JP7629595B2 - Cartilage diagnostic device using OCT - Google Patents

Description

The present invention relates to a device for diagnosing the degree of cartilage degeneration.

Cartilage plays an important role in absorbing load shock and improving joint gliding, but it does not have blood circulation and is difficult to heal on its own. Many elderly people develop osteoarthritis (OA) due to wear of the cartilage, and there is a need to establish diagnostic and treatment methods, especially in countries with an aging society. Cartilage tissue is composed of 80% water and 20% matrix (extracellular matrix), which contains collagen and proteoglycan. In particular, proteoglycan bound to collagen fibers is thought to be greatly involved in the excellent viscoelastic properties of cartilage, such as determining the flow properties inside the cartilage. OA develops due to the loss of the viscoelastic properties of the cartilage.

With the recent advancement of medical diagnostic technology, optical coherence tomography (OCT) has been developed. OCT allows for micro-tomographic visualization of the inside of biological tissues in a non-invasive and non-contact manner. In addition, the acquisition rate of two-dimensional OCT tomographic images is equal to or higher than the video rate, and has high time resolution. A method has been proposed for using OCT to perform tomographic visualization of the mechanical properties of cartilage (Patent Document 1). According to this method, a predetermined stress is applied to the cartilage to perform tomographic visualization of the degree of deformation of the cartilage tissue, making it possible to distinguish between normal cartilage and degenerated cartilage.

Patent No. 6623163

The technology described in Patent Document 1 is considered to be one method for diagnosing early-stage cartilage diseases using OCT, but essentially, a large number of OCT tomographic images are acquired continuously over time, and then post-processed to display diagnostic images. For this reason, there is room for improvement in terms of practical application from the perspective of realizing rapid diagnosis in the medical field. In addition, the technology described in Patent Document 1 requires that the cross-section from which the OCT tomographic images are acquired be fixed for signal processing reasons, making it difficult to put into practical use in actual clinical settings in terms of body movement and doctor's techniques.

The present invention was made in consideration of these problems, and one of its objectives is to make cartilage diagnosis using OCT more practical.

One aspect of the present invention is a cartilage diagnostic device for diagnosing articular cartilage. This device includes an optical unit including an optical system using optical coherence tomography, a probe connected to the optical unit and configured such that its tip can be inserted into an articular cavity, the probe having a light-transmitting contact surface capable of contacting the cartilage to transmit deformation energy, and an optical mechanism for directing light from the optical unit to the cartilage, a control and calculation unit that controls the drive of the optical mechanism, processes the optical interference signal output from the optical unit in response to the application of deformation energy to the cartilage to calculate the Doppler velocity, and calculates a diagnostic evaluation value of the cartilage tissue based on the Doppler velocity, and a display device that displays the diagnostic evaluation value of the cartilage tissue.

The present invention makes cartilage diagnosis using OCT more practical.

1 is a diagram illustrating a schematic configuration of a cartilage diagnostic device according to an embodiment. FIG. 2 is a diagram illustrating a schematic configuration of a probe. FIG. 1 is a diagram showing a schematic configuration of an experimental apparatus. FIG. 13 is a diagram showing experimental results. FIG. 13 is a diagram showing the results of an experiment verifying the relationship between Doppler velocity and tissue fluid flow velocity and the degree of cartilage degeneration. 13 is a flowchart showing the flow of cartilage diagnosis processing. 13 is a diagram illustrating a schematic configuration of a probe according to a modified example. FIG.

One embodiment of the present invention is a cartilage diagnostic device that uses OCT. This cartilage diagnostic device captures an OCT tomographic image while applying deformation energy to the cartilage, and provides an image for cartilage diagnosis based on the displacement speed of the cartilage tissue calculated from the OCT tomographic image. A user such as a doctor can diagnose the degree of cartilage degeneration by looking at the image.

This cartilage diagnostic device includes an optical unit including an OCT optical system, and a probe connected to the optical unit. The tip of this probe can be inserted into the joint cavity, and has a contact surface that can contact the cartilage to transmit deformation energy (load), and an optical mechanism for directing light from the optical unit to the cartilage. The tip of the probe may be composed of a syringe needle. In order not to damage the surface of the cartilage, a light-transmitting resin, glass, or the like may be placed at the tip of the syringe needle. A flexible sheath may be coaxially placed inside the syringe needle, and glass, or the like, may be placed at the tip of the sheath.

This probe may be one that can be operated manually by a doctor, or one that is automatically driven as part of a device. The former is preferable from the viewpoint of practical use in a wide range of medical settings. Since the contact surface of the probe is optically transparent, the light from the optical unit passes through the contact surface and is irradiated onto the cartilage. The light reflected from the cartilage passes through the contact surface and is captured by the probe.

When the doctor lightly presses the tip of the probe against the patient's cartilage, deformation energy is transmitted. The degree of cartilage degeneration can be evaluated by measuring the response at this time using OCT. This is because, as will be described later, the displacement speed of the cartilage tissue (including the displacement speed of the matrix and the flow speed of tissue fluid) is expressed in different forms depending on the degree of degeneration.

