Fluorescence imaging system

The fluorescent image system addresses the complexity and noise issues in existing systems by employing a near-infrared light source and optical filter to separate and adjust background and fluorescent images independently, resulting in improved detection sensitivity and image clarity.

WO2025079796A1PCT designated stage expired Publication Date: 2025-04-17KOREA ELECTROTECH RES INST
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Patent Information

Application Number
PCT/KR2024/005407
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-10
Filing Date
2024-04-22
Publication Date
2025-04-17

AI Technical Summary

Technical Problem

Existing fluorescent image systems require complex structures and controls to separate wavelength light paths spatially and temporally, and they suffer from linked light intensity and fluorescent signal issues, as well as background noise from lighting sources.

Method used

A simplified fluorescent image system using a near-infrared light source and an optical filter to separate background and fluorescent images, allowing for independent adjustment of light intensity and fluorescent signal without spatial and temporal wavelength separation.

Benefits of technology

The system achieves a simple structure and control, prevents fluorescent background noise, and provides a fluorescent signal that is not linked with light intensity, enhancing the detection of targeted tissue areas in real-time surgery.

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Abstract

A fluorescence imaging system according to one embodiment of the present invention comprises: a light source unit for irradiating light at a target region; and a detection unit for detecting light incident from the target region, wherein the light source unit includes: a near-infrared light source for emitting light having a peak wavelength in the near-infrared region; and an excitation light source that emits excitation light for exciting a fluorophore, and the detection unit includes: an optical filter for blocking the excitation light source and transmitting fluorescence emitted from the fluorophore and near-infrared light; and an image sensor for detecting the fluorescence and the near-infrared light transmitted through the optical filter.
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Description

Fluorescence imaging system

[0001] The present invention relates to a fluorescence imaging system, and more particularly, to a fluorescence imaging system capable of acquiring a fluorescence image together with a background image.

[0002] Distinguishing between cancerous and normal tissue is crucial for the early diagnosis and treatment of cancer. Fluorescence-based imaging technology offers the advantages of high sensitivity and selectivity in diagnosing small changes not visible with white light imaging, facilitates visualization, and is convenient to use.

[0003] Endogenous fluorophores, such as aromatic amino acids (AAA), nicotinamide adenine dinucleotide (NAD), or porphyrins, exhibit autofluorescence in biological tissues. Endogenous fluorophores exhibit altered autofluorescence emission depending on metabolic status, microenvironmental changes, and other factors. While decreased autofluorescence is observed in tumor lesions compared to normal tissue, false positives can occur due to inflammation or blood vessels.

[0004] Induced fluorescence diagnosis, based on the use of exogenous fluorophore probes such as porphyrin, chlorin, phthalocyanine, or 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), which have less ambiguity compared to autofluorescence and selectively accumulate in tumor tissues to express strong fluorescence signals, is very useful for improving the specificity of detecting pathological lesion tissues.

[0005] Meanwhile, in fluorescence imaging technology, high detection sensitivity in vivo is required to identify suspicious tissue regions during clinical applications such as real-time surgery. The detection sensitivity of exogenous fluorophore probes is influenced not only by their properties, such as probe-tissue binding affinity, quantum efficiency, absorption coefficient, and fluorescence wavelength, but also by the design and performance of the device targeting the fluorophore probe, operating conditions, such as operating distance, and other factors.

[0006] Currently, 5-aminolevulinic acid (5-ALA) or protoporphyrin IX (PpIX)-based drugs and chlorin e6 (Ce6)-based drugs are being clinically applied. The Soret band (approximately 405 nm) is most commonly used as the excitation wavelength for PpIX and Ce6, and fluorescence signals can be observed in the 620-720 nm wavelength range.

[0007] In general, since the intensity of the fluorescence signal is weak compared to the intensity of the excitation light, there are limitations in using the excitation light as a background light source to observe the background image and the targeted lesion tissue and surrounding tissue using fluorescence. Therefore, technologies are being used or studied to visualize the background image and fluorescence signal by spatially separating the optical path by wavelength using a multi-channel detector (image sensor or channel) to simultaneously acquire images of different wavelengths to create a fusion image, or by acquiring images in a selective and sequential detection manner for a specific wavelength range and creating a fusion image through image processing, or by adjusting the ratio of the fluorescence signal to the excitation light through optical attenuation using an optical filter, etc. in the detection unit.

