WO2006022342A1 - 生体組織測定用の光干渉トモグラフィー用光発生装置及び生体組織測定用の光干渉トモグラフィー装置 - Google Patents
生体組織測定用の光干渉トモグラフィー用光発生装置及び生体組織測定用の光干渉トモグラフィー装置 Download PDFInfo
- Publication number
- WO2006022342A1 WO2006022342A1 PCT/JP2005/015457 JP2005015457W WO2006022342A1 WO 2006022342 A1 WO2006022342 A1 WO 2006022342A1 JP 2005015457 W JP2005015457 W JP 2005015457W WO 2006022342 A1 WO2006022342 A1 WO 2006022342A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- light
- optical interference
- interference tomography
- wavelength
- measurement
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/102—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for optical coherence tomography [OCT]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0062—Arrangements for scanning
- A61B5/0066—Optical coherence imaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
- A61B5/4538—Evaluating a particular part of the muscoloskeletal system or a particular medical condition
- A61B5/4542—Evaluating the mouth, e.g. the jaw
- A61B5/4547—Evaluating teeth
Definitions
- the present invention relates to a light generation device for optical interference tomography for measurement of biological tissue and an optical interference tomography device for measurement of biological tissue, and in particular, when obtaining a tomographic image of the anterior segment and examining the eye. It is extremely effective when applied to.
- OCT apparatus has also been tried (for example, see Non-patent Document 1 below).
- This OCT can observe a tomographic image of a living body with a resolution of tens of meters, and has already been introduced in the medical field for observation of the retina (for example, see Non-patent Document 2 below).
- OCT which has been put to practical use, irradiates the retina with measurement light through a transparent tissue such as the cornea, the crystalline lens, and the vitreous, so that the tomogram of the retina is photographed to observe the retina.
- the observation of the corner angle by OCT has been performed only experimentally, and a clear image has not been obtained.
- FIG. 6 shows the schematic structure of the eye
- FIG. 7 shows the schematic structure of the eye suffering from angle-closure glaucoma.
- Patent Document 1 US Pat. No. 4,896,325
- Non-Patent Document 1 Edited by Brett E. Boumaet al., Handbook of Optical Coherence Tomography, USA), Marcel Dekker Inc., 2002, p.498-500.
- Non-Patent Document 2 Kenji Chen, “Microscopic diagnosis by optical coherence tomography for clinical application”, Optrotus, Optrotus, Inc., July 10, 2002, No. 247, p. l 79-183
- Non-Patent Document 3 Yuzo Yoshikuni, “Development Trends of Wavelength Tunable Lasers and Their Expectations for System Applications”, Applied Physics, Japan Society of Applied Physics, 2002, No. 71, No. 11, P.1362- 1366 4: Edited by Brett E. Bouma et al., Handbook of Optical Coherence Tomography graphy USA), Marcel Dekker Inc., 2002, p. 364-367
- Non-Patent Document 5 Togashi Togaku et al., "High-speed 'high-resolution OFDR-OCTJ using SSG-DBR laser", Proceedings of the 28th Optical Symposium, Japan Society of Applied Physics, Enomoto Optical Society, 2003 6 Moon 19 ⁇ , p.39-40
- Non-Patent Document 6 Masamitsu Haruna, “Biological measurement and tomographic imaging using low-coherent optical interference”, Applied Optics, 2003, 2nd, p.
- UBM as described above is a contact-type device, there is a risk of infection and mechanical invasion.
- acoustic impedance matching is performed by covering the eye with an instrument and filling it with water, so if the eye is pressed by the instrument and deformed, the problem will be
- UBM has problems in that the measurement is complicated and the patient is overburdened.
- the conventional OCT apparatus as described above is a non-contact type apparatus, it does not cause a problem like the above-mentioned UBM! It was difficult to measure the angle of the sclera, cornea, and iris. For this reason, attempts have been made to measure the corner angle using light in the long wavelength band (1.3 / zm), which is usually used in the wavelength band (0.8 8 111). It is difficult to obtain and However, the measurement range does not reach. In addition, the measurement must be completed in a short time to prevent image distortion due to eye movement, resulting in a narrow horizontal measurement range, which is necessary for the diagnosis of glaucoma It was difficult to fully measure the entire shape of the cornea and iris area.
- OCT includes OCDR (optical 'coherence' domain 'reflectometer) method, FD (frequency 1' domain) method, OFDR (optical 'frequency 1' domain 'reflectometer) method (eg There are three main methods (see Patent Document 5).
- the OC DR method uses a super 'luminescence' diode (SLD) as a light source, and the incident light is incident on the interferometer to obtain depth information by changing the optical path length of the reference optical path. .
- SLD super 'luminescence' diode
- the FD method uses an SLD as the light source as in the OCDR method, but the optical path length of the reference optical path remains fixed, and the optical spectrum obtained by spectrally separating the interference light is Fourier transformed to obtain the depth direction.
- Information used.
- the OFDR method uses a variable wavelength light source as the light source and Fourier transforms the interference light spectrum obtained by changing the wave number of the emitted light to obtain information in the depth direction. .
- the only OCT apparatus in practical use is based on the OCDR-OCT method.
- the OCT device using the OCDR-OCT method mechanical scanning of the reference mirror to change the optical path length of the reference light is essential, and the mechanical scanning becomes the rate-determining of the measurement speed, so high-speed measurement is difficult.
- the measurement range in the depth direction of the tomographic image is not only narrow, but the measurement range in the horizontal direction is as narrow as about 1 to 2 mm. Limited to the range.
- the measurement of the anterior segment requires a measurement range of at least about 3 mm, and the narrowness of the measurement range associated with the movement of the living body makes it difficult to observe the entire anterior segment using the OCDR-OCT method. It was a cause to do.
