Device for detecting fluorescence images

Abstract

The present invention relates to an apparatus (1) for generating and / or displaying fluorescent images, particularly fluorescent images used in ophthalmology and / or eye diagnosis, comprising a emitting device (2) that emits excitation light for exciting fluorescent light and a detection device (3) that can detect fluorescent light generated by the excitation light, wherein the emitting device (2) has a plurality of different light sources, each emitting excitation light of a different wavelength, for generating and / or displaying at least one fluorescent image and / or a multicolor fluorescent image created from a plurality of individual fluorescent images, and / or the emitting device (2) has at least one light source that emits red excitation light for generating and / or displaying a multicolor fluorescent image and / or a fluorescent image.

Description

Technical Field

[0001] The present invention relates to the apparatus described in the preamble of claim 1.

Background Art

[0002] The name optical coherence tomography (usually abbreviated as OCT in English) is understood as an imaging method. By using this method, two-dimensional and three-dimensional images can be obtained from a light-scattering structure. In this method, usually, light of a specific bandwidth is split into two partial beams by a beam splitter. The first partial beam hits the sample to be inspected, and the second partial beam passes through a reference path. The light reflected from the sample interferes with the reference beam. From the signal of the interference, the sample is depth-resolved, that is, it can be inspected at the depth of the optical axis of the first partial beam. When the sample is scanned in the plane or lateral direction with the first partial beam, a three-dimensional image of the sample, a so-called OCT image, is obtained.

[0003] The multi-color mode MC (MC is multicolor) of the reflection image has already been successfully implemented in the apparatus "Spectralis" (trademark).

[0004] In this mode, three different laser light sources that emit light of 486 nm, 518 nm, and 815 nm, respectively, are used to detect the reflection image for each row. The reflected signal is recorded and displayed as three individual images and, furthermore, as a so-called multi-color image, in which case the three channels are combined into one artificial color image.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Based on this, the present invention is based on the problem of providing an apparatus that can detect and / or display a fluorescence image, particularly a fluorescence image used in ophthalmology and eye diagnosis, as problem-free and quickly as possible.

Means for Solving the Problems

[0006] The present invention solves the above problem by the features of claim 1.

[0007] According to the present invention, the above-described imaging mode, i.e., the multicolor mode, is converted to fluorescence imaging, i.e., preferably using three different excitation light wavelengths.

[0008] Fluorescence imaging is already available using blue (BAF) and green (GAF) excitation lasers. For multicolor autofluorescence (MCAF) mode, an additional excitation laser, such as a red laser, needs to be implemented.

[0009] According to the present invention, it has been recognized that red lasers exhibit a good signal-to-noise ratio (SNR) and image quality comparable to NIR-AF. No photoreceptor fading effect occurs. Patients can experience greater comfort compared to the use of blue and green excitation sources, particularly lasers. No macular pigment shadows, as known with BAF, occur.

[0010] Red wavelengths are less affected by the light transmittance of the lens and cataracts.

[0011] Autofluorescence imaging, for example in relation to endogenous fluorophores that may be used in pathological courses, can provide insights into pathology at the molecular level and therefore potentially provide more information faster than structural reflection imaging or OCT imaging.

[0012] The invention described herein relates, in particular, to the simultaneous detection of fluorescence images at three (or more) excitation wavelengths, and / or the display of autofluorescent images detected in the form of pseudocolor images at three different excitation wavelengths.

[0013] White balance can be performed so that healthy retinal tissue appears gray (similar intensity across all three channels). In this case, such normalization will highlight structures exhibiting various autofluorescence properties in various hues, such as the region beneath the macular pigment.

[0014] Currently, from a clinical standpoint, there are the following drawbacks. Specifically, autofluorescence imaging known in ophthalmology is performed using three excitation wavelengths: 488 nm, 520 nm, and 785 nm. Each of these wavelengths has its own drawbacks. At 488nm, absorption by macular pigment creates dark areas, often failing to clearly distinguish them from atrophic areas. Due to the high scattering rate, image degradation may occur in cataract patients, and the image changes during detection due to the fading effect of the photochromic pigment. At 518nm, in patients with cataracts, the scattering rate is high, which can lead to image degradation. Furthermore, the image changes during detection due to the fading effect of the photochromic pigment, and partial absorption by the macular pigment occurs. At 785nm, the autofluorescence intensity is low, resulting in a noisy image.

