Diagnosis system and diagnosis method

Abstract

A diagnosis system and a diagnosis method are provided. More specifically, embodiments of the present disclosure relate to a diagnosis system for detection of corneal degeneration impacting the biomechanical stability of the human cornea and a diagnosis method for detection of corneal degeneration impacting the biomechanical stability of the human cornea. Still more specifically, embodiments of the present disclosure relate to a diagnosis system for early detection of corneal degeneration impacting the biomechanical stability of the human cornea and a diagnosis method for early detection of corneal degeneration impacting the biomechanical stability of the human cornea.

Claims

1. A diagnosis system, comprising: an optical coherence tomography (OCT) device configured to emit a first light beam having a first wavelength .sub.1; a Brillouin scattering (BS) spectrometer configured to emit a second light beam having a second wavelength .sub.2 different from the first wavelength .sub.1; a beam combiner comprising a dichroic mirror arranged: in the optical path of the first light beam and having a first reflectivity for transmitting the first light beam in an optical path towards a cornea, the first reflectivity being at least within a first wavelength range R.sub.1 covering at least the first wavelength .sub.1 of the first light beam and a spectral bandwidth .sub.1 of the OCT device; and in the optical path of the second light beam and having a second reflectivity for reflecting the second light beam in the optical path towards the cornea, the second reflectivity at least within a second wavelength range R.sub.2 covering the second wavelength .sub.2 of the second light beam and a spectral bandwidth .sub.2, wherein the first wavelength range R.sub.1 and the second wavelength range R.sub.2 are disjoint and the first reflectivity and the second reflectivity are different; wherein the transmission of the first light beam and the reflection of the second light beam combines the first light beam and the second light beam and propagates the combined beam along the same optical path towards a cornea; a beam guiding and focusing device configured to focus the first light beam and the second light beam together at a predetermined position (x,y,z) on or in the cornea; and a control and analysis device configured to scan a directional orientation (k.sub.x,k.sub.y,k.sub.z) of the first light beam and the second light beam along that the first light beam and the second light beam enter the focus (x,y,z) on or in the cornea; the OCT device is further configured to interferometrically analyze the first light beam backscattered from the cornea via the beam combiner to provide OCT data representing a position dependent structural property of the cornea; and the BS spectrometer is further configured to spectroscopically analyze the second light beam backscattered from the cornea via the beam combiner to provide BS data representing a position dependent frequency shift (f.sub.B(x,y,z)) of a Brillouin scattering caused side band of the backscattered second light beam; wherein the control and analysis device further configured to: control the beam guiding and focusing device to scan the predetermined position (x,y,z) in a three-dimensional manner; calculate, using a lookup table in a memory location, a local optical density and a local mass density of the cornea.

2. The diagnosis system of claim 1, wherein the BS spectrometer is further configured to spectroscopically analyze the second light beam backscattered from the cornea via the beam combiner to provide BS data representing also a position dependent line width (f.sub.B(x,y,z)) of the Brillouin scattering caused side band of the backscattered second light beam.

3. The diagnosis system of claim 1, wherein: the beam guiding and focusing device is further configured to adjust the directional orientation (k.sub.x,k.sub.y,k.sub.z) of the first light beam and the second light beam, along which the first light beam and the second light beam enter the focus on or in the cornea; and the BS spectrometer is further configured to spectroscopically analyze the second light beam backscattered from the cornea via the beam combiner to provide BS data also representing a direction dependent frequency shift (f.sub.B(x,y,z,k.sub.x,k.sub.y,k.sub.z)) of the Brillouin scattering caused side band.

4. The diagnosis system of claim 1, wherein: the beam guiding and focusing device is further configured to adjust the directional orientation (k.sub.x,k.sub.y,k.sub.z) of the first light beam and the second light beam, along which the first light beam and the second light beam enter the focus on or in the cornea; and the BS spectrometer is further configured to spectroscopically analyze the second light beam backscattered from the cornea via the beam combiner to provide BS data also representing a direction dependent line width (f.sub.B(x,y,z,k.sub.x,k.sub.y,k.sub.z)) of the Brillouin scattering caused side band.

5. The diagnosis system of claim 1, the control and analysis device further configured to: control the beam guiding and focusing device to scan the predetermined position (x,y,z) of the focus on or in the cornea in a one-, two-, or three-dimensional manner; and calculate a spatially resolved topological or morphological structure from the OCT data or calculate spatially resolved elastomechanical or viscoelastic properties of the cornea from the BS data.