- the FD method does not require mirror scanning, so high-speed measurement is possible and there is no problem that the measurement range becomes narrow due to the movement of the living body, but the measurement range in the depth direction is used for spectroscopic measurement. Because it is determined by the resolution of the spectroscope (about 2.5 mm), it is difficult to fully observe the entire image of the anterior segment even by the FD method.
- a first invention for solving the above-mentioned problems is as follows: 1. For optical interference tomography for measuring biological yarn and weaving, characterized by being capable of emitting light in the wavelength region of 1.553-1.85 / zm It is a light generator.
- a second invention is the light generation apparatus for optical interference tomography for measuring a biological tissue, characterized in that the light can be emitted while switching the wavelength of the light in the first invention.
- a third invention switching the wavelength in the coherence length 1. 2 ⁇ 10- 3 / ⁇ ⁇ 1 following wavenumber interval 1. 4 mm or more light in air discontinuously (intermittently) It is a light generating device for optical interference tomography for biological tissue measurement, characterized in that the light can be emitted.
- a fourth invention in the second invention, the coherence length in air of the light is on 1. 4 mm or more, 1.
- the light 2 X 10- 3 / zm 1 following wavenumber interval This is a light generating device for optical interference tomography for measurement of biological yarn and weaving, characterized in that the wavelength can be switched discontinuously (intermittently).
- a fifth invention is the optical interference tomography for measuring a biological yarn and weaving according to any one of the second to fourth inventions, wherein the light can be emitted while switching the wavelength of the light stepwise.
- Light generator
- a sixth invention is the optical interference tomography for measurement of biological yarn and weaving according to any one of the second to fifth inventions, characterized in that the light source for generating light is a variable wavelength semiconductor laser. This is a single light generator.
- the tunable semiconductor laser according to the sixth aspect is characterized in that a super-periodic structure diffraction grating distributed reflection type semiconductor laser, sampled grating distributed reflection type semiconductor laser, grating, coupler, sampled
- a super-periodic structure diffraction grating distributed reflection type semiconductor laser, sampled grating distributed reflection type semiconductor laser, grating, coupler, sampled This is a light generating device for optical interference tomography for biological tissue measurement, characterized by being one of a reflector and a laser.
- An eighth invention is an optical interference tomography apparatus for measuring biological tissue, comprising the light generation device for optical interference tomography for measuring biological tissue of the first invention.
- the ninth invention is a variable wavelength light generating means using the light generation apparatus for optical interference tomography for biological tissue measurement according to any one of the second to seventh inventions as a light source, and the variable wavelength light generating means.
- Main splitting means for splitting the light generated from the stage into measurement light and reference light, measurement light irradiation means for irradiating the target living tissue while scanning the measurement light split by the main splitting means,
- a signal light capturing unit that captures signal light that has been irradiated onto a living tissue and reflected or backscattered, and the signal light captured by the signal light capturing unit and the reference light that has been divided by the main dividing unit are combined.
- An optical interference tomography apparatus for measuring biological tissue comprising: an arithmetic control unit that obtains a tomographic image of the biological tissue based on the intensity of the light.
- a tenth invention is the optical interference for biological tissue measurement according to the ninth invention, characterized in that the main division means and the multiplexing means are both main division and multiplexing means in the ninth invention.
- Tomography is a device.
- An eleventh invention according to the ninth or tenth invention is an irradiation'capturing means in which the measurement light irradiating means and the signal light capturing means are combined. This is an optical interference tomography apparatus.
- a thirteenth aspect of the present invention is the optical interference tomography apparatus for biological tissue measurement according to the twelfth aspect of the present invention, wherein the biological yarn and weave is an eye.
- a fourteenth aspect of the invention is an optical interference tomography apparatus for measuring a living tissue, characterized in that, in the thirteenth aspect, the anterior segment of the eye is measured.
- a fifteenth aspect of the present invention includes, in the thirteenth or fourteenth aspect, a fixing support means for fixing and supporting the face of the subject in a state where the subject is sitting and the eyes are oriented in the horizontal direction.
- An optical interference tomography apparatus for measuring biological tissue.
- the first, third to seventh inventions 1.53-: Since light in the wavelength region of L 85 m is used as measurement light, the influence of light absorption by water is suppressed. The effect of light scattering can be reduced while, for example, a tomographic image of a tissue behind a scatterer such as the sclera of the eye or iris can be taken clearly.
- the second to seventh inventions to optical frequency domain coherent interferometry (OFDR—OCT method)
- faults in a wide range can be achieved due to its high-speed operation. Even when an image is taken, the image does not blur due to the movement of the measurement target.
- the wave number interval during wavelength sweep is 3.9 X 10— 4 m 1 or less.
- the measurement depth for an eye with an average refractive index of 1.35 can be set to 3 mm, and the measurement required for the measurement of the anterior segment (the area where the anterior corneal force also reaches the posterior surface of the lens), especially the corner angle The depth can be secured.
- the measurement depth lmm necessary for measuring the anterior segment of these measurement objects is secured by setting the wave number interval to 1.2 X 10-m 1 or less.
- the measurement depth can be set to 10 mm.
- Such deep measurements are not possible with other OCT methods. It cannot be implemented easily.
- OFDR-OCT is characterized by extremely high sensitivity compared to the conventional OCDR-OCT, and this point is also necessary for taking a clear tomographic image of the tissue behind the scatterer such as the sclera. It works extremely advantageously.
- the high sensitivity of OFDR-OCT is based on the fact that the signal intensity of the tomographic image increases in proportion to the number of waves used for measurement (or its square).
- a variable wavelength semiconductor laser as a light source for generating light in the wavelength region of the OFDR-OCT method, in particular, a super-periodic structure developed for communication and having a high degree of perfection.
- Grating Coupled Sampled Reflector Laser GCSR Sampled Grating Distributed Bragg Reflection (SG-DBR Laser), Grating Coupler, Sampled Reflector Laser The above operation can be easily obtained by using a laser.
- the influence of light scattering can be reduced while suppressing the influence of light absorption of water, so that it is clear in a living tissue having a water content of 60% or more.
