WO2016031697A1 - Cartilage diagnosis device and diagnostic probe - Google Patents

Cartilage diagnosis device and diagnostic probe Download PDF

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Publication number
WO2016031697A1
WO2016031697A1 PCT/JP2015/073485 JP2015073485W WO2016031697A1 WO 2016031697 A1 WO2016031697 A1 WO 2016031697A1 JP 2015073485 W JP2015073485 W JP 2015073485W WO 2016031697 A1 WO2016031697 A1 WO 2016031697A1
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cartilage
deformation
tomographic
optical
distribution
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PCT/JP2015/073485
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French (fr)
Japanese (ja)
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佐伯壮一
池渕充彦
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公立大学法人大阪市立大学
日本シグマックス株式会社
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Priority to JP2016545485A priority Critical patent/JP6623163B2/en
Publication of WO2016031697A1 publication Critical patent/WO2016031697A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements

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  • the present invention relates to an apparatus for diagnosing the degree of cartilage degeneration.
  • Cartilage plays important roles such as relaxation of load impact and improvement of joint slidability, but it is a tissue that has no blood circulation and is difficult to self-heal. Many elderly people develop osteoarthritis (Osteoarthritis: hereinafter referred to as “OA”) due to cartilage wear, and the establishment of a diagnostic treatment method is required especially in countries with an aging society. .
  • Articular cartilage contains 80% moisture and 20% matrix, which is composed of collagen and proteoglycans. In particular, it is believed that proteoglycans constrained by the collagen fibers determine the flow characteristics inside the cartilage and are largely involved in the excellent viscoelastic properties of the cartilage. OA is caused by a loss of the viscoelastic properties of the cartilage.
  • OCT optical coherence tomography
  • a microtomography can be visualized inside a living tissue in a non-invasive and non-contact manner.
  • the acquisition rate of the two-dimensional OCT tomographic image is equal to or higher than the video rate and has a high temporal resolution.
  • Non-Patent Document 1 a technique has been proposed in which the OCT is used to visualize the tomographic characteristics of cartilage dynamics. According to this technique, there is a possibility that normal cartilage and degenerated cartilage can be distinguished by applying a predetermined stress to the cartilage and visualizing the stress relaxation process.
  • Non-Patent Document 1 provides a powerful foothold for micromechanics visualization diagnosis related to cartilage, there is room for improvement in terms of diagnostic efficiency and diagnostic accuracy. Moreover, it did not disclose a specific device configuration in the case where the cartilage of a living human body is a diagnosis target. For this reason, it has not yet reached practical use.
  • the present invention has been made in view of such problems, and one of its purposes is to make cartilage diagnosis using OCT more practical.
  • a certain aspect of the present invention is a cartilage diagnostic apparatus for diagnosing articular cartilage.
  • This cartilage diagnostic apparatus is configured to include an optical unit including an optical system that uses optical coherence tomography, and is connected to the optical unit, and a tip portion thereof is configured to be inserted into a joint cavity, and guides light from the optical unit to the cartilage for scanning.
  • a probe including a load device for applying a predetermined deformation energy to the cartilage, and controls the drive of the load device and the optical mechanism, and is output from the optical unit based on the drive.
  • the optical interference signal is processed, and a change in the predetermined mechanical feature amount due to the deformation inside the cartilage due to the application of deformation energy is calculated in association with the tomographic position of the cartilage.
  • the cartilage tissue A control calculation unit that calculates the degree of damage of the cartilage, and a display device that displays the degree of damage of the cartilage tissue in a manner of visualizing a tomogram.
  • a diagnosis target is obtained by a calculation process using the fact that there is a correspondence between the change in the mechanical feature amount generated in the cartilage when a predetermined deformation energy is applied and the degree of damage to the cartilage tissue.
  • the degree of cartilage damage is visualized by tomography. For this reason, a doctor or the like can easily perform cartilage diagnosis by confirming the display of the tomographic visualization. That is, cartilage diagnosis using OCT can be more practically used.
  • This diagnostic probe is a probe that enables diagnosis of a target site by being connected to an optical unit including an optical system that uses optical coherence tomography, and includes a tip portion configured to be able to contact the target site, An optical mechanism for guiding the light from the optical unit to the cartilage to scan, and a load device for applying a predetermined deformation energy to the target site.
  • cartilage diagnosis using OCT can be more practically used.
  • One embodiment of the present invention is a cartilage diagnostic apparatus for diagnosing articular cartilage.
  • This cartilage diagnostic apparatus takes a tomographic image of cartilage using OCT while applying a predetermined deformation energy (load) to the cartilage, and calculates the degree of damage (degeneration degree) from the behavior of the cartilage tissue with respect to the load. Is. Since the calculation result is visualized on the display device in the form of a tomographic image of cartilage, a doctor or the like can make a cartilage diagnosis by viewing the tomographic image.
  • This cartilage diagnostic apparatus includes an optical unit including an OCT optical system and a probe connected to the optical unit.
  • This probe has a tip portion that can be inserted into a joint cavity, and includes an optical mechanism and a load mechanism (functioning as a “load device”) for obtaining a physical quantity used for OCT calculation processing.
  • the tip of the probe may be inserted into the joint cavity, for example, through a syringe needle.
  • a predetermined load is applied to the cartilage by driving the load mechanism in a state where the tip of the probe is in contact with the surface (or the vicinity thereof) of the cartilage.
  • the degree of cartilage degeneration can be evaluated by tomographically measuring the response of the cartilage tissue to the load by OCT.
  • the optical mechanism irradiates and scans the cartilage with object light from the optical unit, acquires the reflected light, and sends it to the optical unit.
  • the optical unit combines the reflected light and the reference light, and sends the optical interference signal to the control calculation unit.
  • the control calculation unit processes the optical interference signal while controlling the driving of the load mechanism and the optical mechanism, and associates the change in the mechanical feature amount due to the deformation in the cartilage due to the load load described above with the tomographic position of the cartilage.
  • the “mechanical feature amount” here may be obtained based on the spatial distribution of the deformation vector of the cartilage tissue. For example, a deformation rate vector obtained by temporally differentiating the deformation vector or a strain rate tensor obtained by further spatially differentiating the deformation rate vector may be used.
  • the load loading method using a load mechanism may be based on a stress relaxation method in which a constant strain is applied to a measurement target (cartilage) and a time change of stress is measured. Or based on the dynamic viscoelasticity method which gives the dynamic strain with respect to a measuring object, and measures the maximum value and phase difference of stress. Alternatively, it may be based on a creep method in which a time-dependent change in strain is measured by applying a certain amount of stress to the measurement object.
  • the control calculation unit calculates the degree of damage of the cartilage tissue based on the change in the mechanical feature value, and visualizes it on the screen of the display device.
  • the control calculation unit may execute the following processing based on the stress relaxation method. That is, the stress is relaxed after a predetermined load is applied to the cartilage by driving the load mechanism, and the deformation velocity vector corresponding to the tomographic position of the cartilage is determined based on the tomographic image data before and after the stress is taken by the optical unit. You may calculate as a mechanical feature-value. Then, the tomographic distribution of the attenuation coefficient obtained from the change of the deformation velocity vector may be visualized as a tomographic equivalent as the distribution of the damage degree of the cartilage tissue.
  • the “front and back tomographic image data” here may be based on two tomographic images that are continuously captured, or may be based on two tomographic images that are not consecutive but are captured at a predetermined time.
  • the control calculation unit calculates a strain rate tensor by spatially differentiating the deformation rate vector calculated as a mechanical feature amount, and the fault distribution of the strain rate attenuation coefficient is equivalent to the distribution of the degree of damage of the cartilage tissue. It may be made visible.
  • the strain rate tensor in this way, physical implications such as compression, expansion and shearing of the cartilage tissue can be given to the fault distribution of the attenuation coefficient. From this physical meaning, the degree of cartilage degeneration can be directly transmitted to a doctor or the like as a mechanical deformability.
  • the control calculation unit may calculate the deformation velocity vector with sub-pixel accuracy based on the cross-correlation of the tomographic image data acquired sequentially, the displacement of the luminance gradient, and the deformation of the luminance pattern. Since the resolution of OCT is limited, by introducing such sub-pixel analysis, cartilage diagnosis with higher accuracy can be realized.
  • the control calculation unit may execute the following processing based on the dynamic viscoelasticity method. That is, a predetermined dynamic load (dynamic force) is applied to the cartilage by driving the load mechanism, and each cartilage of the cartilage is determined based on the tomographic image data taken by the optical unit during the vibration of the cartilage due to the dynamic load.
  • the deformation velocity vector at the tomographic position is calculated as a mechanical feature
  • the viscoelastic tomographic distribution of cartilage is calculated based on at least one of the amplitude and phase difference of the specific deformation velocity vector that is the excitation frequency component of the deformation velocity vector.
  • the viscoelastic fault distribution may be visualized as equivalent to the distribution of the damage degree of the cartilage tissue.
  • the “front and back tomographic image data” here may be based on two tomographic images that are continuously captured, or may be based on two tomographic images that are not consecutive but are captured at a predetermined time.
  • the strain rate tensor at each tomographic position of the cartilage is calculated as a mechanical feature, and the viscoelasticity of the cartilage is determined based on at least one of the amplitude and phase difference of the specific strain rate tensor that is the excitation frequency component of the strain rate tensor.
  • the fault distribution may be calculated.
  • the load mechanism may include a sensor capable of measuring a load (force) applied to the cartilage.
  • the control calculation unit calculates the tomographic distribution of the viscoelasticity of the cartilage based on at least one of the amplitude and phase difference of the excitation frequency component of the calculated mechanical feature and the load value measured by the sensor, The tomographic distribution may be visualized as equivalent to the distribution of the degree of damage of the cartilage tissue.
  • the probe can also be applied to diagnosis of a target site other than cartilage, for example, for diagnosing internal organs during surgery. That is, the probe may be configured as a diagnostic probe that enables diagnosis of a predetermined target site by being connected to an optical unit including an OCT optical system.
  • This probe has a tip that is configured to be able to contact the target part, an optical mechanism for guiding the light from the optical unit to the cartilage and scanning it, and applying a predetermined deformation energy (stress) to the target part.
  • a load mechanism load device
  • a cartilage diagnostic method using the above technique may be constructed.
  • the method includes a step of applying a predetermined deformation energy (load) to the cartilage, a step of displaying the degree of deformation of the cartilage according to the application of the deformation energy (load of load) as a tomographic image by optical coherence tomography, And a step of diagnosing the degree of damage to the cartilage tissue based on the tomographic image.
  • FIG. 1 is a diagram schematically illustrating the configuration of the cartilage diagnostic apparatus according to the first embodiment.
  • FIG. 2 is a diagram schematically illustrating a configuration of a diagnostic probe that configures the cartilage diagnostic apparatus.
  • the cartilage diagnostic apparatus of this embodiment can diagnose the degree of cartilage tissue damage (degeneration degree) by applying a predetermined stress to the articular cartilage to be diagnosed and visualizing the degree of cartilage tissue deformation against that stress. It is what. OCT is used for this tomographic visualization.
  • a cartilage diagnostic apparatus 1 includes an optical unit 2 including an optical system using OCT, a diagnostic probe 4 connected to the optical unit 2, and cartilage tissue based on optical interference data obtained by OCT.
  • an optical system based on a Mach-Zehnder interferometer is shown as the optical unit 2, but a Michelson interferometer or other optical system may be employed.
  • SS-OCT Single Source OCT
  • TD-OCT Time Domain OCT
  • SD-OCT Spectrum Domain OCT
  • SS-OCT does not require mechanical optical delay scanning such as reference mirror scanning, and is preferable in that high time resolution and high position detection accuracy can be obtained.
  • the optical unit 2 includes a light source 10, an object arm 12, a reference arm 14, and a photodetector 16. Each optical element is connected to each other by an optical fiber.
  • the light emitted from the light source 10 is divided by a coupler 18 (beam splitter), one of which becomes object light guided to the object arm 12 and the other becomes reference light guided to the reference arm 14.
  • the object light guided to the object arm 12 is guided to the probe 4 through the circulator 20, and is irradiated to the cartilage that is the object of diagnosis. This object light is reflected as backscattered light on the surface and cross section of the cartilage, returns to the circulator 20, and is guided to the coupler 22.
  • the reference light guided to the reference arm 14 is guided to the reflecting mirror 26 via the circulator 24.
  • the reference light is condensed on the reflecting mirror 26 by the condenser lens 30 through the collimator lens 28.
  • the reference light is reflected by the reflecting mirror 26, returns to the circulator 24, and is guided to the coupler 22. That is, the object light and the reference light are combined (superposed) by the coupler 22, and the interference light is detected by the photodetector 16.
  • the probe 4 constitutes the object arm 12 of the optical unit 2, and an optical fiber 34 extending from the circulator 20 is inserted into the main body 32 thereof.
  • a syringe needle 36 is attached to the distal end of the main body 32, and the distal end portion of the probe 4 can be inserted into the living body (patient's knee K) through the syringe needle 36.
  • the main body 32 includes an optical mechanism for guiding the light from the optical unit 2 to the cartilage of the knee K to scan, a load mechanism for applying a predetermined load (stress) to the cartilage, and these mechanisms.
  • a drive unit 38 (actuator) for driving is provided. The optical mechanism irradiates light toward the cartilage and guides the reflected light to the object arm 12. Details of each mechanism will be described later.
  • Interference light combined by the coupler 22 is input to the photodetector 16.
  • the photodetector 16 detects this as an optical interference signal (a signal indicating the intensity of interference light).
  • This optical interference signal is input to the control calculation unit 6 via the A / D converter 40.
  • the A / D converter 40 converts the analog signal output from the photodetector 16 into a digital signal and outputs the digital signal to the control calculation unit 6.
  • the control calculation unit 6 includes a CPU, a ROM, a RAM, a hard disk, and the like.
  • the hardware and software control the entire optical system of the optical unit 2, drive control of the probe 4, and image output by OCT.
  • the control calculation unit 6 controls the driving of the loading mechanism and the optical mechanism of the probe 4, processes the optical interference signal output from the optical unit 2 based on the driving, and acquires a tomographic image of the cartilage by OCT. Based on the tomographic image data, the degree of damage to the cartilage tissue is calculated by a method described later.
  • the display device 8 includes, for example, a liquid crystal display, and displays the damage degree of the cartilage tissue calculated by the control calculation unit 6 on the screen in a manner of visualizing the tomography.
  • the probe 4 has a syringe needle 36 as a puncture portion attached to the tip of a cylindrical main body 32.
  • a cylindrical sheath 50 with a bottom is coaxially provided inside the syringe needle 36, and a piezoelectric element 52 (piezo element) capable of driving the sheath 50 in the axial direction is provided inside the main body 32.
  • the piezoelectric element 52 is supported by a support mechanism (not shown) provided inside the main body 32.
  • the distal end of the sheath 50 is closed, and the rear end opening is fixed to the distal end of the piezoelectric element 52.
  • the distal end surface of the sheath 50 is a contact surface that can contact the surface of the cartilage J of the patient.
  • the tip of the optical fiber 34 is inserted inside the sheath 50, a GRIN lens 54 is connected to the tip, and a prism mirror 56 is connected to the tip.
  • the optical fiber 34, the GRIN lens 54, and the prism mirror 56 constitute a light guide integrated in the axial direction.
  • the GRIN lens 54 exhibits a condensing function by continuously changing the refractive index in the lens.
  • the prism mirror 56 is a reflecting surface whose tip surface is inclined with respect to the axis.
  • the GRIN lens 54 is used as an optical element that adjusts the diameter of the irradiation beam, the focal length, the beam spot diameter, etc., but other optical elements that can perform the same function may be used. .
  • the prism mirror 56 is employed as an optical element that reflects the beam in a specified direction, other optical elements that can exhibit the same function may be employed.
  • the light guided to the probe 4 by the optical fiber 34 is emitted from the distal end of the sheath 50 through the GRIN lens 54 and the prism mirror 56, and irradiated to the cartilage J (see the dotted arrow). Thereby, the light reflected on the surface or cross section of the cartilage J is taken into the GRIN lens 54 and guided to the object arm 12 of the optical unit 2 through the optical fiber 34.
  • the piezoelectric element 52 is provided with an insertion hole 58 penetrating along the axis.
  • the optical fiber 34 is inserted into the insertion hole 58 and introduced into the sheath 50.
  • a load from the piezoelectric element 52 can be applied to the sheath 50 without applying a mechanical load to the optical fiber 34.
  • the piezoelectric element 52 extends in the axial direction, and the sheath 50 can be driven to the distal end side in the axial direction.
  • This driving force is applied to the cartilage J as a pressing force (compressive stress) by the distal end surface of the sheath 50. That is, the sheath 50 and the piezoelectric element 52 function as a “load device (load mechanism)”.
  • the sheath 50 is biased rearward by a biasing member (not shown), and is configured to be accommodated inside the syringe needle 36 when the piezoelectric element 52 is not energized. When the piezoelectric element 52 is energized, the distal end surface of the sheath 50 can project from the syringe needle 36 as shown in the figure.
  • a rotating mechanism 60 (optical rotary joint) for rotating the optical fiber 34 around the axis is provided behind the piezoelectric element 52 inside the main body 32.
  • the rotation mechanism 60 has a rotor fixed coaxially with the optical fiber 34.
  • the optical fiber 34 and the GRIN lens 54 can be rotated around the own axis, and the direction of the prism mirror 56 can be changed. That is, the tip of the optical fiber 34, the GRIN lens 54, the prism mirror 56, and the rotation mechanism 60 function as an “optical mechanism”.
  • the object light can be scanned with respect to the cartilage J.
  • Energization control to the piezoelectric element 52 and the rotation mechanism 60 is performed by the control calculation unit 6.
  • the object light (reflected light from the cartilage J) that has passed through the object arm 12 and the reference light that has passed through the reference arm 14 are combined and detected by the photodetector 16 as an optical interference signal.
  • the control calculation unit 6 can acquire the optical interference signal as a tomographic image of the cartilage J based on the interference light intensity.
  • the coherence length l c which is the resolution in the optical axis direction (depth direction) of OCT is determined by the autocorrelation function of the light source.
  • the coherence length l c is the half-width of the comprehensive line of the autocorrelation function and can be expressed by the following formula (1).
  • ⁇ c is the center wavelength of the laser beam
  • is the full width at half maximum of the laser beam.
  • the resolution in the direction perpendicular to the optical axis is 1 ⁇ 2 of the beam spot diameter D based on the light condensing performance of the condensing lens.
  • the beam spot diameter D can be expressed by the following formula (2).
  • d B is the beam diameter incident on the condenser lens
  • f is a focal point of the condenser lens.
  • This detection method calculates a deformation vector distribution by applying a digital cross-correlation method to two OCT tomographic images before and after deformation of a measurement object, and detects a strain rate tensor distribution inside a living tissue on a microscale. It is a technique.
  • the recursive cross-correlation method which performs repeated cross-correlation processing.
  • This is a technique of applying a cross-correlation method by referring to a deformation vector calculated at a low resolution, limiting an exploration area and hierarchically reducing an inspection area. Thereby, a high-resolution deformation vector can be acquired.
  • an adjacent cross-correlation multiplication method (Adjacent cross-correlation Multiplication) that performs multiplication with a correlation value distribution in an adjacent inspection region is used. Then, the maximum correlation value is searched from the correlation value distribution that has been multiplied to increase the SN.
  • the sub-pixel accuracy of the deformation vector is important.
  • both the up-stream gradient method using brightness gradient (Up-stream Gradientmethod) and the image deformation method considering image expansion and shear (Image Deformation method) are used together to detect deformation vectors with high accuracy.
  • the “windward gradient method” here is a kind of gradient method (optical flow method).
  • the deformation velocity vector distribution is calculated by time differentiation of the deformation vector thus obtained, and the strain rate tensor distribution is calculated by further spatial differentiation.
  • the attenuation coefficient of the strain rate tensor of the cartilage tissue can be regarded as equivalent to the damage degree (degeneration degree) of the cartilage, this is visualized as a tomogram as the cartilage damage degree.
  • FIG. 3 is a diagram schematically showing a processing procedure by the recursive cross correlation method.
  • FIG. 4 is a diagram schematically showing a processing procedure by subpixel analysis.
  • FIG. 5 is a diagram illustrating a result obtained by each process.
  • FIGS. 3A to 3C show processing steps by the recursive cross-correlation method. Each figure shows tomographic images before and after continuous imaging by OCT. The previous tomographic image (Image1) is shown on the left side, and the later tomographic image (Image2) is shown on the right side.
  • the cross-correlation method is a method for evaluating the local speckle pattern similarity based on the correlation value R ij based on the following equation (3). Therefore, as shown in FIG. 3A, with respect to the preceding and following OCT images, an inspection area S1 to be inspected with similarity to the previous tomographic image (Image1) is set, and the subsequent tomographic image is displayed. In (Image2), a search area S2 that is a search range of similarity is set.
  • the Z axis is set in the optical axis direction
  • the X axis is set in the direction perpendicular to the optical axis.
  • f (X i , Z j ) and g (X i , Z j ) are in the inspection area S1 (N x ⁇ N z pixels) of the center position (X i , Z j ) set in the OCT images before and after the deformation. Represents a speckle pattern.
  • a correlation value distribution R i, j ( ⁇ X, ⁇ Z) in the search area S2 (M x ⁇ M z pixels) is calculated, and pattern matching is performed as shown in FIG.