[0015] There is no single autofluorescence mode that is optimal for imaging in clinical routines. Therefore, it is necessary to detect three autofluorescence images in a single rapid run. The technical challenge in this case is to set and design a cut filter that can suppress the three excitation wavelengths of 486 nm, 518 nm, and 642 nm with high efficiency (more than 10⁻⁵), while collecting as much fluorescence as possible in the ranges of 530-635 nm and >655 nm. Furthermore, temperature drift of the laser diode must be considered to avoid potential losses.

[0016] MCAF mode, like MC reflection mode, may only be available at 768x768 pixels (HS). However, it can be advantageously combined with high-resolution algorithms, such as 1536x536 pixels, which fill every other row and every other column during ART mode.

[0017] The feasibility and quality (signal intensity) of red autofluorescence (RAF) imaging are challenges. Appropriate cut filters (LWP 530nm and an additional dip at 642nm (Senke)) were developed and tested within the scope of this invention. The cut filters enable quasi-simultaneous (line-by-line) detection of autofluorescence images using three different excitation lasers.

[0018] One of the key parts of the present invention is the realization of a multicolor autofluorescence mode that can simultaneously detect autofluorescence images at three (or more) different excitation wavelengths. The detected images are displayed as pseudocolor images, where each color channel represents a signal at one excitation wavelength. This allows for the rapid visualization and detection of pathological structures that exhibit different autofluorescence emission behavior at different excitation wavelengths.

[0019] According to the present invention, it is possible to take advantage of the fact that different lesions exhibit different emission patterns at short and long excitation wavelengths. Furthermore, the MCAF imaging mode provides information from three or more autofluorescent channels in a single image detection, thus enabling improved efficiency.

[0020] Advantageously, various combinations of wavelengths are possible, that is At 486nm, 518nm, and 642nm, Visualization of macular pigment distribution, visualization of macular autofluorescence distribution independent of macular pigment, visualization of differences in autofluorescence emission patterns at 486 / 518 nm relative to 642 nm. At 470nm, 520nm, and 642nm, Additional visualization of FPF (flavin protein fluorescence) allows oxidized FPF to be used as a biomarker for mitochondrial dysfunction.

[0021] Other wavelength combinations are possible, depending on the excitation spectrum of specific phosphors within the retina.

[0022] The main components of the device described herein may be a red laser module, a cleanup filter, an output coupling beam splitter, and a cut filter (LWP530 and a dip at 642 nm). Particularly in the case of FPF applications, embodiments with three detection channels (480 - 510 nm, 530 - 630 nm, and >650 nm) are also conceivable.

[0023] Within the scope of the present invention, a multi - color autofluorescence mode (MCAF) is proposed that simultaneously detects three autofluorescence images and then displays the three channels as a pseudo - color image. For example, macular pigment can be displayed in yellow because the green and red channels cooperate.

[0024] Advantageously, this mode can be implemented relatively easily in existing devices.

[0025] The imaging mode described herein utilizes three different laser light sources for fluorescence excitation and can thus operate selectively according to the excitation light wavelength.

[0026] To reliably correct eye movements in the simultaneous mode, it is also conceivable to implement the imaging mode described herein with multiple detectors (for example, the 530 - 630 nm channel and the 650 nm - 730 nm channel) and combine it with a reflected laser at a wavelength of 730 nm, which is even - line AF486 nm (SWC) and 642 nm (LWC) / odd - line AF518 nm (SWC) and DR reflection 730 nm (LWC).

[0027] The quantitative autofluorescence mode (486 nm, BAF) is interesting but not yet established in clinical routine. This is associated with drawbacks such as patient acceptance, fading of the light pigment (decrease in reproducibility), and transparency of the ocular media (decrease in comparability between patients).

[0028] These drawbacks can be overcome with a red excitation light wavelength. The MCAF mode can be advantageously used for further analysis, such as evaluating lens turbidity (classification of cataracts).