- a tomogram can be taken. That is, 1.53 ⁇ : OCT that uses light in the wavelength region of L 85 / zm as measurement light can reduce the effects of light scattering while suppressing the effects of water absorption. And other than that, it has a high water content! (60% or more) It is effective for tomographic imaging of living tissue.
- the measurement light in the wavelength region (1.53-1.85 m) is moderately absorbed in water. As it becomes hydraulic, it hardly penetrates the vitreous body of the eye having a size of about 2 cm and reaches the retina. For this reason, safety for the retina, which is extremely important as an eye tissue, can be greatly enhanced. Therefore, according to the present invention, for example, in the eye, a clear tomographic image of the entire shape of the vicinity of the corner composed of the sclera, cornea, and iris can be safely measured.
- the eye can be diagnosed without imposing a burden on the patient.
- the OCT method which is a non-contact method
- there is no need to hold the eye with an instrument there is no deformation of the eye being measured.
- an inexpensive OCT diagnostic apparatus can be constructed by using an existing slit lamp microscope. That is, there is no fixing support means for fixing and supporting the face of the subject while the subject is sitting in the horizontal direction and the means for irradiating the measurement light to the eye is attached to the slit lamp microscope.
- an optical interference tomography apparatus for eye diagnosis can be easily constructed. Since the fixed support means is not cheap, an optical interference tomography apparatus for diagnosing the eye can be constructed at low cost by using a slit lamp microscope existing in the ophthalmic clinic. This apparatus can be applied to an optical interference tomography apparatus using a light source in any wavelength region.
- the following steps can be realized. That is, the step of irradiating the tissue constituting the eye with the light generated by the optical interference tomography light generation device for measuring the biological tissue, and detecting the reflected light or the back scattered light generated inside the tissue constituting the eye And a step of generating a structure in the depth direction of the tissue constituting the eye by the optical interference tomography device for measuring biological tissue based on the detection data detected by the detector. Therefore, according to the present invention, a method for diagnosing the tissue constituting the eye can be realized.
- FIG. 1 is a schematic configuration diagram of an embodiment when an optical interference tomography apparatus for measuring biological tissue according to the present invention is applied to an optical interference tomography apparatus for measuring eyes.
- FIG. 2 is a schematic configuration diagram of the measuring head of FIG.
- FIG. 3 is an explanatory diagram of a scanning method of the wavelength of the emitted light.
- FIG. 5 is a graph showing the relationship between the wavelength of water measurement light and the light absorption coefficient.
- FIG. 6 is a schematic structural diagram of an eye.
- FIG. 7 is a schematic structural diagram of an eye suffering from angle-closure glaucoma.
- FIG. 8 A tomographic image of the anterior segment.
- FIG. 9 It is a schematic configuration diagram of means for attaching the measuring head to the slit lamp microscope.
- Second coupler 14 Aiming 'light' source
- the OCT diagnostic machine used for ophthalmic tomography is mainly used for observation of the retina and has not been used for diagnosis of the anterior segment. Even if the anterior segment was measured with this device, it was not possible to observe the corners that were partially hidden behind the sclera and the ciliary body on the back of the iris.
- the OCT apparatus in practical use is a super 'luminescent' diode with a center wavelength of 0.83 m.
- a light source SLD
- SLD light source
- the morphology of the cornea, sclera, and iris near the corner is observed by UBM as a whole.
- the OCT method image measured with light with a center wavelength of 1.31 m is unclear despite the longer measurement wavelength and the effect of light scattering is reduced. It is not possible to observe the entire iris. This is presumably because the measurement light is scattered by scatterers such as the sclera and iris, and the measurement light cannot reach the root of the iris hidden behind the sclera and the back of the iris.
- 1.53- For light in the wavelength region of L 85 m, a clear image can be obtained in which the influence of water absorption hardly becomes a problem. When you get it, it ’s the power to sing, and it ’s clear. This is because, in the light of the wavelength region of 1.53-1.85 / zm, the absorption coefficient of water, which is relatively small at 10 cm 1, is difficult to reveal the effect of water absorption, and light scattering by living tissue. Since the intensity of light suddenly weakens as the wavelength increases, it is presumed that the measurement light reaches deeper due to the decrease in scattering due to the longer wavelength of the measurement light.
- the wavelength region of the measurement light is more preferably 1.58 to L 80 m, and even more preferably 1.68 to 1.70 / zm.
- the wavelength range of the measurement light is 1.59 ⁇ 1.79 ⁇ m, 1.60 ⁇ : L 78 m, 1.61 ⁇ 1. ⁇ ⁇ ⁇ , 1.62 ⁇ : L 76 / ⁇ ⁇ , 1.63 ⁇ : L 75 m in this order.
- light source From the viewpoint of availability, reliability, etc., the wavelength region of the measurement light is a wavelength band that has been developed for communications. 1.
- the advantage of using the light in the wavelength region as the measurement light is other than the above.
- the absorption coefficient for water in the above wavelength region is relatively small at about 10 cm 1 , 99% is still water, and the measurement light reaches the retina through a vitreous body having a diameter of about 2 cm. Almost no. Therefore, the safety of the retina, which is extremely important as an eye tissue, is extremely high.
- 1.53 to: OCT using light in the wavelength region of L 85 m as measurement light is suitable for measuring the entire tomographic image reaching the rear surface force of the iris.
- the surface force of the sclera is suitable for measuring the entire tomographic image reaching the back surface. Therefore, it is suitable for measuring a tomographic image of a part or the whole of the anterior eye portion (the region of the frontal surface of the cornea that reaches the rear surface of the crystalline lens).
- the wavelength region of the light used as the measurement light is in the range of 1.53 to L 85 m, but it is necessary to use only the wavelength of this entire region as the measurement light.
- light in a part of the wavelength region such as 1.53-1.57 m, or wavelength including all of the region such as 1.50 to L 90 m.