The optical unit combines the object light reflected by the cartilage with the reference light, and sends the resulting optical interference signal to the control and calculation unit. The control and calculation unit controls the driving of the optical mechanism, while also processing the optical interference signal to calculate the Doppler velocity (described below), and calculates a diagnostic evaluation value for the cartilage tissue based on the Doppler velocity. The display device displays the diagnostic evaluation value on a screen.

The "diagnostic evaluation value" may be the Doppler velocity itself. This is because experimental results described below show a correlation between the Doppler velocity and the degree of cartilage degeneration. By displaying the cross-sectional distribution of the Doppler velocity, the degree of cartilage degeneration can be intuitively grasped. This Doppler velocity is obtained as the displacement velocity of the cartilage tissue, which is the combination of the displacement velocity of the matrix (extracellular matrix) of the cartilage tissue and the velocity (flow velocity) of the tissue fluid (water).

On the other hand, as described below, it is believed that the velocity of tissue fluid has a large effect on the early stages of cartilage degeneration. The displacement velocity of the matrix can be calculated from OCT tomographic measurements. For this reason, the velocity of tissue fluid can be calculated based on the difference between the Doppler velocity and the displacement velocity of the matrix, and the tomographic distribution of this velocity can be displayed as a "diagnostic evaluation value."

The display format of the "diagnostic evaluation value" can be set appropriately, taking into consideration the user's visibility. For example, the numerical value itself may be displayed, or a numerical range (which numerical range the value belongs to) may be displayed. Specifically, the visibility of the Doppler velocity and interstitial fluid velocity may be changed, for example, by color-coding each certain velocity range.

These tomographic distributions may be displayed in a time series manner, with images obtained by scanning only the depth direction (z direction) of the cartilage (i.e., one-dimensional images in one axis direction) displayed over time. Alternatively, two-dimensional or three-dimensional images obtained by scanning in the depth direction and perpendicular directions may be displayed. When performing real-time diagnosis in a medical setting, it is preferable to display one-dimensional images.

More specifically, the control and calculation unit may calculate a diagnostic evaluation value based on two lines of tomographic signals in the depth direction that are acquired continuously over time for the cartilage. The screen of the display device may be updated each time a diagnostic evaluation value is calculated based on the two lines of tomographic signals.

The method of transmitting deformation energy (load) may be based on a compression test method in which a constant strain rate is applied to the measurement object (cartilage), or a stress relaxation method in which a constant strain is applied and then stopped. Alternatively, it may be based on a dynamic viscoelasticity method in which a dynamic strain is applied to the measurement object. Alternatively, it may be based on a creep method in which a constant amount of stress is applied to the measurement object.

A cartilage diagnostic method may also be developed using the above technology. This method may include a step of transmitting a predetermined deformation energy (load) to the cartilage, a step of calculating the Doppler velocity by processing an optical interference signal of the OCT corresponding to the application of the deformation energy (load application), and a step of outputting a diagnostic evaluation value of the cartilage tissue based on the Doppler velocity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.
[Example]
FIG. 1 is a diagram showing a schematic configuration of a cartilage diagnostic device according to an embodiment.
The cartilage diagnostic device of this embodiment displays a diagnostic evaluation value for evaluating the degree of degeneration of cartilage tissue based on an OCT tomographic image of articular cartilage.

The cartilage diagnostic device 1 includes an optical unit 2, a probe 4, a control and calculation unit 6, and a display device 8. The optical unit 2 includes a light source 10, an object arm 12, a reference arm 14, an optical mechanism 16, and a light detection device 18. The probe 4 is connected to the optical unit 2 and constitutes one end of the object arm 12.

The optical elements of the optical unit 2 are connected to each other by optical fibers. In the illustrated example, an optical system based on a Mach-Zehnder interferometer is shown, but a Michelson interferometer or other optical system can also be used. In this embodiment, TD-OCT (Time Domain OCT) is used as the OCT, but SS-OCT (Swept Source OCT), SD-OCT (Spectral Domain OCT), or other OCTs can also be used.

The light emitted from the light source 10 is split by the coupler 20 (beam splitter), one of which is guided to the object arm 12 to become the object light, and the other is guided to the reference arm 14 to become the reference light. The object light from the object arm 12 is guided to the probe 4 via the circulator 22 and irradiated onto the cartilage, which is the subject of diagnosis. This object light is reflected as backscattered light on the surface and cross section of the cartilage, taken into the probe 4, and guided to the coupler 24 via the circulator 22.

An optical fiber 32 extending from the circulator 22 is inserted into the main body 30 of the probe 4. A syringe needle 34 is attached to the tip of the main body 30, and the tip of the probe 4 can be inserted into a living body (the patient's knee K) via the syringe needle 34. The main body 30 is provided with an optical mechanism for directing light from the optical unit 2 to the cartilage of the knee K, and an indenter (contact surface) for contacting the cartilage to transmit a predetermined load (stress). The optical mechanism irradiates light toward the cartilage and directs the reflected light to the object arm 12.