[0029] Red lasers can also be used for reflection imaging, but because the lens coatings are not optimally designed for 642nm, relatively strong lens artifacts are likely to occur. However, when combined with a center cut filter, it may be possible to obtain reflection images with a red 55° wavelength.

[0030] Red autofluorescence does not cause fading, and the signal-to-noise ratio (SNR) is better than that of 785nm IRAF. There is no concern about phototoxicity. Cataracts have little impact on image quality.

[0031] Multicolor autofluorescence (MCAF) generates three autofluorescence images in a single scan. Relative intensity changes (color changes in the MCAF images) may indicate the presence of different molecular phosphors.

[0032] These phosphors can often be distinguished better by excitation than by emission bands. This is useful for distinguishing markers, particularly "red tomato," against a uniform lipofuscin background. [Brief explanation of the drawing]

[0033] [Figure 1] This is a schematic diagram of the transmission behavior of the cut filter used in the apparatus described herein. [Figure 2] This is a schematic diagram of the structure of the apparatus described herein. [Figure 2A] This is a schematic diagram of the structure of the apparatus described herein. [Figure 3] The image on the left is a magnified view of the multicolor fluorescence image (MC-AF), while the image on the right shows four smaller images: the top left image is the multicolor fluorescence image (MC-AF), the top right image is the red fluorescence image (Red AF), the bottom left image is the green fluorescence image (Green AF), and the bottom right image is the blue fluorescence image (Blue AF). [Figure 4] This is a schematic diagram of an exemplary embodiment of the apparatus according to the present invention, which has a monitor. [Modes for carrying out the invention]

[0034] Figure 1 shows the transmission behavior of cut filters using laser light wavelengths. Dips are assigned to the blue excitation laser (BAF) and green excitation laser (GAF), which are very similar to the case of LWP 530 nm, but another dip is provided at approximately 640 nm to suppress the light from the red excitation source.

[0035] Fluorescence emission from a red laser is detectable at approximately 652 nm and above. In principle, fluorescence may be detectable up to 900 nm, but in practice, the OCT channel limits the detectable emission range to below the lower limit of the OCT spectrum.

[0036] The imaging modes described here are advantageous for comparing autofluorescence patterns of various diseases. Systematically comparing diverse autofluorescence patterns may reveal new diagnostic biomarkers for retinal diseases.

[0037] The use of MCAF mode may be useful in animal experiments to distinguish between various phosphors (e.g., dT tomato) that have been specially injected or otherwise introduced.

[0038] By comparing the signal intensity of autofluorescence signals, it may be possible to obtain information about the density of cataracts.

[0039] Figures 2 and 2A schematically illustrate the apparatus described herein using the product "Spectralis". The multicolor mode MC (MC stands for Multicolor) of reflected images has already been successfully implemented in the "Spectralis" (trademark) apparatus. In this mode, three different laser light sources emitting light at 486 nm, 518 nm, and 815 nm, respectively, are used to detect the reflected image row by row. The reflected signals are recorded and displayed in three individual images, and further, as a so-called multicolor image, in which case the three channels are combined into a single artificial color image.

[0040] According to the present invention, the above-described imaging mode, i.e., the multicolor mode, is converted to fluorescence imaging, i.e., preferably using three different excitation light wavelengths.

[0041] For other specific exemplary embodiments, please refer to the description above.

[0042] Figure 4 schematically shows an exemplary embodiment of an apparatus 1 for generating and / or displaying fluorescence images, particularly fluorescence images used in ophthalmology and eye diagnosis, comprising a emitting device 2 that emits excitation light to excite fluorescence and a detection device 3 that can detect fluorescence generated by the excitation light.

[0043] The radiating device 2 has a plurality of different light sources, each light source emitting excitation light of a different wavelength to generate and / or display at least one fluorescence image and / or a multicolor fluorescence image from individual fluorescence images. The radiating device 2 has at least one light source emitting red excitation light to generate and / or display a multicolor fluorescence image and / or a fluorescence image.

