera provided with a microlens array, and is an optical element capable of detecting the phase of light incident on each pixel unit.

The “1951 USAF Test Target” is an element used for the purpose of evaluating and calibrating the performance of the imaging optical system, and is a resolution test pattern standardized by the US Air Force in 1951.
“Spatial frequency” is the number of patterns per unit length, and the larger this value, the better the resolution.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
FIG. 1 is a conceptual diagram of an optical system in the biological image acquisition apparatus of the present invention. In the figure, a tissue 10 to be examined is a cancer cell located in a specific organ such as a patient's larynx, skin, or breast. Cancer cells are classified into carcinoma, which is a malignant neoplasm of epithelial tissue, and sarcoma, which is a malignant neoplasm of non-epithelial tissue. The lipid tissue 12 exists between the tissue 10 to be examined and the epidermis, and distorts the optical image of the tissue 10 to be examined during the pathological examination of the tissue to become an obstacle to the pathological examination. The optical distortion caused by the lipid tissue 12 can be displayed as a component using, for example, a Zernike polynomial.

    The deformable mirror 20 is composed of individual regions whose tilt angle and height direction can be controlled in position and orientation, and can be obtained from, for example, the Fraunhofer Institute in the Federal Republic of Germany. The deformable mirror 20 has an actuator that is displaced in the height direction for each individual region, and has a continuous mirror surface formed by vapor-depositing silver, gold, aluminum, or the like on an elastically deformable film. The number of actuators may be suitably provided, for example, from about 25 to about 1000 according to the required resolution.

  The beam splitter 22 branches the observation light reflected by the deformable mirror 20, and one branch light is sent to the wavefront sensor 30, and the other branch light is sent to the image receiving surface of the observation light.

  As the wavefront sensor 30, for example, a Shack-Hartmann sensor or a curvature sensor is used. The Shack-Hartmann sensor measures image shift by a fine lens array. Each lens of the lens array corresponds to a pixel of the wavefront sensor 30 in this specification. The curvature sensor captures the state of the wavefront due to wave interference by capturing changes in light intensity by moving the sensor body.

The wavefront reconstruction calculation unit 32 inputs information on the received light signal captured by the wavefront sensor 30 and calculates a control signal vector voltage for controlling the deformable mirror 20. This wavefront reconstruction calculation is based on a matrix calculation of adjacent sensor groups. As a result, the wavefront reconstruction calculating unit 32 inputs the incident light of the wavefront sensor 30 for each pixel and compensates for the component distorted by the lipid tissue 12 in the observation light of the examination target tissue 10. Then, the control amount necessary for wavefront reconstruction for controlling the tilt angle of each individual region of the deformable mirror 20 and the position and orientation in the height direction is calculated.
For the light receiving unit 40, for example, a CCD (Charge Coupled Device) camera is used.

    Next, the operation of the biological image acquisition apparatus configured as described above will be described. Observation light from the examination target tissue 10 reaches the wavefront sensor 30 through the lipid tissue 12 and the deformable mirror 20. The observation light is visible light supplied from a light source (not shown), typically transmitted light or reflected light. The lipid tissue 12 acts as a scatterer of observation light, but does not impart strong scattering such as bending to the observation light. Here, “bending” refers to a type that is transmitted by being scattered 180 degrees from the traveling direction of the observation light and then again being scattered 180 degrees. Therefore, the lipid tissue 12 reaches the wavefront sensor 30 after undergoing multiple scattering of observation light.

The wavefront sensor 30 detects the phase difference from the plane wave, and the wavefront reconstruction calculation unit 32 calculates the correction amount fed back to the deformable mirror 20 that independently drives the phase difference at each wavefront. Then, the wavefront reconstruction calculating unit 32 outputs this correction amount to the deformable mirror 20 to return the observation light distorted by the lipid tissue 12 to a plane wave.
That is, the distortion compensation of the observation light of the examination target tissue 10 guided to the optical path is performed by the wavefront reconstruction by the wavefront reconstruction calculation unit 32. Therefore, in the light receiving unit 40, an observation image of the examination target tissue 10 in which the component distorted in the lipid tissue 12 is compensated is obtained.