Meanwhile, the reference light from the reference arm 14 is guided to the optical mechanism 16 (functioning as the "second optical mechanism") via the circulator 26. This reference light is reflected by the reference mirror 28 of the optical mechanism 16, returns to the circulator 26, and is guided to the coupler 24. That is, the object light and the reference light are combined (superimposed) by the coupler 24, and the interference light is detected by the optical detection device 18. The optical detection device 18 detects this as an optical interference signal (a signal indicating the intensity of the interference light). This optical interference signal is input to the control and calculation unit 6 via the A/D converter 36.

The control and calculation unit 6 controls the entire optical system and performs calculation processing for image output by OCT. The command signal of the control and calculation unit 6 is input to the light source 10, the optical mechanism 16, etc. via a D/A converter (not shown). The control and calculation unit 6 processes the optical interference signal input to the photodetector 18 and obtains a tomographic image of the cartilage by OCT. Then, based on the tomographic image data, an evaluation value (referred to as the "diagnostic evaluation value") for diagnosing the degree of degeneration of the cartilage tissue is calculated using the method described below.

More details are as follows.
The light source 10 is a broadband light source made of a super luminescent diode (hereinafter referred to as "SLD"). The light emitted from the light source 10 is split into an object light and a reference light by a coupler 20, and these are guided to an object arm 12 and a reference arm 14, respectively. The object arm 12 and the reference arm 14 use single mode fibers as optical fibers.

The optical mechanism 16 is a mechanism of the RSOD type (Rapid Scanning Optical Delay Line) and constitutes the reference arm 14. This RSOD may be a single-pass type in which light is irradiated to the diffraction grating 42 (described below) once in a round trip, or a double-pass type in which light is irradiated to the diffraction grating 42 twice in a round trip. The optical mechanism 16 includes a collimator lens 40, a diffraction grating 42, a lens 44, and a reference mirror 28 (resonant mirror).

The light that has passed through the circulator 26 is guided to the diffraction grating 42 via the collimator lens 40. This light is split into wavelengths by the diffraction grating 42, and the phases of the wavelengths are adjusted and then focused at different positions on the reference mirror 28 by the lens 44. By rotating the reference mirror 28 at a small angle, high-speed optical path scanning and frequency modulation are possible in a state where the phases of the wavelengths are adjusted (a state where the Doppler modulation frequency can be detected). The reflected light from the reference mirror 28 returns to the circulator 26 as reference light and is guided to the coupler 24. It is then superimposed with the object light and sent to the photodetector 18 as interference light. In a modified example, the light that has passed through the diffraction grating 42 may be focused on the reference mirror 28 by a curved mirror instead of the lens 44.

The light detection device 18 includes a photodetector 50, a filter 52, and an amplifier 54. The interference light obtained by passing through the coupler 24 is detected as an optical interference signal by the photodetector 50. This optical interference signal has noise removed or reduced by the filter 52, and is input to the control calculation unit 6 via the amplifier 54 and the A/D converter 36.

The control and calculation unit 6 has a CPU, ROM, RAM, hard disk, etc. Using this hardware and software, the control and calculation unit 6 controls the entire optical system and performs calculation processing for image output by OCT. The control and calculation unit 6 controls the drive of the optical mechanism 16, processes the optical interference signal output from the photodetector 18 based on the drive, and obtains a tomographic image of the cartilage by OCT. Then, based on the tomographic image data, it calculates a diagnostic evaluation value of the cartilage tissue using the method described below.

The display device 8 is, for example, a liquid crystal display, and displays the diagnostic evaluation value of the cartilage tissue calculated by the control and calculation unit 6 on the screen in a form that visualizes the cartilage tissue in cross-section.

FIG. 2 is a diagram illustrating a schematic configuration of the probe 4. As shown in FIG.
The probe 4 has a syringe needle 34 attached as a puncture part to the tip of a stepped cylindrical body 30. The lower half of the body 30 is a narrow-diameter part 35 whose outer diameter is slightly larger than that of the syringe needle 34, improving the visibility of the syringe needle 34 when a doctor operates the probe 4.

A depressor 64 that can come into contact with the cartilage is coaxially disposed at the tip of the syringe needle 34. The depressor 64 is a light-transmitting member, and its tip surface forms a contact surface 65 that can come into contact with the surface of the cartilage J. In this embodiment, the depressor 64 is made of glass, but plastic or other materials can be selected as long as they are strong enough to not break or deform when pressed against the cartilage and can transmit object light.

A collimator lens 60 is disposed in the upper half of the main body 30, and an achromatic lens 62 (objective lens) is disposed at the boundary between the narrow diameter section 35 and the syringe needle 34. The optical fiber 32 passes through the wall of the main body 30 and is connected to the collimator lens 60. The collimator lens 60, achromatic lens 62, and indenter 64 are arranged on the same straight line, and constitute a "first optical mechanism."

The light guided to the probe 4 by the optical fiber 32 is emitted via the collimator lens 60, the achromatic lens 62, and the indenter 64, and is irradiated onto the cartilage J. As a result, the light reflected on the surface or inside of the cartilage J is captured by the probe 4 and guided to the object arm 12 of the optical unit 2 via the optical fiber 32.

The calculation processing method up to presenting the diagnostic evaluation value of the cartilage tissue will be described below.
As described above, the object light (light reflected 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 as a low-coherence optical interference signal by the optical detection device 18. The control and calculation unit 6 acquires this optical interference signal as a tomographic image of the cartilage J based on the intensity of the interference light.