- the light source for the light generator of the OCDR OCT device and the FD-OCT device is used.
- the central wavelength of the light is from 1.53 to L in the wavelength range of 85 m.
- the OCT method is a non-contact method, as described in the following examples, tissue observation of the eye can be performed while sitting. This is an excellent feature that UBM needs to measure in the supine position. Moreover, since there is no need to hold the eye with an instrument, there is no deformation of the eye being measured. [0051] Further, it is also effective for measuring foreign matter (metal fragments) that has entered the eye just by measuring the corner angle, and for measuring the anterior eye portion (such as the back of the iris or ciliary body) other than the corner angle. In addition, because it is possible to measure the lens, it is also effective for pre- and post-operative diagnosis of cataract surgery. A portion of the vitreous can also be measured after passing through the anterior segment.
- the only OCT apparatus in practical use is based on the OCDR-OCT method.
- OCT— OCT equipment based on the OCT method requires mechanical scanning of the reference mirror to change the optical path length of the reference light, and the mechanical scanning becomes the rate-determining rate of measurement, making high-speed measurement difficult.
- the measurement range in the depth direction of the tomographic image is limited to a narrow range of about 1 to 2 mm.
- the OFDR-OCT method developed by the present inventors does not require mechanical scanning of the reference mirror or spectroscopic measurement by using variable wavelength light, enabling high-speed measurement and a measurement range of 3 mm. This can be easily done.
- the OFDR-OCT method also has the advantage that the signal strength is about 10 to L000 times stronger than other OCT methods.
- the measurement range ⁇ z in the depth direction in a tissue having a refractive index n is expressed by the following equation:
- the coherence distance of light is the distance length of the optical path that is obtained by dividing the intensity (power intensity) of the interference light generated when the light is incident on the Michelson interferometer. This is the full width at half maximum when measured as a function of the difference in distance to the wave point.
- the wave number interval does not include 0 ⁇ m ⁇ 1 because the wave number is never one.
- OCT using a tunable semiconductor laser as the light source can easily widen the measurement range in the depth direction, and can also perform two-dimensional scanning over a wide range with its high-speed force. It is suitable for measurement of tomographic images of the anterior segment).
- the corner angle in particular, the adhesion force between the iris and the sclera, the entire side of the iris that reaches the pupil, the corneal (and scleral) force located on that side, and the half of the anterior eye that is the corneal (and scleral) force
- the entire anterior eye part which is the iris and the corneal (and scleral) force located on the iris from one of the attached part of the iris and sclera to the other attached part of the iris and sclera. It is preferable to measure the iris up to the back surface, but it is possible to diagnose glaucoma and the like without necessarily measuring the back surface.
- OCT that uses light in the wavelength range of 1.553-1.85 m as measurement light can reduce the effects of light scattering while suppressing the effects of light absorption by water, so it can contain moisture other than the eye. It is also effective for tomographic imaging of a large amount of living tissue.
- the moisture content of typical biological tissues is shown in Table 1 below.
- biological tissues other than the skeleton (including teeth) and adipose tissue have a water content of 60% by weight or more, and OCT using light in the above-described wavelength region as measurement light.
- the tomographic imaging by the method can be performed satisfactorily.
- the water content of the living tissue that can be satisfactorily performed tomographic imaging by the OCT method using the light in the wavelength region described above as the measurement light is preferably 60% by weight or more. 80% by weight or more is even more preferable.
- a variable wavelength laser satisfying the above conditions can be easily obtained.
- a typical example is a superperiodic structure grating distributed reflection type variable wavelength semiconductor laser (SSG-DBR laser) ( For example, see Non-Patent Document 3).
- SSG-DBR laser superperiodic structure grating distributed reflection type variable wavelength semiconductor laser
- SG-DBR laser sampled 'dalling distributed reflection type variable wavelength semiconductor laser
- GCSR laser GCSR laser
- FIG. 1 is a schematic configuration diagram of an optical interference tomography apparatus for eye measurement
- FIG. 2 is a schematic configuration diagram of the measurement head of FIG.
- a semiconductor laser having a super periodic structure diffraction grating distributed reflection type semiconductor laser for example, see Non-Patent Document 3 etc.
- the first directional coupler 12 is also optically connected to the light receiving port of the first force bra 12.
- the light transmission outlet on one side (division ratio 90% side) of the first force bra 12 is a main dividing means that also has a directional coupler equal force that divides light into two parts (for example, 70:30). Optically connected to the light inlet of the second force bra 13. At the light receiving port of the second force bra 13, a light emitting port of an aiming 'light' source 14, which is a visible light source that emits light in the visible region for visually confirming the irradiation position of the measurement light, is optically provided. Connected to
- the light transmission port on one side of the second force bra 13 (the division ratio side of 70%) is optically connected to the light reception port of the optical circulator 15.
- the light transmission port on the other side (division ratio 30% side) of the second coupler 13 is a third force block that is a multiplexing means that also has a directional coupler equal force that divides light into two (for example, 50:50).
- the optical outlet of the optical circulator 15 is optically connected to the optical inlet of the third coupler 16 and is connected to the proximal end side of the measuring head 40.
- the measuring head 40 is attached to a movable stage 51 provided on a support 50 and has a structure as shown in FIG.
- the member comprising the support 50 for supporting the measurement head, the support arms 52 and 53 for supporting the subject's face in the sitting position, and the microscope 60 for observing the eye of the subject is not necessarily another member such as the variable wavelength light source 11. There ’s no need to build it together.
- These members are used as standard in ophthalmic medicine, and are all provided in slit lamp microscopes. Therefore, if a means for attaching the measuring head to the slit lamp microscope is added to other members, the ophthalmic clinic In addition, it can be attached to an existing slit lamp microscope to make it possible to easily construct an optical interference tomography apparatus for eye diagnosis.
- FIG. 9 shows an example of means 201 for attaching the measurement head to the slit lamp microscope.