Next, details of the wavefront sensor will be described. 2A to 2E are diagrams illustrating optical characteristics of the wavefront sensor. FIG. 2A is a reference image, FIG. 2B is a test image, and FIG. 2C is a result of measuring the difference between the reference image and the test image for each pixel. 2D is a contour display of the shift for each pixel, and FIG. 2E is a shift direction and shift amount display for each pixel.
First, the wavefront when the plane wave is not subjected to phase modulation is recorded {FIG. 2A}. Next, the wavefront sensor 30 receives the light whose phase is disturbed {FIG. 2B}. Thereafter, the difference between the reference wavefront and the actual wavefront is obtained for each microlens array using the software of the wavefront reconstruction calculating unit 32 {(FIG. 2C). Also, the phase shift of the light is displayed as a contour line. It is also possible to {(FIG. 2D}. Further, it is also possible to indicate the direction and amount of shift for each pixel {(FIG. 2E}).

  FIG. 3 is a diagram showing an example of calculating the displacement in the individual region of the deformable mirror and the amount of displacement to be corrected. (A) is a 3D perspective view of the amount of correction required for the entire deformable mirror, and (B) is acceptable. 3D perspective view for explaining the distribution of the required correction amount of the deformable mirror, (C) is the correction amount required for each pixel of the deformable mirror, and (D) is the correction required in which the enlargement ratio in the height direction is different from (A). 3E is a 3D perspective view of the quantity, and FIG. 3E is a 3D perspective view illustrating the wavefront distribution for each pixel. The wavefront reconstruction calculation unit 32 calculates a shift for each pixel of the wavefront sensor 30 and a signal for correcting the shift.

Next, details of the wavefront reconstruction calculation of the wavefront reconstruction calculation unit 32 will be described.
FIG. 4 is a flowchart for explaining the details of the wavefront reconstruction calculation, and shows step 1. First, the wavefront sensor 30 starts a measurement operation (S100), and reads m × n pixel data of the wavefront sensor 30 (S102). The deformable mirror 20 also starts a measurement operation (S110), and reads data of M × N pixels of the deformable mirror 20 (S112).

  Subsequently, step 1 is started. The wavefront reconstruction calculating unit 32 captures data of (1, 1) pixels of the wavefront sensor 30 (S104) and captures data of (1, 1) pixels of the deformable mirror 20 (S114). Then, the wavefront reconstruction calculation unit 32 calculates the amount of distortion of the wavefront from the plane direction, and specifically performs a displacement direction, a displacement amount, and conversion data input (S120). Then, it is determined whether the displacement direction and the displacement amount are zero (S122). If No, a control amount ΔSG for compensating the distortion amount is calculated for the deformable mirror 20 (S124), and the process returns to S120. On the other hand, if Yes, step 1 is ended and the process proceeds to the next step 2.

  FIG. 5 is a flowchart for explaining the details of the wavefront reconstruction calculation, and shows step 2. First, at the start of step 2, the wavefront reconstruction calculating unit 32 takes in the data of (1,2) pixels of the wavefront sensor 30 (S204) and the data of (1,2) pixels of the deformable mirror 20 as well. Capture (S214). Then, the wavefront reconstruction calculation unit 32 calculates the amount of distortion of the wavefront from the plane direction, and specifically performs a displacement direction, a displacement amount, and conversion data input (S220). Then, it is determined whether the displacement direction and the displacement amount are zero (S222). If No, a control amount ΔSG for compensating the distortion amount is calculated for the deformable mirror 20 (S224), and the process returns to S220. On the other hand, if Yes, step 2 is terminated and the process proceeds to the next step.

  Hereinafter, the coordinates of the pixels of the wavefront sensor 30 and the deformable mirror 20 are (1,3), (1,4),..., (1, n), (2,1), (2,2), (2 , 3), ..., (2, n), ..., (m, 1), (m, 2), (m, 3), ..., (m, n), the steps are repeated. Therefore, all steps are completed with the number of times M × N.