ここで、λ_ｃはビームの中心波長であり、Δλはビーム波長帯幅の半値全幅である。 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 at half maximum of the envelope of the autocorrelation function, and can be expressed by the following formula (1).

where λ _c is the central wavelength of the beam and Δλ is the full width at half maximum of the beam bandwidth.

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距離である。 On the other hand, the resolution in the direction perpendicular to the optical axis (beam scanning direction) is set to ½ of the beam spot diameter D based on the focusing performance of the focusing lens. The beam spot diameter ΔΩ can be expressed by the following formula (2).

Here, d is the diameter of the beam incident on the condenser lens, and f is the focal length of the condenser lens.

ここで、Ｉ_ｉｎｃは測定対象への照射光強度を示す。Ｒ(z)は測定対象内部の奥行き位置ｚにおける反射係数であり、Ｇ(z)はコヒーレンス関数である。ｆ_ＲＳＯＤは参照鏡２８の走査によって生じるドップラー変調周波数であり、ｆ_ｄは測定対象内部の変位（変形、変動、流動）によって生じるドップラー変調周波数である。ｖは参照鏡２８の走査速度である。なお、「ドップラー変調周波数」とは、光の反射対象が変位したり、測定対象の屈折率が時間変化することで生じ、「ドップラー効果によりシフトする周波数」を意味する。 (Doppler velocity detection)
The optical interference signal intensity I _det (z) acquired by OCT is obtained by the convolution integral shown in the following formula (3).

Here, I _inc indicates the intensity of light irradiated onto the measurement target. R(z) is the reflection coefficient at depth position z inside the measurement target, and G(z) is the coherence function. _{f RSOD} is the Doppler modulation frequency caused by the scanning of the reference mirror 28, and f _d is the Doppler modulation frequency caused by the displacement (deformation, fluctuation, flow) inside the measurement target. v is the scanning speed of the reference mirror 28. Note that the "Doppler modulation frequency" refers to the "frequency shifted by the Doppler effect" that occurs when the object reflecting the light is displaced or the refractive index of the measurement target changes over time.

The optical interference signal intensity I _det (z) is subjected to a fast Fourier transform, and a Hilbert transform of the following formula (4) is applied to obtain a spectrum S^(f) with a phase delay of π/2 in the frequency domain. An inverse Fourier transform is applied to this spectrum S^(f) to obtain an analytic signal Γ(t) = s(t) + is^(t). The square root of the sum of the squares of the real part s(t) and the imaginary part s^(t) of this analytic signal (instantaneous amplitude) gives the signal intensity (signal envelope) of the OCT tomographic image.

By using the Hilbert transform, it is possible to obtain not only the instantaneous amplitude but also the instantaneous phase. The instantaneous frequency can also be calculated from the time derivative of the instantaneous phase. For this reason, it is particularly effective when processing high-frequency modulated signals as in this embodiment. This improves the detection resolution of the Doppler modulation frequency, enabling highly accurate and real-time detection to be achieved.

ここで、ΔＴは光干渉信号の取得時間間隔、つまりＡスキャンの時間間隔を表している。もしくは信号処理を施すＡスキャンの時間間隔であってもよい。Ａ(t)は光干渉信号の振幅（つまり後方散乱強度）を表す。 Here, the adjacent autocorrelation method is used to obtain the Doppler modulation frequency _fd generated by internal fluctuations in the measurement target (cartilage) in real time. That is, for an optical interference signal (RF interference signal) acquired by a depth z-direction scan (A-scan), the j-th and j+1-th adjacent analytic signals in an x-direction scan (or the j-th and j+1-th analytic signals with the x-direction fixed) are defined as Γ _j and Γ _j+1 , respectively. In this case, Γ _j+1 is expressed by the following formula (5).

Here, ΔT represents the time interval for acquiring the optical interference signal, i.e., the time interval for the A-scan. Alternatively, it may be the time interval for the A-scan to be subjected to signal processing. A(t) represents the amplitude of the optical interference signal (i.e., the backscattering intensity).

Since the scanning (rotational drive) of the reference mirror 28 by the RSOD is periodic, the Doppler modulation frequency f _RSOD is assumed to be constant. In this case, by using the phase difference φ _i,j derived by the adjacent autocorrelation between the analytic signals Γ _j and Γ _j+1 , the Doppler modulation frequency f _d can be calculated from the following formula (6). Here, i represents the number of sampling points of the optical interference signal in the depth z direction, and j represents the number of lines of the optical interference signal to be detected. Note that Γ _i,j ^* is the complex conjugate of Γ _i,j . The following formula (6) utilizes the fact that instantaneous phase can be detected by the Hilbert transform. Furthermore, the detection accuracy of the Doppler modulation frequency f d can be improved by performing ensemble averaging processing on the phase difference φ _{i ,j} of N lines of A scans (or N times of A scans) and performing pixel averaging (average for each pixel) in the z direction. In addition, the time t corresponds to the number of sampling points i of the optical interference signal in the depth z direction.