6. The diagnosis system of claim 5, wherein the control and analysis device is further configured to calculate $M_1=\frac{{}_2^2.Math.}{4.Math.n^2}.Math.f_B^2\mathrm{or}$ $M_2=\frac{{}_2^2.Math.}{4.Math.n^2}.Math.f_B.Math.f_B,$ where M.sub.1 is the real part of the complex longitudinal modulus M=M.sub.1+iM.sub.2 of the cornea, M.sub.2 is the imaginary part of the complex longitudinal modulus M=M.sub.1+iM.sub.2 of the cornea, .sub.2 is the second wavelength of the second light beam, is the mass density of the cornea, n is the optical density of the cornea, f.sub.B is the frequency shift of the Brillouin scattering caused side band of the backscattered second light beam, and f.sub.B is the line width of the Brillouin scattering caused side band of the backscattered second light beam.

7. The diagnosis system of claim 5, wherein the control and analysis device is further configured to spatially correlate the OCT data with the BS data such that for each spatial position (x,y,z) the topological or morphological structure of the cornea is associated with the corresponding elastomechanical or viscoelastic properties of the cornea.

Description

(1) Further features, advantages and technical effects of the disclosure will become apparent from the following description of exemplary embodiments with reference to the accompanying drawings, in which:

(2) FIG. 1 schematically illustrates a diagnosis system,

(3) FIG. 2 schematically illustrates the transmission and reflectivity of a beam combiner of the diagnosis system in FIG. 1 (not drawn to scale), and

(4) FIG. 3 schematically illustrates a diagnosis method executed by the diagnosis system of FIG. 1.

(5) FIG. 1 shows a diagnosis system 10, which comprises an optical coherence tomography (short: OCT) device 12, which is configured to emit a first coherent light beam 14 having a first wavelength .sub.1 around 800 nm. As an example, the OCT device 12 is based on OCT in the Fourier domain (in short: FD-OCT) and comprises a light source that emits the first light beam 14 as broadband light of a particular spectral bandwidth .sub.1, i.e. the full width at half maximum (short: FWHM) of the spectral distribution of the first light beam 14 is around 100 nm. The first wavelength .sub.1 of the first light beam 14 is the central wavelength of the OCT-spectrum, i.e. of the spectral bandwidth .sub.1. The spectral distribution of the first light beam 14 is schematically illustrated by the dashed lines in FIG. 2. The OCT device has exemplarily an axial resolution of less than 10 m.

(6) The diagnosis system 10 additionally comprises a Brillouin scattering (short: BS) spectrometer 16, which is configured to emit a second coherent light beam 18 having a second wavelength .sub.2 around 532 nm. The FWHM of the spectral distribution of the (un-scattered) second light beam 18 is less than 10 MHz. The spectral distribution of the (un-scattered) first light beam 18 is schematically illustrated by the dot lined peak at .sub.2 in FIG. 2.

(7) A beam combiner 20 of the diagnosis system 10 is configured to combine the first light beam 14 and the second light beam 18 such that the first light beam 14 and the second light beam 18 propagate along a same optical path 22 towards a cornea 24 of an eye 26.

(8) As an example, the beam combiner 20 is realized as a dichroic mirror. As shown in FIG. 2, the beam combiner 20 has a transmission T() around 90% or less e.g., around 95% or more at least within a first wavelength range R.sub.1 covering at least the first wavelength .sub.1 of the first light beam 14 and the spectral bandwidth .sub.1 of the OCT device 12. The minimum value of the first wavelength range R.sub.1 is smaller than .sub.1.sub.1/2 and the maximum value of the first wavelength range R.sub.1 is larger than .sub.1+.sub.1/2. The beam combiner 20 has a reflectivity R(A) around 90% or more, e.g., 95% or more at least within a second wavelength range R.sub.2 covering the second wavelength .sub.2 of the second light beam 18 and a spectral bandwidth .sub.2. It applies: T()=1R(). The second spectral bandwidth .sub.2 corresponds to around 30 GHz. The minimum value of the second wavelength range R.sub.2 is smaller than .sub.2.sub.2/2 and the maximum value of the second wavelength range R.sub.2 is larger than .sub.2+.sub.2/2. The beam combiner 20 is configured such that the first wavelength range R.sub.1 and the second wavelength range R.sub.2 are disjoint.