[0008] However, the above technologies have the disadvantage that the structure and control of the fluorescence imaging system are complicated, or that the excitation light intensity needs to be adjusted to adjust the background image brightness, and ultimately, the background image brightness, excitation light intensity adjustment, and fluorescence signal are interrelated.

[0009] The problem to be solved by the present invention is to provide a fluorescence imaging system with a simple structure capable of acquiring a background image and a fluorescence image without the need to spatially and temporally separate the optical paths for each wavelength.

[0010] The problem to be solved by the present invention is to provide a fluorescence imaging system capable of providing a fluorescence image signal in which the fluorescence signal and the excitation light intensity are not correlated with each other even when the background image brightness is adjusted.

[0011] Another problem to be solved by the present invention is to provide a fluorescence imaging system capable of preventing the occurrence of autofluorescence background noise excited and expressed by an illumination light source.

[0012] A fluorescence imaging system according to one embodiment of the present invention comprises: a light source unit for irradiating light to a target region; and a detection unit for detecting light incident from the target region, wherein the light source unit comprises: a near-infrared light source for emitting light having a peak wavelength in a near-infrared region; and an excitation light source for emitting excitation light that excites a fluorophore; and the detection unit comprises: an optical filter for blocking the excitation light source and transmitting fluorescence and the near-infrared light emitted from the fluorophore; and an image sensor for detecting fluorescence and the near-infrared light transmitted through the optical filter.

[0013] The above light source may have a peak wavelength in the visible or ultraviolet region.

[0014] The fluorescence emitted from the above fluorescent molecule may have a peak wavelength in the red region.

[0015] The above fluorophore may comprise PpIX or Ce6.

[0016] The light source unit may further include a white light source that emits white light, and the white light source may emit light in a white light mode, and at least a portion of light emitted from the white light source and reflected from the target area may be detected by the image sensor by passing through the optical filter. The near-infrared light source and the excitation light source may emit near-infrared light and excitation light in a fluorescence excitation mode. The white light mode and the fluorescence excitation mode may be switched with each other.

[0017] The image sensor may include a pixel array, each pixel being assigned a color filter that transmits light of a different color. Each of the pixels may have a sensitivity intensity of at least 30% of the maximum sensitivity intensity of the image sensor for the near infrared.

[0018] The difference in sensitivity intensities of the pixels of the image sensor to near-infrared light may be less than 10% of the maximum sensitivity intensities of the image sensor.

[0019] The pixel array of the above image sensor may have a Bayer filter pattern.

[0020] The above fluorescence imaging system may further include an image processing unit that processes an image signal detected by the image sensor.

[0021] The above image processing unit can convert a background image signal by near-infrared light detected by the image sensor into an image signal of a different color.

[0022] The above image processing unit can correct the intensity of the fluorescence image signal based on the change in the intensity of the detection signal of near-infrared reflected light according to the operating distance from the target area.

[0023] The above fluorescent imaging system may further include a control unit; a brightness driving unit; and a display unit, wherein the control unit controls the image processing unit and the brightness driving unit, the brightness driving unit adjusts the brightness of each light source of the light source unit, and the display unit can display an image signal processed by the image processing unit.

[0024] According to embodiments of the present invention, since background image information is obtained using near-infrared light different from the excitation light source, background images and fluorescence images can be obtained using the same detector, thereby providing a fluorescence imaging system with a simple structure and control. Furthermore, since the fluorescence imaging system of the present invention obtains background image information using near-infrared light, it does not generate autofluorescence background noise that is generated when excited by the illumination light source.

[0025] In addition, according to embodiments of the present invention, since the excitation light source is blocked by the optical filter, it is not detected by the image sensor, and thus, a fluorescence imaging system can be provided that provides a fluorescence signal in which the fluorescence signal and the excitation light signal are not correlated with each other.

[0026] FIG. 1 is a schematic block diagram illustrating a fluorescence imaging system according to one embodiment of the present invention.

[0027] FIG. 2 is a schematic diagram illustrating a light source unit of a fluorescence imaging system according to one embodiment of the present invention.

[0028] FIG. 3 is a schematic diagram illustrating a detection unit of a fluorescence imaging system according to one embodiment of the present invention.

[0029] FIG. 4a is a schematic graph illustrating an example of a white light source of a fluorescence imaging system according to one embodiment of the present invention.

[0030] FIG. 4b is a schematic graph illustrating another example of a white light source of a fluorescence imaging system according to one embodiment of the present invention.

[0031] FIG. 5 is a schematic graph illustrating an example of an excitation light source of a fluorescence imaging system according to one embodiment of the present invention.