Subsequently, another aspect of the wavefront reconstruction calculation of the wavefront reconstruction calculation unit 32 will be described. Here, one pixel of the wavefront sensor 30 corresponds to a plurality of pixels in the deformable mirror 20 so that the inclination of the plane wave can be corrected.
FIG. 6 is a flowchart for explaining the details of the wavefront reconstruction calculation, and shows sub-step 1. First, the wavefront sensor 30 starts the measurement operation of step 1 (S300), and reads 1 × 1 pixel data corresponding to the step of the wavefront sensor 30 (S302). The deformable mirror 20 also starts a measurement operation (S310), and reads K × L pixel data corresponding to the step of the deformable mirror 20 (S312).

  Subsequently, sub-step 1 of step 1 is started. The wavefront reconstruction calculating unit 32 takes in the data of the (1, 1) pixel of the wavefront sensor 30 (S304) and takes in the data of the (1, 1) pixel of the deformable mirror 20 (S314). Then, the wavefront reconstruction calculation unit 32 calculates the amount of distortion of the wavefront from the plane direction, specifically, the displacement direction, the amount of displacement, and conversion data input (S320). Then, it is determined whether the displacement direction and the displacement amount are zero (S322). If No, a control amount ΔSG for compensating the distortion amount is calculated for the deformable mirror 20 (S324), and the process returns to S320. On the other hand, if Yes, the sub-step 1 is terminated and the process proceeds to the next sub-step 2.

  FIG. 7 is a flowchart for explaining the details of the wavefront reconstruction calculation, and shows sub-step 2. First, at the start of sub-step 2 corresponding to the step, the wavefront reconstruction calculation unit 32 takes in data of (1, 2) pixels of the wavefront sensor 30 corresponding to the step (S404), The data of (1, 2) pixels of the corresponding deformable mirror 20 is taken in (S414). Then, the wavefront reconstruction calculation unit 32 calculates the amount of distortion of the wavefront from the plane direction, specifically, the displacement direction, the displacement amount, and conversion data input (S420). Then, it is determined whether the displacement direction and the displacement amount are zero (S422). If No, a control amount ΔSG for compensating the distortion amount is calculated for the deformable mirror 20 (S424), and the process returns to S420. On the other hand, if Yes, the sub-step 2 is terminated and the process proceeds to the next sub-step.

Hereinafter, the coordinates of the pixels of the wavefront sensor 30 and the deformable mirror 20 are (1,3), (1,4),..., (1, L), (2,1), (2,2), (2 , 3), ..., (2, L), ..., (K, 1), (K, 2), (K, 3), ..., (K, L), the sub-steps are repeated. Therefore, all substeps are completed with the number of substeps K × L.
Therefore, when the number of steps M × N for all steps is used as a reference, the number of all sub-steps for all steps is M × N × K × L.

  FIG. 8 is an explanatory diagram of an embodiment in which the wavefront sensor 30 and the deformable mirror 20 are combined to compensate an image distorted by the lipid tissue 12, where (A) is a distorted image and (B) is an image after compensation. Is shown. The resolution of the image {FIG. 8 (B)} when the adaptive optics is applied is clearly improved as compared to {FIG. 8 (A)} where the adaptive optics combining the wavefront sensor 30 and the deformable mirror 20 is not applied. The image is clear.

  FIG. 9 is an optical system implementation diagram showing an embodiment of the biological image acquisition apparatus of the present invention. Here, a biometric image acquisition device for examining breast cancer is configured. 9 that have the same functions as those in FIG. 1 are denoted by the same reference numerals and description thereof is omitted.

    In general, cancer cells are detected using the fact that the light absorption coefficient varies depending on the cell type. Since the cancer cells to be detected at this time are embedded in three-dimensional biological lipids, it is necessary to expand the two-dimensional detection technique shown in the first embodiment to three dimensions. is there. At this time, the lipid corresponds to a scatterer, but it is assumed that the light is not extremely bent by the lipid, and a deformable mirror is placed behind the incident light with respect to the site where breast cancer exists. In the case of the deformable mirror 20 provided by the Fraunhofer Institute, the size of the deformable mirror 20 including the housing is 28 mm × 28 mm × 3 mm (light receiving surface 14.3 × 14.3 mm). Light can be received in the plane.