  • the movement amount U i, j giving the maximum correlation value is determined as the deformation vector before and after the deformation.
  • f ⁇ and g ⁇ represent average values of f (X i , Z j ) and g (X i , Z j ) in the inspection region S1.
  • This method employs a recursive cross-correlation method that increases the spatial resolution by repeating the cross-correlation process while reducing the inspection area S1.
  • the spatial resolution is doubled.
  • the inspection area S1 is divided into 1 ⁇ 4, and the search area S2 is reduced by referring to the deformation vector calculated in the previous hierarchy.
  • the search area S2 is also divided into 1 ⁇ 4.
  • a threshold value using the average deviation ⁇ of a total of nine deformation vectors including eight coordinates around the coordinates being calculated is set, and error vectors are removed. Suppresses error propagation associated with recursive processing.
  • Um represents the median value of the vector quantity, and the coefficient ⁇ serving as a threshold is arbitrarily set.
  • an adjacent cross-correlation multiplication method is introduced as a method for determining an accurate maximum correlation value from a highly random correlation value distribution affected by speckle noise.
  • the correlation value distribution Ri, j ( ⁇ x, ⁇ z) in the inspection region S1 and Ri + ⁇ i, j ( ⁇ x, ⁇ z) with respect to the adjacent inspection region overlapping with the inspection region S1 Multiplication of Ri, j + ⁇ j ( ⁇ x, ⁇ z) is performed, and a maximum correlation value is retrieved using a new correlation value distribution R′i, j ( ⁇ x, ⁇ z).
  • Windward gradient method 4A to 4C show a processing process by subpixel analysis. Each figure shows tomographic images before and after continuous imaging by OCT. The previous tomographic image (Image1) is shown on the left side, and the later tomographic image (Image2) is shown on the right side.
  • an upwind gradient method and an image deformation method are used for subpixel analysis.
  • the final movement amount is calculated by an image deformation method described later
  • the windward gradient method is applied prior to the image deformation method because of the problem of convergence of the calculation.
  • the image deformation method and the windward gradient method for detecting the sub-pixel movement amount with high accuracy are applied under the condition of the inspection area size being small and the high spatial resolution.
  • the subpixel movement amount is calculated by the windward gradient method.
  • the luminance difference before and after deformation at the point of interest is represented by the luminance gradient and movement amount of each component.
  • the sub-pixel movement amount can be determined using the least square method from the luminance gradient data in the inspection region S1.
  • the windward difference method is used which gives the windward brightness gradient before the subpixel deformation.
  • the windward gradient method calculates the movement of the point of interest in the inspection region S1 not only with the pixel accuracy shown in FIG. 4A but also with the sub-pixel accuracy shown in FIG. 4B.
  • Each grid in the figure represents one pixel. Actually, it is considerably smaller than the tomographic image shown in the figure, but for the convenience of explanation, it is shown in large size.
  • This windward gradient method is a method for formulating the change of the luminance distribution before and after the minute deformation by the luminance gradient and the moving amount.
  • f is the luminance
  • the following equation (Taylor expansion of the minute deformation f (x + ⁇ x, z + ⁇ z) is performed. 7).
  • the above formula (7) indicates that the luminance difference before and after the deformation of the attention point is represented by the luminance gradient and the movement amount before the deformation. Since the movement amount ( ⁇ x, ⁇ z) cannot be determined only by the above equation (7), the movement amount is considered to be constant in the inspection region S1, and is calculated by applying the least square method.
  • the luminance difference before and after the movement at each point of interest on the right side can only be obtained uniquely. Therefore, how accurately the luminance gradient is calculated is directly related to the accuracy of the movement amount.
  • the primary accuracy upwind difference is used. This is because applying high-order differences in differentiating requires a lot of data and is greatly affected when noise is included.
  • the high-order difference based on each point in the inspection area S1 uses a lot of data outside the inspection area S1, and there is a problem that the amount of movement of the inspection area S1 itself is lost. is there.
  • the difference on the windward side is applied before the deformation.
  • the windward is not the actual movement direction but the direction of the subpixel movement amount with respect to the pixel movement amount, and the upwind is determined by performing parabolic approximation on the maximum correlation value peak.
  • the luminance difference on the leeward side after the deformation moves in the opposite direction, a difference in luminance at the point of interest occurs, so the difference on the leeward side is applied after the deformation.
  • the position of the point of interest before (after) deformation is obtained from the amount of subpixel movement when parabolic approximation is performed.
  • the luminance gradient is calculated from the ratio thereof. Specifically, the following formula (8) is used.
  • the amount of movement was determined by applying the least square method using the luminance gradient thus calculated and the luminance change.
  • the cross-correlation is performed between the inspection region S1 before the tissue deformation and the inspection region S1 in consideration of the expansion and contraction and shear deformation after the tissue deformation, and the sub-pixel deformation amount is determined by iterative calculation based on the correlation value. Note that the expansion and contraction and the shear deformation of the inspection region S1 are linearly approximated.
  • the image deformation method is generally used in a material surface strain measurement method, and is applied to an image obtained by photographing a material surface coated with a random pattern with a high spatial resolution camera.
  • the OCT tomogram not only contains a lot of speckle noise, but especially in a living tissue, the refractive index changes with the flow of the substrate and water in the tissue, so the deformation to the speckle pattern is large. For this reason, a local deformation
  • Reduction of the examination area S1 in this method is indispensable for detecting local tissue mechanical characteristics. Therefore, in the image deformation method, the amount of deformation obtained by the windward gradient method is adopted as the initial value of the convergence calculation, and further, low robustness is realized even when the inspection area S1 is reduced by bicubic function interpolation of the luminance distribution. ing. In the modification, an interpolation function other than bicubic function interpolation may be used.
  • a bicubic function interpolation method is applied to the luminance distribution of the OCT tomogram before tissue deformation, and the luminance distribution is made continuous.
  • the bicubic function interpolation method is a technique for reproducing spatial continuity of luminance information using a convolution function obtained by piecewise approximating a sinc function.
  • a point spread function depending on the optical system is convolved. Therefore, by performing deconvolution using a sinc function, the original continuous luminance distribution is restored.
  • the convolution function h (x) is expressed by the following equation (9).
  • the value of a is determined based on the verification result by the numerical experiment using the pseudo OCT tomogram.
  • the inspection region S1 calculated in consideration of expansion and contraction and shear deformation is accompanied by deformation as it moves.
  • the values of x * , z * Is represented by the following formula (10).
  • ⁇ x and ⁇ z are distances from the center of the inspection region S1 to the coordinates x and z
  • u and v are deformation amounts in the x and z directions, respectively
  • ⁇ u / ⁇ x and ⁇ v / ⁇ z are x, respectively.
  • the deformation amount in the vertical direction of the inspection region S1 in the z direction, ⁇ u / ⁇ z, and ⁇ v / ⁇ x are the deformation amounts in the shear direction of the inspection region S1 in the x and z directions, respectively.
  • the Newton-Raphson method is used for the numerical solution, and the correlation value derivative with 6 variables (u, v, ⁇ u / ⁇ x, ⁇ u / ⁇ z, ⁇ v / ⁇ x, ⁇ v / ⁇ z) is 0. That is, iterative calculation is performed so as to obtain the maximum correlation value.
  • the sub-pixel movement amount obtained by the windward gradient method is used as the initial movement amount in the x and z directions.
  • the Hessian matrix for the correlation value R is H and the Jacobian vector for the correlation value is ⁇ R
  • the update amount ⁇ Pi obtained in one iteration is expressed by the following equation (11).
  • the present embodiment employs the sub-pixel movement amount obtained by the windward gradient method.
  • a deformation velocity vector distribution as shown in FIG. 5B can be calculated by differentiating the deformation vector of subpixel accuracy obtained as described above with respect to time.
  • a strain rate tensor can be calculated by spatially differentiating the deformation rate vector distribution.
  • MLSM Moving least square method
  • MLSM is a technique that enables smooth calculation of a differential coefficient while smoothing a movement amount distribution.
  • the square error equation used in MLSM is expressed by the following equation (12).
  • equation (12) parameters a to k that minimize S (x, z, t) are obtained. That is, the following equation (13) is adopted as a three-variable quadratic polynomial in the horizontal direction x, the depth direction z, and the time direction t as an approximation function. Based on the least square approximation, an optimal derivative is calculated from the following equation (14) and smoothed.
  • the strain rate tensor shown in the following formula (15) can be calculated.
  • fx and fz indicate the strain increment of each axis, and the strain rate is calculated from the amount of change over time.
  • FIG. 6 and 7 are diagrams illustrating a processing procedure of the cartilage diagnosis processing.
  • the above-described methods are applied to the cartilage diagnostic apparatus 1.
  • the control calculation unit 6 sequentially stores the deformation velocity vector distribution calculated as described above (FIG. 6A), and is obtained by spatially differentiating each deformation velocity vector distribution.
  • the strain rate tensor distribution is sequentially stored (FIG. 6B).
  • FIG. 7A the strain rate tensor distribution can be displayed in the form of a tomographic image so as to be identifiable for each predetermined range. In the figure, the region where the strain rate is negative indicates the compression region, and the positive region indicates the expansion region.
  • the control calculation unit 6 causes the display device 8 to visualize the tomographic distribution by making the tomographic distribution of the attenuation coefficient equivalent to the distribution of the degree of damage of the cartilage tissue.
  • the fault distribution of the attenuation coefficient itself is presented as the degree of cartilage tissue damage (degeneration degree). Therefore, a region with a large attenuation coefficient is indicated as a region with a high degree of damage (modification degree), and a region with a low attenuation coefficient is indicated as a region with a low degree of damage (modification degree).
  • the hatching part in a figure shows the area
  • FIG. 8 is a diagram schematically illustrating the configuration of the experimental apparatus.
  • FIG. 9 is a diagram illustrating a test piece used in the experiment.
  • FIG. 10 is a graph showing a state of a load applied to the test piece during the experiment. In FIG. 8, the same components as those shown in FIG.
  • this experimental apparatus is configured by connecting a compression tester 70 to the optical unit 2 shown in FIG.
  • the compression tester 70 applies a compressive load to the test piece W instead of the probe 4 shown in FIG.
  • cartilage of the knee joint of a pig is used as the test piece W.
  • the compression tester 70 includes a glass window 72 that contacts the test piece W, a metal indenter 74 that sandwiches the test piece W between the glass window 72, a linear actuator 76 that drives the metal indenter 74 in the axial direction, and the test piece W.
  • the load cell 78 etc. which detect the load loaded on is provided.
  • control arithmetic unit 6 is composed of two personal computers 80 and 82, one of which drives the optical unit 2 and OCT arithmetic processing, and the other drives the compression tester 70.
  • a test probe 84 is connected to the object arm 12.
  • the test probe 84 includes an optical mechanism capable of scanning the object light toward the test piece W instead of the probe 4 shown in FIG.
  • FIG. 9A shows an installation mode of the test piece W to the compression tester 70
  • FIG. 9B shows a side view and the size of the test piece W
  • FIG. The front view and its size are shown.
  • a cartilage tissue sample of a femoral condyle of a knee joint of a pig about 6 months old was collected in a cylindrical shape having a diameter of 5.5 mm.
  • simulated degenerated cartilage was prepared by enzyme treatment and compared with normal cartilage.
  • collagenase type 2 (C6885, Sigma Ardrich) that degrades collagen fibers maintaining the elasticity of articular cartilage was used.
  • Normal articular cartilage is placed in 30 [unit / ml] collagenase solution prepared by dissolving collagenase in phosphate buffered saline (10010, Invitrogen) at pH 7.4, and 0.5 [37] at 37 [° C.].
  • the treatment is performed with a time setting of 1 hour, 2 hours, and collagen fiber degeneration is simulated as the degree of OA degeneration.
  • the lower bone side of the test piece W was fixed to the metal indenter 74 and pressed against the glass window 72 installed in the compression tester 70 to cause compression deformation in the cartilage tissue.
  • An OCT tomographic image during the stress relaxation test was continuously acquired at 27.03 [flame / sec] by implanting an OCT beam through the glass window 72.
  • the compression amount was fixed at 10 [%] strain, and the compression speed was fixed at 0.1 [% / sec].
  • the compression load loading time was 100 [sec], and after reaching 10 [%] strain, the behavior of the cartilage tissue during stress relaxation was observed.
  • the recursive cross-correlation method is set to two layers for reducing the inspection area from 9 [pixel] to 5 [pixel], and the subpixel accuracy is set at a vector density of 6.5 ⁇ 15.62 [ ⁇ m].
  • the deformation velocity vector distribution of was calculated.
  • FIG. 10 shows stress time series data detected by the load cell 78 in this stress relaxation test.
  • the horizontal axis indicates time [sec] from the start of load application, and the vertical axis indicates compressive stress [MPa].
  • the stress increases during compression (0 to 100 seconds), and stress relaxation occurs after the end of compression (100 seconds). It was observed that an equilibrium state was reached around 1200 seconds.
  • the stress is attenuated exponentially in this way, it is understood that the cartilage is a viscoelastic body whose relaxation elastic modulus changes with time.
  • FIG. 11 and FIG. 12 are diagrams in which a change in strain rate distribution over time by a stress relaxation test is visualized as a fault.
  • FIG. 11 shows the calculation results for normal cartilage, (A) is 0.31 [sec] from the start of loading, (B) is 50.35 [sec], (C) is 100.29 [sec], ( D) is 101.96 [sec], (E) is 110.95 [sec], (F) is 120.12 [sec], (G) is 130.52 [sec], and (H) is 140.51. [sec] and (I) show the result of 150.49 [sec].
  • FIG. 12 shows the calculation results for the simulated degenerated cartilage, (A) is 1.07 [sec] from the start of loading, (B) is 50.07 [sec], and (C) is 100.99 [sec]. ], (D) is 101.99 [sec], (E) is 110.98 [sec], (F) is 120.97 [sec], (G) is 130.96 [sec], (H) is 140.95 [sec], (I) shows the result of 150.94 [sec]. That is, (A) and (B) in each figure indicate that compression is in progress, and (C) to (I) indicate that stress is being relaxed (see FIG. 10).
  • the degree of degeneration of articular cartilage can be evaluated by focusing on the relaxation time and comparing. From this, it is considered that the degree of cartilage degeneration can be evaluated by comparing the attenuation coefficient calculated from the change in strain rate with time.
  • the distribution of the attenuation coefficient is calculated from the strain rate tensor distribution. That is, the tomographic distribution of the strain rate attenuation coefficient is visualized on the screen as the equivalent of the distribution of the damage degree of the cartilage tissue, thereby enabling cartilage diagnosis.
  • FIG. 13 is a view showing a comparison of attenuation coefficients of normal cartilage and simulated degenerated cartilage.
  • the horizontal axis in the figure indicates the enzyme treatment time (H: hour), and the vertical axis indicates the attenuation coefficient.
  • the results of 0H, 0.5H, 1H, and 2H are shown as the enzyme treatment time. Note that 0H indicates zero enzyme treatment time, that is, normal cartilage.
  • the result shown is a spatial average of the attenuation coefficient distribution in the surface layer region, and a logarithmic process is applied to the relaxation behavior from the start of stress relaxation to 50 seconds.
  • the attenuation coefficient increases as the enzyme treatment time increases.
  • the proteoglycans that govern viscosity also occur.
  • the water retention property is significantly increased due to the decrease in water retention property due to proteoglycan detachment, and the viscosity property is considered to be impaired. Since the increase in water permeability means failure of the load support mechanism due to viscosity, it is considered that the damping coefficient of the relaxation elastic coefficient decreases as shown in the figure.
  • the simulated degenerated cartilage sample used in this experiment has no change in appearance as compared with normal cartilage, and is denatured to the extent that it cannot be judged by visual diagnosis with X-rays or CT. Therefore, it can be seen that the present method can diagnose early knee osteoarthritis that could not be diagnosed.
  • FIG. 14 is a flowchart showing a flow of cartilage diagnosis processing executed by the control calculation unit 6.
  • This cartilage diagnosis process is started in a state where the tip of the probe 4 is inserted into the patient's knee joint by a doctor or the like.
  • the control calculation unit 6 drives the drive unit 38 to execute the stress load and stress relaxation processing shown in FIG. 10, while executing the processing shown in FIG.
  • the control calculation unit 6 reads two consecutive OCT tomographic images I (x, z, t) and I (x, z, t + ⁇ t) taken at different times (S10). Subsequently, processing by a recursive cross correlation method is executed.
  • a cross-correlation process is executed at the minimum resolution (inspection area of the maximum size) to obtain a correlation coefficient distribution (S12).
  • a product of adjacent correlation coefficient distributions is calculated by the adjacent cross correlation multiplication method (S14).
  • error vectors are removed by a spatial filter such as a standard deviation filter (S16), and interpolation of the removal vectors is executed by a least square method or the like (S18).
  • the cross correlation process is continued by increasing the resolution by reducing the inspection area (S20). That is, the cross-correlation process is executed based on the reference vector at the low resolution. If the resolution at this time is not the predetermined maximum resolution (N in S22), the process returns to S14.
  • FIG. 15 is a flowchart showing in detail the modification degree calculation presenting process of S36 in FIG.
  • the control calculation unit 6 executes the smoothing of the deformation velocity vector distribution calculated in S34 by the spatiotemporal movement least square method (S40). Then, a strain rate tensor is calculated by performing spatial differentiation on the smoothed deformation rate vector (S42). Then, logarithmic transformation is performed on the strain rate time-series data (S44), and the strain rate attenuation coefficient is calculated by the least square method (S46).
  • the distribution of the attenuation coefficient obtained in this way is regarded as equivalent to the degree of cartilage tissue damage, and a tomographic visualization is made on the display device 8 (S48). That is, for example, the degree of cartilage degeneration is presented in the manner shown in FIG.
  • a diagnosis target is obtained by an arithmetic process using the correspondence between the strain rate change (attenuation coefficient) due to stress relaxation and the degree of cartilage tissue damage.
  • the degree of cartilage damage is visualized as a tomogram. For this reason, it becomes possible for a doctor or the like to easily perform cartilage diagnosis by confirming the image visualized by the tomography. That is, cartilage diagnosis using OCT can be more practically used.
  • a predetermined vibration load (dynamic force, dynamic load) is generated by the probe 4 shown in FIGS. That is, when the probe 4 is energized, the piezoelectric element 52 vibrates at a predetermined excitation frequency, and a vibration load is applied to the cartilage J. Thereby, the dynamic viscoelasticity of the cartilage J is evaluated, and the degree of damage (degree of degeneration) is visualized as a tomogram.
  • FIG. 16 is a flowchart showing in detail the modification degree calculation presenting process according to the second embodiment. This process is executed in place of the process shown in FIG. 15 of the first embodiment.
  • the control calculation unit 6 drives the drive unit 38 to apply a dynamic load (dynamic force, vibration load) to the cartilage J, while executing the processing shown in FIGS. 14 and 16.
  • a dynamic load dynamic force, vibration load
  • the luminance distribution is formulated using the following equation (16) instead of the above equation (7).
  • ⁇ f / ⁇ t ⁇ f / ⁇ x ⁇ ⁇ x + ⁇ f / ⁇ y ⁇ ⁇ y + ⁇ f / ⁇ z ⁇ ⁇ z (16)
  • the control calculation unit 6 executes the smoothing of the deformation velocity vector distribution calculated in S34 by the spatio-temporal moving least square method (S240). Then, Fourier transformation is performed on the smoothed deformation velocity vector (S242). As a result, a bandpass filter process for extracting only the component synchronized with the excitation frequency ⁇ of the probe 4 in the deformation velocity vector is executed (S244). Thereafter, the fault distribution of the deformation velocity vectors U ⁇ (x, z, t) and W ⁇ (x, z, t) of the excitation frequency component is calculated by inverse Fourier transform (S246).
  • W ⁇ (x, z, t) is the x-direction component of the deformation speed vector.
  • W ⁇ (x, z, t) can be expressed, for example, in the form of the following formula (17).
  • W ⁇ (x, z, t ) A ⁇ (x, z) sin ( ⁇ t + ⁇ ⁇ (x, z)) ⁇ (17)
  • the tomographic distribution of the normalized amplitude A ′ ⁇ (x, z) and the phase difference ⁇ ⁇ (x, z) of the deformation velocity vector related to the excitation frequency component is calculated from the displacement information of the piezoelectric element 52 (S248).
  • the normalized amplitude A ′ ⁇ (x, z) and the phase difference ⁇ ⁇ (x, z) may be directly calculated by the least square method.
  • the dynamic viscoelasticity of the cartilage is calculated based on at least one tomographic distribution of the normalized amplitude A ′ ⁇ (x, z) and the phase difference ⁇ ⁇ (x, z) (S250). Then, based on the calculated dynamic viscoelasticity, the damage degree of the cartilage tissue is visualized as a tomogram (S48).
  • the dynamic viscoelastic modulus becomes small at a location where the normalized amplitude A ′ ⁇ (x, z) is large. That is, the normalized amplitude A ′ ⁇ (x, z) is relatively large in the surface layer where the rigidity in the depth direction of the cartilage is low, and relatively small in the middle layer. As the cartilage degeneration progresses, the rigidity in the depth direction of the surface layer is further reduced, and thus the normalized amplitude A ′ ⁇ (x, z) is considered to be further increased.
  • phase connection processing (unwrapping processing) may be performed.