ここで、λ_ｃは光源の中心波長、ｎ_ｔは測定対象内部の屈折率であり、θは光軸と変位方向とのなす角である。 The Doppler velocity _vd can be obtained by calculating the following equation (7) using this Doppler modulation frequency _fd . Since the time t corresponds to the number of sampling points i of the optical interference signal in the depth z direction, it means the Doppler velocity at the depth z position. The Doppler velocity _vd detected for cartilage is obtained as a combined value of the displacement velocity of the matrix of the cartilage tissue and the flow velocity of the tissue fluid.

Here, λ _c is the central wavelength of the light source, n _t is the refractive index inside the measurement object, and θ is the angle between the optical axis and the displacement direction.

(Stabilization of Doppler modulation detection ability)
In this embodiment, instead of the autocorrelation for each sampling point shown in the above formula (6) (hereinafter also referred to as "point autocorrelation"), an integral-type autocorrelation (autocorrelation based on correlation integral: hereinafter also referred to as "autocorrelation integral") shown in the following formula (8) is calculated.

ここで，Ｒ_ｉ，ｊは座標（ｉ，ｊ）に対応する自己相関係数を表している。 Here, when calculating the autocorrelation of two lines of A-scan data adjacent to each other in time, an integral interval ( _-Tw /2≦t≦ _Tw /2) is set in the depth direction (z direction) to reduce fluctuations in the calculation of the phase difference. _Tw represents the window width. Then, the Doppler modulation frequency _fd at an arbitrary position on the z coordinate within the integral interval is determined. The degree of noise reduction can be adjusted by setting this integral interval.

Here, R _i,j represents the autocorrelation coefficient corresponding to the coordinates (i,j).

上記式（９）から得られるドップラー変調周波数ｆ_ｄを用いて上記式（７）を演算することにより、ドップラー速度ｖ_ｄを得ることができる。 When calculating the phase difference φ _i,j , the ensemble average of N lines of A-scan (N A-scans) is calculated using the following formula (9), thereby making it possible to suppress system noise that fluctuates like shot noise.

The Doppler velocity _vd can be obtained by calculating the above equation (7) using the Doppler modulation frequency _fd obtained from the above equation (9).

ここで、ｉは奥行ｚ方向についての光干渉信号のサンプリング点数を表し、ｊは検出される光干渉信号のライン数を表している。この振幅Ａ_ｉ，ｊは、ＯＣＴ断層像の信号強度（信号包絡線）であることから、組織形態分布を表している。 (Detection of tissue displacement velocity and interstitial fluid flow velocity)
The square root of the sum of the squares of the real part s(t) and the imaginary part s^(t) of the analytic signal Γ(t) described above (instantaneous amplitude) gives the amplitude A(t) = A _i,j of the above equation (5), as shown in the following equation (10).

Here, i represents the number of sampling points of the optical interference signal in the depth z direction, and j represents the number of lines of the detected optical interference signal. The amplitude A _i,j is the signal intensity (signal envelope) of the OCT tomographic image, and therefore represents the tissue morphology distribution.

Therefore, in order to detect the amount of movement (displacement speed) of the cartilage tissue, the correlation coefficient R ^A _i+Δi,j of the instantaneous amplitude shown in the following formula (11) is used. R ^A _i+Δi,j is calculated by changing the number of sampling points i, which represents the depth z position of the tissue morphology distribution, by Δi.

This correlation coefficient indicates the similarity of the depth pattern in the tissue morphology distribution. Therefore, as shown in the following formula (12), the position i+Δi of the sampling point at which the correlation coefficient R ^A _i+Δi,j is maximized represents the tissue movement in the depth z-axis direction of the tissue morphology distribution.

Therefore, as shown in the following formula (13), the displacement velocity _vt of the matrix of the cartilage tissue is detected taking into consideration the distance Δz between the sampling points.

As described above, the Doppler velocity in the above formula (7) is considered to include the displacement velocity of the matrix in the above formula (13). The displacement velocity of the matrix and the flow velocity of the interstitial fluid are calculated at each time and each position, and are detected cross-sectionally as a spatiotemporal distribution. Therefore, the velocity _vw of a liquid component such as interstitial fluid is given by the difference between the two, as shown in the following formula (14).

The velocity _vw of the liquid component is considered to be the tissue fluid flow velocity component of tissue permeation. In a living body, it is considered to represent the tissue permeation of plasma components leaking from capillaries present just below the skin epidermis, and in cultured regenerated tissue, it is considered to represent the permeation rate of culture fluid, and is considered to be a parameter for evaluating the activity of cell tissue. In the case of cartilage tissue, it represents the flow rate of the tissue fluid and is an index for evaluating the degree of degeneration of the cartilage.

In the above method, the movement amount (displacement speed) of the tissue is detected by applying the correlation method to the signal of the amplitude A(t) shown in the above formula (10), but it is also possible to use I _det (z) = I _i,j in the above formula (3), which is the low coherence interference signal (RF interference signal) itself, or the analytic signal Γ _i,j of the RF interference signal. For example, when the analytic signal Γ _i,j is used, the number of sampling points i of the optical interference signal in the z direction is changed by Δi to calculate the correlation coefficient R ^Γ _{i + Δi,j} , as shown in the following formula (15).