    In FIG. 9, a HeNe laser light source 14 is used as reference light, and passes through the soybean oil layer 13 that directly substitutes the lipid tissue without passing through the tissue 10 to be examined, so that the deformable mirror 20, the wavefront sensor 30, and the light reception. Sent to the unit 40. The LED light source 16 is used as irradiation light of the examination target tissue 10, and the transmitted light of the examination target tissue 10 passes through the soybean oil layer 13 and is sent to the deformable mirror 20, the wavefront sensor 30, and the light receiving unit 40. As the HeNe laser light source 14, for example, a HeNe laser manufactured by Meris Griot, wavelength 632.8 nm, and output 15 mW can be used. As the LED light source 16, for example, an LED light source manufactured by Therlab with a wavelength of 505 nm and a maximum output of 4.5 mW can be used.

The biological image acquisition apparatus includes various concavo-convex lenses on an optical path, and includes dichroic beam splitters 22 and 26, a polarization beam splitter 24, and a Zernike polarizing plate 28. The Zernike polarizing plate 28 is used to calibrate the biological image acquisition apparatus by configuring the biological image acquisition apparatus using known parts. The Zernike polarizing plate 28 uses, for example, terms corresponding to the third-order coma aberration and the third-order spherical aberration in the orthogonal definition of the Zernike polynomial. When the wavefront aberration is decomposed by using the Zernike polynomial, each Zernike polynomial corresponds to an independent wavefront shape, and each also corresponds to a classic aberration, and an aberration component can be obtained.
The Object portion is a part where a marker for calibration of the imaging optical system such as the tissue 10 to be examined and the 1951 USAF test target is provided.
For the light receiving unit 40, for example, a CCD camera such as C4880 manufactured by Hamamatsu Photonics may be used.

    Next, the operation of the biological image acquisition apparatus configured as described above will be described. First, the biological image acquisition apparatus is calibrated by the Zernike polarizing plate 28 using the LED light source 16. Subsequently, the HeNe laser light source 14 is used to irradiate the soybean oil layer 13 that is assumed to be a lipid, and the applicability of the biological image acquisition apparatus is verified. That is, the irradiation light from the HeNe laser light source 14 passes through the soybean oil layer 13 simulating an actual living body, so that an image after wavefront phase correction can be obtained at each pixel of the deformable mirror 20 and the wavefront sensor 30. The image obtained at this time is a surface image corresponding to a cancer site when viewed from each direction when it is assumed that the cancer cells of the tissue 10 to be examined are in the Object portion of FIG.

  Here, although the wave incident on the examination target tissue 10 from the LED light source 16 is a plane wave, when it is scattered at the position of each cell, the location of the cell becomes a new wave source and propagates as a spherical wave. The optical compensation of the image acquisition device is applied to the spherical wave. On the other hand, the time resolution needs to be considered at the frame rate of the adaptive optics system, for example, 100 Hz. An important problem in ecological observation is dynamic behavior due to biological activity, and examples of such factors include blood flow. In order to reduce the influence that the dynamic behavior contributes as a scatterer, for example, the noise component can be removed by temporal averaging of the image, but this causes a side effect that the spatial resolution deteriorates. Therefore, if image compensation information can be obtained at a high speed of about 100 Hz, an image can be obtained without being hindered by biological activity.

  FIG. 10 is a diagram showing an example of the analysis result of the image distorted by soybean oil with the wavefront sensor. FIG. 10A is a numerical diagram showing the analysis result with the wavefront sensor, and FIG. 10B is the orthogonal basis of the Zernike polynomial. The figure which shows a numerical value, (C) is a figure which shows the whole measured value of a wavefront sensor, (D) is an enlarged view which shows the measured value of the local peak vicinity of a wavefront sensor, (E) is an enlarged figure which shows the wavefront correlation of (D). (F) is a diagram showing evaluation of the Zernike polynomial of (D), (G) is a diagram showing a point spread function of the Zernike polynomial of (F), and (H) is a modulation of (G). It is a transfer function.

  As soybean oil, soybean oil (S7381 manufactured by Sigma-Aldrich) having the same amount as that of the active ingredient for intravenous fat emulsion used for the purpose of supplementing lipids which are important as a biological component was used. The soybean oil layer 13 using this soybean oil is placed in a 10 × 10 × 40 mm (optical path length 10 mm) glass cell and placed in the optical path. In FIG. 10, the change of the wave front when the soybean oil layer 13 is put in the optical path and not compensated by the deformable mirror is shown according to the analysis result.