  • it can be evaluated as follows. That is, the phase difference ⁇ ⁇ (x, z) in the depth direction is zero on the surface of the cartilage, and gradually increases on the surface layer toward the deep part due to the viscoelastic effect of the surface layer. That is, the phase is delayed.
  • the viscosity characteristics of the surface layer are impaired, so that the phase difference ⁇ ⁇ (x, z) in the depth direction becomes small (that is, it exhibits elastic behavior).
  • the degree of degeneration can also be diagnosed by the magnitude of the spatial differential ( ⁇ ⁇ / ⁇ z) of the phase difference ⁇ ⁇ (x, z).
  • a portion where ⁇ ⁇ / ⁇ z is large has a low degree of modification (that is, normal), and a portion where ⁇ ⁇ / ⁇ z is small is said to have a high degree of modification (that is, the viscosity effect is impaired). Based on such knowledge, it is possible to visualize the degree of damage to the cartilage tissue.
  • the attenuation coefficient of the strain rate is calculated and the tomographic visualization is equivalent to the degree of cartilage damage.
  • the deformation rate attenuation coefficient may be calculated, and the tomographic visualization may be made equivalent to the degree of cartilage damage.
  • the example in which the viscoelasticity is evaluated from the normalized amplitude A ′ ⁇ (x, z) and the phase difference ⁇ ⁇ (x, z) has been shown.
  • the normalized amplitude A ′ ⁇ (x, z ) A value expressing a viscoelastic physical quantity may be newly defined from z) and the phase difference ⁇ ⁇ (x, z), and viscoelasticity evaluation may be performed based on the value.
  • the viscoelasticity of the cartilage is evaluated based on the tomographic distribution of the deformation velocity vector in the modification degree calculation presenting process shown in FIG.
  • the tomographic distribution of the strain rate tensor may be calculated, and the viscoelasticity of the cartilage may be similarly evaluated based on the calculated tomographic distribution.
  • This strain rate tensor can be calculated by spatially differentiating the deformation rate vector.
  • a sensor such as a load cell may be attached to the probe 4 to measure the load applied to the cartilage.
  • the complex elastic modulus (storage elastic modulus, loss elastic modulus, complex viscosity, etc.) of the cartilage tissue can be calculated, and the normalized amplitude A ′ ⁇ (x, z) and the phase difference ⁇ ⁇ (x, z ) makes it easy to define physical quantities for evaluating viscoelasticity.
  • an amplitude value of strain rate and a time delay (phase delay) of strain rate may be adopted as the “mechanical feature amount”.
  • the strain rate fluctuates between a positive value and a negative value in the process of repeatedly applying and relaxing stress.
  • the strain rate also varies so as to follow the variation of the load.
  • the magnitude (amplitude value) of the strain rate fluctuation and the followability (responsiveness) of the strain rate fluctuation to the load fluctuation tend to change corresponding to the degree of cartilage damage.
  • the amplitude value of the strain rate increases and the time delay (phase delay) tends to decrease. Therefore, the fault distribution may be calculated with respect to the amplitude value of the strain rate and the time delay (phase delay).
  • the fault distribution with the amplitude or time delay (phase delay) may be visualized as equivalent to the distribution of the damage degree of the cartilage tissue.
  • the median value of the periodic fluctuation of the strain rate may be adopted as the “mechanical feature value”.
  • the strain rate fluctuates between a positive value and a negative value in the process of repeatedly applying and relaxing stress.
  • the center of the fluctuation of the strain rate tends to deviate slightly from zero due to the balance between the viscous force and the elastic force.
  • the amount of deviation tends to change corresponding to the degree of cartilage damage. Therefore, the fault distribution may be calculated for the amount of deviation from zero of the variation center (median value) of the strain rate.
  • the tomographic distribution of the deviation amount may be visualized as a tomogram equivalent to the distribution of the degree of damage of the cartilage tissue.
  • a load mechanism that applies stress by contact with a piezoelectric element or the like is illustrated as a load device for applying predetermined deformation energy (load) to cartilage.
  • a load device that applies a load (excitation force) to the cartilage in a non-contact manner using ultrasonic waves (sound pressure), photoacoustic waves, electromagnetic waves, or the like may be employed.
  • this invention is not limited to the said Example and modification, A component can be deform
  • Various inventions may be formed by appropriately combining a plurality of constituent elements disclosed in the above-described embodiments and modifications. Moreover, you may delete some components from all the components shown by the said Example and modification.

Abstract

 A cartilage diagnosis device 1 is provided with: an optical unit 2 including an OCT optical system; a probe including an optical mechanism connected to the optical unit 2 and configured so that a distal-end part thereof is insertable into an articular cavity, the optical mechanism for guiding light from the optical unit 2 to cartilage and causing the light to scan, and a weight mechanism capable of loading a predetermined weight on the cartilage; a control computation unit 6 for controlling driving of the weight mechanism and the optical mechanism, processing an optical interference signal outputted from the optical unit 2 on the basis of the driving of the weight mechanism and the optical mechanism, performing computation whereby a change in a predetermined dynamic characteristic quantity accompanying deformation in the cartilage due to weight loading is correlated with a tomographic position of the cartilage, and computing the degree of damage of cartilage tissue on the basis of the change in the dynamic characteristic quantity; and a display device 8 for displaying the degree of damage of the cartilage tissue in the form of a tomographic visualization.

Description

軟骨診断装置および診断用プローブCartilage diagnostic apparatus and diagnostic probe
 本発明は、軟骨の変性度を診断するための装置に関する。 The present invention relates to an apparatus for diagnosing the degree of cartilage degeneration.
 軟骨は荷重衝撃の緩和や関節滑動性の向上等の重要な役割を担っているが、血液の循環がなく、自己治癒が困難な組織である。高齢者の多くは軟骨の磨耗による変形性膝関節症(Osteoarthritis:以下「OA」と表記する)を発症しており、特に高齢化社会を迎える国ではその診断治療法の確立が求められている。関節軟骨は80%の水分と20%のマトリクスを含み、そのマトリクスはコラーゲンとプロテオグリカンから構成される。特に、そのコラーゲン線維に拘束されるプロテオグリカンは軟骨内部の流動特性を決定し、軟骨の優れた粘弾性特性に大きく関与すると考えられている。OAは、その軟骨の粘弾性特性の損失によって発症する。 Cartilage plays important roles such as relaxation of load impact and improvement of joint slidability, but it is a tissue that has no blood circulation and is difficult to self-heal. Many elderly people develop osteoarthritis (Osteoarthritis: hereinafter referred to as “OA”) due to cartilage wear, and the establishment of a diagnostic treatment method is required especially in countries with an aging society. . Articular cartilage contains 80% moisture and 20% matrix, which is composed of collagen and proteoglycans. In particular, it is believed that proteoglycans constrained by the collagen fibers determine the flow characteristics inside the cartilage and are largely involved in the excellent viscoelastic properties of the cartilage. OA is caused by a loss of the viscoelastic properties of the cartilage.
 近年の医療診断技術の発達に伴い、光コヒーレンス断層画像(Optical Coherence Tomography:以下「OCT」という)が開発されている。このOCTによれば、非侵襲、非接触にて生体組織内部をマイクロ断層可視化できる。また、2次元OCT断層画像の取得レートはビデオレート以上であり、高時間分解能を有している。そこで、このOCTを用いて軟骨力学特性を断層可視化する手法も提案されている(非特許文献1)。この手法によれば、軟骨に所定の応力を負荷してその応力緩和過程を断層可視化することで、正常軟骨と変性軟骨とを識別できる可能性がある。 With the recent development of medical diagnostic technology, optical coherence tomography (Optical Coherence Tomography: hereinafter referred to as “OCT”) has been developed. According to this OCT, a microtomography can be visualized inside a living tissue in a non-invasive and non-contact manner. Further, the acquisition rate of the two-dimensional OCT tomographic image is equal to or higher than the video rate and has a high temporal resolution. In view of this, a technique has been proposed in which the OCT is used to visualize the tomographic characteristics of cartilage dynamics (Non-Patent Document 1). According to this technique, there is a possibility that normal cartilage and degenerated cartilage can be distinguished by applying a predetermined stress to the cartilage and visualizing the stress relaxation process.
 非特許文献1に記載の技術は、軟骨に関するマイクロメカニクス可視化診断への有力な足掛かりとなるものの、診断効率や診断精度の面で改善の余地があった。また、生きた人体の軟骨を診断対象とする場合の具体的装置構成について開示するものではなかった。このため、未だ実用化には到っていない。 Although the technology described in Non-Patent Document 1 provides a powerful foothold for micromechanics visualization diagnosis related to cartilage, there is room for improvement in terms of diagnostic efficiency and diagnostic accuracy. Moreover, it did not disclose a specific device configuration in the case where the cartilage of a living human body is a diagnosis target. For this reason, it has not yet reached practical use.
 本発明はこのような課題に鑑みてなされたものであり、その目的の一つは、OCTを用いた軟骨診断をより実用に供し得るものとすることにある。 The present invention has been made in view of such problems, and one of its purposes is to make cartilage diagnosis using OCT more practical.
 本発明のある態様は、関節軟骨を診断するための軟骨診断装置である。この軟骨診断装置は、光コヒーレンストモグラフィーを用いる光学系を含む光学ユニットと、光学ユニットに接続される一方、先端部が関節腔に挿入可能に構成され、光学ユニットからの光を軟骨に導いて走査させるための光学機構と、軟骨に対して所定の変形エネルギーを付与するための負荷装置とを含むプローブと、負荷装置および光学機構の駆動を制御し、それらの駆動に基づいて光学ユニットから出力された光干渉信号を処理し、変形エネルギーの付与による軟骨内部の変形に伴う所定の力学特徴量の変化をその軟骨の断層位置に対応づけて演算し、その力学特徴量の変化に基づいて軟骨組織の損傷度合いを演算する制御演算部と、軟骨組織の損傷度合いを断層可視化する態様で表示する表示装置と、を備える。 A certain aspect of the present invention is a cartilage diagnostic apparatus for diagnosing articular cartilage. This cartilage diagnostic apparatus is configured to include an optical unit including an optical system that uses optical coherence tomography, and is connected to the optical unit, and a tip portion thereof is configured to be inserted into a joint cavity, and guides light from the optical unit to the cartilage for scanning. And a probe including a load device for applying a predetermined deformation energy to the cartilage, and controls the drive of the load device and the optical mechanism, and is output from the optical unit based on the drive. The optical interference signal is processed, and a change in the predetermined mechanical feature amount due to the deformation inside the cartilage due to the application of deformation energy is calculated in association with the tomographic position of the cartilage. Based on the change in the mechanical feature amount, the cartilage tissue A control calculation unit that calculates the degree of damage of the cartilage, and a display device that displays the degree of damage of the cartilage tissue in a manner of visualizing a tomogram.
 この態様によると、所定の変形エネルギーが付与されたときに軟骨に生じる力学特徴量の変化と、軟骨組織の損傷度合いとの間に対応関係があることを利用した演算処理により、診断対象である軟骨の損傷度合いが断層可視化される。このため、医師等がその断層可視化された表示を確認することにより、軟骨診断を容易に行えるようになる。すなわち、OCTを用いた軟骨診断をより実用に供し得るものとすることができる。 According to this aspect, a diagnosis target is obtained by a calculation process using the fact that there is a correspondence between the change in the mechanical feature amount generated in the cartilage when a predetermined deformation energy is applied and the degree of damage to the cartilage tissue. The degree of cartilage damage is visualized by tomography. For this reason, a doctor or the like can easily perform cartilage diagnosis by confirming the display of the tomographic visualization. That is, cartilage diagnosis using OCT can be more practically used.
 本発明の別の態様は、診断用プローブである。この診断用プローブは、光コヒーレンストモグラフィーを用いる光学系を含む光学ユニットに接続されることにより、対象部位の診断を可能とするプローブであって、対象部位に当接可能に構成された先端部と、光学ユニットからの光を軟骨に導いて走査させるための光学機構と、対象部位に対して所定の変形エネルギーを付与するための負荷装置と、を備える。 Another aspect of the present invention is a diagnostic probe. This diagnostic probe is a probe that enables diagnosis of a target site by being connected to an optical unit including an optical system that uses optical coherence tomography, and includes a tip portion configured to be able to contact the target site, An optical mechanism for guiding the light from the optical unit to the cartilage to scan, and a load device for applying a predetermined deformation energy to the target site.
 この態様の診断用プローブを対象部位としての軟骨に当接させ、光学ユニットを作動させることにより、上述した軟骨の損傷度合いを断層可視化することが可能となる。すなわち、OCTを用いた軟骨診断をより実用に供し得るものとすることができる。 By bringing the diagnostic probe of this aspect into contact with the cartilage as the target site and operating the optical unit, it becomes possible to visualize the degree of damage of the cartilage described above. That is, cartilage diagnosis using OCT can be more practically used.
 本発明によれば、OCTを用いた軟骨診断をより実用に供し得るものとできる。 According to the present invention, cartilage diagnosis using OCT can be more practically used.
第1実施例に係る軟骨診断装置の構成を概略的に表す図である。It is a figure which represents roughly the structure of the cartilage diagnostic apparatus which concerns on 1st Example. 軟骨診断装置を構成する診断プローブの構成を概略的に表す図である。It is a figure which represents roughly the structure of the diagnostic probe which comprises a cartilage diagnostic apparatus. 再帰的相互相関法による処理手順を概略的に示す図である。It is a figure which shows roughly the process sequence by a recursive cross correlation method. サブピクセル解析による処理手順を概略的に示す図である。It is a figure which shows the process sequence by a subpixel analysis roughly. 各処理により得られる結果を示す図である。It is a figure which shows the result obtained by each process. 軟骨診断処理の処理手順を表す図である。It is a figure showing the process sequence of a cartilage diagnostic process. 軟骨診断処理の処理手順を表す図である。It is a figure showing the process sequence of a cartilage diagnostic process. 実験装置の構成を概略的に表す図である。It is a figure showing the composition of an experimental device roughly. 実験に用いた試験片を表す図である。It is a figure showing the test piece used for experiment. 実験に際して試験片に与えた荷重負荷状態を示すグラフである。It is a graph which shows the load state applied to the test piece in the experiment. 応力緩和試験によるひずみ速度分布の時間変化を断層可視化した図である。It is the figure which visualized the tomographic change of the strain rate distribution by the stress relaxation test. 応力緩和試験によるひずみ速度分布の時間変化を断層可視化した図である。It is the figure which visualized the tomographic change of the strain rate distribution by the stress relaxation test. 正常軟骨と模擬変性軟骨の減衰係数の比較を表す図である。It is a figure showing the comparison of the attenuation coefficient of a normal cartilage and a simulation degenerated cartilage. 制御演算部により実行される軟骨診断処理の流れを示すフローチャートである。It is a flowchart which shows the flow of the cartilage diagnostic process performed by a control calculating part. 図14におけるS36の変性度合い演算提示処理を詳細に示すフローチャートである。It is a flowchart which shows in detail the modification | denaturation degree calculation presentation process of S36 in FIG. 第2実施例に係る変性度合い演算提示処理を詳細に示すフローチャートである。It is a flowchart which shows the modification | denaturation degree calculation presentation process which concerns on 2nd Example in detail.
 本発明の一実施形態は、関節軟骨を診断するための軟骨診断装置である。この軟骨診断装置は、軟骨に所定の変形エネルギー(荷重)を負荷する一方でOCTを用いて軟骨の断層画像を撮影し、その荷重に対する軟骨組織の挙動からその損傷度合い(変性度)を演算するものである。その演算結果が軟骨の断層画像の態様で表示装置に可視化されるため、医師等がその断層画像を見ることで軟骨診断を行うことができる。 One embodiment of the present invention is a cartilage diagnostic apparatus for diagnosing articular cartilage. This cartilage diagnostic apparatus takes a tomographic image of cartilage using OCT while applying a predetermined deformation energy (load) to the cartilage, and calculates the degree of damage (degeneration degree) from the behavior of the cartilage tissue with respect to the load. Is. Since the calculation result is visualized on the display device in the form of a tomographic image of cartilage, a doctor or the like can make a cartilage diagnosis by viewing the tomographic image.
 この軟骨診断装置は、OCTの光学系を含む光学ユニットと、その光学ユニットに接続されるプローブを備える。このプローブは、関節腔に挿入可能な先端部を有するとともに、OCTの演算処理に用いられる物理量を取得するための光学機構と荷重機構(「負荷装置」として機能する)を備える。プローブの先端部は、例えばシリンジ針に挿通されるなどして関節腔に挿入されるものでもよい。プローブの先端を軟骨の表面(又はその近傍)に当接させた状態で荷重機構を駆動することにより、軟骨に対して所定の荷重が負荷される。その荷重に対する軟骨組織の応答をOCTにより断層計測することにより、軟骨の変性度を評価することができる。後述のように、変性度の進行度合いに応じてその応答が異なる形で表れるからである。光学機構は、この軟骨組織の挙動を断層画像として取得するために光学ユニットからの物体光を軟骨に照射して走査させ、その反射光を取得して光学ユニットに送る。 This cartilage diagnostic apparatus includes an optical unit including an OCT optical system and a probe connected to the optical unit. This probe has a tip portion that can be inserted into a joint cavity, and includes an optical mechanism and a load mechanism (functioning as a “load device”) for obtaining a physical quantity used for OCT calculation processing. The tip of the probe may be inserted into the joint cavity, for example, through a syringe needle. A predetermined load is applied to the cartilage by driving the load mechanism in a state where the tip of the probe is in contact with the surface (or the vicinity thereof) of the cartilage. The degree of cartilage degeneration can be evaluated by tomographically measuring the response of the cartilage tissue to the load by OCT. This is because, as will be described later, the response appears differently depending on the progress of the degree of denaturation. In order to acquire the behavior of the cartilage tissue as a tomographic image, the optical mechanism irradiates and scans the cartilage with object light from the optical unit, acquires the reflected light, and sends it to the optical unit.
 光学ユニットは、その反射光と参照光とを合波し、その光干渉信号を制御演算部へ送る。制御演算部は、荷重機構および光学機構の駆動を制御する一方でその光干渉信号を処理し、上述した荷重負荷による軟骨内部の変形に伴う力学特徴量の変化をその軟骨の断層位置に対応づけて演算する。ここでいう「力学特徴量」は、軟骨組織の変形ベクトルの空間分布に基づいて得られるものでよい。例えば、変形ベクトルを時間微分した変形速度ベクトルであってもよいし、変形速度ベクトルをさらに空間微分したひずみ速度テンソルであってもよい。 The optical unit combines the reflected light and the reference light, and sends the optical interference signal to the control calculation unit. The control calculation unit processes the optical interference signal while controlling the driving of the load mechanism and the optical mechanism, and associates the change in the mechanical feature amount due to the deformation in the cartilage due to the load load described above with the tomographic position of the cartilage. To calculate. The “mechanical feature amount” here may be obtained based on the spatial distribution of the deformation vector of the cartilage tissue. For example, a deformation rate vector obtained by temporally differentiating the deformation vector or a strain rate tensor obtained by further spatially differentiating the deformation rate vector may be used.
 荷重機構による荷重負荷方法については、測定対象(軟骨)に対して一定のひずみを与えて応力の時間変化を測定する応力緩和法に基づくものでもよい。あるいは、測定対象に対して動的ひずみを与えて応力の最大値および位相差を測定する動的粘弾性法に基づくものでもよい。あるいは、測定対象に対して一定の大きさの応力を与えてひずみの時間変化を測定するクリープ法に基づくものでもよい。制御演算部は、上記力学特徴量の変化に基づいて軟骨組織の損傷度合いを演算し、それを表示装置の画面に断層可視化する。 The load loading method using a load mechanism may be based on a stress relaxation method in which a constant strain is applied to a measurement target (cartilage) and a time change of stress is measured. Or based on the dynamic viscoelasticity method which gives the dynamic strain with respect to a measuring object, and measures the maximum value and phase difference of stress. Alternatively, it may be based on a creep method in which a time-dependent change in strain is measured by applying a certain amount of stress to the measurement object. The control calculation unit calculates the degree of damage of the cartilage tissue based on the change in the mechanical feature value, and visualizes it on the screen of the display device.
 制御演算部は、応力緩和法に基づいて以下の処理を実行してもよい。すなわち、荷重機構の駆動により軟骨に所定の荷重を負荷した後に応力緩和させ、その応力緩和中に光学ユニットにより撮影された前後の断層画像データに基づき、軟骨の断層位置に対応した変形速度ベクトルを力学特徴量として演算してもよい。そして、その変形速度ベクトルの変化から得られる減衰係数の断層分布を、軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。なお、ここでいう「前後の断層画像データ」は、連続撮影された2枚の断層画像によるものでもよいし、連続しないものの所定時間をあけて撮影された2枚の断層画像によるものでもよい。 The control calculation unit may execute the following processing based on the stress relaxation method. That is, the stress is relaxed after a predetermined load is applied to the cartilage by driving the load mechanism, and the deformation velocity vector corresponding to the tomographic position of the cartilage is determined based on the tomographic image data before and after the stress is taken by the optical unit. You may calculate as a mechanical feature-value. Then, the tomographic distribution of the attenuation coefficient obtained from the change of the deformation velocity vector may be visualized as a tomographic equivalent as the distribution of the damage degree of the cartilage tissue. The “front and back tomographic image data” here may be based on two tomographic images that are continuously captured, or may be based on two tomographic images that are not consecutive but are captured at a predetermined time.