This correlation represents the similarity of the depth patterns of low-coherence interference signals (RF interference signals). The position i+Δi of the sampling point where the correlation coefficient R ^Γ _i+Δi,j is maximum represents the tissue movement in the depth z direction of the j+1th RF interference signal. Therefore, the tissue displacement velocity and tissue fluid velocity can be detected based on the above equations (12) and (13).

In this way, when using the RF interference signal I _det (z)=I _i,j or the analytic signal Γ _i,j , the correlation is calculated using a signal that also contains information on the tissue fluid flow, so it is possible to use information that is contaminated with noise. However, since the amount of tissue movement can be expected to be greater than the amount of tissue fluid flow, it is thought that the use of the analytic signal Γ _i,j is also useful in evaluating the degree of cartilage degeneration.

Next, the effectiveness of the above-mentioned technique will be described.
As described above, in this embodiment, the Doppler velocity of the cartilage tissue is calculated using OCT, and the degree of degeneration of the cartilage tissue can be evaluated based on the Doppler velocity. Here, the results of an experiment conducted to verify that the cartilage diagnostic device 1 can visually display the difference between normal cartilage and degenerated cartilage will be described.

In a typical diagnosis, a doctor holds the probe 4 and inserts its tip into the patient's knee joint. The doctor then brings the tip surface (contact surface 65) of the indenter 64 into contact with the surface of the cartilage J and presses it slightly. The expected amount of pressing is, for example, about 10 to 20 μm. In this experimental device, this process is reproduced mechanically in place of the doctor.

FIG. 3 is a diagram showing a schematic configuration of the experimental apparatus.
This experimental device is configured by connecting a compression tester 70 to the optical unit 2 shown in Fig. 1. The compression tester 70 includes a mounting table 72 for mounting a test piece W, a support mechanism 74 for supporting the probe 4 in the vertical direction above the mounting table 72, and a load cell 76 capable of applying a downward pressing load (i.e., toward the test piece W) to the rear end of the probe 4. The load cell 76 is driven by the control and calculation unit 6. The pressing force of the probe 4 can also be detected by the load cell 76.

In this experiment, a cartilage tissue sample from the lateral femoral condyle of a pig's knee joint was collected in a cylindrical shape with a diameter of 7 mm, and this was used as a normal cartilage test piece W. As a comparative example, this test piece W was subjected to an enzyme treatment to create a simulated denatured cartilage (OA test piece in which the degree of denaturation was artificially controlled to simulate cartilage). For this enzyme treatment, collagenase was used, which breaks down the collagen fibers that maintain the elasticity of articular cartilage. That is, normal cartilage was placed in a solution of collagenase dissolved in phosphate buffered saline at pH 7.4, and the solution was left to stand for 2 hours while maintaining the temperature of the solution at 37°C, to obtain a simulated denatured cartilage.

Figure 4 shows the experimental results. Figure 4(A) shows the experimental results for normal cartilage, and Figure 4(B) shows the experimental results for simulated degenerated cartilage. The top of each figure shows the time change in the OCT tomographic image, and the middle shows the time change in the displacement velocity (Doppler velocity) of the cartilage tissue. The bottom of each figure shows the relationship between the pressure acting on the test piece W and the stroke of the probe 4 as well as the time change.

The experimental conditions were as follows. That is, an LSD broadband light source with a central wavelength λ _c =1317.7 nm and a full width at half maximum Δλ=102.0 nm was used as the light source 10. The compression amount by the compression tester 70 was 100 μm, and the compression speed was 100 μm/sec. The scanning frequency of the reference mirror 28 was about 4.0 kHz, the depth resolution was 7.5 μm, and the depth tomographic scanning range was 1130 μm. The sampling frequency by the OCT was 20 MHz.

From the bottom of Figure 4, the stroke of the probe 4 is zero until time t = 0.7 sec, and the compression testing machine 70 is stopped. At time t = 0.7 sec, the compression testing machine 70 starts driving the probe 4, and it displaces at a constant speed until about time 2.8 sec. During that time, the indenter 64 approaches the test piece W, and at about time 1.2 sec, it comes into contact with the surface of the test piece W. At about time t = 2.8 sec, the position of the probe 4 is fixed. As a result, stress relaxation occurs in the test piece W from that point on.

In the upper part of Figure 4, the area approximately 200 μm from the cartilage surface corresponds to the superficial layer, and below that corresponds to the intermediate layer. In the OCT tomographic image (tissue morphology tomographic distribution), it can be seen that a high-brightness signal moves diagonally upward from when compression of the cartilage begins and a load response can be confirmed until the indenter 64 comes to rest. This indicates that the cartilage tissue is displaced in the direction approaching the indenter 64, and the amount of displacement. From the upper part of Figure 4, it can be qualitatively confirmed that the amount of displacement of the simulated degenerated cartilage (t = 1.3 to 2.9 sec) is greater than the amount of displacement of normal cartilage (t = 1.2 to 2.8 sec).

In the middle of Figure 4, the time change in Doppler velocity is displayed in different colors. The Doppler velocity during compression of the cartilage shows that in both normal cartilage and simulated degenerated cartilage, the cartilage tissue or tissue fluid moves toward the cartilage surface. This is easily visualized on the screen.