(9) The diagnosis system 10 further comprises a beam guiding and focusing device 28, which is arranged in the optical path 22 between the beam combiner 20 and the cornea 24. The beam guiding and focusing device 28 is configured to focus the first light beam 14 and the second light beam 18 together at a predetermined position x,y,z on or in the cornea 24. In this sense, the beam guiding and focusing device 28 is configured to adjust the spatial position x,y,z, where the first light beam 14 and the second light beam 18 are focused in or on the cornea 24. Additionally, the beam guiding and focusing device 28 is configured to adjust the directional orientation k.sub.x,k.sub.y,k.sub.z of the first light beam 14 and the second light beam 18, along which the first light beam 14 and the second light beam 18 enter the focus on or in the cornea 24 at the spatial position x,y,z, (compare FIGS. 1 and 3).

(10) For example, beam guiding and focusing device 28 comprises a scanning unit 30 with at least one pair of galvanometer mirrors (not shown) rotatable around two perpendicularly oriented rotation axis. The scanning unit 30 is configured to scan the focal position x,y,z in a two-dimensional manner along spatial directions x and y (compare the coordinate system in FIGS. 1 and 3). The beam guiding and focusing device 28 further comprises an objective 32 for focusing the first light beam 14 and the second light beam 18 on or in the cornea 24 and for collecting light, which has been deflected/reflected/scattered by and from the cornea 24. The objective 32 is configured such that a lateral resolution of the OCT device 12 and the resolution of the BS spectrometer 16 is less than 100 m, e.g., 50 m. The focal length of the objective 32 is changeable along spatial direction z to scan the focal position x,y,z in a one-dimensional manner along spatial direction z (compare again the coordinate system in FIGS. 1 and 3).

(11) By and from the cornea 24, the first and the second light beam 14, 18 are partially deflected/reflected/scattered back into and along the opposite direction of the first and the second light beam 14, 18 that have entered the focus at the predetermined position x,y,z on/in the cornea 24 before (compare the arrows along 14, 18, 22 in FIG. 1). The backscattered first and second light beams 14, 18 re-pass through the beam guiding and focusing device 28 towards the beam combiner 20. The beam combiner 20 splits the first and the second light beam 14, 18 backscattered from the cornea 24 such that the first backscattered light beam 14 enters the OCT device 12 and the second backscattered light beam 18 enters the BS spectrometer 16. In this sense, the beam combiner 20 is also a beam splitter.

(12) The OCT device 12 is configured to interferometrically analyze the first light beam 14 backscattered from the cornea 24 via the beam combiner 20 to provide OCT data representing a position dependent structural property of the cornea 24. For example, the OCT device 12 is configured to provide OCT data representing an image of the cornea 24 at or in the vicinity of the focal position x,y,z and to provide OCT data representing a position dependent optical density n(x,y,z) of the cornea 24 as well as a position dependent mass density p(x,y,z) of the cornea 24.

(13) The BS spectrometer 16 is configured to spectroscopically analyze the second light beam 18 backscattered from the cornea 24 via the beam combiner 20 to provide BS data representing a position and direction dependent frequency shift f.sub.B(x,y,z) as well as a position and direction dependent line width f.sub.B(x,y,z) of the Brillouin scattering caused side band of the backscattered second light beam 18. The spectral distribution of the Brillouin scattered second light beam 18 is schematically illustrated by the dot lined peak at .sub.2 and the two dot lined side bands/peaks in FIG. 2. The frequency shift f.sub.B corresponds to a wavelength shift .sub.B via |f.sub.B|c.Math.n.Math.|.sub.B|/.sup.2 and frequency line width f.sub.B corresponds to a wavelength line width .sub.B via |f.sub.B|c.Math.n.Math.|.sub.B|/.sup.2 for |.sub.B|<<.

(14) The diagnosis system 10 also comprises a control and analysis device 34. The control and analysis device 34 is connected with the OCT device 12 and the BS spectrometer 16 via respective connection lines 36 and 38 to control the OCT device 12 and the BS spectrometer 16 and to receive the OCT data and the BS data. The control and analysis device 34 is also connected to the beam guiding and focusing device 28 via connecting line 40 to control the beam guiding and focusing device 28 such that the beam guiding and focusing device 28 scans the predetermined position x,y,z of the focus on or in the cornea 24 in a predetermined three-dimensional manner and also scans the directional orientation k.sub.x,k.sub.y,k.sub.z along that the first light beam 14 and the second light beam 18 enter the focus on or in the cornea 24 at x,y,z in a predetermined manner.