 あるいは、制御演算部は、力学特徴量として演算した変形速度ベクトルを空間微分することによりひずみ速度テンソルを演算し、そのひずみ速度の減衰係数の断層分布を軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。このようにひずみ速度テンソルを演算することで、減衰係数の断層分布に軟骨組織の圧縮、膨張、剪断などの物理的意味合いをもたせることができる。なお、この物理的な意味合いから、軟骨変性度を力学的変形能として直接的に医師等に伝えることもできる。 Alternatively, the control calculation unit calculates a strain rate tensor by spatially differentiating the deformation rate vector calculated as a mechanical feature amount, and the fault distribution of the strain rate attenuation coefficient is equivalent to the distribution of the degree of damage of the cartilage tissue. It may be made visible. By calculating the strain rate tensor in this way, physical implications such as compression, expansion and shearing of the cartilage tissue can be given to the fault distribution of the attenuation coefficient. From this physical meaning, the degree of cartilage degeneration can be directly transmitted to a doctor or the like as a mechanical deformability.
 制御演算部は、順次取得する断層画像データの相互相関、輝度勾配の変位および輝度パターンの変形に基づき変形速度ベクトルをサブピクセル精度にて演算してもよい。OCTの解像度には限界があるため、このようなサブピクセル解析を導入することにより、より高精度な軟骨診断が実現可能となる。 The control calculation unit may calculate the deformation velocity vector with sub-pixel accuracy based on the cross-correlation of the tomographic image data acquired sequentially, the displacement of the luminance gradient, and the deformation of the luminance pattern. Since the resolution of OCT is limited, by introducing such sub-pixel analysis, cartilage diagnosis with higher accuracy can be realized.
 制御演算部は、動的粘弾性法に基づいて以下の処理を実行してもよい。すなわち、荷重機構の駆動により軟骨に所定の動的荷重(動的力)を負荷し、その動的荷重による軟骨の振動中に光学ユニットにより撮影された前後の断層画像データに基づき、軟骨の各断層位置における変形速度ベクトルを力学特徴量として演算し、その変形速度ベクトルのうち加振周波数成分である特定変形速度ベクトルの振幅および位相差の少なくとも一方に基づき軟骨の粘弾性の断層分布を演算し、その粘弾性の断層分布を軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。軟骨の粘弾性がその軟骨の変性度に応じて変化することに着目したものである。なお、ここでいう「前後の断層画像データ」も、連続撮影された2枚の断層画像によるものでもよいし、連続しないものの所定時間をあけて撮影された2枚の断層画像によるものでもよい。 The control calculation unit may execute the following processing based on the dynamic viscoelasticity method. That is, a predetermined dynamic load (dynamic force) is applied to the cartilage by driving the load mechanism, and each cartilage of the cartilage is determined based on the tomographic image data taken by the optical unit during the vibration of the cartilage due to the dynamic load. The deformation velocity vector at the tomographic position is calculated as a mechanical feature, and the viscoelastic tomographic distribution of cartilage is calculated based on at least one of the amplitude and phase difference of the specific deformation velocity vector that is the excitation frequency component of the deformation velocity vector. Alternatively, the viscoelastic fault distribution may be visualized as equivalent to the distribution of the damage degree of the cartilage tissue. This is because the viscoelasticity of the cartilage changes depending on the degree of degeneration of the cartilage. The “front and back tomographic image data” here may be based on two tomographic images that are continuously captured, or may be based on two tomographic images that are not consecutive but are captured at a predetermined time.
 あるいは、軟骨の各断層位置におけるひずみ速度テンソルを力学特徴量として演算し、そのひずみ速度テンソルのうち加振周波数成分である特定ひずみ速度テンソルの振幅および位相差の少なくとも一方に基づき軟骨の粘弾性の断層分布を演算してもよい。 Alternatively, the strain rate tensor at each tomographic position of the cartilage is calculated as a mechanical feature, and the viscoelasticity of the cartilage is determined based on at least one of the amplitude and phase difference of the specific strain rate tensor that is the excitation frequency component of the strain rate tensor. The fault distribution may be calculated.
 また、荷重機構が、軟骨に付与される荷重(力)を計測可能なセンサを含んでもよい。制御演算部は、演算された力学特徴量の加振周波数成分の振幅および位相差の少なくとも一方と、センサにより計測された荷重値に基づき軟骨の粘弾性の断層分布を演算し、その粘弾性の断層分布を軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。 Further, the load mechanism may include a sensor capable of measuring a load (force) applied to the cartilage. The control calculation unit calculates the tomographic distribution of the viscoelasticity of the cartilage based on at least one of the amplitude and phase difference of the excitation frequency component of the calculated mechanical feature and the load value measured by the sensor, The tomographic distribution may be visualized as equivalent to the distribution of the degree of damage of the cartilage tissue.
 なお、上記プローブは、例えば手術中の内臓を診断するなど、軟骨以外の対象部位の診断に適用することも可能である。すなわち、プローブが、OCTの光学系を含む光学ユニットに接続されることにより、所定の対象部位の診断を可能とする診断用プローブとして構成されてもよい。このプローブは、対象部位に当接可能に構成された先端部と、光学ユニットからの光を軟骨に導いて走査させるための光学機構と、対象部位に対して所定の変形エネルギー(応力)を負荷するための荷重機構(負荷装置)とを備える。 The probe can also be applied to diagnosis of a target site other than cartilage, for example, for diagnosing internal organs during surgery. That is, the probe may be configured as a diagnostic probe that enables diagnosis of a predetermined target site by being connected to an optical unit including an OCT optical system. This probe has a tip that is configured to be able to contact the target part, an optical mechanism for guiding the light from the optical unit to the cartilage and scanning it, and applying a predetermined deformation energy (stress) to the target part. A load mechanism (load device).
 また、上記技術を利用した軟骨診断方法を構築してもよい。この方法は、軟骨に対して所定の変形エネルギー(荷重)を負荷するステップと、変形エネルギーの付与(荷重の負荷)に応じた軟骨の変形度合いを光コヒーレンストモグラフィーにより断層画像として表示させるステップと、断層画像に基づいて軟骨組織の損傷度合いを診断するステップとを備えるものでよい。 Also, a cartilage diagnostic method using the above technique may be constructed. The method includes a step of applying a predetermined deformation energy (load) to the cartilage, a step of displaying the degree of deformation of the cartilage according to the application of the deformation energy (load of load) as a tomographic image by optical coherence tomography, And a step of diagnosing the degree of damage to the cartilage tissue based on the tomographic image.
 以下、図面を参照しつつ本発明を具体化した実施例について詳細に説明する。
[第1実施例]
 図1は、第1実施例に係る軟骨診断装置の構成を概略的に表す図である。図2は、軟骨診断装置を構成する診断プローブの構成を概略的に表す図である。本実施例の軟骨診断装置は、診断対象である関節軟骨に所定の応力を負荷し、その応力に対する軟骨組織の変形度合いを断層可視化することにより、軟骨組織の損傷度合い(変性度)を診断可能とするものである。この断層可視化にOCTを利用する。
DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments embodying the present invention will be described below in detail with reference to the drawings.
[First embodiment]
FIG. 1 is a diagram schematically illustrating the configuration of the cartilage diagnostic apparatus according to the first embodiment. FIG. 2 is a diagram schematically illustrating a configuration of a diagnostic probe that configures the cartilage diagnostic apparatus. The cartilage diagnostic apparatus of this embodiment can diagnose the degree of cartilage tissue damage (degeneration degree) by applying a predetermined stress to the articular cartilage to be diagnosed and visualizing the degree of cartilage tissue deformation against that stress. It is what. OCT is used for this tomographic visualization.
 図1に示すように、軟骨診断装置1は、OCTを用いる光学系を含む光学ユニット2、光学ユニット2に接続される診断用のプローブ4、OCTにより得られた光干渉データに基づいて軟骨組織の損傷度合いを演算する制御演算部6、および軟骨組織の損傷度合いを断層可視化する態様で表示する表示装置8を備える。図示の例では、光学ユニット2としてマッハツェンダー干渉計をベースとした光学系が示されているが、マイケルソン干渉計その他の光学系を採用することもできる。 As shown in FIG. 1, a cartilage diagnostic apparatus 1 includes an optical unit 2 including an optical system using OCT, a diagnostic probe 4 connected to the optical unit 2, and cartilage tissue based on optical interference data obtained by OCT. A control calculation unit 6 for calculating the degree of damage of the cartilage, and a display device 8 for displaying the degree of damage of the cartilage tissue in a manner of visualizing the tomogram. In the illustrated example, an optical system based on a Mach-Zehnder interferometer is shown as the optical unit 2, but a Michelson interferometer or other optical system may be employed.
 本実施例では、OCTとして波長走査型レーザを光源とするSS-OCT(Swept Source OCT)を用いるが、TD-OCT(Time Domain OCT)、SD-OCT(Spectral Domain OCT)その他のOCTを用いることもできる。SS-OCTは、TD-OCTとは異なり、参照鏡走査などの機械的な光遅延走査を必要としないため、高い時間分解能と高い位置検出精度が得られる点で好ましい。 In this embodiment, SS-OCT (Swept Source OCT) using a wavelength scanning laser as a light source is used as OCT, but TD-OCT (Time Domain OCT), SD-OCT (Spectral Domain OCT) or other OCT is used. You can also. Unlike TD-OCT, SS-OCT does not require mechanical optical delay scanning such as reference mirror scanning, and is preferable in that high time resolution and high position detection accuracy can be obtained.
 光学ユニット2は、光源10、オブジェクトアーム12、リファレンスアーム14、および光検出器16を備える。各光学要素は、光ファイバーにて互いに接続されている。光源10から出射された光は、カプラ18(ビームスプリッタ)にて分けられ、その一方がオブジェクトアーム12に導かれる物体光となり、他方がリファレンスアーム14に導かれる参照光となる。オブジェクトアーム12に導かれた物体光は、サーキュレータ20を介してプローブ4に導かれ、診断対象である軟骨に照射される。この物体光は、軟骨の表面および断面にて後方散乱光として反射されてサーキュレータ20に戻り、カプラ22に導かれる。 The optical unit 2 includes a light source 10, an object arm 12, a reference arm 14, and a photodetector 16. Each optical element is connected to each other by an optical fiber. The light emitted from the light source 10 is divided by a coupler 18 (beam splitter), one of which becomes object light guided to the object arm 12 and the other becomes reference light guided to the reference arm 14. The object light guided to the object arm 12 is guided to the probe 4 through the circulator 20, and is irradiated to the cartilage that is the object of diagnosis. This object light is reflected as backscattered light on the surface and cross section of the cartilage, returns to the circulator 20, and is guided to the coupler 22.
 一方、リファレンスアーム14に導かれた参照光は、サーキュレータ24を介して反射鏡26に導かれる。このとき、参照光は、コリメートレンズ28を経て集光レンズ30にて反射鏡26に集光される。この参照光は、反射鏡26にて反射されてサーキュレータ24に戻り、カプラ22に導かれる。すなわち、物体光と参照光とがカプラ22にて合波(重畳)され、その干渉光が光検出器16により検出される。 On the other hand, the reference light guided to the reference arm 14 is guided to the reflecting mirror 26 via the circulator 24. At this time, the reference light is condensed on the reflecting mirror 26 by the condenser lens 30 through the collimator lens 28. The reference light is reflected by the reflecting mirror 26, returns to the circulator 24, and is guided to the coupler 22. That is, the object light and the reference light are combined (superposed) by the coupler 22, and the interference light is detected by the photodetector 16.
 プローブ4は、光学ユニット2のオブジェクトアーム12を構成し、その本体32にはサーキュレータ20から延びる光ファイバー34が挿通されている。本体32の先端にはシリンジ針36が取り付けられており、プローブ4の先端部は、そのシリンジ針36を介して生体内(患者の膝K)に挿入可能とされている。本体32には、光学ユニット2からの光を膝Kの軟骨に導いて走査させるための光学機構と、軟骨に対して所定の荷重(応力)を負荷するための荷重機構と、これらの機構を駆動するための駆動部38(アクチュエータ)が設けられている。光学機構は、軟骨に向けて光を照射し、その反射光をオブジェクトアーム12に導く。各機構の詳細については後述する。 The probe 4 constitutes the object arm 12 of the optical unit 2, and an optical fiber 34 extending from the circulator 20 is inserted into the main body 32 thereof. A syringe needle 36 is attached to the distal end of the main body 32, and the distal end portion of the probe 4 can be inserted into the living body (patient's knee K) through the syringe needle 36. The main body 32 includes an optical mechanism for guiding the light from the optical unit 2 to the cartilage of the knee K to scan, a load mechanism for applying a predetermined load (stress) to the cartilage, and these mechanisms. A drive unit 38 (actuator) for driving is provided. The optical mechanism irradiates light toward the cartilage and guides the reflected light to the object arm 12. Details of each mechanism will be described later.
 カプラ22にて合波された干渉光は、光検出器16に入力される。光検出器16は、これを光干渉信号(干渉光強度を示す信号)として検出する。この光干渉信号は、A/D変換器40を介して制御演算部6に入力される。A/D変換器40は、光検出器16から出力されたアナログ信号をデジタル信号に変換して制御演算部6へ出力する。 Interference light combined by the coupler 22 is input to the photodetector 16. The photodetector 16 detects this as an optical interference signal (a signal indicating the intensity of interference light). This optical interference signal is input to the control calculation unit 6 via the A / D converter 40. The A / D converter 40 converts the analog signal output from the photodetector 16 into a digital signal and outputs the digital signal to the control calculation unit 6.
 制御演算部6は、CPU、ROM、RAM、ハードディスクなどを有し、これらのハードウェア、およびソフトウェアによって、光学ユニット2の光学系全体の制御と、プローブ4の駆動制御と、OCTによる画像出力のための演算処理を行う。制御演算部6は、プローブ4の荷重機構および光学機構の駆動を制御し、それらの駆動に基づいて光学ユニット2から出力された光干渉信号を処理し、OCTによる軟骨の断層画像を取得する。そして、その断層画像データに基づき、後述の手法により軟骨組織の損傷度合いを演算する。 The control calculation unit 6 includes a CPU, a ROM, a RAM, a hard disk, and the like. The hardware and software control the entire optical system of the optical unit 2, drive control of the probe 4, and image output by OCT. For this purpose. The control calculation unit 6 controls the driving of the loading mechanism and the optical mechanism of the probe 4, processes the optical interference signal output from the optical unit 2 based on the driving, and acquires a tomographic image of the cartilage by OCT. Based on the tomographic image data, the degree of damage to the cartilage tissue is calculated by a method described later.
 表示装置8は、例えば液晶ディスプレイからなり、制御演算部6にて演算された軟骨組織の損傷度合いを断層可視化する態様で画面に表示させる。 The display device 8 includes, for example, a liquid crystal display, and displays the damage degree of the cartilage tissue calculated by the control calculation unit 6 on the screen in a manner of visualizing the tomography.
 図2に示すように、プローブ4は、筒状の本体32の先端に穿刺部としてのシリンジ針36が取り付けられる。シリンジ針36の内方には有底円筒状のシース50が同軸状に設けられ、本体32の内方にはシース50を軸線方向に駆動可能な圧電素子52(ピエゾ素子)が設けられている。圧電素子52は、本体32の内部に設けられた図示略の支持機構に支持されている。シース50は、その先端が閉止されており、後端開口部が圧電素子52の先端部に固定されている。シース50の先端面は、患者の軟骨Jの表面に当接可能な当接面となっている。 As shown in FIG. 2, the probe 4 has a syringe needle 36 as a puncture portion attached to the tip of a cylindrical main body 32. A cylindrical sheath 50 with a bottom is coaxially provided inside the syringe needle 36, and a piezoelectric element 52 (piezo element) capable of driving the sheath 50 in the axial direction is provided inside the main body 32. . The piezoelectric element 52 is supported by a support mechanism (not shown) provided inside the main body 32. The distal end of the sheath 50 is closed, and the rear end opening is fixed to the distal end of the piezoelectric element 52. The distal end surface of the sheath 50 is a contact surface that can contact the surface of the cartilage J of the patient.
 シース50の内方には光ファイバー34の先端部が挿通され、その先端にGRINレンズ54が連設され、さらにその先端にプリズムミラー56が連設されている。すなわち、光ファイバー34、GRINレンズ54およびプリズムミラー56は、軸線方向に一体化された導光体を構成している。GRINレンズ54は、レンズ内の屈折率を連続的に変えることで集光機能を発揮する。プリズムミラー56は、その先端面が軸線に対して傾斜した反射面とされている。なお、本実施例では、照射ビームの径と焦点距離・ビームスポット径などを整える光学素子としてGRINレンズ54を採用しているが、同様の機能を発揮できる他の光学素子を採用してもよい。また、ビームを指定方向に反射する光学素子としてプリズムミラー56を採用しているが、同様の機能を発揮できる他の光学素子を採用してもよい。 The tip of the optical fiber 34 is inserted inside the sheath 50, a GRIN lens 54 is connected to the tip, and a prism mirror 56 is connected to the tip. In other words, the optical fiber 34, the GRIN lens 54, and the prism mirror 56 constitute a light guide integrated in the axial direction. The GRIN lens 54 exhibits a condensing function by continuously changing the refractive index in the lens. The prism mirror 56 is a reflecting surface whose tip surface is inclined with respect to the axis. In this embodiment, the GRIN lens 54 is used as an optical element that adjusts the diameter of the irradiation beam, the focal length, the beam spot diameter, etc., but other optical elements that can perform the same function may be used. . Further, although the prism mirror 56 is employed as an optical element that reflects the beam in a specified direction, other optical elements that can exhibit the same function may be employed.
 光ファイバー34によりプローブ4に導かれた光は、GRINレンズ54およびプリズムミラー56を介してシース50の先端から出射され、軟骨Jに照射される(点線矢印参照)。それにより軟骨Jの表面又は断面にて反射された光がGRINレンズ54に取り込まれ、光ファイバー34を介して光学ユニット2のオブジェクトアーム12に導かれる。 The light guided to the probe 4 by the optical fiber 34 is emitted from the distal end of the sheath 50 through the GRIN lens 54 and the prism mirror 56, and irradiated to the cartilage J (see the dotted arrow). Thereby, the light reflected on the surface or cross section of the cartilage J is taken into the GRIN lens 54 and guided to the object arm 12 of the optical unit 2 through the optical fiber 34.
 圧電素子52には軸線に沿って貫通する挿通孔58が設けられている。光ファイバー34は、この挿通孔58に挿通され、シース50内に導入されている。このような構成により、光ファイバー34に機械的負荷をかけることなく、圧電素子52による荷重をシース50に負荷することができる。圧電素子52への通電によりその圧電素子52が軸線方向に伸長し、シース50を軸線方向先端側に駆動することができる。この駆動力は、シース50の先端面による押圧力(圧縮応力)となって軟骨Jに負荷される。すなわち、シース50および圧電素子52が、「負荷装置(荷重機構)」として機能する。 The piezoelectric element 52 is provided with an insertion hole 58 penetrating along the axis. The optical fiber 34 is inserted into the insertion hole 58 and introduced into the sheath 50. With such a configuration, a load from the piezoelectric element 52 can be applied to the sheath 50 without applying a mechanical load to the optical fiber 34. By energizing the piezoelectric element 52, the piezoelectric element 52 extends in the axial direction, and the sheath 50 can be driven to the distal end side in the axial direction. This driving force is applied to the cartilage J as a pressing force (compressive stress) by the distal end surface of the sheath 50. That is, the sheath 50 and the piezoelectric element 52 function as a “load device (load mechanism)”.
 なお、シース50は、図示しない付勢部材により後方に付勢されており、圧電素子52の非通電時にはシリンジ針36の内方に収容されるように構成されている。圧電素子52に通電されると、図示のようにシース50の先端面がシリンジ針36から突出できる構成とされている。 The sheath 50 is biased rearward by a biasing member (not shown), and is configured to be accommodated inside the syringe needle 36 when the piezoelectric element 52 is not energized. When the piezoelectric element 52 is energized, the distal end surface of the sheath 50 can project from the syringe needle 36 as shown in the figure.
 本体32の内方における圧電素子52の後方には、光ファイバー34を軸線周りに回動させるための回動機構60(光ロータリージョイント)が設けられている。回動機構60は、光ファイバー34と同軸状に固定された回転子を有する。回動機構60への通電により、光ファイバー34およびGRINレンズ54を自軸周りに回動させ、プリズムミラー56の向きを変化させることができる。すなわち、光ファイバー34の先端部、GRINレンズ54、プリズムミラー56および回動機構60が、「光学機構」として機能する。回動機構60の駆動により、物体光を軟骨Jに対して走査させることができる。圧電素子52および回動機構60への通電制御は、制御演算部6によってなされる。 A rotating mechanism 60 (optical rotary joint) for rotating the optical fiber 34 around the axis is provided behind the piezoelectric element 52 inside the main body 32. The rotation mechanism 60 has a rotor fixed coaxially with the optical fiber 34. By energizing the rotation mechanism 60, the optical fiber 34 and the GRIN lens 54 can be rotated around the own axis, and the direction of the prism mirror 56 can be changed. That is, the tip of the optical fiber 34, the GRIN lens 54, the prism mirror 56, and the rotation mechanism 60 function as an “optical mechanism”. By driving the rotation mechanism 60, the object light can be scanned with respect to the cartilage J. Energization control to the piezoelectric element 52 and the rotation mechanism 60 is performed by the control calculation unit 6.