- the means 201 for attaching to the slit lamp microscope is composed of two flat plates 202, and two rows of holes 203 penetrating these flat plates are female screws, and a male screw (not shown) is fitted in each. It is integrated by. In the center of the integrated mounting means 201, it corresponds to the shape of the cross section of the support 50. Space 204 is provided.
- the attachment means 201 is fixed to the support tool 50 by sandwiching the support tool 50 in this space and fastening the screw.
- the movable stage 51 is fixed to the left end of the attachment means 201.
- the measuring head 40 is supported by the movable stage 51 of the support arm 50, and a main body cylinder 41 in which an entrance / exit light window 41a is formed in a part of the peripheral wall on the front end side;
- a collimating lens 42 optically connected to the optical circulator 15 disposed on the proximal end side inside the main body cylinder 41; and a collimating lens 42 disposed on the front end side inside the main body cylinder 41 for measuring light.
- a galvanometer mirror 43 capable of changing the traveling direction and movable in scanning, and a collimating lens 42 inside the main body cylinder 41 and a focusing lens 44 disposed between the galvanometer mirror 43 are provided.
- the support tool 50 is provided with support arms 52 and 53 for fixing and supporting the subject's face in a sitting position with the subject's eyes oriented horizontally, the irradiation position confirmation means A visual confirmation microscope 60 is attached.
- the optical circulator 15 force measuring head 40 has a measuring tube 40 and the measurement light incident on the collimating lens 42 inside the main body tube 41 is formed into a parallel beam and condensed by the focusing lens 44, and then the galvano mirror.
- the signal light that has exited from the entrance / exit light window 41a of the main body cylinder 41 through 43 and is reflected (backscattered) by being irradiated on the eye 100 enters the inside through the entrance / exit light window 41a of the main body cylinder 41, and The light is reflected by the galvanometer mirror 43 and enters the optical circulator 15 from the base end side of the main body cylinder 41 through the focusing lens 44 and the collimating lens 42.
- the optical circulator 15, the measurement head 40, etc. constitute an irradiation / capturing means that serves as both the measurement light irradiating means and the signal light capturing means, and the support 50, etc. ⁇ It also serves as a capture means position adjustment means and a fixed support means.
- the light transmission ports on one side and the other side of the third force bra 16 are optically connected to the light reception port of the first differential amplifier 17 having a light detection function. Connected.
- the Log output section of the first differential amplifier 17 is electrically connected to the Log input section of the second differential amplifier 18 that performs correction calculation for fluctuations in the input signal intensity.
- the light transmission port on the other side (the division ratio 10% side) of the first force bra 12 is a photodetector. It is optically connected to 19 light inlets. The output part of the photodetector 19 is electrically connected to the input part of the Log amplifier 20. The Log output unit of the Log amplifier 20 is electrically connected to the Log input unit of the second differential amplifier 18.
- the output unit of the second differential amplifier 18 synthesizes a coherent interference waveform, that is, a backscattering intensity distribution (see, for example, Non-Patent Document 5). It is electrically connected via Z digital converter.
- the output unit of the calculation control device 21 is electrically connected to the input unit of the display device 22 such as a monitor or a printer that displays the calculation result.
- the arithmetic and control unit 21 can control the variable wavelength light generator 11 based on the input information.
- the subject's face is fixedly supported on the support arms 52, 53 of the support device 50 in the sitting position, and the aiming 'light' source 14 is activated and measured.
- the light beam for visual recognition from the aiming “light” source 14 emitted from the distal end side of the head 40 is visually confirmed by the microscope 60 and is irradiated to a target portion of the eye 100 of the subject.
- Adjust movable stage 51 is provided.
- variable wavelength light generator 11 (wavelength variable range: 1.530 to 1.570 / ⁇ ⁇ , wave number interval) : 2.3 X 10— 4 / ⁇ ⁇ 1 , spectral frequency width: 10 MHz or less, coherence distance in air: 13 mm or more, or wavelength tunable range: 1.68 to: L 70 ⁇ m, wave number interval: 9 7 X 10— 5 / zm— ⁇
- Spectral frequency width 10 MHz or less, coherence distance in air: 13 mm or more, and the coherence distance in air is calculated using equation (4) in Non-Patent Document 5.
- Spectral frequency width force was also calculated.
- the wave number of the light for measurement is generated while switching so as to change stepwise with respect to the sweep time.
- the switching method (sweep method) is, for example, shown in FIG. Show As shown in Fig. 3 (b), it can be gradually reduced, or as shown in Fig. 3 (c), it can be said that it can be changed irregularly.
- all the predetermined wave numbers may be scanned within the measurement time.
- the present inventors changed the tomographic image by changing the wave number of the measurement light generated in the OFDR-OCT light source force stepwise with respect to the sweep time. I found out that it was clear.
- the “predetermined wave number” is preferably a set of wave numbers arranged at equal intervals, but is not necessarily limited to this. For example, by considering calculation processing when creating a tomographic image, Even if the interval is not constant and the set of wave numbers is applicable.
- the light generated from the variable wavelength light generator 11 is divided into two (90:10) by the first force bra 12.
- the light on one side (90% side) divided into two by the first force bra 12 is divided into two (70:30) by the second force bra 13.
- the other side (10% side) light (correction light) divided into two by the first force bra 12 is sent to the photodetector 19.
- the light (measurement light) on one side (70% side) divided into two by the second force bra 13 passes through the measurement head 40 via the optical circulator 15 together with the visible light. As described above, the light is emitted from the distal end side of the measuring head 40 to irradiate the eye 100 of the subject.
- the light combined by the third force bra 16 is sent to the first differential amplifier 17.
- the first differential amplifier 17 outputs the Log output signal to the second differential amplifier 18.
- the light detector 19 converts the light (correction light) on the other side (10% side) divided into two by the first force bra 12 into an electrical signal and outputs it to the Log amplifier 20.