[0032] FIG. 6 is a schematic graph illustrating an example of a near-infrared light source of a fluorescence imaging system according to one embodiment of the present invention.

[0033] FIG. 7 is a schematic graph illustrating an optical filter of a fluorescence imaging system according to one embodiment of the present invention.

[0034] FIG. 8 is a schematic diagram for explaining a Bayer filter pattern of an image sensor of a fluorescent imaging system according to one embodiment of the present invention.

[0035] Figure 9 is a graph showing the relative sensitivity of an image sensor having a Bayer filter pattern.

[0036] FIG. 10 is a schematic diagram illustrating an image that can be displayed by a fluorescent imaging system according to one embodiment of the present invention.

[0037] Figure 11 is a schematic diagram illustrating a laparoscopic fluorescence imaging system according to one embodiment of the present invention.

[0038] FIG. 12 is a photograph showing close-range images displayed using a fluorescence imaging system according to one embodiment of the present invention.

[0039] FIG. 13 is a photograph showing long-distance images displayed using a fluorescence imaging system according to one embodiment of the present invention.

[0040] Figure 14 is a photograph showing close-range images displayed using a fluorescence imaging system according to the prior art.

[0041] Figure 15 is a photograph showing long-distance images displayed using a fluorescence imaging system according to the prior art.

[0042] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings. The embodiments introduced below are provided as examples to ensure that the spirit of the present invention can be sufficiently conveyed to those skilled in the art. Therefore, the present invention is not limited to the embodiments described below and may be embodied in other forms. Like reference numbers designate like elements throughout the specification.

[0043] FIG. 1 is a schematic block diagram for explaining a fluorescent imaging system (100) according to one embodiment of the present invention, FIG. 2 is a schematic configuration diagram for explaining a light source unit (10) of a fluorescent imaging system according to one embodiment of the present invention, and FIG. 3 is a schematic configuration diagram for explaining a detection unit (20) of a fluorescent imaging system according to one embodiment of the present invention.

[0044] The fluorescence imaging system (100) according to the present embodiment can be used in a white light mode for obtaining a color image of a target area and a fluorescence excitation mode for obtaining a fluorescence image, and the white light mode and the fluorescence excitation mode can be switched with each other.

[0045] First, referring to FIG. 1, a fluorescence imaging system (100) according to one embodiment includes a light source unit (10) and a detection unit (20). Furthermore, the fluorescence imaging system (100) may further include a control unit (30), an image processing unit (40), and a display unit (50).

[0046] Referring to FIGS. 1 and 2, the light source unit (10) may include a light source (11), a brightness driver (13), and a light transmission mechanism (15). The light source (11) may emit white light in a white light mode and emit near-infrared light together with excitation light in a fluorescence excitation mode. The light source (11) is not particularly limited, and for example, a discharge lamp that emits light of various wavelengths, such as a xenon lamp, may be used in combination with various types of optical filters. As another example, an LED or a laser diode may be used.

[0047] In one embodiment, the light source (11) may include at least three independent light sources, a first light source (11a), a second light source (11b), and a third light source (11c), as illustrated in FIG. 2. In one embodiment, the first light source (11a) may be a near-infrared light source that emits near-infrared rays, the second light source (11b) may be a white light source that emits white light, and the third light source (11c) may be an excitation light source that emits excitation light.

[0048] A white light source can emit white light, for example, by combining an LED and a phosphor, and can emit cool white light having a spectrum as shown in Fig. 4a or warm white light having a spectrum as shown in Fig. 4b. However, the white light source is not limited to using an LED, and a discharge lamp such as a xenon lamp can also be used as a white light source.

[0049] Here, the light source can be an LED or a laser light source. In this embodiment, the light source is used to excite a fluorophore. Although an endogenous fluorophore can be used, the use of an exogenous fluorophore is more preferred to reduce ambiguity such as false positives. In particular, PpIX or Ce6-based drugs can be suitably used as exogenous fluorophore probes. An excitation light source having a peak wavelength within the Soret band can be used to excite these PpIX or Ce6-based exogenous fluorophore probes. The excitation light source can have a peak wavelength in the visible or ultraviolet region less than about 420 nm, for example, as shown in FIG. 6, the peak wavelength can be about 405 nm. PpIX or Ce6 absorbs the excitation light and then emits fluorescence, and PpIX or Ce6 emits red fluorescence with a peak wavelength in the range of about 620 nm to 720 nm.