This figure shows that the Doppler velocity in the middle layer of cartilage is approximately 20 μm/sec in normal cartilage, while in the simulated denatured cartilage it is more than twice as high at approximately 50 μm/sec. Since the Doppler velocity has a spatial distribution that increases in the depth z direction, it can also be confirmed that a larger strain occurs in the surface layer of the cartilage than in the middle layer. This is thought to be due to the fact that the elastic modulus of the surface layer is lower than that of the middle layer due to the orientation characteristics of the collagen fibers. It is also thought that the elastic and viscous properties of the simulated denatured cartilage are further reduced due to the destruction of collagen fibers and the detachment of proteoglycans, which is why a large displacement velocity was detected.

As shown in the lower part of Figure 4, stress relaxation begins after time t = 2.8 sec in normal cartilage and after time t = 2.9 sec in simulated degenerated cartilage. As shown in the middle part of Figure 4, the Doppler velocity approximately 0.5 sec after the start of stress relaxation is detected as 5 μm/sec or less in normal cartilage, and movement quickly stops. In contrast, the Doppler velocity is high at around 20 μm/sec in simulated degenerated cartilage. This is also thought to be due to the improved tissue permeability in the simulated degenerated cartilage, i.e., the decreased viscosity characteristics.

Figure 5 shows the results of an experiment verifying the relationship between Doppler velocity and tissue fluid flow velocity and the degree of cartilage degeneration. Figure 5(A) shows the relationship between Doppler velocity and the degree of cartilage degeneration, and Figure 5(B) shows the relationship between tissue fluid flow velocity and the degree of cartilage degeneration. The vertical axis shows velocity during compression in Figure 5(A) and during stress relaxation in Figure 5(B). On the horizontal axis, "Con" shows normal cartilage, and "2H" shows simulated degenerated cartilage.

As shown in Figure 5(A), a significant difference was observed between normal cartilage and the simulated degenerated cartilage in terms of Doppler velocity. As shown in Figure 5(B), a significant difference was also observed between normal cartilage and the simulated degenerated cartilage in terms of tissue fluid flow velocity.

The above experiments confirmed a correlation between the distribution of Doppler velocity and tissue fluid flow velocity and the mechanical behavior of cartilage, and found that they differ significantly between normal cartilage and simulated degenerated cartilage. In other words, it was suggested that diagnosing degenerated cartilage using the OCT of this embodiment is effective. For this reason, for example, the distribution of Doppler velocity shown in the middle of Figure 4 can be displayed as a diagnostic evaluation value for cartilage. In addition, although not shown in this experiment, the tissue fluid flow velocity obtained from the difference between the Doppler velocity and the matrix displacement velocity can also be displayed as a diagnostic evaluation value. In the early stages of cartilage degeneration, the ability to retain water (the function of keeping tissue fluid stable) is lost, which may lead to the discovery of a tendency to degeneration.

Next, a specific flow of processing executed by the control and calculation unit 6 will be described.
6 is a flowchart showing the flow of the cartilage diagnosis process. Note that this cartilage diagnosis process is performed by a doctor or the like with the tip of the probe 4 inserted into the knee joint of a patient, and is repeatedly executed at a predetermined calculation cycle when the drive of the optical unit 2 is started.

The control and calculation unit 6 acquires the OCT interference signal (S10) and performs a Fourier transform (FFT) (S12). The control and calculation unit 6 then performs bandpass filtering based on the carrier frequency to improve the signal S/N ratio (S14), and then performs a Hilbert transform (S16). The analytic signal obtained by the Hilbert transform is used to perform adjacent autocorrelation processing to find the phase difference (S18), and the Doppler modulation frequency is obtained (S20).

The control and calculation unit 6 calculates the Doppler velocity _vd (the displacement velocity of the entire cartilage tissue) based on the above formula (7) using the Doppler modulation frequency (S22). Meanwhile, the control and calculation unit 6 calculates the displacement velocity _vt of the matrix of the cartilage tissue based on the above formula (12) (S24). Then, the control and calculation unit 6 calculates the interstitial fluid velocity _vw based on the above formula (13) (S26). The control and calculation unit 6 displays either or both of the Doppler velocity _vd and the interstitial fluid velocity _vw on the screen of the display device 8 as diagnostic evaluation values (S28).

As described above, according to this embodiment, the diagnostic evaluation value of the cartilage to be diagnosed is visualized in a cross-sectional view based on the knowledge that there is a correspondence between the Doppler velocity calculated from the OCT cross-sectional image of the cartilage and the degree of degeneration of the cartilage. Therefore, a doctor or the like can easily perform a cartilage diagnosis by checking the cross-sectionally visualized image.

In particular, since it is sufficient to obtain an OCT tomographic image (one-dimensional tomographic distribution) in the depth z direction, diagnostic images can be displayed in a short time, enabling real-time diagnosis in the medical field. Even with an OCT tomographic image (two-dimensional tomographic distribution) in the depth z direction, it is also possible to display a two-dimensional tomographic color map of Doppler velocity in real time, since only the correlation of one axis of the A-scan is used. In addition, there is no need to fix the position of the probe 4 relative to the cartilage when taking the image. Therefore, the patient's body movement or the doctor's technique are less likely to affect the diagnosis. Therefore, cartilage diagnosis using OCT can be made more practical in actual clinical settings.