[0044] The radiating device 2 emits red excitation light in the wavelength range of 630 to 650 nm, preferably excitation light with a wavelength of 642 nm, and the detection device 3 detects fluorescence light in the wavelength range exceeding 650 nm, or in the wavelength range of 650 to 900 nm, or 652 to 735 nm.

[0045] The radiating device 2 emits blue excitation light in the wavelength range of 470 to 490 nm, preferably excitation light with a wavelength of 486 nm or 488 nm, and the detection device 3 detects fluorescence light in the wavelength range of 480 to 510 nm, 530 nm to 630 nm, or 500 to 720 nm.

[0046] The radiating device 2 emits green excitation light in the wavelength range of 500 to 530 nm, preferably excitation light with a wavelength of 518 nm or 520 nm, and the detection device 3 detects fluorescent light in the wavelength range of 500 to 720 nm, 530 to 630 nm, or 530 to 720 nm.

[0047] The radiating device 2 has a first light source designed as a laser that emits blue excitation light, a second light source designed as a laser that emits green excitation light, and a third light source designed as a laser that emits red excitation light.

[0048] To detect the fluorescence excited by the excitation light, a cut filter 4 is placed in front of the detection device 3. This cut filter 4 does not transmit excitation light of specific wavelengths, particularly those reflected, namely in the wavelength ranges of 450-530 nm, 470-490 nm, 500-530 nm, and / or 630-650 nm. Alternatively, this cut filter 4 suppresses the reflected excitation light, or reduces the intensity of the reflected excitation light by at least 1 / 10,000 times upon passing through the cut filter 4, so that the intensity of the transmitted, particularly reflected excitation light is only 1 / 10,000 of the intensity of the particularly reflected excitation light incident on the cut filter 4.

[0049] The image generation device 5 is provided, which generates and / or displays at least one fluorescent image from the fluorescent light recorded and processed by the image generation device, and the fluorescent light is excited by each light source.

[0050] The image generation device 5 generates and / or displays a multicolor fluorescent image as a whole image from a plurality of fluorescent images, preferably captured simultaneously, preferably three different colored fluorescent images.

[0051] In a multicolor fluorescence image, individual, preferably different colored fluorescence images are combined, particularly after being weighted by a color correction algorithm.

[0052] The image generation device 5 generates and / or displays at least one fluorescence image, or an overall image from fluorescence images, as a pseudo-color image.

[0053] Each color channel in the pseudo-color image is assigned a signal of the corresponding wavelength of the excitation light.

[0054] The three excitation light wavelengths used individually or in combination include 486 nm, 518 nm, and 642 nm, or 470 nm, 520 nm, and 642 nm.

[0055] The image generation device 5 performs white balance on the fluorescence image or the overall image derived from the fluorescence image in order to display healthy tissue in gray or another color tone.

[0056] The image generation device 5 generates fluorescence images row by row and / or column by column, with every other row and / or column being generated by an algorithm that enhances the resolution of the fluorescence images, preferably by a high-resolution algorithm of 1536 × 1536 pixels.

[0057] At least one fluorescence image is a red fluorescence image generated by detecting red excited fluorescence light.

[0058] A cleaning filter is provided to suppress the sidebands of red light sources, particularly red lasers.

[0059] A beam splitter 6 is provided for output coupling p-polarized excitation light, particularly a red laser.

[0060] Device 1 can be switched to a mode that can generate and / or display red fluorescence images. Device 1 can be switched to a mode that can generate and / or display multicolor fluorescence images. Device 1 can be switched to a mode that can generate and / or display a fluorescence image or an overall image from a fluorescence image as a pseudocolor image.

[0061] Device 1 generates both a fluorescence image and a reflection image. Device 1 generates both a reflection image and a fluorescence image using the same light source, or generates them simultaneously.

[0062] A monitor 7 is provided that can display red and / or blue and / or green fluorescent images, and / or multicolor fluorescent images combining the aforementioned fluorescent images, and / or pseudocolor images of at least one of the aforementioned images.

[0063] A monitor 7 is provided that can display both fluorescent and reflective images.

[0064] Monitor 7 is part of device 1.

[0065] The detection device 3 has a chip 8 that includes at least one or just one detection channel for detecting each fluorescence light.