- the Log amplifier 20 outputs a Log output signal to the second differential amplifier 18.
- the second differential amplifier 18 performs an input intensity correction operation, and then outputs the information signal to the analog Z-digital converter.
- the analog Z-digital converter converts the input information signal into a digital signal and outputs the digital signal to the arithmetic control device 21.
- the arithmetic and control unit 21 performs arithmetic processing based on various kinds of input information (see, for example, Non-Patent Document 5), obtains a coherence interference waveform, that is, the intensity of the signal light, and based on the intensity or the like A tomographic image of the eye 100 is obtained and the result is displayed on the display device 22.
- FIG. 4 shows an example of the measurement result of the eye 100 using the optical interference tomography apparatus for eye measurement as described above (wavelength variable range: 1.53 to: L 57 ⁇ m, wave number interval). : 2.3 X 10 "spectral frequency width: taken at 10 MHz). The time required to obtain the tomographic image as shown in Fig. 4 is only 1 second.
- FIG. 8 is a tomographic image of the anterior segment taken separately. Even in the scleral shadow, the iris is clearly projected. The strong observation of even the shadow of the sclera, which is a scatterer, seems to be due to the fact that the selected measurement wavelength was suitable and the high sensitivity of OFDR-OCT. It is easy to increase the measurement speed, and it is possible to measure for 0.1 seconds or less by increasing the wave number switching speed of the light source.
- the second force bra 13 and the third force bra 16 are used by constructing a Mach-Zender interferometer using the optical circulator 15.
- constructing a Michelson interferometer it is also possible to apply a main division / combination means that combines the main division means and the multiplexing means.
- the force to which the optical circulator 15 is applied is applied.
- the optical circulator 15 does not operate with visible light generated by an aiming 'light' source, Instead of the circulator 15, it is possible to apply a force bra, for example.
- the measurement light is obtained by using the optical circulator 15. Force to apply the measurement head 40 capable of performing both the emission guide and the signal light entrance guide in the same optical path.
- the optical circulator 15 is omitted, and It is also possible to provide two optical fibers in parallel so that one optical fiber can guide the emission of measurement light and the other optical fiber can guide the incidence of signal light.
- the optical fibers of the two optical fibers are slightly deviated from each other, resulting in a difference in the optical axes of the outgoing measurement light and the incident signal light. There will be no inconvenience.
- the force OCDR-OCT or FD-OCT described in the case of OFDR-OCT can also be applied.
- the present invention can be applied to a cheap OCT method (see, for example, Non-Patent Document 4).
- the present invention can be applied even if the wavelength of the light source is continuously switched in OFDR-OCT.
- the light source is an SLD capable of emitting measurement light with a center wavelength of 1.55 m or 1.69 ⁇ m and an emission spectrum width of 30 nm, and an interference system
- a Michelson interferometer for example, see FIG. 4 of Non-Patent Document 6
- other means such as the measurement light irradiation means are the same as those in this embodiment, and a tomogram is obtained.
- a means for construction for example, a construction using a photodiode (PD), a computer (PC), or the like as described in FIG.
- the wavelength when applied to the chirp OCT method, in this embodiment, instead of the variable wavelength light generator 11, the wavelength can be continuously switched, and the wavelength is continuously switched. However, it may be measured.
- the intensity of the interference light generated by changing the wavelength of the light source linearly with respect to time is Fourier-transformed on the time axis, and the depth is detected by detecting the frequency of the beat signal. Get direction information.
- the intensity of the interference light obtained in the same way is Fourier transformed with respect to the wave number instead of the time, information approximate to OFDR-OCT can be detected.
- the sample optical path the optical path where the measurement target exists
- the optical path length difference between the optical path and the reference optical path the other optical path
- the present invention can be applied to a method that cannot capture an image.