[0050] The near-infrared light source may be an LED or a laser light source, for example, a vertical cavity surface emitting laser (VCSEL). The near-infrared light source may have a peak wavelength, for example, in the range of 800 nm to 850 nm, and in one embodiment, as illustrated in FIG. 6, may have a peak wavelength of about 808 nm.

[0051] The light transmitting optical system (15) transmits the light emitted from the light source (11) to the light guide unit (17) so that the light (L1) is irradiated to the target area. The light transmitting mechanism (15) may include, for example, an optical lens (15a) and a dichroic mirror (15b), as illustrated in FIG. 2. The optical lens (15a) collimates or focuses the light emitted from the light sources (11a, 11b, 11c). For example, the optical lenses (15a) positioned close to the light sources (11, 11b, 11c) may be collimating lenses, and the optical lens (15a) positioned close to the light guide unit (17) may be focusing lenses.

[0052] The dichroic mirrors (15b) reflect or transmit light of a specific wavelength range. For example, a dichroic mirror (15b, left dichroic mirror) positioned close to the first light source (11a) transmits light emitted from the first light source (11a) and reflects light emitted from the second light source (11b). Meanwhile, a dichroic mirror (15b, right dichroic mirror) positioned far from the first light source (11a) transmits light emitted from the first and second light sources (11a, 11b) and reflects light emitted from the third light source (11c).

[0053] As described above, when the first, second, and third light sources (11a, 11b, 11c) are a near-infrared light source, a white light source, and an excitation light source, respectively, the left dichroic mirror (15b) may be a long-wavelength pass dichroic mirror that transmits near-infrared light and reflects visible light, and the right dichroic mirror (15b) may be a long-wavelength pass dichroic mirror that reflects excitation light and transmits white light and near-infrared light.

[0054] In the above embodiment, the first light source (11a) is described as a near-infrared light source, the second light source (11b) is a white light source, and the third light source (11c) is an excitation light source. However, the present invention is not limited thereto, and the arrangement of the light sources may be changed. In addition, as the arrangement of the light sources is changed, the characteristics of the dichroic mirrors (15b) may also be changed.

[0055] For example, the first light source (11a) may be a white light source, the second light source (11b) may be an excitation light source, and the third light source (11c) may be a near-infrared light source. In this case, the left dichroic mirror may transmit white light and reflect excitation light, and the right dichroic mirror may transmit white light and excitation light and reflect near-infrared light.

[0056] As another example, the first light source (11a) may be an excitation light source, the second light source (11b) may be a white light source, and the third light source (11c) may be a near-infrared light source. In this case, the left dichroic mirror may transmit the excitation light and reflect the white light, and the right dichroic mirror may transmit the white light and the excitation light and reflect the near-infrared light.

[0057] Light emitted from light sources (11a, 11b, 11c) is incident on a light guide unit (17) through a light transmission mechanism (15) and is irradiated onto a target area through the light guide unit (17). The light guide unit (17) may include, for example, an optical fiber and may be composed of multiple bundles of optical fibers.

[0058] The brightness driving unit (13) controls the brightness of the light sources (11a, 11b, 11c) through the control of the control unit (30). The brightness driving unit (13) can turn off the excitation light source and the near-infrared light in the white light mode and turn on the white light source, and can turn off the white light and turn on the excitation light source and the near-infrared light source in the fluorescence excitation mode. The brightness driving unit (13) can also change the brightness of the light sources (11a, 11b, 11c) to adjust the signal intensity detected by the image sensor (25).

[0059] Referring to FIGS. 1 and 3, the detection unit (20) includes an optical filter (23) and an image sensor (25), and may include an optical lens (11). The optical lens (11) may be, for example, an objective lens, and may focus light (L2) incident from a target area onto the image sensor (25).

[0060] Light emitted from a light source (11) may be reflected from a target area or absorbed by a fluorophore in the target area to induce fluorescence. The reflected light or fluorescence is incident on an optical filter (23) in the target area. The optical filter (23) blocks the excitation light emitted from the excitation light source and transmits the near-infrared light emitted from the near-infrared light source. The optical filter (23) also transmits most of the white light emitted from the white light source.