The above describes a preferred embodiment of the present invention, but it goes without saying that the present invention is not limited to this specific embodiment, and various modifications are possible within the scope of the technical concept of the present invention.

[Modification]
FIG. 7 is a diagram illustrating a schematic configuration of a probe according to a modified example.
The probe 104 of this modified example includes an optical mechanism 80. The optical mechanism 80 constitutes the object arm 12 and includes a mechanism for directing light from the light source 10 to the measurement object (cartilage J) to scan it, and a drive unit for driving the mechanism. The optical mechanism 80 includes a collimator lens 60, a two-axis galvanometer mirror 82 of an optical unit, and an achromatic lens 62. The light that has passed through the circulator 22 is directed to the galvanometer mirror 82 via the collimator lens 60, and is irradiated onto the measurement object while being scanned in the x-axis and y-axis directions. The reflected light from the measurement object is taken in by the probe 104.

By providing such an optical mechanism 80 to the probe 104, OCT measurement of two-dimensional and three-dimensional tomographic distribution becomes possible. This makes it possible to display the diagnostic evaluation value of the cartilage in two or three dimensions.

[Other Modifications]
Although not mentioned in the above embodiment, a sensor such as a load cell may be attached to the probe 4 itself, making it possible to measure the load applied to the cartilage. This makes it possible to display the degree of stress relaxation, for example, as shown in the lower part of Fig. 4, and by reading this together with the displacement velocity image shown in the middle part of Fig. 4, it is possible to display the diagnostic evaluation value of the cartilage tissue from various angles.

In the above embodiment, as shown in FIG. 2, it is assumed that the pressing force by the probe 4 is applied manually by the user (doctor). In a modified example, a load device may be provided on the probe 4 so that a predetermined deformation energy (load) can be applied to the cartilage. As such a load device, a loading mechanism that applies stress by contact with a piezoelectric element or the like may be used. Alternatively, a load device that applies a load (excitation force) to the cartilage in a non-contact manner using ultrasound (sound pressure), photoacoustic waves, electromagnetic waves, etc. may be used.

The present invention is not limited to the above-mentioned embodiment and modified examples, and the components can be modified without departing from the spirit of the invention. Various inventions can be created by appropriately combining multiple components disclosed in the above-mentioned embodiment and modified examples. In addition, some components can be deleted from all the components shown in the above-mentioned embodiment and modified examples.

1 Cartilage diagnostic device, 2 Optical unit, 4 Probe, 6 Control and calculation unit, 8 Display device, 10 Light source, 12 Object arm, 14 Reference arm, 16 Optical mechanism, 18 Photodetector, 20 Coupler, 22 Circulator, 24 Coupler, 26 Circulator, 28 Reference mirror, 30 Main body, 32 Optical fiber, 34 Syringe needle, 35 Thin-diameter section, 40 Collimator lens, 42 Diffraction grating, 44 Lens, 50 Photodetector, 52 Filter, 54 Amplifier, 60 Collimator lens, 62 Achromatic lens, 64 Indenter, 65 Contact surface, 70 Compression tester, 72 Placement table, 74 Support mechanism, 76 Load cell, 80 Optical mechanism, 82 Galvanometer mirror, 104 Probe, J Cartilage, K Knee, W Test piece.

Claims (2)

A cartilage diagnostic device for diagnosing articular cartilage, comprising:
an optical unit including an optical system using optical coherence tomography;
a probe connected to the optical unit, the probe having a tip portion configured to be insertable into a joint cavity, the probe having a light-transmitting contact surface capable of contacting cartilage to transmit deformation energy, and an optical mechanism for guiding light from the optical unit to the cartilage;
a control and calculation unit that controls the driving of the optical mechanism, processes an optical interference signal output from the optical unit in response to the application of deformation energy to the cartilage, calculates a Doppler velocity, and calculates a diagnostic evaluation value of the cartilage tissue based on the Doppler velocity;
A display device that displays the diagnostic evaluation value of the cartilage tissue;
Equipped with
The control calculation unit is
calculating a displacement velocity of the matrix of the cartilage by processing an optical interference signal output from the optical unit in response to the application of deformation energy to the cartilage;
A cartilage diagnostic device characterized by calculating a velocity of tissue fluid of the cartilage based on a difference between the Doppler velocity and the displacement velocity of the matrix, and calculating a diagnostic evaluation value of the cartilage tissue based on the velocity of the tissue fluid . A first optical mechanism provided on an object arm passing through the cartilage and functioning as the optical mechanism;
a second optical mechanism provided on the reference arm that does not pass through the cartilage and that guides light from a light source to a reference mirror and reflects the light;
a light detection device that detects interference light obtained by superimposing an object light reflected by the cartilage and a reference light reflected by the reference mirror;
Equipped with
The cartilage diagnostic device according to claim 1 , wherein the control and calculation unit performs frequency analysis on the optical interference signal input from the photodetector, and calculates the Doppler velocity using a Doppler modulation frequency.

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