  FIG. 11 is an explanatory diagram of an embodiment in which a wavefront sensor and a deformable mirror are combined to compensate for an image distorted with soybean oil. (A) shows a distorted image, and (B) shows an image after compensation. Yes. Here, an image of a 1951 USAF test target is used in place of the cancer cells in the tissue 10 to be examined. Comparing the image of the wavefront before and after compensation with the deformable mirror shown in FIG. 11, the resolution of the image after compensation is clearly improved as compared with the image before compensation, and the spatial frequency is 57.02. Books / mm can be clearly resolved.

  FIG. 12 is a diagram showing a detailed example when an image distorted with soybean oil is compensated with a deformable mirror. FIG. 12A is a numerical diagram showing an analysis result of the wavefront sensor, and FIG. (C) is an enlarged view showing measured values near the local peak of the wavefront sensor, (D) is an enlarged view showing the wavefront correlation of (C), and (E) is an evaluation of the Zernike polynomial of (C). (F) is a diagram showing a point spread function of the Zernike polynomial of (E), and (G) is a modulation transfer function of (F).

In the above embodiment, the biometric image acquisition apparatus is described using the apparatus shown in FIGS. 1 and 9, but the present invention is not limited to these, and those skilled in the art Various design changes can be made within the obvious range. For example, the material of the deformable mirror is not limited to aluminum, and it is sufficient that the reflectivity is equal to or higher than that of aluminum. The light receiving surface size of the deformable mirror is not limited to 14.3 × 14.3 mm, and may be larger than this. The wavelength of the laser light is not limited to 632.8 nm, and preferably around 808 nm. The wavelength of the LED light source is not limited to 505 nm, and is preferably around 808 nm as long as it can be distinguished from the wavelength of the laser light. The Object part is not limited to the 1951 USAF test target, but can be replaced if it can identify the spatial resolution.
Furthermore, the affected area to which the biological image acquisition apparatus of the present invention is applied is not limited to cancer, and other diseases associated with tissue lesions of human organs can also be targeted.

  The biological image acquisition apparatus of the present invention can acquire an image of a tissue of interest under lipid, which has been difficult until now, with higher resolution by applying to an optical tissue examination such as cancer detection of a living body. It becomes possible.

DESCRIPTION OF SYMBOLS 10 Test target tissue 12 Lipid tissue 13 Soybean oil 20 Deformable mirror 22 Beam splitter 30 Wavefront sensor 32 Wavefront reconstruction calculating part 40 Light receiving part

Claims (4)

A deformable mirror that receives observation light reflected or emitted from a tissue to be examined through a lipid tissue. The deformable mirror can control the position and orientation of the tilt angle and height direction in a local region. The deformable mirror configured; and
A beam splitter that branches the observation light reflected by the deformable mirror;
A wavefront sensor for entering observation light branched by the beam splitter;
The incident light of this wavefront sensor is input for each pixel separately, and the inclination of each individual region of the deformable mirror is compensated for the component distorted by the lipid tissue in the observation light of the tissue to be examined. A wavefront reconstruction calculating unit for calculating a control amount necessary for wavefront reconstruction for performing position and orientation control in the angle and height directions;
The wavefront reconstruction control amount of the wavefront reconstruction calculation unit is sent to each corresponding region of the deformable mirror, the wavefront reconstruction of the deformable mirror is performed, and the distortion component in the lipid tissue is compensated for A light receiving unit that receives observation light of the tissue to be examined;
A biological image acquisition device comprising: Each individual region of the deformable mirror has a telescopic actuator that moves in the height direction provided for each individual region, and
The living body image acquiring apparatus according to claim 1, wherein the deformable mirror includes a surface mirror layer that connects the individual regions in a continuous state.   The range in which the position and orientation in the height direction can be controlled in each individual region of the deformable mirror is at least one quarter of the wavelength included in the observation light and not more than one wavelength. Living body image acquisition apparatus. The shape of each individual region of the deformable mirror is larger than a single cell shape of the tissue to be examined and has a shape smaller than twice the maximum length of the cell shape. The biological image acquisition device according to any one of 3.