[0061] The optical filter (23) may be, for example, a long-wavelength transmission filter or a band-pad filter having a cut-off wavelength on the short-wavelength side in the visible light range, as illustrated in FIG. 7. The cut-off wavelength may be longer than the excitation wavelength of the excitation light source, for example, 410 nm or longer. In addition, the cut-off wavelength may be 450 nm or shorter to minimize blocking of white light emitted from the white light source. For example, the cut-off wavelength may be about 420 nm. In this case, the optical filter (23) may transmit visible light and near-infrared light of about 420 nm or longer, and block visible light and ultraviolet light of less than about 420 nm. The optical filter (23) transmits near-infrared light emitted from the near-infrared light source. The optical filter (23) may have a cut-off wavelength that is longer than the wavelength of near-infrared light emitted from the near-infrared light source. For example, the optical filter (23) may be a bandpass filter having a cutoff wavelength that is larger than the near-infrared wavelength emitted from the near-infrared light source and smaller than about 1000 nm, or further smaller than about 920 nm.

[0062] The optical filter (23) may be, for example, an interference filter in which high-refractive-index material layers and low-refractive-index material layers are alternately laminated, but is not limited thereto, and may also be an inorganic or organic absorption filter.

[0063] Conventional color cameras that implement color images typically have a built-in near-infrared cutoff filter to block near-infrared light incident on the image sensor. However, recent advancements in image sensor and image processing technology have made it possible to achieve the color reproducibility of the image sensor without a near-infrared cutoff filter. In the present invention, color can be implemented without a near-infrared cutoff filter even in white light mode, which implements color using a white light source. Therefore, the optical filter (23) can be used in white light mode as well as fluorescence excitation mode. Furthermore, when detecting an image by irradiating light into an area without ambient light, such as the inside of a human body, noise due to near-infrared light can be excluded because there is no near-infrared ambient light in white light mode.

[0064] The image sensor (25) detects light transmitted through the optical filter (23). In white light mode, the image sensor (25) can detect white light reflected from a target area to obtain a color image, and in fluorescence excitation mode, it can detect near-infrared light reflected from the target area and fluorescence emitted by a fluorophore in the target area.

[0065] The image sensor (25) may be a CMOS or CCD image sensor, and may include a pixel array in which a color filter is arranged at each pixel to detect color light. Color filters that transmit light of different colors may be assigned to each pixel. For example, the pixel array of the image sensor may have a Bayer filter pattern as illustrated in FIG. 8. The Bayer filter pattern is such that rows in which green filters and red filters are alternately arranged and rows in which blue filters and green filters are alternately arranged are alternately arranged, and the green filter is arranged in an area of ​​50%, and the red filter and the blue filter are arranged in an area of ​​25% each. In addition, two red filters and two blue filters are arranged above and below and left and right around one green filter, four red filters and four green filters are alternately arranged around one blue filter, and four blue filters and four green filters are alternately arranged around one red filter.

[0066] The image sensor detects an image of the color assigned to each pixel and generates a detection signal (Bayer pattern image). When implementing an image, color value interpolation is performed from surrounding pixels to complete the missing color information in each pixel. For this purpose, various known demosaic algorithms are used.

[0067] Meanwhile, the relative sensitivity intensities of blue, green, and red pixels according to the Bayer filter pattern are shown in Fig. 9.

[0068] Referring to Fig. 9, it can be seen that the blue pixels, green pixels, and red pixels have relatively high sensitivity intensities in the blue region, green region, and red region, respectively. In addition, it can be seen that the blue pixels, green pixels, and red pixels have generally similar sensitivity intensities for near-infrared light in the region of about 800 nm to about 875 nm. In Fig. 9, the sensitivity intensities of each pixel are expressed relative to the maximum sensitivity intensity of the image sensor, i.e., the maximum sensitivity intensity of the red pixel. All of the above pixels have a sensitivity intensity of 30% or more of the maximum sensitivity intensity of the image sensor (25) for near-infrared light in the region of about 800 nm to about 875 nm. In addition, the difference in the sensitivity intensities of the pixels for near-infrared light is minimal, and is less than 10% of the maximum sensitivity intensity of the image sensor (25).

[0069] The present invention utilizes the characteristic that pixels have relatively high sensitivity intensities in different wavelength ranges of the visible light region, while having similar sensitivity intensities for near-infrared light, and by using the above pixels, color light is detected in white light mode, and near-infrared light and fluorescence are detected in fluorescence excitation mode.