 以下、軟骨組織の損傷度合いを提示するまでの演算処理方法について説明する。
 上述のように、オブジェクトアーム12を経た物体光(軟骨Jからの反射光)と、リファレンスアーム14を経た参照光とが合波され、光検出器16により光干渉信号として検出される。制御演算部6は、この光干渉信号を干渉光強度に基づく軟骨Jの断層画像として取得することができる。
Hereinafter, a calculation processing method until the degree of cartilage tissue damage is presented will be described.
As described above, the object light (reflected light from the cartilage J) that has passed through the object arm 12 and the reference light that has passed through the reference arm 14 are combined and detected by the photodetector 16 as an optical interference signal. The control calculation unit 6 can acquire the optical interference signal as a tomographic image of the cartilage J based on the interference light intensity.
 ところで、OCTの光軸方向(奥行き方向)の分解能であるコヒーレンス長lは、光源の自己相関関数によって決定される。ここでは、コヒーレンス長lを自己相関関数の包括線の半値半幅とし、下記式(1)にて表すことができる。
Figure JPOXMLDOC01-appb-M000001
 ここで、λはレーザビームの中心波長であり、Δλはレーザビームの半値全幅である。
Incidentally, the coherence length l c which is the resolution in the optical axis direction (depth direction) of OCT is determined by the autocorrelation function of the light source. Here, the coherence length l c is the half-width of the comprehensive line of the autocorrelation function and can be expressed by the following formula (1).
Figure JPOXMLDOC01-appb-M000001
Here, λ c is the center wavelength of the laser beam, and Δλ is the full width at half maximum of the laser beam.
 一方、光軸垂直方向(ビーム走査方向)の分解能は、集光レンズによる集光性能に基づき、ビームスポット径Dの1/2とされる。そのビームスポット径Dは、下記式(2)にて表すことができる。
Figure JPOXMLDOC01-appb-M000002
 ここで、dは集光レンズに入射するビーム径、fは集光レンズの焦点である。このようにOCTによる分解能には限界があるところ、本実施例では後述するサブピクセル解析の導入などにより、軟骨組織の診断をマイクロスケールにて行うことを可能にしている。以下、その詳細について説明する。
On the other hand, the resolution in the direction perpendicular to the optical axis (beam scanning direction) is ½ of the beam spot diameter D based on the light condensing performance of the condensing lens. The beam spot diameter D can be expressed by the following formula (2).
Figure JPOXMLDOC01-appb-M000002
Here, d B is the beam diameter incident on the condenser lens, f is a focal point of the condenser lens. As described above, the resolution by OCT is limited, but in this embodiment, the diagnosis of cartilage tissue can be performed on a micro scale by introducing a subpixel analysis described later. The details will be described below.
 まず、OCTを利用したマイクロスケールの力学特性検出法について説明する。この検出法は、計測対象の変形前後の2枚のOCT断層画像にデジタル相互相関法を適用することで変形ベクトル分布を算出し、マイクロスケールにて生体組織内部のひずみ速度テンソル分布を断層検出する手法である。 First, a microscale mechanical property detection method using OCT will be described. This detection method calculates a deformation vector distribution by applying a digital cross-correlation method to two OCT tomographic images before and after deformation of a measurement object, and detects a strain rate tensor distribution inside a living tissue on a microscale. It is a technique.
 変形ベクトル分布を算出する際には、繰り返し相互相関処理を実施する再帰的相互相関法(Recursive Cross-correlation method)を適用する。これは、低解像度において算出された変形ベクトルを参照し、探査領域を限定するとともに階層的に検査領域を縮小して相互相関法を適用する手法である。これにより、高解像度な変形ベクトルを取得することができる。さらに、スペックル・ノイズ低減法として、隣接検査領域の相関値分布との乗算を行う隣接相互相関乗法(Adjacent Cross-correlation Multiplication)を用いる。そして、乗算されることによって高SN化した相関値分布から最大相関値を探索する。 When calculating the deformation vector distribution, the recursive cross-correlation method (Recursive Cross-correlation method), which performs repeated cross-correlation processing, is applied. This is a technique of applying a cross-correlation method by referring to a deformation vector calculated at a low resolution, limiting an exploration area and hierarchically reducing an inspection area. Thereby, a high-resolution deformation vector can be acquired. Further, as a speckle noise reduction method, an adjacent cross-correlation multiplication method (Adjacent cross-correlation Multiplication) that performs multiplication with a correlation value distribution in an adjacent inspection region is used. Then, the maximum correlation value is searched from the correlation value distribution that has been multiplied to increase the SN.
 また、マイクロスケールにおける微小変形解析では、変形ベクトルのサブピクセル精度が重要となる。このため、輝度勾配を利用する風上勾配法(Up-stream Gradientmethod)と、伸縮および剪断を考慮した画像変形法(Image Deformation method)の両サブピクセル解析法を併用し、変形ベクトルの高精度検出を実現する。なお、ここでいう「風上勾配法」は、勾配法(オプティカルフロー法)の一種である。 Also, in the micro deformation analysis on the micro scale, the sub-pixel accuracy of the deformation vector is important. For this reason, both the up-stream gradient method using brightness gradient (Up-stream Gradientmethod) and the image deformation method considering image expansion and shear (Image Deformation method) are used together to detect deformation vectors with high accuracy. Is realized. The “windward gradient method” here is a kind of gradient method (optical flow method).
 このようにして得られた変形ベクトルを時間微分することにより変形速度ベクトル分布を演算し、それをさらに空間微分することによりひずみ速度テンソル分布を演算する。後述のように、軟骨組織のひずみ速度テンソルの減衰係数はその軟骨の損傷度合い(変性度)と等価とみることができるため、これを軟骨の損傷度合いとして断層可視化する。 The deformation velocity vector distribution is calculated by time differentiation of the deformation vector thus obtained, and the strain rate tensor distribution is calculated by further spatial differentiation. As will be described later, since the attenuation coefficient of the strain rate tensor of the cartilage tissue can be regarded as equivalent to the damage degree (degeneration degree) of the cartilage, this is visualized as a tomogram as the cartilage damage degree.
 以下、各手法について詳細に説明する。図3は、再帰的相互相関法による処理手順を概略的に示す図である。図4は、サブピクセル解析による処理手順を概略的に示す図である。図5は、各処理により得られる結果を示す図である。 Hereinafter, each method will be described in detail. FIG. 3 is a diagram schematically showing a processing procedure by the recursive cross correlation method. FIG. 4 is a diagram schematically showing a processing procedure by subpixel analysis. FIG. 5 is a diagram illustrating a result obtained by each process.
(再帰的相互相関法)
 図3(A)~(C)は、再帰的相互相関法による処理過程を示している。各図にはOCTにより連続的に撮影される前後の断層画像が示されている。左側には先の断層画像(Image1)が示され、右側には後の断層画像(Image2)が示されている。
(Recursive cross correlation method)
FIGS. 3A to 3C show processing steps by the recursive cross-correlation method. Each figure shows tomographic images before and after continuous imaging by OCT. The previous tomographic image (Image1) is shown on the left side, and the later tomographic image (Image2) is shown on the right side.
 相互相関法とは、局所的なスペックル・パターンの類似度を下記式(3)に基づく相関値Rijより評価する方法である。そのため、図3(A)に示すように、連続的に撮影された前後のOCT画像について、先の断層画像(Image1)に類似度の検査対象となる検査領域S1が設定され、後の断層画像(Image2)に類似度の探査範囲となる探査領域S2が設定される。
Figure JPOXMLDOC01-appb-M000003
 ここで、空間座標として、光軸方向にZ軸、光軸と垂直方向にX軸を設定している。f(X,Z)とg(X,Z)は、変形前後のOCT画像において設置された中心位置(X,Z)の検査領域S1(N×Nピクセル)のスペックル・パターンを表している。
The cross-correlation method is a method for evaluating the local speckle pattern similarity based on the correlation value R ij based on the following equation (3). Therefore, as shown in FIG. 3A, with respect to the preceding and following OCT images, an inspection area S1 to be inspected with similarity to the previous tomographic image (Image1) is set, and the subsequent tomographic image is displayed. In (Image2), a search area S2 that is a search range of similarity is set.
Figure JPOXMLDOC01-appb-M000003
Here, as the spatial coordinates, the Z axis is set in the optical axis direction, and the X axis is set in the direction perpendicular to the optical axis. f (X i , Z j ) and g (X i , Z j ) are in the inspection area S1 (N x × N z pixels) of the center position (X i , Z j ) set in the OCT images before and after the deformation. Represents a speckle pattern.
 探査領域S2(M×Mピクセル)内における相関値分布Ri,j(ΔX,ΔZ)を算出し、図3(B)に示すようにパターンマッチングを行う。実際には、下記式(4)に示すように、最大相関値を与える移動量Ui,jを変形前後の変形ベクトルとして決定する。
Figure JPOXMLDOC01-appb-M000004
 なお、fとgはf(X,Z)とg(X,Z)の検査領域S1内の平均値を表している。
A correlation value distribution R i, j (ΔX, ΔZ) in the search area S2 (M x × M z pixels) is calculated, and pattern matching is performed as shown in FIG. Actually, as shown in the following equation (4), the movement amount U i, j giving the maximum correlation value is determined as the deformation vector before and after the deformation.
Figure JPOXMLDOC01-appb-M000004
Note that f and g represent average values of f (X i , Z j ) and g (X i , Z j ) in the inspection region S1.
 本手法では、検査領域S1を縮小しながら相互相関処理を繰り返して空間解像度を高める再帰的相互相関法を採用している。なお、本実施例では解像度を上げる際には空間解像度が倍になるようにしている。図3(C)に示すように、検査領域S1を1/4に分割し、前階層にて算出された変形ベクトルを参照し、探査領域S2を縮小している。ここで探査領域S2も1/4に分割している。再帰的相互相関法を用いることで、高解像度において多発する過誤ベクトルの抑制を可能にしている。このような再帰的相互相関処理を施すことにより、図5(A)に示すように変形ベクトルの解像度を高めることができる。 This method employs a recursive cross-correlation method that increases the spatial resolution by repeating the cross-correlation process while reducing the inspection area S1. In this embodiment, when the resolution is increased, the spatial resolution is doubled. As shown in FIG. 3C, the inspection area S1 is divided into ¼, and the search area S2 is reduced by referring to the deformation vector calculated in the previous hierarchy. Here, the search area S2 is also divided into ¼. By using the recursive cross-correlation method, it is possible to suppress erroneous vectors that occur frequently at high resolution. By performing such recursive cross-correlation processing, the resolution of the deformation vector can be increased as shown in FIG.
 また、これに加え、下記式(5)により、演算中の座標を中心とする周囲8つの座標を含む合計9つの変形ベクトルの平均偏差σを用いた閾値を設定し、過誤ベクトルの除去を行い再帰処理に伴う誤差伝播を抑制する。
Figure JPOXMLDOC01-appb-M000005
 ここで、Umはベクトル量の中央値を表し、閾値となる係数κは任意に設定した。
In addition to this, by using the following equation (5), a threshold value using the average deviation σ of a total of nine deformation vectors including eight coordinates around the coordinates being calculated is set, and error vectors are removed. Suppresses error propagation associated with recursive processing.
Figure JPOXMLDOC01-appb-M000005
Here, Um represents the median value of the vector quantity, and the coefficient κ serving as a threshold is arbitrarily set.
(隣接相互相関乗法)
 本実施例では、スペックルノイズの影響を受けたランダム性の強い相関値分布から正確な最大相関値を決定する方法として、隣接相互相関乗法を導入している。下記式(6)により、隣接相互相関乗法では検査領域S1における相関値分布Ri,j(Δx,Δz)と、その検査領域S1にオーバーラップする隣接検査領域に対するRi+Δi,j(Δx,Δz)とRi,j+Δj(Δx,Δz)の乗算を行い、新たな相関値分布R'i,j(Δx,Δz)を用いて最大相関値を検索する。
Figure JPOXMLDOC01-appb-M000006
(Adjacent cross-correlation multiplication)
In this embodiment, an adjacent cross-correlation multiplication method is introduced as a method for determining an accurate maximum correlation value from a highly random correlation value distribution affected by speckle noise. According to the following equation (6), in the adjacent cross-correlation multiplication method, the correlation value distribution Ri, j (Δx, Δz) in the inspection region S1 and Ri + Δi, j (Δx, Δz) with respect to the adjacent inspection region overlapping with the inspection region S1 Multiplication of Ri, j + Δj (Δx, Δz) is performed, and a maximum correlation value is retrieved using a new correlation value distribution R′i, j (Δx, Δz).
Figure JPOXMLDOC01-appb-M000006
 これにより、相関値同士の乗算によってランダム性を低減させることが可能になる。上述した検査領域S1の縮小と共に干渉強度分布の情報量も減少するため、スペックル・ノイズを原因とする複数相関ピークの出現が計測精度の悪化を招いていると考えられる。一方、隣接境界同士の移動量には相関があるため、最大相関値座標付近では強い相関値が残存する。この隣接相互相関乗法の導入によって最大相関値ピークが明瞭化され計測精度が向上し、正確な移動座標を抽出することが可能となる。また、この隣接相互相関乗法をOCTの各ステージに導入することで、誤差伝播が抑制され、スペックル・ノイズに対するロバスト性が向上する。それにより、高空間解像度においても高精度な変形ベクトルとひずみ分布の算出が可能となる。 This makes it possible to reduce randomness by multiplying correlation values. Since the amount of information of the interference intensity distribution decreases with the reduction of the inspection area S1 described above, it is considered that the appearance of multiple correlation peaks caused by speckle noise causes a deterioration in measurement accuracy. On the other hand, since the amount of movement between adjacent boundaries has a correlation, a strong correlation value remains in the vicinity of the maximum correlation value coordinate. By introducing this adjacent cross-correlation multiplication method, the maximum correlation value peak is clarified, the measurement accuracy is improved, and accurate moving coordinates can be extracted. In addition, by introducing this adjacent cross-correlation multiplication method in each stage of OCT, error propagation is suppressed, and robustness against speckle noise is improved. This makes it possible to calculate the deformation vector and strain distribution with high accuracy even at high spatial resolution.
(風上勾配法)
 図4(A)~(C)は、サブピクセル解析による処理過程を示している。各図にはOCTにより連続的に撮影される前後の断層画像が示されている。左側には先の断層画像(Image1)が示され、右側には後の断層画像(Image2)が示されている。
(Windward gradient method)
4A to 4C show a processing process by subpixel analysis. Each figure shows tomographic images before and after continuous imaging by OCT. The previous tomographic image (Image1) is shown on the left side, and the later tomographic image (Image2) is shown on the right side.
 本実施例では、サブピクセル解析のために風上勾配法と画像変形法を採用する。最終的な移動量の算出は後述の画像変形法によるが、計算の収束性の問題から、画像変形法より先に風上勾配法を適用する。検査領域サイズが小さく高空間解像度の条件において、サブピクセル移動量を高精度検出する画像変形法及び風上勾配法を適用している。画像変形法におけるサブピクセル移動量の検出が困難な場合において、風上勾配法によりサブピクセル移動量を算出する。 In this embodiment, an upwind gradient method and an image deformation method are used for subpixel analysis. Although the final movement amount is calculated by an image deformation method described later, the windward gradient method is applied prior to the image deformation method because of the problem of convergence of the calculation. The image deformation method and the windward gradient method for detecting the sub-pixel movement amount with high accuracy are applied under the condition of the inspection area size being small and the high spatial resolution. When it is difficult to detect the subpixel movement amount in the image deformation method, the subpixel movement amount is calculated by the windward gradient method.
 サブピクセル解析では、注目点における変形前後の輝度差が各成分の輝度勾配と移動量によって表される。このため、検査領域S1内の輝度勾配データより最小二乗法を用いてサブピクセル移動量を決定することができる。本実施例では、輝度勾配を求める際に、サブピクセル変形前の風上側の輝度勾配を与える風上差分法を採用している。 In sub-pixel analysis, the luminance difference before and after deformation at the point of interest is represented by the luminance gradient and movement amount of each component. For this reason, the sub-pixel movement amount can be determined using the least square method from the luminance gradient data in the inspection region S1. In the present embodiment, when obtaining the brightness gradient, the windward difference method is used which gives the windward brightness gradient before the subpixel deformation.
 サブピクセル解析は計測誤差からだけではなく、組織の散乱効果や偏光特性に複雑に関係したスペックル・ノイズに強く依存している。さらに、ひずみテンソル分布の算出には移動量の空間微係数が必要となるため、サブピクセルエラーが微係数算出の数値不安定を増大させ、ひずみテンソル分布の不安定化を招いてしまう。サブピクセル解析は様々な手法が存在するが、本実施例では検査領域サイズが小さく高空間解像度の条件においても、サブピクセル移動量を高精度検出する勾配法を採用している。 サ ブ Subpixel analysis strongly depends not only on measurement errors, but also on speckle noise intricately related to tissue scattering effects and polarization characteristics. Furthermore, since the spatial differential coefficient of the movement amount is required for calculating the strain tensor distribution, the subpixel error increases the numerical instability of the differential coefficient calculation, leading to instability of the strain tensor distribution. Various methods exist for the subpixel analysis. In this embodiment, the gradient method for detecting the subpixel movement amount with high accuracy is adopted even under the condition of a small inspection area size and high spatial resolution.
 風上勾配法は、検査領域S1内の注目点の移動を、図4(A)に示すピクセル精度に留まらず、図4(B)に示すサブピクセル精度にて算出するものである。なお、図中の各格子は1ピクセルを表している。実際には図示の断層画像と比較して相当小さいが、説明の便宜上、大きく表記している。この風上勾配法は、微小変形前後における輝度分布の変化を輝度勾配と移動量によって定式化する手法であり、fを輝度とすると、微小変形f(x+Δx,z+Δz)をテイラー展開する下記式(7)として表される。
Figure JPOXMLDOC01-appb-M000007
The windward gradient method calculates the movement of the point of interest in the inspection region S1 not only with the pixel accuracy shown in FIG. 4A but also with the sub-pixel accuracy shown in FIG. 4B. Each grid in the figure represents one pixel. Actually, it is considerably smaller than the tomographic image shown in the figure, but for the convenience of explanation, it is shown in large size. This windward gradient method is a method for formulating the change of the luminance distribution before and after the minute deformation by the luminance gradient and the moving amount. When f is the luminance, the following equation (Taylor expansion of the minute deformation f (x + Δx, z + Δz) is performed. 7).
Figure JPOXMLDOC01-appb-M000007
 上記式(7)は、注目点の変形前後の輝度差が変形前の輝度勾配と移動量によって表されることを示している。なお、移動量(Δx,Δz)については上記式(7)のみでは決定できないため、検査領域S1内で移動量が一定と考え、最小二乗法を適用して算出している。 The above formula (7) indicates that the luminance difference before and after the deformation of the attention point is represented by the luminance gradient and the movement amount before the deformation. Since the movement amount (Δx, Δz) cannot be determined only by the above equation (7), the movement amount is considered to be constant in the inspection region S1, and is calculated by applying the least square method.
 上記式(7)を用いて移動量を算出する際には、右辺の各注目点における移動前後の輝度差は一意にしか求まらない。そのため輝度勾配をどれだけ正確に算出するかが移動量の精度に直結する。輝度勾配の差分化では、一次精度風上差分を用いている。差分化において高次差分を適用すると、多くのデータが必要になり、ノイズが含まれていた際に影響を大きく受けてしまうためである。また、検査領域S1内の各点を基準とした高次差分では、検査領域S1外のデータを多く使用することとなり、検査領域S1そのものの移動量ではなくなってしまうという問題点も存在するからである。 When calculating the amount of movement using the above equation (7), the luminance difference before and after the movement at each point of interest on the right side can only be obtained uniquely. Therefore, how accurately the luminance gradient is calculated is directly related to the accuracy of the movement amount. In the difference of the brightness gradient, the primary accuracy upwind difference is used. This is because applying high-order differences in differentiating requires a lot of data and is greatly affected when noise is included. In addition, the high-order difference based on each point in the inspection area S1 uses a lot of data outside the inspection area S1, and there is a problem that the amount of movement of the inspection area S1 itself is lost. is there.
 輝度勾配を求める際に変形前の風上側の輝度勾配が移動することによって注目点の輝度差が生まれると考えることができるので、変形前は風上側の差分を適用する。ここでいう風上は、実際の移動方向ではなく、ピクセル移動量に対するサブピクセル移動量の向きのことであり、最大相関値ピークに放物線近似を施すことによって風上側を決定する。逆に、変形後の風下側の輝度勾配が逆に移動することによって注目点の輝度差が生じると考えることができるため、変形後は風下側の差分を適用する。 When calculating the brightness gradient, it can be considered that the brightness gradient on the windward side before the deformation moves, so that the brightness difference at the point of interest is generated. Therefore, the difference on the windward side is applied before the deformation. The windward here is not the actual movement direction but the direction of the subpixel movement amount with respect to the pixel movement amount, and the upwind is determined by performing parabolic approximation on the maximum correlation value peak. On the contrary, since it can be considered that the luminance difference on the leeward side after the deformation moves in the opposite direction, a difference in luminance at the point of interest occurs, so the difference on the leeward side is applied after the deformation.