- optical interference tomography light generation device for biological tissue measurement and the optical interference tomography device for biological tissue measurement according to the present invention can easily perform, for example, eye examination. It is used in the manufacturing industry for precision equipment.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP05774696A EP1787588A4 (en) | 2004-08-26 | 2005-08-25 | TOMOGRAPHIC LIGHT GENERATION DEVICE AND OPTICAL TISSUE MEASUREMENT INTERFERENCE AND OPTICAL INTERFERENCE TOMOGRAPHIC DEVICE FOR EYE MEASUREMENT |
JP2006532592A JP4654357B2 (ja) | 2004-08-26 | 2005-08-25 | 生体組織測定用の光干渉トモグラフィー用光発生装置及び生体組織測定用の光干渉トモグラフィー装置 |
US11/660,971 US20070268456A1 (en) | 2004-08-26 | 2005-08-25 | Tissue Measuring Optical Coherence Tomography-Use Light Source and Tissue Measuring Optical Coherence Tomography System |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004-246293 | 2004-08-26 | ||
JP2004246293 | 2004-08-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006022342A1 true WO2006022342A1 (ja) | 2006-03-02 |
Family
ID=35967549
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/015457 WO2006022342A1 (ja) | 2004-08-26 | 2005-08-25 | 生体組織測定用の光干渉トモグラフィー用光発生装置及び生体組織測定用の光干渉トモグラフィー装置 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20070268456A1 (ja) |
EP (1) | EP1787588A4 (ja) |
JP (1) | JP4654357B2 (ja) |
WO (1) | WO2006022342A1 (ja) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008145188A (ja) * | 2006-12-07 | 2008-06-26 | Fujifilm Corp | 光断層画像化装置 |
JP2009291517A (ja) * | 2008-06-09 | 2009-12-17 | Tomey Corporation | 前眼部断面画像の解析方法及び前眼部撮影装置、その記録媒体およびそのプログラム |
JP2010522055A (ja) * | 2007-03-20 | 2010-07-01 | トプコン・ユーロペ・メディカル・ビーブイ. | 眼を観察するための装置及び方法とoctモジュール |
JP2011516176A (ja) * | 2008-04-02 | 2011-05-26 | リフォーカス グループ、インコーポレイテッド | 強膜補綴物を眼に挿入する場所を特定するためのシステム及び方法 |
JP2011196695A (ja) * | 2010-03-17 | 2011-10-06 | Kitasato Institute | オプティカル・コヒーレンス・トモグラフィー装置とその光源 |
JP2014057899A (ja) * | 2014-01-07 | 2014-04-03 | Nidek Co Ltd | 眼科撮影装置 |
WO2014200093A1 (ja) * | 2013-06-14 | 2014-12-18 | 国立大学法人名古屋大学 | 光断層画像撮影装置 |
JP2015043844A (ja) * | 2013-08-28 | 2015-03-12 | 株式会社ニデック | 眼科撮影装置及び眼科撮影プログラム |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1677095A1 (en) * | 2003-09-26 | 2006-07-05 | The Kitasato Gakuen Foundation | Variable-wavelength light generator and light interference tomograph |
EP2090223A1 (en) * | 2008-02-15 | 2009-08-19 | OPTOPOL Technology Spolka Akcyjna | Optical set for examining of objects and method for examining of objects using optical devices |
DE102008063225A1 (de) | 2008-12-23 | 2010-07-01 | Carl Zeiss Meditec Ag | Vorrichtung zur Swept Source Optical Coherence Domain Reflectometry |
JP5601612B2 (ja) * | 2009-06-02 | 2014-10-08 | 株式会社ニデック | 眼科撮影装置 |
US9506740B2 (en) | 2009-12-01 | 2016-11-29 | The Brigham And Women's Hospital | System and method for calibrated spectral domain optical coherence tomography and low coherence interferometry |
JP2011212432A (ja) * | 2010-03-15 | 2011-10-27 | Nidek Co Ltd | 眼科撮影装置 |
WO2012149420A1 (en) * | 2011-04-29 | 2012-11-01 | Optovue, Inc. | Improved imaging with real-time tracking using optical coherence tomography |
TWI473037B (zh) * | 2011-10-11 | 2015-02-11 | Univ Nat Taiwan | 鏡像消除方法 |
KR101641260B1 (ko) * | 2012-04-18 | 2016-07-20 | 엘지전자 주식회사 | 광간섭성 단층 촬영 장치 및 이의 제어 방법 |
WO2014156785A1 (ja) * | 2013-03-28 | 2014-10-02 | 株式会社ニデック | 光断層像撮影装置および医療用観察装置 |
WO2014194317A1 (en) | 2013-05-31 | 2014-12-04 | Covidien Lp | Surgical device with an end-effector assembly and system for monitoring of tissue during a surgical procedure |
US11666223B2 (en) * | 2017-02-22 | 2023-06-06 | University Of Maryland, Baltimore | Apparatus and method for tooth pulp vitality detection |
US11963722B2 (en) | 2021-04-13 | 2024-04-23 | Amo Development, Llc | Methods and systems for determining change in eye position between successive eye measurements |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09196812A (ja) * | 1996-01-22 | 1997-07-31 | Atr Hikari Denpa Tsushin Kenkiyushiyo:Kk | 光の屈折率変化が生じる位置を測定する装置 |
JPH11108763A (ja) * | 1997-09-30 | 1999-04-23 | Seitai Hikarijoho Kenkyusho:Kk | 光計測装置 |
JPH11326182A (ja) * | 1998-05-21 | 1999-11-26 | Kao Corp | 皮膚の計測装置 |
JP2002095663A (ja) * | 2000-09-26 | 2002-04-02 | Fuji Photo Film Co Ltd | センチネルリンパ節光断層画像取得方法および装置 |
JP2002113017A (ja) * | 2000-10-05 | 2002-04-16 | Fuji Photo Film Co Ltd | レーザ治療装置 |
JP2002214127A (ja) * | 1996-02-27 | 2002-07-31 | Massachusetts Inst Of Technol <Mit> | 光ファイバ撮像ガイドワイヤ、カテーテルまたは内視鏡を用いて光学測定を行う方法および装置 |
JP2004033277A (ja) * | 2002-06-28 | 2004-02-05 | Nidek Co Ltd | 眼科装置及びこれを備えるレーザ治療装置 |
JP2004167080A (ja) * | 2002-11-21 | 2004-06-17 | Shimizu Kimiya | 酸素飽和度測定装置 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4552440A (en) * | 1983-10-12 | 1985-11-12 | Guyton D L | Apparatus for determination of potential visual acuity utilizing a slit lamp microscope |
US5956355A (en) * | 1991-04-29 | 1999-09-21 | Massachusetts Institute Of Technology | Method and apparatus for performing optical measurements using a rapidly frequency-tuned laser |