[0066] Chip 8 has a blue detection channel for detecting fluorescence in the wavelength range of 480-510 nm, and / or a green detection channel for detecting fluorescence in the wavelength range of 530-560 nm or 530-630 nm, and / or a red detection channel for detecting fluorescence above 650 nm, or in the wavelength range of 650 nm-900 nm, or 650-730 nm.

[0067] Eye movements can be corrected during fluorescence image generation. Even lines in the fluorescence image are generated by blue and red fluorescence light with wavelengths of 486 nm and 642 nm, respectively, while odd lines are generated by green fluorescence light and a reflected laser with wavelengths of 518 nm and 730 nm, respectively.

[0068] The arrangement comprises the apparatus 1 described in one of the claims below and a spectrometer 9 capable of performing optical coherence tomography (OCT). [Explanation of symbols]

[0069] 1 device 2 Radiating device 3. Detection device 4-cut filter 5. Image generation device 6-beam splitter 7 1 monitor 8 3 chips 9. Spectrometer

Claims

1. In a device (1) for generating and / or displaying fluorescent images, particularly fluorescent images used in ophthalmology and / or eye diagnosis, the device comprises a emitting device (2) that emits excitation light for exciting fluorescent light and a detection device (3) that can detect the fluorescent light generated by the excitation light, The emitting device (2) has a plurality of different light sources, each emitting excitation light of a different wavelength, in order to generate and / or display a multicolor fluorescence image created from at least one fluorescence image and / or a plurality of individual fluorescence images, and / or The radiation device (2) has at least one light source that emits red excitation light in order to generate and / or display a multicolor fluorescence image and / or a fluorescence image. Apparatus (1) characterized by the following.

2. The apparatus according to claim 1, wherein the emitting device (2) emits red excitation light in the wavelength range of 630 to 650 nm, preferably excitation light with a wavelength of 642 nm, and the detection device (3) detects fluorescent light in the wavelength range exceeding 650 nm, or in the wavelength range of 650 to 900 nm or 652 to 735 nm.

3. The apparatus according to claim 1 or 2, characterized in that the emitting device (2) emits blue excitation light in the wavelength range of 470 to 490 nm, preferably excitation light with a wavelength of 486 or 488 nm, and the detection device (3) detects fluorescent light in the wavelength range of 480 to 510 nm, 530 to 630 nm, or 500 to 720 nm.

4. The apparatus according to any one of claims 1 to 3, characterized in that the emitting device (2) emits green excitation light in the wavelength range of 500 to 530 nm, preferably excitation light with a wavelength of 518 or 520 nm, and the detection device (3) detects fluorescent light with a wavelength of 500 to 720 nm, 530 to 630 nm, or 530 to 720 nm.

5. The apparatus according to any one of claims 1 to 4, characterized in that the radiating device (2) has a first light source designed as a laser that emits blue excitation light, the radiating device (2) has a second light source designed as a laser that emits green excitation light, and the radiating device (2) has a third light source designed as a laser that emits red excitation light.

6. The apparatus according to any one of claims 1 to 5, characterized in that, in order to detect the fluorescence excited by the excitation light, a cut filter (4) is placed in front of the detection device (3), and the cut filter (4) either does not transmit excitation light of specific wavelengths that are particularly reflected, i.e., excitation light in the wavelength ranges of 450-530 nm, 470-490 nm, 500-530 nm and / or 630-650 nm, or the cut filter (4) suppresses particularly reflected excitation light, or the cut filter (4) reduces the intensity of particularly reflected excitation light to at least 1 / 10,000 when it passes through the cut filter (4), so that the intensity of the particularly reflected excitation light that has passed through is only 1 / 10,000 of the intensity of the particularly reflected excitation light incident on the cut filter (4).

7. The apparatus according to any one of claims 1 to 6, characterized in that an image generating device (5) is provided which generates and / or displays at least one fluorescent image each time from the fluorescent light recorded and processed thereby, and the fluorescent light is excited by each of the light sources.

8. The image generation device (5) is characterized in that it generates and / or displays a multicolor fluorescent image as an overall image from a plurality of fluorescent images, preferably simultaneously recorded, preferably three different colored fluorescent images, according to claim 7.