(15) For example, both the first and the second beam 14, 18 are indicated as dashed arrows in FIG. 3. In a first state of the beam guiding and focusing device 28, the first and the second beam 14, 18 enter a first focal position x1,y1,z1 along a first direction kx1,ky1,kz1 and are scattered therefrom back into the opposite direction of kx1,ky1,kz1. In a second state of the beam guiding and focusing device 28, the first and the second beam 14, 18 enter the first focal position x1,y1,z1 along a second direction kx2,ky2,kz2 and are scattered therefrom back into the opposite direction of kx2,ky2,kz2. In a third state of the beam guiding and focusing device 28, the first and the second beam 14, 18 enter the first focal position x1,y1,z1 along a third direction kx3,ky3,kz3 and are scattered therefrom back into the opposite direction of kx3,ky3,kz3. In a fourth state of the beam guiding and focusing device 28, the first and the second beam 14, 18 enter a second focal position x2,y2,z2 along the first direction kx1,ky1,kz1 and are scattered therefrom back into the opposite direction of kx1,ky1,kz1. The first direction kx1,ky1,kz1 may correspond to the x direction, the second direction kx2,ky2,kz2 may correspond to the y direction and the third direction kx3,ky3,kz3 may correspond to the z direction of the coordinate system of the coordinate system as shown in FIGS. 1 and 3.

(16) The control and analysis device 34 is configured to calculate a spatially resolved topological and morphological structure from the OCT data. For example, the control and analysis device 34 is configured to generate from the OCT data an image of the cornea 24 at or in the vicinity of the focal position x,y,z. Additionally, the control and analysis device 34 is configured to generate from the OCT data at the focal position x,y,z a local optical density n(x,y,z) (when n(x,y,z) is not disturbed by a phonon) and a local mass density p(x,y,z) of the cornea 24. For example, the control and analysis device 34 identifies by image processing from the OCT data, in which part of the inherent structure of the cornea 24 the focal position x,y,z is localized, and associates for this inherent structural part a corresponding local optical density n(x,y,z) as well as a corresponding local mass density p(x,y,z) of the cornea 24 by use of a look-up table stored in a memory (not shown) of the control and analysis device 34. Hence, for each point x,y,z within a topography/morphology of the cornea, the corresponding local optical density n(x,y,z) and local mass density p(x,y,z) of the cornea 24 is determined.

(17) The control and analysis device 34 is also configured to calculate spatially and directionally resolved elastomechanical and viscoelastic properties of the cornea 24 from the BS data. For example, the control and analysis device 34 calculates

(18) $M_1=\frac{{}_2^2.Math.}{4.Math.n^2}.Math.f_B^2\mathrm{and}$$M_2=\frac{{}_2^2.Math.}{4.Math.n^2}.Math.f_B.Math.f_B,$ where: M.sub.1 is the real part of the complex longitudinal modulus M=M.sub.1+iM.sub.2 of the cornea 24, M.sub.2 is the imaginary part of the complex longitudinal modulus M=M.sub.1+iM.sub.2 of the cornea 24, .sub.2 is the second wavelength of the second light beam 18, =(x,y,z) is the local mass density of the cornea 24 extracted from the OCT data, n=n(x,y,z) is the local optical density of the cornea 24 also extracted from the OCT data, f.sub.B is the frequency shift of the Brillouin scattering caused side band of the backscattered second light beam 18 extracted from the BS data, and f.sub.B is the line width of the Brillouin scattering caused side band of the backscattered second light beam 18 extracted from the BS data.

(19) The control and analysis device 34 is further configured to spatially correlate the OCT data with the BS data such that for each spatial position x,y,z the topological and morphological structure of the cornea 24 is associated with the corresponding elastomechanical and viscoelastic properties of the cornea 24.

(20) As a result, for the same area of the cornea 24 it is known both the morphology (such as highly resolved local curving, thickness variations of the stroma, thickness of the epithelium dislocation of Bowman's membrane and the like) and correlated therewith spatially and directionally resolved elastomechanical and viscoelastic parameters. Therefore, it can be extracted spatially resolved geometry of the cornea 24 together with spatially and directionally resolved stiffness of the cornea 24.

(21) Unless expressly stated otherwise, identical reference symbols in the Figures stand for identical or identically-acting elements. Also, an arbitrary combination of the features and/or modifications elucidated in the Figures in connection with individual embodiments is conceivable.