 変形前の風上差分と変形後の風下差分を用いて2通りの解を求め、それらの平均をとった。さらに、実際には移動量が軸方向に沿わない場合には、変形前や変形後の輝度勾配が注目点と同一軸上に無く、ずれた位置の勾配を求める必要がある。つまり、X方向の勾配を求めたい場合には、Z方向の移動も考慮して勾配を求めなければならない。そのため、輝度の内挿による輝度勾配の推定をすることで、精度向上を図っている。基本的には変形前(もしくは変形後)の位置を予測し、その位置での勾配を内挿により求める。 2) Two solutions were obtained using the windward difference before deformation and the windward difference after deformation, and the average was taken. Furthermore, when the movement amount does not actually follow the axial direction, the luminance gradient before and after the deformation is not on the same axis as the target point, and it is necessary to obtain a gradient at a shifted position. In other words, when it is desired to obtain the gradient in the X direction, the gradient must be obtained in consideration of movement in the Z direction. Therefore, accuracy is improved by estimating the luminance gradient by luminance interpolation. Basically, a position before deformation (or after deformation) is predicted, and a gradient at the position is obtained by interpolation.
 変形前(後)の注目点の位置は放物線近似を施した際のサブピクセル移動量により求める。その注目点位置が囲まれる8つの座標を用い、それらの比によって輝度勾配を算出する。具体的には、下記式(8)を用いる。そのようにして算出された輝度勾配と、輝度変化を用いて最小二乗法を適用し移動量を決定した。
Figure JPOXMLDOC01-appb-M000008
The position of the point of interest before (after) deformation is obtained from the amount of subpixel movement when parabolic approximation is performed. Using the eight coordinates that surround the position of the point of interest, the luminance gradient is calculated from the ratio thereof. Specifically, the following formula (8) is used. The amount of movement was determined by applying the least square method using the luminance gradient thus calculated and the luminance change.
Figure JPOXMLDOC01-appb-M000008
(画像変形法)
 上述した風上勾配法までは検査領域S1の形状は変更せず、正方形を保ったまま変形ベクトルの算出を行っている。しかし、現実には計測対象の変形に合わせて検査領域S1も変形していると考えられるため、検査領域S1の微小変形を考慮したアルゴリズムを導入し、変形ベクトル算出を高精度にて算出する必要がある。このため、本実施例ではサブピクセル精度での変形ベクトルの算出に画像変形法を導入している。すなわち、組織変形前の検査領域S1と組織変形後の伸縮及びせん断変形を考慮した検査領域S1とで相互相関を実施し、相関値ベースの反復計算によってサブピクセル変形量を決定している。なお、検査領域S1の伸縮及びせん断変形は線形で近似している。
(Image transformation method)
Until the windward gradient method described above, the shape of the inspection region S1 is not changed, and the deformation vector is calculated while keeping the square. However, in reality, it is considered that the inspection region S1 is also deformed in accordance with the deformation of the measurement target. Therefore, it is necessary to introduce an algorithm that takes into account the minute deformation of the inspection region S1 and calculate the deformation vector with high accuracy. There is. For this reason, in this embodiment, an image deformation method is introduced to calculate a deformation vector with sub-pixel accuracy. That is, the cross-correlation is performed between the inspection region S1 before the tissue deformation and the inspection region S1 in consideration of the expansion and contraction and shear deformation after the tissue deformation, and the sub-pixel deformation amount is determined by iterative calculation based on the correlation value. Note that the expansion and contraction and the shear deformation of the inspection region S1 are linearly approximated.
 画像変形法は一般的に、材料の表面ひずみ計測法に用いられ、ランダムパターンを塗布した材料表面を高空間分解能なカメラで撮影した画像に対して適用される。一方、OCT断層像はスペックルノイズを多く含むだけでなく、特に生体組織では組織内の基質や水分の流動も伴い屈折率が変化するため、スペックルパターンに対する変形が大きい。このため、複雑組織にて局所的な変形が発生し、検査領域S1に膨張、収縮、剪断等の変形が伴う場合には解の収束解が著しく低下する。本手法における検査領域S1の縮小は、局所的な組織力学特性を検出するために必要不可欠である。そこで画像変形法では、風上勾配法で得られた変形量を収束計算の初期値として採用し、さらに、輝度分布の双三次関数補間によって検査領域S1を縮小した際でも低ロバスト性を実現している。なお、変形例においては、双三次関数補間以外の補間関数を用いてもよい。 The image deformation method is generally used in a material surface strain measurement method, and is applied to an image obtained by photographing a material surface coated with a random pattern with a high spatial resolution camera. On the other hand, the OCT tomogram not only contains a lot of speckle noise, but especially in a living tissue, the refractive index changes with the flow of the substrate and water in the tissue, so the deformation to the speckle pattern is large. For this reason, a local deformation | transformation generate | occur | produces in a complicated structure | tissue, and when the deformation | transformation of expansion | swelling, contraction, shearing, etc. accompanies inspection area | region S1, the convergence solution of a solution will fall remarkably. Reduction of the examination area S1 in this method is indispensable for detecting local tissue mechanical characteristics. Therefore, in the image deformation method, the amount of deformation obtained by the windward gradient method is adopted as the initial value of the convergence calculation, and further, low robustness is realized even when the inspection area S1 is reduced by bicubic function interpolation of the luminance distribution. ing. In the modification, an interpolation function other than bicubic function interpolation may be used.
 より詳細には、以下の手順にて演算を実行する。まず、組織変形前のOCT断層像の輝度分布に双三次関数補間法を適用し、輝度分布の連続化を実施する。双三次関数補間法とは、sinc関数を区分的に三次関数近似した畳み込み関数を用い、輝度情報の空間連続性を再現する手法である。本来は連続的な輝度分布を画像計測する際には光学系に依存した点広がり関数が畳み込まれるため、sinc関数を用いた逆畳み込みを行うことにより、本来の連続的な輝度分布が復元される。離散的な一軸信号f(x)の補間をする場合、畳み込み関数h(x)は下記式(9)にて表される。
Figure JPOXMLDOC01-appb-M000009
More specifically, the calculation is executed according to the following procedure. First, a bicubic function interpolation method is applied to the luminance distribution of the OCT tomogram before tissue deformation, and the luminance distribution is made continuous. The bicubic function interpolation method is a technique for reproducing spatial continuity of luminance information using a convolution function obtained by piecewise approximating a sinc function. Originally, when measuring an image of a continuous luminance distribution, a point spread function depending on the optical system is convolved. Therefore, by performing deconvolution using a sinc function, the original continuous luminance distribution is restored. The When interpolating a discrete uniaxial signal f (x), the convolution function h (x) is expressed by the following equation (9).
Figure JPOXMLDOC01-appb-M000009
 なお、OCT計測条件の違いによって輝度補間関数h(x)の形状も変更する必要がある。そこで輝度補間関数h(x)のx=1での微係数aを可変とし、aの値を変更することで輝度補間関数h(x)の形状を変更可能なアルゴリズムとした。本実施例では、擬似OCT断層像を用いた数値実験による検証結果を元にし、aの値を決定した。以上のように画像補間をすることで、伸縮及びせん断変形を考慮した検査領域S1の各点にて、OCT輝度値を求めることが可能となる。 Note that the shape of the luminance interpolation function h (x) also needs to be changed depending on the OCT measurement conditions. Therefore, the differential coefficient a at x = 1 of the luminance interpolation function h (x) is variable, and the shape of the luminance interpolation function h (x) can be changed by changing the value of a. In the present embodiment, the value of a is determined based on the verification result by the numerical experiment using the pseudo OCT tomogram. By performing the image interpolation as described above, it is possible to obtain the OCT luminance value at each point in the inspection region S1 in consideration of expansion and contraction and shear deformation.
 伸縮及びせん断変形を考慮して算出した検査領域S1は、図4(C)に示すように、移動とともに変形を伴う。組織変形前のOCT断層像におけるある検査領域S1内の整数ピクセル位置での座標(x,z)が組織変形後に座標(x,z)に移動すると考えると、x,zの値は下記式(10)にて表される。
Figure JPOXMLDOC01-appb-M000010
As shown in FIG. 4C, the inspection region S1 calculated in consideration of expansion and contraction and shear deformation is accompanied by deformation as it moves. Assuming that coordinates (x, z) at integer pixel positions in a certain examination region S1 in the OCT tomogram before tissue deformation move to coordinates (x * , z * ) after tissue deformation, the values of x * , z * Is represented by the following formula (10).
Figure JPOXMLDOC01-appb-M000010
 ここで、Δx,Δzはそれぞれ検査領域S1中心から座標x,zまでの距離、u,vはそれぞれx,z方向への変形量、∂u/∂x,∂v/∂zはそれぞれx,z方向における検査領域S1の垂直方向への変形量、∂u/∂z,∂v/∂xはそれぞれx,z方向における検査領域S1のせん断方向への変形量である。数値解法にはNewton-Raphson法を用い、6変数(u,v,∂u/∂x,∂u/∂z,∂v/∂x,∂v/∂z)での相関値微係数が0となるように、すなわち最大相関値を得るように反復計算を行う。なお、反復計算の収束性を高めるため、x,z方向の移動量初期値には風上勾配法で得られたサブピクセル移動量を用いる。相関値Rに対するヘッセ行列をH、相関値対するヤコビベクトルを▽Rとすると、1回の反復で得られる更新量ΔPiは下記式(11)にて表される。
Figure JPOXMLDOC01-appb-M000011
Here, Δx and Δz are distances from the center of the inspection region S1 to the coordinates x and z, u and v are deformation amounts in the x and z directions, respectively, and ∂u / ∂x and ∂v / ∂z are x, respectively. The deformation amount in the vertical direction of the inspection region S1 in the z direction, ∂u / ∂z, and ∂v / ∂x are the deformation amounts in the shear direction of the inspection region S1 in the x and z directions, respectively. The Newton-Raphson method is used for the numerical solution, and the correlation value derivative with 6 variables (u, v, ∂u / ∂x, ∂u / ∂z, ∂v / ∂x, ∂v / ∂z) is 0. That is, iterative calculation is performed so as to obtain the maximum correlation value. In order to improve the convergence of the iterative calculation, the sub-pixel movement amount obtained by the windward gradient method is used as the initial movement amount in the x and z directions. When the Hessian matrix for the correlation value R is H and the Jacobian vector for the correlation value is ▽ R, the update amount ΔPi obtained in one iteration is expressed by the following equation (11).
Figure JPOXMLDOC01-appb-M000011
 収束の判定には、反復計算で随時得られる漸近解が収束解の近傍で十分小さくなることを用いる。しかし、スペックルパターンの変化が激しい領域においては、線形変形では追従できないために正しい収束解が得られない場合がある。その場合、本実施例では風上勾配法によって求めたサブピクセル移動量を採用している。 For convergence judgment, it is used that the asymptotic solution obtained at any time by iterative calculation is sufficiently small in the vicinity of the convergence solution. However, in a region where the speckle pattern changes drastically, a correct convergence solution may not be obtained because it cannot be followed by linear deformation. In this case, the present embodiment employs the sub-pixel movement amount obtained by the windward gradient method.
 以上のようにして得られるサブピクセル精度の変形ベクトルを時間微分することにより、図5(B)に示すような変形速度ベクトル分布を算出することができる。そして、その変形速度ベクトル分布を空間微分することにより、ひずみ速度テンソルを算出することが可能となる。 A deformation velocity vector distribution as shown in FIG. 5B can be calculated by differentiating the deformation vector of subpixel accuracy obtained as described above with respect to time. A strain rate tensor can be calculated by spatially differentiating the deformation rate vector distribution.
(時空間移動最小二乗法)
 ひずみ速度テンソルの算出には移動最小二乗法(Moving Least Square Method:以下「MLSM」という)を用いる。MLSMは、移動量分布を平滑化すると共に、微係数の安定算出を可能とする手法である。MLSMにおいて用いる二乗誤差式は下記式(12)にて表される。
Figure JPOXMLDOC01-appb-M000012
(Time-space moving least squares method)
For the calculation of the strain rate tensor, a moving least square method (hereinafter referred to as “MLSM”) is used. MLSM is a technique that enables smooth calculation of a differential coefficient while smoothing a movement amount distribution. The square error equation used in MLSM is expressed by the following equation (12).
Figure JPOXMLDOC01-appb-M000012
 上記式(12)において、S(x,z,t)を最小とするa~kのパラメータを求める。すなわち、近似関数として水平方向x,奥行き方向z,時間方向tの3変数2次多項式として下記式(13)を採用する。そして、最小二乗近似に基づき、下記式(14)から最適な微係数を算出して平滑化する。
Figure JPOXMLDOC01-appb-M000013
In the above equation (12), parameters a to k that minimize S (x, z, t) are obtained. That is, the following equation (13) is adopted as a three-variable quadratic polynomial in the horizontal direction x, the depth direction z, and the time direction t as an approximation function. Based on the least square approximation, an optimal derivative is calculated from the following equation (14) and smoothed.
Figure JPOXMLDOC01-appb-M000013
 この微係数を用いることにより、下記式(15)に示すひずみ速度テンソルを算出することができる。fx,fzは各軸のひずみ増分を示し、その時間変化量からひずみ速度を算出している。
Figure JPOXMLDOC01-appb-M000014
By using this derivative, the strain rate tensor shown in the following formula (15) can be calculated. fx and fz indicate the strain increment of each axis, and the strain rate is calculated from the amount of change over time.
Figure JPOXMLDOC01-appb-M000014
 次に、上述した各手法を用いて行われる軟骨診断処理について説明する。図6および図7は、軟骨診断処理の処理手順を表す図である。
 本実施例では、上述した各手法を軟骨診断装置1に適用する。図6に示すように、制御演算部6は、上述のようにして演算された変形速度ベクトル分布を順次記憶するとともに(図6(A))、各変形速度ベクトル分布を空間微分して得られたひずみ速度テンソル分布を順次記憶する(図6(B))。なお、ひずみ速度テンソル分布は、図7(A)に示すように、所定範囲ごとに識別可能に断層画像の態様で分布表示することができる。図中においてひずみ速度がマイナスの領域は圧縮領域を示し、プラスの領域は膨張領域を示す。
Next, the cartilage diagnosis process performed using each of the above-described methods will be described. 6 and 7 are diagrams illustrating a processing procedure of the cartilage diagnosis processing.
In this embodiment, the above-described methods are applied to the cartilage diagnostic apparatus 1. As shown in FIG. 6, the control calculation unit 6 sequentially stores the deformation velocity vector distribution calculated as described above (FIG. 6A), and is obtained by spatially differentiating each deformation velocity vector distribution. The strain rate tensor distribution is sequentially stored (FIG. 6B). As shown in FIG. 7A, the strain rate tensor distribution can be displayed in the form of a tomographic image so as to be identifiable for each predetermined range. In the figure, the region where the strain rate is negative indicates the compression region, and the positive region indicates the expansion region.
 そして、断層画像における個々の座標についてのひずみ速度の時間変化を演算すると、図7(B)に示すような演算結果が得られる。同図の横軸は時間の経過を示し、縦軸はひずみ速度を示している。このように演算されたひずみ速度の時間変化に対して平滑化処理を行い、各座標についてひずみ速度の減衰係数を演算すると、図7(C)に示すような減衰係数分布を得ることができる。この減衰係数の断層分布は、後述の実験結果からも分かるように、軟骨組織の損傷度合いの分布に対応するものと評価することができる。そこで、制御演算部6は、この減衰係数の断層分布を軟骨組織の損傷度合いの分布と等価として、表示装置8に断層可視化させる。 Then, when the temporal change in strain rate for each coordinate in the tomographic image is calculated, a calculation result as shown in FIG. 7B is obtained. In the figure, the horizontal axis indicates the passage of time, and the vertical axis indicates the strain rate. When smoothing processing is performed on the time change of the strain rate calculated in this way, and the strain rate attenuation coefficient is calculated for each coordinate, an attenuation coefficient distribution as shown in FIG. 7C can be obtained. This tomographic distribution of the attenuation coefficient can be evaluated as corresponding to the distribution of the degree of damage of the cartilage tissue, as can be seen from the experimental results described later. Therefore, the control calculation unit 6 causes the display device 8 to visualize the tomographic distribution by making the tomographic distribution of the attenuation coefficient equivalent to the distribution of the degree of damage of the cartilage tissue.
 本実施例では、減衰係数の断層分布そのものを軟骨組織の損傷度合い(変性度)として提示する。このため、減衰係数が大きい領域は損傷度(変性度)が大きい領域として示され、減衰係数が小さい領域は損傷度(変性度)が小さい領域として示される。なお、図中のハッチング部はひずみ速度が小さく、正負の値に振れる領域(精度が低い領域)を示し、軟骨診断においては無視することができる。 In this embodiment, the fault distribution of the attenuation coefficient itself is presented as the degree of cartilage tissue damage (degeneration degree). Therefore, a region with a large attenuation coefficient is indicated as a region with a high degree of damage (modification degree), and a region with a low attenuation coefficient is indicated as a region with a low degree of damage (modification degree). In addition, the hatching part in a figure shows the area | region (area | region with low precision) which has a small strain rate and shakes to a positive / negative value, and can be disregarded in cartilage diagnosis.
 次に、減衰係数の断層分布が軟骨組織の損傷度合いの分布に対応することを検証するために行った実験結果について説明する。図8は、実験装置の構成を概略的に表す図である。図9は、実験に用いた試験片を表す図である。図10は、実験に際して試験片に与えた荷重負荷状態を示すグラフである。なお、図8において、図1に示すものと同様の構成については同一の符号を付している。 Next, the results of experiments conducted to verify that the fault distribution of the attenuation coefficient corresponds to the distribution of the degree of damage of the cartilage tissue will be described. FIG. 8 is a diagram schematically illustrating the configuration of the experimental apparatus. FIG. 9 is a diagram illustrating a test piece used in the experiment. FIG. 10 is a graph showing a state of a load applied to the test piece during the experiment. In FIG. 8, the same components as those shown in FIG.
 図8に示すように、本実験装置は、図1に示した光学ユニット2に対して圧縮試験機70を接続して構成される。圧縮試験機70は、図1に示したプローブ4に代わり、試験片Wに対して圧縮荷重を負荷するものである。試験片Wとしては、ブタの膝関節の軟骨を用いている。圧縮試験機70は、試験片Wに接触するガラス窓72、ガラス窓72との間に試験片Wを挟む金属圧子74、金属圧子74を軸線方向に駆動するためのリニアアクチュエータ76、試験片Wに負荷される荷重を検出するロードセル78等を備えている。 As shown in FIG. 8, this experimental apparatus is configured by connecting a compression tester 70 to the optical unit 2 shown in FIG. The compression tester 70 applies a compressive load to the test piece W instead of the probe 4 shown in FIG. As the test piece W, cartilage of the knee joint of a pig is used. The compression tester 70 includes a glass window 72 that contacts the test piece W, a metal indenter 74 that sandwiches the test piece W between the glass window 72, a linear actuator 76 that drives the metal indenter 74 in the axial direction, and the test piece W. The load cell 78 etc. which detect the load loaded on is provided.
 本実験では、制御演算部6を2台のパーソナルコンピュータ80,82にて構成し、その一方により光学ユニット2の駆動およびOCTの演算処理を実行し、他方により圧縮試験機70を駆動した。オブジェクトアーム12には、試験用プローブ84が接続されている。試験用プローブ84は、図1に示したプローブ4に代わり、物体光を試験片Wに向けて走査可能な光学機構を備えている。 In this experiment, the control arithmetic unit 6 is composed of two personal computers 80 and 82, one of which drives the optical unit 2 and OCT arithmetic processing, and the other drives the compression tester 70. A test probe 84 is connected to the object arm 12. The test probe 84 includes an optical mechanism capable of scanning the object light toward the test piece W instead of the probe 4 shown in FIG.
 図9(A)は圧縮試験機70への試験片Wの設置態様を示し、図9(B)は試験片Wの側面視およびその大きさを示し、図9(C)は試験片Wの正面視およびその大きさを示している。試験片Wとして、生後約6ヶ月のブタの膝関節大腿骨外側顆の軟骨組織サンプルを直径5.5mmの円筒形状にて採取した。また、変性軟骨の力学特性を診断評価するため、酵素処理により模擬変性軟骨を作製し、正常軟骨との比較を行った。酵素処理には、関節軟骨の弾性を保っているコラーゲン線維を分解するcollagenase type2(C6885,Sigma Ardrich)を用いた。pH7.4のリン酸緩衝生理食塩水(10010,Invitrogen)にcollagenaseを溶解させて作製した30[unit/ml]のcollagenase溶液に正常関節軟骨を入れ,37[℃]の状態下で0.5時間,1時間,2時間の時間設定で処理を施し,コラーゲン線維変性をOA変性度として模擬している。 9A shows an installation mode of the test piece W to the compression tester 70, FIG. 9B shows a side view and the size of the test piece W, and FIG. The front view and its size are shown. As a test piece W, a cartilage tissue sample of a femoral condyle of a knee joint of a pig about 6 months old was collected in a cylindrical shape having a diameter of 5.5 mm. In addition, in order to diagnose and evaluate the mechanical properties of degenerated cartilage, simulated degenerated cartilage was prepared by enzyme treatment and compared with normal cartilage. For the enzyme treatment, collagenase type 2 (C6885, Sigma Ardrich) that degrades collagen fibers maintaining the elasticity of articular cartilage was used. Normal articular cartilage is placed in 30 [unit / ml] collagenase solution prepared by dissolving collagenase in phosphate buffered saline (10010, Invitrogen) at pH 7.4, and 0.5 [37] at 37 [° C.]. The treatment is performed with a time setting of 1 hour, 2 hours, and collagen fiber degeneration is simulated as the degree of OA degeneration.