9. The apparatus according to claim 8, characterized in that, in the multicolor fluorescence image, individual, preferably different colored fluorescence images are combined, particularly after being weighted by a color correction algorithm.

10. The apparatus according to any one of claims 1 to 9, characterized in that the image generating apparatus (5) generates and / or displays a pseudo-color image of at least one fluorescence image, or an overall image created from multiple fluorescence images.

11. The apparatus according to claim 10, characterized in that the signals of each wavelength of the respective excitation light are assigned to each color channel of the pseudo-color image.

12. The apparatus according to claim 10 or 11, characterized in that the three wavelengths of excitation light used individually or in combination include 486 nm, 518 nm, and 642 nm, or 470 nm, 520 nm, and 642 nm.

13. The apparatus according to any one of claims 1 to 12, characterized in that, in order to display healthy tissue in gray or a different color tone, the image generating device (5) performs white correction on a fluorescent image or an overall image created from a plurality of fluorescent images.

14. The apparatus according to any one of claims 1 to 13, characterized in that the image generation apparatus (5) generates fluorescence images row by row and / or column by column, and every other row and / or every other column is generated by an algorithm that increases the resolution of the fluorescence images, preferably by a high-resolution algorithm of 1536 × 1536 pixels.

15. The apparatus according to any one of claims 1 to 14, characterized in that at least one fluorescence image is a red fluorescence image produced by detecting red excited fluorescence light.

16. The apparatus according to any one of claims 1 to 15, characterized in that it is provided with a cleaning filter that suppresses the sidebands of a red light source, particularly a red laser.

17. The apparatus according to any one of claims 1 to 16, characterized in that a beam splitter (6) for decoupling p-polarized excitation light, particularly a red laser, is provided.

18. The apparatus according to any one of claims 1 to 17, characterized in that the apparatus (1) is switchable to a mode in which a red fluorescence image is generated and / or displayed, and / or the apparatus (1) is switchable to a mode in which a multicolor multiple fluorescence image is generated and / or displayed, and / or the apparatus (1) is switchable to a mode in which a fluorescence image or an overall image created by multiple fluorescence images is generated and / or displayed as a pseudocolor image.

19. The apparatus according to any one of claims 1 to 18, characterized in that the apparatus (1) also generates multiple reflection images in addition to the multiple fluorescence images, and / or the apparatus (1) generates or simultaneously generates multiple reflection images and multiple fluorescence images using the same multiple light sources.

20. The apparatus according to any one of claims 1 to 19, characterized in that a monitor (7) is provided that can display a red and / or blue and / or green fluorescent image, and / or a multicolor fluorescent image combining the plurality of fluorescent images, and / or a pseudocolor image of at least one of the plurality of images.

21. The apparatus according to any one of claims 1 to 20, characterized in that a monitor (7) capable of displaying reflection images in addition to multiple fluorescence images is provided.

22. The apparatus according to any one of claims 1 to 21, characterized in that the detection device (3) has a chip (8) including at least one or just one detection channel for detecting each of the fluorescent lights.

23. The apparatus according to claim 22, characterized in that the chip (8) has a blue detection channel for detecting fluorescent light in the wavelength range of 480 to 510 nm, and / or a green detection channel for detecting fluorescent light in the wavelength range of 530 to 560 nm or 530 to 630 nm, and / or a red detection channel for detecting fluorescent light exceeding 650 nm, or in the wavelength range of 650 nm to 900 nm or 650 to 730 nm.

24. The apparatus according to any one of claims 1 to 23, characterized in that eye movements during fluorescence image generation are compensated, and / or even lines of the fluorescence image are generated by blue fluorescence and red fluorescence, particularly blue fluorescence and red fluorescence with wavelengths of 486 nm and 642 nm, respectively, and odd lines are generated by green fluorescence and a reflective laser, particularly green fluorescence and a reflective laser with wavelengths of 518 nm and 730 nm, respectively.

25. An arrangement comprising the apparatus (1) described in any one of claims 1 to 24 and a spectrometer (9) capable of performing optical coherence tomography (OCT).

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