US6201608B1 (en) * | 1998-03-13 | 2001-03-13 | Optical Biopsy Technologies, Inc. | Method and apparatus for measuring optical reflectivity and imaging through a scattering medium |
US5975697A (en) * | 1998-11-25 | 1999-11-02 | Oti Ophthalmic Technologies, Inc. | Optical mapping apparatus with adjustable depth resolution |
JP3564373B2 (ja) * | 2000-09-08 | 2004-09-08 | 独立行政法人 科学技術振興機構 | 光計測システム |
US6711203B1 (en) * | 2000-09-22 | 2004-03-23 | Blueleaf, Inc. | Optical transmitter comprising a stepwise tunable laser |
JP2003090792A (ja) * | 2001-09-20 | 2003-03-28 | Fuji Photo Film Co Ltd | 光断層画像化装置 |
JP3785576B2 (ja) * | 2002-04-24 | 2006-06-14 | 株式会社モリタ製作所 | 被写体ブレ補正手段、これを用いた医療用x線撮影装置 |
US7133137B2 (en) * | 2002-06-27 | 2006-11-07 | Visx, Incorporated | Integrated scanning and ocular tomography system and method |
-
2005
- 2005-08-25 EP EP05774696A patent/EP1787588A4/en not_active Withdrawn
- 2005-08-25 JP JP2006532592A patent/JP4654357B2/ja active Active
- 2005-08-25 US US11/660,971 patent/US20070268456A1/en not_active Abandoned
- 2005-08-25 WO PCT/JP2005/015457 patent/WO2006022342A1/ja active Application Filing
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09196812A (ja) * | 1996-01-22 | 1997-07-31 | Atr Hikari Denpa Tsushin Kenkiyushiyo:Kk | 光の屈折率変化が生じる位置を測定する装置 |
JP2002214127A (ja) * | 1996-02-27 | 2002-07-31 | Massachusetts Inst Of Technol <Mit> | 光ファイバ撮像ガイドワイヤ、カテーテルまたは内視鏡を用いて光学測定を行う方法および装置 |
JPH11108763A (ja) * | 1997-09-30 | 1999-04-23 | Seitai Hikarijoho Kenkyusho:Kk | 光計測装置 |
JPH11326182A (ja) * | 1998-05-21 | 1999-11-26 | Kao Corp | 皮膚の計測装置 |
JP2002095663A (ja) * | 2000-09-26 | 2002-04-02 | Fuji Photo Film Co Ltd | センチネルリンパ節光断層画像取得方法および装置 |
JP2002113017A (ja) * | 2000-10-05 | 2002-04-16 | Fuji Photo Film Co Ltd | レーザ治療装置 |
JP2004033277A (ja) * | 2002-06-28 | 2004-02-05 | Nidek Co Ltd | 眼科装置及びこれを備えるレーザ治療装置 |
JP2004167080A (ja) * | 2002-11-21 | 2004-06-17 | Shimizu Kimiya | 酸素飽和度測定装置 |
Non-Patent Citations (1)
Title |
---|
See also references of EP1787588A4 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008145188A (ja) * | 2006-12-07 | 2008-06-26 | Fujifilm Corp | 光断層画像化装置 |
JP2010522055A (ja) * | 2007-03-20 | 2010-07-01 | トプコン・ユーロペ・メディカル・ビーブイ. | 眼を観察するための装置及び方法とoctモジュール |
JP2011516176A (ja) * | 2008-04-02 | 2011-05-26 | リフォーカス グループ、インコーポレイテッド | 強膜補綴物を眼に挿入する場所を特定するためのシステム及び方法 |
JP2009291517A (ja) * | 2008-06-09 | 2009-12-17 | Tomey Corporation | 前眼部断面画像の解析方法及び前眼部撮影装置、その記録媒体およびそのプログラム |
JP2011196695A (ja) * | 2010-03-17 | 2011-10-06 | Kitasato Institute | オプティカル・コヒーレンス・トモグラフィー装置とその光源 |
WO2014200093A1 (ja) * | 2013-06-14 | 2014-12-18 | 国立大学法人名古屋大学 | 光断層画像撮影装置 |
JPWO2014200093A1 (ja) * | 2013-06-14 | 2017-02-23 | 国立大学法人名古屋大学 | 光断層画像撮影装置 |
JP2015043844A (ja) * | 2013-08-28 | 2015-03-12 | 株式会社ニデック | 眼科撮影装置及び眼科撮影プログラム |
JP2014057899A (ja) * | 2014-01-07 | 2014-04-03 | Nidek Co Ltd | 眼科撮影装置 |
Also Published As
Publication number | Publication date |
---|---|
JPWO2006022342A1 (ja) | 2008-05-08 |
US20070268456A1 (en) | 2007-11-22 |
EP1787588A4 (en) | 2007-10-31 |
JP4654357B2 (ja) | 2011-03-16 |
EP1787588A1 (en) | 2007-05-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4654357B2 (ja) | 生体組織測定用の光干渉トモグラフィー用光発生装置及び生体組織測定用の光干渉トモグラフィー装置 | |
US7859682B2 (en) | Optical interference apparatus | |
US8801180B2 (en) | Ophthalmic tomographic imager with corneo-retinal image analysis | |
US8115934B2 (en) | Device and method for imaging the ear using optical coherence tomography | |
US7835010B2 (en) | Optical coherence tomography system and optical coherence tomography method | |
US7511822B2 (en) | Optical tomographic imaging apparatus | |
JP5679686B2 (ja) | 光干渉断層撮像装置 | |
JP2014144178A (ja) | 眼科用光断層画像表示装置 | |
JP2015102537A (ja) | 光干渉断層計 | |
JP2009520531A (ja) | 眼の生体計測法データを求めるための眼科学測定システムおよび方法 | |
US9918628B2 (en) | Accommodation function evaluation apparatus | |
US20090296102A1 (en) | Coherence tomography device | |
JP2018047099A (ja) | Oct装置 | |
JP2022176282A (ja) | 眼科装置、及びその制御方法 | |
JP2022189969A (ja) | 眼科装置、及び眼科情報処理装置 | |
JP7162539B2 (ja) | 眼科装置、及びその制御方法 | |
RU2328208C1 (ru) | Лазерный конфокальный двухволновый ретинотомограф с девиацией частоты | |
JP2016002382A (ja) | 撮像装置 | |
JP2006267034A (ja) | 断層計測装置及び断層計測方法 | |
JP5998395B2 (ja) | イメージングプローブ | |
US20130128277A1 (en) | Arrangement and method for interferometry | |
JP7231405B2 (ja) | 眼科装置、及びその制御方法 | |
Fercher et al. | Optical coherence tomography in medicine | |
JP7202819B2 (ja) | 眼科装置、及びその制御方法 | |
KR102178998B1 (ko) | 망막의 넓은 범위 혈류속도 측정을 위한 광경로 길이 차이 인코딩 방식의 이중빔 스캐닝 광가간섭 단층촬영 장치 및 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006532592 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 11660971 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005774696 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2005774696 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 11660971 Country of ref document: US |