 図8に戻り、本実験では、試験片Wの下骨側を金属圧子74に固定し、圧縮試験機70内に設置したガラス窓72に押し当て、軟骨組織に圧縮変形を発生させた。ガラス窓72を介してOCTビームを打ち込むことで応力緩和試験中のOCT断層画像を27.03[flame/sec]にて連続取得した。この圧縮実験では、圧縮量を10[%]ひずみ、圧縮速度を0.1[%/sec]として固定した。圧縮荷重負荷時間は100[sec]となり、10[%]ひずみに達した後は応力緩和時の軟骨組織挙動の観察を行った。また、再帰的相互相関法の設定は検査領域を9[pixel]から5[pixel]に縮小する2階層の設定とし、6.5×15.62[μm]毎のベクトル密度にてサブピクセル精度の変形速度ベクトル分布を算出した。 Returning to FIG. 8, in this experiment, the lower bone side of the test piece W was fixed to the metal indenter 74 and pressed against the glass window 72 installed in the compression tester 70 to cause compression deformation in the cartilage tissue. An OCT tomographic image during the stress relaxation test was continuously acquired at 27.03 [flame / sec] by implanting an OCT beam through the glass window 72. In this compression experiment, the compression amount was fixed at 10 [%] strain, and the compression speed was fixed at 0.1 [% / sec]. The compression load loading time was 100 [sec], and after reaching 10 [%] strain, the behavior of the cartilage tissue during stress relaxation was observed. In addition, the recursive cross-correlation method is set to two layers for reducing the inspection area from 9 [pixel] to 5 [pixel], and the subpixel accuracy is set at a vector density of 6.5 × 15.62 [μm]. The deformation velocity vector distribution of was calculated.
 図10は、この応力緩和試験においてロードセル78にて検出された応力時系列データを示す。同図の横軸は荷重負荷開始からの時間[sec]を示し、縦軸は圧縮応力[MPa]を示している。図示のように、圧縮中(0~100秒)では応力が増加し、圧縮終了(100秒)以降は応力緩和が発生している。そして、1200秒付近で平衡状態に達することが観察された。なお、このように応力が指数関数的に減衰していることから、軟骨はその緩和弾性率が時間変化する粘弾性体であることが分かる。 FIG. 10 shows stress time series data detected by the load cell 78 in this stress relaxation test. In the figure, the horizontal axis indicates time [sec] from the start of load application, and the vertical axis indicates compressive stress [MPa]. As shown in the figure, the stress increases during compression (0 to 100 seconds), and stress relaxation occurs after the end of compression (100 seconds). It was observed that an equilibrium state was reached around 1200 seconds. In addition, since the stress is attenuated exponentially in this way, it is understood that the cartilage is a viscoelastic body whose relaxation elastic modulus changes with time.
 図11および図12は、応力緩和試験によるひずみ速度分布の時間変化を断層可視化した図である。図11は正常軟骨についての演算結果を示し、(A)は荷重負荷開始から0.31[sec]、(B)は50.35[sec]、(C)は100.29[sec]、(D)は101.96[sec]、(E)は110.95[sec]、(F)は120.12[sec]、(G)は130.52[sec]、(H)は140.51[sec]、(I)は150.49[sec]の結果を示している。 FIG. 11 and FIG. 12 are diagrams in which a change in strain rate distribution over time by a stress relaxation test is visualized as a fault. FIG. 11 shows the calculation results for normal cartilage, (A) is 0.31 [sec] from the start of loading, (B) is 50.35 [sec], (C) is 100.29 [sec], ( D) is 101.96 [sec], (E) is 110.95 [sec], (F) is 120.12 [sec], (G) is 130.52 [sec], and (H) is 140.51. [sec] and (I) show the result of 150.49 [sec].
 一方、図12は模擬変性軟骨についての演算結果を示し、(A)は荷重負荷開始から1.07[sec]、(B)は50.07[sec]、(C)は100.99[sec]、(D)は101.99[sec]、(E)は110.98[sec]、(F)は120.97[sec]、(G)は130.96[sec]、(H)は140.95[sec]、(I)は150.94[sec]の結果を示している。すなわち、各図の(A)および(B)は圧縮中を示し、(C)~(I)は応力緩和中を示している(図10参照)。 On the other hand, FIG. 12 shows the calculation results for the simulated degenerated cartilage, (A) is 1.07 [sec] from the start of loading, (B) is 50.07 [sec], and (C) is 100.99 [sec]. ], (D) is 101.99 [sec], (E) is 110.98 [sec], (F) is 120.97 [sec], (G) is 130.96 [sec], (H) is 140.95 [sec], (I) shows the result of 150.94 [sec]. That is, (A) and (B) in each figure indicate that compression is in progress, and (C) to (I) indicate that stress is being relaxed (see FIG. 10).
 図11および図12から、試験片Wの表層において大きな圧縮ひずみ速度が発生していることが確認できる。この領域は軟骨の表層領域(表面から15%)に対応し、変形速度ベクトルが急激に変化する領域と対応している。一方、軟骨表面から15~70%は中間層領域と呼ばれ、検出されたひずみ速度は小さく、変形速度ベクトルの急激な変化が見られない領域と対応している。コラーゲン線維の配向特性は、表層と中間層において大きく異なっていることが知られている。特に、表層では軟骨表面に水平配向しているため圧縮方向に対する剛性が低く、圧縮ひずみ速度の集中が発生したと考えられる。 11 and 12, it can be confirmed that a large compressive strain rate is generated in the surface layer of the test piece W. This region corresponds to the surface layer region (15% from the surface) of the cartilage, and corresponds to the region where the deformation rate vector changes rapidly. On the other hand, 15 to 70% from the cartilage surface is called an intermediate layer region and corresponds to a region where the detected strain rate is small and a rapid change in the deformation rate vector is not observed. It is known that the orientation characteristics of collagen fibers are greatly different between the surface layer and the intermediate layer. In particular, since the surface layer is horizontally oriented on the cartilage surface, the rigidity in the compression direction is low, and it is considered that the concentration of the compressive strain rate occurred.
 また、図11と図12とを対比すると、正常軟骨では150.49[sec]でもひずみ速度の残存が確認できるのに対し、模擬変性軟骨では130.96[sec]でほとんどひずみ速度が見られないことがわかる.したがって、緩和時間に着目し比較することで関節軟骨の変性の度合いを評価することが可能であることが分かる。このことから、ひずみ速度の経時変化から算出される減衰係数の比較によって軟骨変性度を評価できると考えられる。本実施例ではこの点に着目し、図7に示したように、ひずみ速度テンソル分布から減衰係数の分布を算出している。すなわち、ひずみ速度の減衰係数の断層分布を、軟骨組織の損傷度合いの分布と等価として画面に断層可視化することで、軟骨診断が可能となるようにした。 Further, when FIG. 11 and FIG. 12 are compared, the remaining strain rate can be confirmed even at 150.49 [sec] in normal cartilage, whereas the strain rate is almost observed at 130.96 [sec] in simulated degenerated cartilage. You can see that there is no. Therefore, it can be seen that the degree of degeneration of articular cartilage can be evaluated by focusing on the relaxation time and comparing. From this, it is considered that the degree of cartilage degeneration can be evaluated by comparing the attenuation coefficient calculated from the change in strain rate with time. In this embodiment, paying attention to this point, as shown in FIG. 7, the distribution of the attenuation coefficient is calculated from the strain rate tensor distribution. That is, the tomographic distribution of the strain rate attenuation coefficient is visualized on the screen as the equivalent of the distribution of the damage degree of the cartilage tissue, thereby enabling cartilage diagnosis.
 図13は、正常軟骨と模擬変性軟骨の減衰係数の比較を表す図である。図中の横軸は酵素処理時間(H:hour)を示し、縦軸が減衰係数を示す。酵素処理時間として0H,0.5H,1H,2Hの結果が示されている。なお、0Hは酵素処理時間がゼロ、つまり正常軟骨を示している。図示の結果は、表層領域部分における減衰係数分布を空間平均したものであり、応力緩和開始から50秒までの緩和挙動に対して対数化処理が施されている。 FIG. 13 is a view showing a comparison of attenuation coefficients of normal cartilage and simulated degenerated cartilage. The horizontal axis in the figure indicates the enzyme treatment time (H: hour), and the vertical axis indicates the attenuation coefficient. The results of 0H, 0.5H, 1H, and 2H are shown as the enzyme treatment time. Note that 0H indicates zero enzyme treatment time, that is, normal cartilage. The result shown is a spatial average of the attenuation coefficient distribution in the surface layer region, and a logarithmic process is applied to the relaxation behavior from the start of stress relaxation to 50 seconds.
 図示の結果より、酵素処理時間が長くなるにつれて、減衰係数が大きくなっていることが分かる。コラゲナーゼ酵素処理では、弾性を支配するコラーゲン線維の分解に伴い、粘性を支配するプロテオグリカンの離脱も発生する。このため、コラーゲン線維分解による多孔度の増大に加え、プロテオグリカン離脱による保水特性の低下によって、透水特性が著しく上昇し粘性特性が損なわれると考えられる。透水特性の増大は粘性による荷重支持機構の破綻を意味することから、図示のように緩和弾性係数の減衰係数が低下すると考えられる。そして図示のように、正常軟骨に対していずれの酵素処理時間の結果においても有意差があり、変性の検出が可能であった。本実験で用いた模擬変性軟骨試料は正常軟骨と比べ、外見上は変化がなくレントゲンやCTでの目視診断では判断できない程度の変性である。したがって、従来診断できなかった初期の変形性膝関節症の診断が、本手法により可能となることが分かる。 From the results shown in the figure, it can be seen that the attenuation coefficient increases as the enzyme treatment time increases. In collagenase enzyme treatment, with the degradation of collagen fibers that govern elasticity, the proteoglycans that govern viscosity also occur. For this reason, in addition to the increase in porosity due to collagen fiber degradation, the water retention property is significantly increased due to the decrease in water retention property due to proteoglycan detachment, and the viscosity property is considered to be impaired. Since the increase in water permeability means failure of the load support mechanism due to viscosity, it is considered that the damping coefficient of the relaxation elastic coefficient decreases as shown in the figure. As shown in the figure, there was a significant difference in the results of any enzyme treatment time with respect to normal cartilage, and it was possible to detect degeneration. The simulated degenerated cartilage sample used in this experiment has no change in appearance as compared with normal cartilage, and is denatured to the extent that it cannot be judged by visual diagnosis with X-rays or CT. Therefore, it can be seen that the present method can diagnose early knee osteoarthritis that could not be diagnosed.
 次に、制御演算部6が実行する具体的処理の流れについて説明する。
 図14は、制御演算部6により実行される軟骨診断処理の流れを示すフローチャートである。なお、この軟骨診断処理は、医師等によりプローブ4の先端部が患者の膝関節に挿入された状態にて開始される。制御演算部6は、駆動部38を駆動して図10に示した応力負荷および応力緩和処理を実行する一方で、図14に示す処理を実行する。
Next, the flow of specific processing executed by the control calculation unit 6 will be described.
FIG. 14 is a flowchart showing a flow of cartilage diagnosis processing executed by the control calculation unit 6. This cartilage diagnosis process is started in a state where the tip of the probe 4 is inserted into the patient's knee joint by a doctor or the like. The control calculation unit 6 drives the drive unit 38 to execute the stress load and stress relaxation processing shown in FIG. 10, while executing the processing shown in FIG.
 すなわち、制御演算部6は、連続撮影された時刻の異なる前後2枚のOCT断層画像I(x,z,t)とI(x,z,t+Δt)を読み込む(S10)。続いて、再帰的相互相関法による処理を実行する。ここではまず、最小解像度(最大サイズの検査領域)での相互相関処理を実行し、相関係数分布を求める(S12)。続いて、隣接相互相関乗法により、隣接する相関係数分布の積を演算する(S14)。このとき、標準偏差フィルタ等の空間フィルタにより過誤ベクトルの除去をし(S16)、最小二乗法等により除去ベクトルの内挿補間を実行する(S18)。続いて、検査領域を小さくすることによって解像度を上げて相互相関処理を継続する(S20)。すなわち、低解像度での参照ベクトルを基に相互相関処理を実行する。このときの解像度が予め定める最高解像度でなければ(S22のN)、S14に戻る。 That is, the control calculation unit 6 reads two consecutive OCT tomographic images I (x, z, t) and I (x, z, t + Δt) taken at different times (S10). Subsequently, processing by a recursive cross correlation method is executed. Here, first, a cross-correlation process is executed at the minimum resolution (inspection area of the maximum size) to obtain a correlation coefficient distribution (S12). Subsequently, a product of adjacent correlation coefficient distributions is calculated by the adjacent cross correlation multiplication method (S14). At this time, error vectors are removed by a spatial filter such as a standard deviation filter (S16), and interpolation of the removal vectors is executed by a least square method or the like (S18). Subsequently, the cross correlation process is continued by increasing the resolution by reducing the inspection area (S20). That is, the cross-correlation process is executed based on the reference vector at the low resolution. If the resolution at this time is not the predetermined maximum resolution (N in S22), the process returns to S14.
 そして、S14~S20の処理を繰り返し、最高解像度での相互相関処理が完了すると(S22のY)、サブピクセル解析を実行する。すなわち、最高解像度(最小サイズの検査領域)での変形ベクトルの分布に基づき、風上勾配法によるサブピクセル移動量を演算する(S24)。そして、このとき算出されたサブピクセル移動量に基づき、画像変形法によるサブピクセル変形量を演算する(S26)。続いて、最大相互相関値によるフィルタ処理により過誤ベクトルの除去をし(S28)、最小二乗法等により除去ベクトルの内挿補間を実行する(S30)。そして、このようにして得られた変形ベクトルの時間微分を行い、その断層画像について変形速度ベクトルの断層分布U(x,z,t),W(x,z,t)を算出し、S10に戻る。ここで、U(x,z,t)は変形速度ベクトル分布のz方向成分であり、W(x,z,t)は変形速度ベクトル分布のx方向成分である。以上の処理を後続の断層画像についても実行する(S34のN)。そして、設定数の断層画像について変形ベクトルの断層分布が求まると(S34のY)、軟骨診断のための変性度合い演算提示処理を実行する(S36)。 Then, the processing of S14 to S20 is repeated, and when the cross-correlation processing at the highest resolution is completed (Y in S22), sub-pixel analysis is executed. That is, based on the distribution of the deformation vector at the maximum resolution (the inspection area of the minimum size), the subpixel movement amount by the windward gradient method is calculated (S24). Based on the sub-pixel movement amount calculated at this time, the sub-pixel deformation amount by the image deformation method is calculated (S26). Subsequently, the error vector is removed by filtering using the maximum cross-correlation value (S28), and interpolation of the removal vector is executed by the least square method or the like (S30). Then, time differentiation of the deformation vector obtained in this way is performed, and the tomographic distribution U (x, z, t), W (x, z, t) of the deformation velocity vector is calculated for the tomographic image, and the process goes to S10. Return. Here, U (x, z, t) is the z-direction component of the deformation velocity vector distribution, and W (x, z, t) is the x-direction component of the deformation velocity vector distribution. The above processing is also executed for subsequent tomographic images (N in S34). Then, when the tomographic distribution of the deformation vector is obtained for the set number of tomographic images (Y in S34), a modification degree calculation presenting process for cartilage diagnosis is executed (S36).
 図15は、図14におけるS36の変性度合い演算提示処理を詳細に示すフローチャートである。変性度合い演算提示処理において、制御演算部6は、時空間移動最小二乗法により、S34にて算出した変形速度ベクトル分布の平滑化を実行する(S40)。そして、その平滑化された変形速度ベクトルに対して空間微分をすることにより、ひずみ速度テンソルを算出する(S42)。そして、ひずみ速度の時系列データについて対数変換を行い(S44)、最小二乗法によりひずみ速度の減衰係数を演算する(S46)。このようにして得られた減衰係数の分布を軟骨組織の損傷度合いと等価とみなして表示装置8に断層可視化する(S48)。すなわち、例えば図7(C)に示した態様にて軟骨の変性度を提示する。 FIG. 15 is a flowchart showing in detail the modification degree calculation presenting process of S36 in FIG. In the modification degree calculation presenting process, the control calculation unit 6 executes the smoothing of the deformation velocity vector distribution calculated in S34 by the spatiotemporal movement least square method (S40). Then, a strain rate tensor is calculated by performing spatial differentiation on the smoothed deformation rate vector (S42). Then, logarithmic transformation is performed on the strain rate time-series data (S44), and the strain rate attenuation coefficient is calculated by the least square method (S46). The distribution of the attenuation coefficient obtained in this way is regarded as equivalent to the degree of cartilage tissue damage, and a tomographic visualization is made on the display device 8 (S48). That is, for example, the degree of cartilage degeneration is presented in the manner shown in FIG.
 以上に説明したように、本実施例によれば、応力緩和によるひずみ速度の変化(減衰係数)と、軟骨組織の損傷度合いとの間に対応関係があることを利用した演算処理により、診断対象である軟骨の損傷度合いが断層可視化される。このため、医師等がその断層可視化された画像を確認することにより、軟骨診断を容易に行うことが可能となる。すなわち、OCTを用いた軟骨診断をより実用に供し得るものとすることができる。 As described above, according to the present embodiment, a diagnosis target is obtained by an arithmetic process using the correspondence between the strain rate change (attenuation coefficient) due to stress relaxation and the degree of cartilage tissue damage. The degree of cartilage damage is visualized as a tomogram. For this reason, it becomes possible for a doctor or the like to easily perform cartilage diagnosis by confirming the image visualized by the tomography. That is, cartilage diagnosis using OCT can be more practically used.
[第2実施例]
 次に、本発明の第2実施例について説明する。本実施例は、応力負荷方法として応力緩和法ではなく、動的粘弾性法を適用した点が異なる以外は第1実施例とほぼ同様である。このため、上記第1実施例と同様の構成部分については必要に応じて同一の符号を付す等して適宜その説明を省略する。
[Second Embodiment]
Next, a second embodiment of the present invention will be described. The present embodiment is almost the same as the first embodiment except that a dynamic viscoelasticity method is applied instead of the stress relaxation method as a stress loading method. For this reason, the same components as those in the first embodiment are denoted by the same reference numerals as necessary, and the description thereof is omitted as appropriate.
 本実施例では、図1および図2に示したプローブ4により所定の振動荷重(動的力、動的荷重)を発生させる。すなわち、プローブ4への通電により、圧電素子52が所定の加振周波数にて振動し、軟骨Jに対して振動荷重を付与する。それにより、軟骨Jの動的粘弾性を評価し、その損傷度合い(変性度)を断層可視化する。 In this embodiment, a predetermined vibration load (dynamic force, dynamic load) is generated by the probe 4 shown in FIGS. That is, when the probe 4 is energized, the piezoelectric element 52 vibrates at a predetermined excitation frequency, and a vibration load is applied to the cartilage J. Thereby, the dynamic viscoelasticity of the cartilage J is evaluated, and the degree of damage (degree of degeneration) is visualized as a tomogram.
 図16は、第2実施例に係る変性度合い演算提示処理を詳細に示すフローチャートである。この処理は、第1実施例の図15に示した処理に置き換えて実行される。制御演算部6は、駆動部38を駆動して軟骨Jに動的荷重(動的力、振動荷重)を付与する一方で、図14および図16に示す処理を実行する。 FIG. 16 is a flowchart showing in detail the modification degree calculation presenting process according to the second embodiment. This process is executed in place of the process shown in FIG. 15 of the first embodiment. The control calculation unit 6 drives the drive unit 38 to apply a dynamic load (dynamic force, vibration load) to the cartilage J, while executing the processing shown in FIGS. 14 and 16.
 なお、本実施例では、図14に示すS24の処理において、上記式(7)に代えて、下記式(16)を用いた輝度分布の定式化を行う。
  δf/δt=δf/δx・Δx+δf/δy・Δy+δf/δz・Δz ・・・(16)
In this embodiment, in the process of S24 shown in FIG. 14, the luminance distribution is formulated using the following equation (16) instead of the above equation (7).
δf / δt = δf / δx · Δx + δf / δy · Δy + δf / δz · Δz (16)
 そして図16に示すように、変性度合い演算提示処理において、制御演算部6は、時空間移動最小二乗法により、S34にて算出した変形速度ベクトル分布の平滑化を実行する(S240)。そして、その平滑化された変形速度ベクトルに対してフーリエ変換を行う(S242)。それにより、変形速度ベクトルにおいてプローブ4の加振周波数ωに同期する成分のみを抽出するバンドパス・フィルタ処理を実行する(S244)。その後、フーリエ逆変換により、加振周波数成分の変形速度ベクトルUω(x,z,t),Wω(x,z,t)の断層分布を演算する(S246)。ここで、Uω(x,z,t)は変形速度ベクトルのz方向成分であり、Wω(x,z,t)は変形速度ベクトルのx方向成分である。Wω(x,z,t)は、例えば下記式(17)の形で表すことができる。
  Wω(x,z,t)=Aω(x,z)sin(ωt+Φω(x,z)) ・・・(17)
Then, as shown in FIG. 16, in the modification degree calculation presenting process, the control calculation unit 6 executes the smoothing of the deformation velocity vector distribution calculated in S34 by the spatio-temporal moving least square method (S240). Then, Fourier transformation is performed on the smoothed deformation velocity vector (S242). As a result, a bandpass filter process for extracting only the component synchronized with the excitation frequency ω of the probe 4 in the deformation velocity vector is executed (S244). Thereafter, the fault distribution of the deformation velocity vectors U ω (x, z, t) and W ω (x, z, t) of the excitation frequency component is calculated by inverse Fourier transform (S246). Here, U ω (x, z, t) is the z-direction component of the deformation speed vector, and W ω (x, z, t) is the x-direction component of the deformation speed vector. W ω (x, z, t) can be expressed, for example, in the form of the following formula (17).