[0070] The image processing unit (40) processes the signal detected by the image sensor (25) in the white light mode and the fluorescence excitation mode under the control of the control unit (30). In the white light mode, implementing color using the signal detected by each pixel can be performed using a conventional demosaicing algorithm. For example, the green light of a green pixel can be interpolated using the signal acquired from the green pixel, while the blue light and red light signals missing from the green pixel can be interpolated by averaging the signals acquired from two blue pixels and two red pixels arranged around the green pixel. In addition, the red light of a red pixel can be interpolated using the signal acquired from the red pixel, while the blue light and green light signals missing from the red pixel can be interpolated by averaging the signals acquired from four blue pixels and four green pixels arranged around the red pixel, respectively. Additionally, the blue light of the blue pixel can be interpolated by using the signal acquired from the blue pixel, while the green light and red light signals missing from the blue pixel can be interpolated by averaging the signals acquired from four green pixels and four red pixels arranged around the blue pixel, respectively.

[0071] In fluorescence excitation mode, each pixel can detect near-infrared light with roughly equal signal sensitivity, while the red pixel can detect fluorescence together with near-infrared light. That is, the signal detected from the red pixel is the red component (R) due to fluorescence. VIS ) and near-infrared component (R NIR ) and red light is blocked in green and blue pixels, so the near-infrared component (G NIR, B NIR ) can be detected. Using the signals detected in the above pixels, the red component (R) by the fluorescence detected in the red pixel VIS ) and near-infrared component (R NIR ) can be separated.

[0072] For example, the near-infrared component of the red pixel (R) is obtained by averaging the near-infrared components detected from four green pixels and four blue pixels placed around the red pixel. NIR ) can be extracted, and the red component (R) due to fluorescence can be obtained by subtracting this average value from the signal detected in the red pixel. VIS ) can be obtained. The missing red light signal from the blue and green pixels can be interpolated using the demosaicing algorithm described above.

[0073] Meanwhile, in the fluorescence excitation mode, fluorescence can be detected not only in red pixels but also in green pixels. For example, fluorescence can be detected not only in red pixels but also in green pixels when fluorescence due to autofluorescence or an exogenous fluorophore emitting green light is included. In this case, since the signal detected from the green pixel contains a fluorescence component along with a near-infrared component, it is not suitable to use it to extract the near-infrared component. Therefore, the near-infrared component of the red pixel can be extracted using the signal detected from the blue pixel. For example, the near-infrared component (R) of the red pixel NIR ) can be extracted by calculating the average value of the near-infrared components detected from four blue pixels arranged around the red pixel. The red component (R) due to the fluorescence of the red pixel VIS ) can be obtained by subtracting this average value from the signal detected in the red pixel. Meanwhile, the near-infrared component (G) of the green pixel NIR ) can be extracted by calculating the average value of the near-infrared components of two blue pixels placed around the green pixel, and the fluorescence component of the green pixel (G VIS ) is the near-infrared component of the green pixel in the signal detected from the green pixel (G NIR ) can be obtained by subtracting .

[0074] Therefore, embodiments of the present invention have a system having a single RGB camera, as well as a system having multiple cameras or sensors, as shown in FIG. 10, in the fluorescence excitation mode, a background image (I NIR ) and fluorescence imaging (I VIS ) can be acquired simultaneously, and these images can be displayed individually or as a fused image (I).

[0075] In addition, since the near-infrared signal and the fluorescence signal can be easily separated, image processing is convenient, and an enhanced image that further emphasizes the fluorescence image can also be easily implemented.

[0076] Meanwhile, as the working distance increases, the detected fluorescence intensity decreases, which may result in a blurred fluorescence image. In one embodiment, the control unit (30) may control the brightness driver (13) to increase the intensity of the light source (11), particularly the excitation light source, when the working distance increases, thereby increasing the intensity of the detection signal by fluorescence.

[0077] However, when the intensity of the light source is increased to increase the fluorescence signal intensity, a photobleaching effect may occur in which the fluorescence intensity decreases as the fluorophore probe emits more fluorescence.

[0078] In another embodiment, a fluorescence image can be corrected by detecting a change in the intensity of a near-infrared reflected light detection signal according to a change in the operating distance and recalculating a fluorescence signal based on the change in the intensity of the near-infrared reflected light detection signal. For example, the fluorescence signal can be recalculated by weighting the intensity of the red component due to fluorescence, thereby making the fluorescence image brighter even in a long-distance image. Therefore, a brighter fluorescence image can be made in a long-distance image without increasing the intensity of the excitation light source.