W ω (x, z, t ) = A ω (x, z) sin (ωt + Φ ω (x, z)) ··· (17)
 続いて、圧電素子52の変位情報から、加振周波数成分に係る変形速度ベクトルの規格化振幅A'ω(x,z)と位相差Φω(x,z)の断層分布を算出する(S248)。ここで、規格化振幅A'ω(x,z)は、振幅Aω(x,z)を圧電素子52の変位情報Wpzt(t)=Apztsin(ωt)の振幅Apztにて除算することにより得られる。なお、変形例においては、規格化振幅A'ω(x,z)および位相差Φω(x,z)を最小二乗法により直接算出してもよい。 Subsequently, the tomographic distribution of the normalized amplitude A ′ ω (x, z) and the phase difference Φ ω (x, z) of the deformation velocity vector related to the excitation frequency component is calculated from the displacement information of the piezoelectric element 52 (S248). ). Here, the normalized amplitude A ′ ω (x, z) is obtained by dividing the amplitude A ω (x, z) by the amplitude A pzt of the displacement information W pzt (t) = A pzt sin (ωt) of the piezoelectric element 52. Can be obtained. In the modification, the normalized amplitude A ′ ω (x, z) and the phase difference Φ ω (x, z) may be directly calculated by the least square method.
 続いて、規格化振幅A'ω(x,z)および位相差Φω(x,z)の少なくとも一方の断層分布に基づいて軟骨の動的粘弾性を演算する(S250)。そして、演算された動的粘弾性に基づいて軟骨組織の損傷度合いを断層可視化する(S48)。 Subsequently, the dynamic viscoelasticity of the cartilage is calculated based on at least one tomographic distribution of the normalized amplitude A ′ ω (x, z) and the phase difference Φ ω (x, z) (S250). Then, based on the calculated dynamic viscoelasticity, the damage degree of the cartilage tissue is visualized as a tomogram (S48).
 なお、この動的粘弾性の評価法については種々考えられる。規格化振幅A'ω(x,z)の断層分布に基づいて粘弾性評価を行う場合、以下のように評価できる。すなわち、規格化振幅A'ω(x,z)が大きい箇所は動的粘弾性率が小さくなる。すなわち、規格化振幅A'ω(x,z)は、軟骨において奥行き方向の剛性が低い表層では相対的に大きくなり、中層では相対的に小さくなる。軟骨の変性が進行すると、表層の奥行き方向の剛性がさらに低くなるため、規格化振幅A'ω(x,z)はさらに大きくなると考えられる。 Various methods for evaluating the dynamic viscoelasticity can be considered. When the viscoelasticity evaluation is performed based on the fault distribution of the normalized amplitude A ′ ω (x, z), it can be evaluated as follows. That is, the dynamic viscoelastic modulus becomes small at a location where the normalized amplitude A ′ ω (x, z) is large. That is, the normalized amplitude A ′ ω (x, z) is relatively large in the surface layer where the rigidity in the depth direction of the cartilage is low, and relatively small in the middle layer. As the cartilage degeneration progresses, the rigidity in the depth direction of the surface layer is further reduced, and thus the normalized amplitude A ′ ω (x, z) is considered to be further increased.
 位相差Φω(x,z)の断層分布に基づいて粘弾性評価を行う場合には、位相接続処理(アンラッピング処理)を施してもよい。この場合、以下のように評価できる。すなわち、奥行き方向の位相差Φω(x,z)は、軟骨の表面ではゼロであり、表層ではその表層の粘弾性効果により深部に向かうにしたがって徐々に大きくなる。つまり、位相が遅れていく。変性軟骨では、表層の粘性特性が損なわれるため、奥行き方向の位相差Φω(x,z)が小さくなる(つまり弾性挙動を示すようになる)。 When viscoelasticity evaluation is performed based on the fault distribution of the phase difference Φ ω (x, z), phase connection processing (unwrapping processing) may be performed. In this case, it can be evaluated as follows. That is, the phase difference Φ ω (x, z) in the depth direction is zero on the surface of the cartilage, and gradually increases on the surface layer toward the deep part due to the viscoelastic effect of the surface layer. That is, the phase is delayed. In denatured cartilage, the viscosity characteristics of the surface layer are impaired, so that the phase difference Φ ω (x, z) in the depth direction becomes small (that is, it exhibits elastic behavior).
 位相差Φω(x,z)の空間微分(∂Φω/∂z)の大きさにより変性度を診断することもできる。∂Φω/∂zが大きい箇所は変性度が低く(つまり正常)、∂Φω/∂zが小さい箇所は変性度が高いといえる(つまり粘性効果が損なわれている)。このような知見のもと、軟骨組織の損傷度合いを断層可視化することができる。 The degree of degeneration can also be diagnosed by the magnitude of the spatial differential (∂Φ ω / ∂z) of the phase difference Φ ω (x, z). A portion where ∂Φ ω / ∂z is large has a low degree of modification (that is, normal), and a portion where ∂Φ ω / ∂z is small is said to have a high degree of modification (that is, the viscosity effect is impaired). Based on such knowledge, it is possible to visualize the degree of damage to the cartilage tissue.
 以上、本発明の好適な実施例について説明したが、本発明はその特定の実施例に限定されるものではなく、本発明の技術思想の範囲内で種々の変形が可能であることはいうまでもない。 The preferred embodiments of the present invention have been described above, but the present invention is not limited to the specific embodiments, and various modifications can be made within the scope of the technical idea of the present invention. Nor.
 上記第1実施例では、ひずみ速度の減衰係数を演算し、軟骨の損傷度合いと等価として断層可視化する例を示した。変形例においては、変形速度の減衰係数を演算し、軟骨の損傷度合いと等価として断層可視化してもよい。 In the first embodiment, an example is shown in which the attenuation coefficient of the strain rate is calculated and the tomographic visualization is equivalent to the degree of cartilage damage. In the modified example, the deformation rate attenuation coefficient may be calculated, and the tomographic visualization may be made equivalent to the degree of cartilage damage.
 上記第2実施例では、規格化振幅A'ω(x,z)と位相差Φω(x,z)から粘弾性評価を行う例を示したが、これら規格化振幅A'ω(x,z)および位相差Φω(x,z)から粘弾性物理量を表現する値を新たに定義し、それに基づいて粘弾性評価を行ってもよい。 In the second embodiment, the example in which the viscoelasticity is evaluated from the normalized amplitude A ′ ω (x, z) and the phase difference Φ ω (x, z) has been shown. However, the normalized amplitude A ′ ω (x, z A value expressing a viscoelastic physical quantity may be newly defined from z) and the phase difference Φ ω (x, z), and viscoelasticity evaluation may be performed based on the value.
 上記第2実施例では、図16に示した変性度合い演算提示処理において、変形速度ベクトルの断層分布に基づいて軟骨の粘弾性を評価することとした。変形例においては、ひずみ速度テンソルの断層分布を演算し、それに基づいて同様に軟骨の粘弾性を評価し、断層可視化してもよい。このひずみ速度テンソルは、変形速度ベクトルを空間微分することにより算出することができる。 In the second embodiment, the viscoelasticity of the cartilage is evaluated based on the tomographic distribution of the deformation velocity vector in the modification degree calculation presenting process shown in FIG. In the modified example, the tomographic distribution of the strain rate tensor may be calculated, and the viscoelasticity of the cartilage may be similarly evaluated based on the calculated tomographic distribution. This strain rate tensor can be calculated by spatially differentiating the deformation rate vector.
 上記第2実施例では明示しなかったが、プローブ4にロードセルなどのセンサを取り付け、軟骨に付与する荷重を計測できる構成としてもよい。これにより、軟骨組織の複素弾性率(貯蔵弾性率、損失弾性率、複素粘性率等)を算出することができ、規格化振幅A'ω(x,z)と位相差Φω(x,z)から粘弾性評価をするための物理量を定義し易くなる。 Although not clearly shown in the second embodiment, a sensor such as a load cell may be attached to the probe 4 to measure the load applied to the cartilage. Thereby, the complex elastic modulus (storage elastic modulus, loss elastic modulus, complex viscosity, etc.) of the cartilage tissue can be calculated, and the normalized amplitude A ′ ω (x, z) and the phase difference Φ ω (x, z ) Makes it easy to define physical quantities for evaluating viscoelasticity.
 上記実施例では述べなかったが、「力学特徴量」として、ひずみ速度の振幅値やひずみ速度の時間遅れ(位相遅れ)を採用してもよい。すなわち、上述した動的粘弾性法を例に挙げると、応力の負荷および緩和を繰り返す過程でひずみ速度が正の値と負の値を行き来するように変動する。この負荷の変動に追従するように、ひずみ速度も変動するようになる。この点につき、その負荷変動に対する、ひずみ速度の変動の大きさ(振幅値)とひずみ速度変動の追従性(応答性)が、軟骨の損傷度合いに対応して変化する傾向がある。具体的には、軟骨の損傷度合いが進むほど、ひずみ速度の振幅値は大きくなり、時間遅れ(位相遅れ)は小さくなる傾向にある。そこで、そのひずみ速度の振幅値や時間遅れ(位相遅れ)について断層分布を演算してもよい。その振幅や時間遅れ(位相遅れ)の断層分布を、軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。 Although not described in the above embodiment, an amplitude value of strain rate and a time delay (phase delay) of strain rate may be adopted as the “mechanical feature amount”. In other words, taking the dynamic viscoelastic method described above as an example, the strain rate fluctuates between a positive value and a negative value in the process of repeatedly applying and relaxing stress. The strain rate also varies so as to follow the variation of the load. In this regard, the magnitude (amplitude value) of the strain rate fluctuation and the followability (responsiveness) of the strain rate fluctuation to the load fluctuation tend to change corresponding to the degree of cartilage damage. Specifically, as the degree of cartilage damage progresses, the amplitude value of the strain rate increases and the time delay (phase delay) tends to decrease. Therefore, the fault distribution may be calculated with respect to the amplitude value of the strain rate and the time delay (phase delay). The fault distribution with the amplitude or time delay (phase delay) may be visualized as equivalent to the distribution of the damage degree of the cartilage tissue.
 あるいは、「力学特徴量」として、ひずみ速度の周期的な変動の中央値を採用してもよい。すなわち、上述した動的粘弾性法を例に挙げると、応力の負荷および緩和を繰り返す過程でひずみ速度が正の値と負の値を行き来するように変動する。そのひずみ速度の変動の中心は、粘性力と弾性力との釣り合いから、ゼロからややずれる傾向がある。そして、そのずれ量が、軟骨の損傷度合いに対応して変化する傾向がある。そこで、ひずみ速度の変動中心(中央値)のゼロからのずれ量について断層分布を演算してもよい。そのずれ量の断層分布を、軟骨組織の損傷度合いの分布と等価として断層可視化させてもよい。 Alternatively, the median value of the periodic fluctuation of the strain rate may be adopted as the “mechanical feature value”. In other words, taking the dynamic viscoelastic method described above as an example, the strain rate fluctuates between a positive value and a negative value in the process of repeatedly applying and relaxing stress. The center of the fluctuation of the strain rate tends to deviate slightly from zero due to the balance between the viscous force and the elastic force. And the amount of deviation tends to change corresponding to the degree of cartilage damage. Therefore, the fault distribution may be calculated for the amount of deviation from zero of the variation center (median value) of the strain rate. The tomographic distribution of the deviation amount may be visualized as a tomogram equivalent to the distribution of the degree of damage of the cartilage tissue.
 上記実施例では、軟骨に所定の変形エネルギー(負荷)を付与するための負荷装置として、圧電素子等の接触により応力を付与する荷重機構を例示した。変形例においては、超音波(音圧)、光音響波、電磁波等によって非接触にて軟骨に負荷(加振力)を付与する負荷装置を採用してもよい。 In the above embodiment, a load mechanism that applies stress by contact with a piezoelectric element or the like is illustrated as a load device for applying predetermined deformation energy (load) to cartilage. In the modified example, a load device that applies a load (excitation force) to the cartilage in a non-contact manner using ultrasonic waves (sound pressure), photoacoustic waves, electromagnetic waves, or the like may be employed.
 なお、本発明は上記実施例や変形例に限定されるものではなく、要旨を逸脱しない範囲で構成要素を変形して具体化することができる。上記実施例や変形例に開示されている複数の構成要素を適宜組み合わせることにより種々の発明を形成してもよい。また、上記実施例や変形例に示される全構成要素からいくつかの構成要素を削除してもよい。 In addition, this invention is not limited to the said Example and modification, A component can be deform | transformed and embodied in the range which does not deviate from the summary. Various inventions may be formed by appropriately combining a plurality of constituent elements disclosed in the above-described embodiments and modifications. Moreover, you may delete some components from all the components shown by the said Example and modification.

Claims (8)

  1.  関節軟骨を診断するための軟骨診断装置であって、
     光コヒーレンストモグラフィーを用いる光学系を含む光学ユニットと、
     前記光学ユニットに接続される一方、先端部が関節腔に挿入可能に構成され、前記光学ユニットからの光を軟骨に導いて走査させるための光学機構と、軟骨に対して所定の変形エネルギーを付与するための負荷装置とを含むプローブと、
     前記負荷装置および前記光学機構の駆動を制御し、それらの駆動に基づいて前記光学ユニットから出力された光干渉信号を処理し、変形エネルギーの付与による軟骨内部の変形に伴う所定の力学特徴量の変化をその軟骨の断層位置に対応づけて演算し、その力学特徴量の変化に基づいて軟骨組織の損傷度合いを演算する制御演算部と、
     前記軟骨組織の損傷度合いを断層可視化する態様で表示する表示装置と、
     を備えることを特徴とする軟骨診断装置。
    A cartilage diagnostic apparatus for diagnosing articular cartilage,
    An optical unit including an optical system using optical coherence tomography;
    An optical mechanism that is connected to the optical unit and has a tip that can be inserted into a joint space, guides the light from the optical unit to the cartilage, and scans the cartilage, and applies predetermined deformation energy to the cartilage. A probe including a load device for
    Controls the driving of the load device and the optical mechanism, processes the optical interference signal output from the optical unit based on the driving, and has a predetermined mechanical characteristic amount associated with deformation inside the cartilage by applying deformation energy A control calculation unit that calculates the change in association with the tomographic position of the cartilage and calculates the degree of damage to the cartilage tissue based on the change in the mechanical feature amount;
    A display device for displaying the degree of damage of the cartilage tissue in a manner to visualize a tomography;
    A cartilage diagnostic apparatus comprising:
  2.  前記制御演算部は、
     前記負荷装置の駆動により軟骨に所定の荷重を負荷した後に応力緩和させ、
     その応力緩和中に前記光学ユニットにより撮影された前後の断層画像データに基づき、軟骨の断層位置に対応した変形速度ベクトルを前記力学特徴量として演算し、その変形速度ベクトルの変化から得られる減衰係数の断層分布を、前記軟骨組織の損傷度合いの分布と等価として断層可視化させることを特徴とする請求項1に記載の軟骨診断装置。
    The control calculation unit is
    Relieving stress after applying a predetermined load to the cartilage by driving the load device,
    Based on tomographic image data taken by the optical unit before and after the stress relaxation, a deformation velocity vector corresponding to a cartilage tomographic position is calculated as the mechanical feature amount, and an attenuation coefficient obtained from the change of the deformation velocity vector The cartilage diagnostic apparatus according to claim 1, wherein the tomographic distribution is visualized as a tomogram equivalent to the distribution of the degree of damage of the cartilage tissue.
  3.  前記制御演算部は、前記力学特徴量として演算した変形速度ベクトルを空間微分することによりひずみ速度テンソルを演算し、そのひずみ速度の減衰係数の断層分布を前記軟骨組織の損傷度合いの分布と等価として断層可視化させることを特徴とする請求項2に記載の軟骨診断装置。 The control calculation unit calculates a strain rate tensor by spatially differentiating the deformation rate vector calculated as the mechanical feature value, and assumes that the fault distribution of the strain rate attenuation coefficient is equivalent to the distribution of the damage degree of the cartilage tissue. The cartilage diagnostic apparatus according to claim 2, wherein a tomographic visualization is performed.
  4.  前記制御演算部は、順次取得する断層画像データの相互相関、輝度勾配の変位および輝度パターンの変形に基づき前記変形速度ベクトルをサブピクセル精度にて演算することを特徴とする請求項2または3に記載の軟骨診断装置。 The said control calculating part calculates the said deformation | transformation speed vector with sub pixel precision based on the cross correlation of the tomographic image data acquired sequentially, the displacement of a brightness | luminance gradient, and the deformation | transformation of a brightness pattern. The cartilage diagnostic apparatus according to the description.
  5.  前記制御演算部は、
     前記負荷装置の駆動により軟骨に所定の動的力を負荷し、
     その動的力による軟骨の振動中に前記光学ユニットにより撮影された前後の断層画像データに基づき、軟骨の各断層位置における変形速度ベクトルを前記力学特徴量として演算し、その変形速度ベクトルのうち加振周波数成分である特定変形速度ベクトルの振幅および位相差の少なくとも一方に基づき軟骨の粘弾性の断層分布を演算し、その粘弾性の断層分布を前記軟骨組織の損傷度合いの分布と等価として断層可視化させることを特徴とする請求項1に記載の軟骨診断装置。
    The control calculation unit is
    A predetermined dynamic force is applied to the cartilage by driving the load device;
    Based on the tomographic image data taken by the optical unit during the vibration of the cartilage due to the dynamic force, a deformation velocity vector at each tomographic position of the cartilage is calculated as the mechanical feature amount, and the deformation velocity vector is added. Calculates the viscoelastic tomographic distribution of cartilage based on at least one of the amplitude and phase difference of the specific deformation velocity vector, which is the vibration frequency component, and visualizes the tomogram as the viscoelastic tomographic distribution is equivalent to the distribution of the degree of damage of the cartilage tissue. The cartilage diagnostic apparatus according to claim 1, wherein:
  6.  前記制御演算部は、
     前記負荷装置の駆動により軟骨に所定の動的力を負荷し、
     その動的力による軟骨の振動中に前記光学ユニットにより撮影された前後の断層画像データに基づき、軟骨の各断層位置におけるひずみ速度テンソルを前記力学特徴量として演算し、そのひずみ速度テンソルのうち加振周波数成分である特定ひずみ速度テンソルの振幅および位相差の少なくとも一方に基づき軟骨の粘弾性の断層分布を演算し、その粘弾性の断層分布を前記軟骨組織の損傷度合いの分布と等価として断層可視化させることを特徴とする請求項1に記載の軟骨診断装置。
    The control calculation unit is
    A predetermined dynamic force is applied to the cartilage by driving the load device;
    Based on the tomographic image data taken by the optical unit during the vibration of the cartilage by the dynamic force, the strain rate tensor at each tomographic position of the cartilage is calculated as the mechanical feature amount, and the strain rate tensor is added. Calculates the viscoelastic tomographic distribution of cartilage based on at least one of the amplitude and phase difference of the specific strain rate tensor, which is the vibration frequency component, and visualizes the tomographic fault as equivalent to the distribution of the degree of damage of the cartilage tissue. The cartilage diagnostic apparatus according to claim 1, wherein:
  7.  前記負荷装置が、軟骨に付与される力又は荷重を計測可能なセンサを含み、
     前記制御演算部は、
     演算された前記力学特徴量の加振周波数成分の振幅および位相差の少なくとも一方と、前記センサによる計測値に基づき軟骨の粘弾性の断層分布を演算し、その粘弾性の断層分布を前記軟骨組織の損傷度合いの分布と等価として断層可視化させることを特徴とする請求項5または6に記載の軟骨診断装置。
    The load device includes a sensor capable of measuring a force or load applied to cartilage,
    The control calculation unit is
    A viscoelastic tomographic distribution of cartilage is calculated based on at least one of the amplitude and phase difference of the excitation frequency component of the calculated mechanical feature quantity and a measured value by the sensor, and the viscoelastic tomographic distribution is calculated as the cartilage tissue. 7. The cartilage diagnostic apparatus according to claim 5 or 6, wherein a tomographic visualization is made equivalent to the distribution of the degree of damage.
  8.  光コヒーレンストモグラフィーを用いる光学系を含む光学ユニットに接続されることにより、対象部位の診断を可能とする診断用プローブであって、
     前記対象部位に当接可能に構成された先端部と、
     前記光学ユニットからの光を軟骨に導いて走査させるための光学機構と、
     前記対象部位に対して所定の変形エネルギーを付与するための負荷装置と、
     を備えることを特徴とする診断用プローブ。
    A diagnostic probe that enables diagnosis of a target site by being connected to an optical unit including an optical system that uses optical coherence tomography,
    A tip portion configured to be able to contact the target portion;
    An optical mechanism for guiding the light from the optical unit to the cartilage and scanning;
    A load device for applying predetermined deformation energy to the target part;
    A diagnostic probe comprising:
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