[0079] In embodiments of the present invention, since the background image is acquired using a near-infrared light source separate from the excitation light source for exciting the fluorophore, it is easy to control the intensity of the near-infrared light source for acquiring the background image, and the brightness of the background image is conveniently controlled. Moreover, since near-infrared light is detected at every pixel, the resolution of the background image is dramatically improved. In addition, since near-infrared light has a higher water permeability than visible light, it causes less specular reflection from surfaces such as organ mucosa, blood, and saline solution, enabling acquisition of clear images.

[0080] Meanwhile, since an image sensor with a Bayer filter pattern has more green pixels than blue or red pixels, a background image using near-infrared light may appear green overall. Such a background image may feel unfamiliar compared to an overall white light image. The image processing unit (40) can convert the color of the background image into a color that is easily recognizable and familiar to biological tissue, and thus, the display unit (50) can display the converted background image color.

[0081] FIG. 11 is a schematic diagram illustrating a laparoscopic fluorescence imaging system (100a) according to one embodiment of the present invention.

[0082] Referring to Fig. 11, a laparoscopic fluorescence imaging system (100a) includes a light source unit (10), a detection unit (20), a control unit (30), an image processing unit (40), a display unit (50), and a laparoscope (60). The laparoscope (60) includes a coupler (65) coupled to the detection unit (20) and a shaft (63) inserted into the body.

[0083] The light source unit (10), detection unit (20), control unit (30), image processing unit (40), and display unit (50) are as described above, so detailed descriptions are omitted to avoid duplication.

[0084] The light source (10) transmits light to the light guide unit, and the light guide unit is coupled to the laparoscope (60) and extends through the inside of the shaft (63). Light emitted from the light source (11) is irradiated to the target area (70) through the light guide unit extending through the inside of the shaft (63).

[0085] Meanwhile, the reflected light reflected from the target area (70) or the fluorescence emitted from the fluorophore in the target area (70) is transmitted to the detection unit (20) through the coupler (65) via optical devices arranged in the shaft (63).

[0086] In the present embodiment, the optical path through which light emitted from the light source (11) is irradiated to the target area (70) is integrated into the laparoscope (60) together with the optical path through which light is incident from the target area (70) to the detection unit (20). However, the present invention is not limited thereto, and the optical path through which light emitted from the light source (11) is irradiated to the target area (70) and the optical path through which light is incident from the target area (70) to the detection unit (20) may be separated from each other by different mechanisms.

[0087] In this embodiment, a laparoscopic fluorescence imaging system (100a) is described as an example, but the fluorescence imaging system of the present invention is not limited to laparoscopy. It can be applied to a fluorescence imaging system for observing internal tissues of a living body, such as various types of endoscopes. However, in addition to internal tissues of a living body, it can also be applied to a fluorescence imaging system for observing lesion tissues by irradiating light on the skin surface. In particular, in the case of a fluorescence imaging system for observing lesion tissues on the skin surface, the light irradiation path and the light detection path can be separated from each other.

[0088] (Experimental example)

[0089] A laparoscopic fluorescence imaging system was fabricated, and internal background images and fluorescence images were detected in fluorescence excitation mode using a silicone rubber phantom. A vertical cavity surface-emitting laser emitting near-infrared light with a peak wavelength of approximately 808 nm was used as a background light source, and an LED emitting short-wavelength visible light with a peak wavelength of approximately 405 nm was used as an excitation light source. The excitation light source was blocked using an optical filter. Images were detected at different working distances, and images (I) and background images (I) were acquired through demosaic image processing without separating the near-infrared and visible light components. NIR ), and fluorescence imaging (I VIS ) are shown in Fig. 12a, Fig. 12b, Fig. 12c, Fig. 13a, Fig. 13b, and Fig. 13c, respectively. Fig. 12a, Fig. 12b, and Fig. 12c are photographs showing close-range images, and Fig. 13a, Fig. 13b, and Fig. 13c are photographs showing long-range images.

[0090] Meanwhile, as a comparative example, an optical filter that blocks part of the excitation light and transmits part of it was placed, and a fluorescence image and a background image generated by the partially transmitted excitation light were detected using the excitation light. An LED emitting short-wavelength visible light with a peak wavelength of about 405 nm was used as the excitation light source. Images were detected by varying the working distance, and the background image and the fluorescence image are displayed in Figs. 14a, 14b, 14c, 15a, 15b, and 15c. Figs. 14a, 14b, and 14c are photographs showing close-range images, and Figs. 15a, 15b, and 15c are photographs showing long-range images.

[0091] Fluorescence images according to the embodiment (I VIS ) image photos (see Figs. 12c and 13c), it can be seen that the background is hardly observed and only the fluorescence image is well extracted. In contrast, the fluorescence image according to the comparative example (I VIS) In the case of image photographs (see Figs. 14c and 15c), it can be seen that the background is still observed, so only the fluorescence image is not well extracted. This is an inevitable problem that occurs because the blue light used as the background light source is partially detected in the green and red pixels of the image sensor.

[0092] Additionally, since the silicone rubber phantom reflects better in the blue wavelength than actual human tissue, the image of the fused image (I) of the comparative example (see FIGS. 14a and 15a) appears clear, but if the image is displayed against an actual human body with less reflection in the blue wavelength, the background will be darker.

[0093] Moreover, in the embodiment, since a near-infrared light source different from the excitation light source is used as the background image, adjusting the illumination intensity to obtain the background image does not affect the fluorescence signal. In contrast, in the comparative example, since the excitation light source is used not only to excite fluorescence but also to obtain the background image, adjusting the illumination intensity of the excitation light source also affects the fluorescence signal. Furthermore, increasing the intensity of the excitation light source not only accelerates photobleaching of fluorophores but also increases autofluorescence, which becomes background noise.

[0094] Although various embodiments of the present invention have been described above, the present invention is not limited to the various embodiments and features described above, and various modifications and changes are possible within a scope that does not depart from the technical idea according to the claims of the present invention.

[0095] (Explanation of symbols)

[0096] 10: light source, 11, 11a, 11b, 11c, light source, 13: brightness driver, 15: light transmission mechanism, 15a: optical lens, 15b; dichroic mirror, 17: light guide unit, 20: detection unit, 21: optical lens, 23: optical filter, 25: image sensor, 30: control unit, 40: image processing unit, 50: display unit, 60: laparoscope, 63: shaft, 65: coupler, 70: target area, L1, L2: optical

Claims

1. A light source for irradiating light to a target area; and Including a detection unit that detects light incident from a target area, The above light source unit, A near-infrared light source that emits light having a peak wavelength in the near-infrared region; and comprising an excitation light source that emits excitation light that excites a fluorophore; The above detection unit, An optical filter that blocks the above light source and transmits the fluorescence emitted from the above fluorescent moiety and the near-infrared light; and A fluorescence imaging system comprising an image sensor that detects fluorescence and near-infrared light passing through the optical filter.

2. In claim 1, The above-described light source is a fluorescence imaging system having a peak wavelength in the visible or ultraviolet region.

3. In claim 2, A fluorescence imaging system in which fluorescence emitted from the above fluorophore has a peak wavelength in the red region.

4. In claim 3, The above fluorophore is a fluorescence imaging system comprising PpIX or Ce6.

5. In claim 1, The above light source unit further includes a white light source that emits white light, The above white light source emits light in white light mode, At least a portion of the light emitted from the white light source and reflected from the target area passes through the optical filter and is detected by the image sensor, The above near-infrared light source and excitation light source emit near-infrared light and excitation light in fluorescence excitation mode, A fluorescence imaging system in which the above white light mode and the above fluorescence excitation mode are switched with each other.

6. In claim 1, The image sensor includes a pixel array, wherein each pixel is assigned a color filter that transmits light of a different color, A fluorescence imaging system wherein each of the pixels has a sensitivity intensity of at least 30% of the maximum sensitivity intensity of the image sensor for the near-infrared light.

7. In claim 6, A fluorescence imaging system in which the difference in sensitivity intensities of pixels of the image sensor to near-infrared light is less than 10% of the maximum sensitivity intensities of the image sensor.

8. In claim 6, A fluorescent imaging system in which the pixel array of the image sensor has a Bayer filter pattern.

9. In claim 1, A fluorescence imaging system further comprising an image processing unit that processes an image signal detected by the image sensor.

10. In claim 9, The above image processing unit is a fluorescence imaging system that converts a background image signal by near-infrared light detected by the image sensor into an image signal of a different color.

11. In claim 9, The above image processing unit is a fluorescence imaging system that corrects the intensity of a fluorescence image signal based on a change in the intensity of a detection signal of near-infrared reflected light according to an operating distance from a target area.

12. In claim 9, Control unit; Brightness driver; and Including more display parts, The above control unit controls the image processing unit and the brightness driving unit, The above brightness driving unit controls the brightness of each light source of the above light source unit, A fluorescent imaging system in which the display unit displays an image signal processed by the image processing unit.

Citation Information

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