Endoscope illumination system for a fluorescent agent

Abstract

The invention provides an illumination device for outputting an output light, the illumination device comprising a first light source, a second light source; the first light source being configured to emit first light at a first peak wavelength in a first range of 660 nm to 699 nm, the second light source being configured to emit second light at a second peak wavelength in a second range of 689 nm to 705 nm; wherein the second peak wavelength is at least 5 nm larger than the first peak wavelength; the second light source being configured to be turned on and off independently of the first light source; the device being configured to output the first light as the output light in case the second light source is off, and to output the first light and the second light as the output light in case the second light source is on.

Description

Background Technology

[0001] NIR-PIT (Near-Infrared Photoelectroimmunotherapy) is expected to be a novel cancer therapy. The drug in NIR-PIT has a conjugated structure with IRDye700DX (hereinafter: IR700), serving as both a photoelectrorea and an antibody drug. The drug's primary functions are as a drug delivery system (DDS) for molecularly targeted therapy, fluorescence imaging with good differentiation against autofluorescence (510 nm), and therapies (see https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC6704485 / ).

[0002] The excitation and emission characteristics of IR700 are shown in Figure 1 In the figure, the peak wavelength of the excitation sensitivity (the maximum excitation sensitivity is at λ) is shown in the table. p,ex =689nm) and the peak wavelength of fluorescence emission (λ) p,em =699nm) are very close to each other.

[0003] When imaging a scene is intended to be achieved using fluorescence transmitted through an IR700 (which is excited by an excitation light), the excitation light should have a wavelength close to that of the emitted fluorescence. However, such excitation light interferes with imaging via fluorescence. Separating these two types of light becomes difficult if the imaging system acquires a sufficient fluorescence signal without a large amount of excitation light.

[0004] On the other hand, for therapeutic applications, high specific energy accumulation is required, such as 50 J / cm at the peak excitation wavelength (689 nm) of IR700 and a few nm around the peak excitation wavelength. 2 Otherwise, it could take a long time to process the treatment response.

[0005] In cases where imaging and therapy are performed via a single endoscope, the requirements for imaging and therapeutic uses are conflicting.

[0006] CIE 1931 linked the distribution of wavelengths in the electromagnetic visible spectrum with the physiological perception of color in human color vision. Figure 2 The color gamut (xy plane, taken from people.cs.clemson.edu) according to CIE 1931 is shown. The middle region (without color annotations) represents white light. The numbers at the boundaries of the color gamut indicate the wavelength (in nm) of the corresponding net spectral light. White light has coordinates x = 1 / 3; y = 1 / 3 and z = 1 / 3. Summary of the Invention

[0007] The objective of this invention is to improve upon existing technologies.

[0008] The present invention provides an improved illumination system that allows for both fluorescence-based imaging and therapeutic applications of IR700, such as in cancer therapy.

[0009] The present invention provides an illumination device for outputting an output light, the illumination device comprising a first light source and a second light source; the first light source is configured to emit first light at a first peak wavelength in a first range of 660 nm to 699 nm, and the second light source is configured to emit second light at a second peak wavelength in a second range of 689 nm to 705 nm; wherein the second peak wavelength is at least 5 nm larger than the first peak wavelength; the second light source is configured to be turned on and off independently of the first light source; the device is configured to output the first light as output light when the second light source is off, and to output both the first light and the second light as output light when the second light source is on. Attached Figure Description

[0010] Other details, features, objectives, and advantages will become apparent from the following detailed description of preferred embodiments of the invention, which is considered in conjunction with the accompanying drawings, wherein:

[0011] Figure 1 The excitation and emission spectra of the IR700 are shown.

[0012] Figure 2 The color gamut according to CIE 1931 is shown;

[0013] Figure 3 A lighting device is shown according to an embodiment of the present invention;

[0014] Figure 4 It shows the use of Figure 3 The reflectivity of the bicolor interface of orthogonal blocks in lighting equipment;

[0015] Figure 5 The transmittance of filters included in an imaging system is shown in some embodiments of the present invention;

[0016] Figure 6 A lighting device is shown according to an embodiment of the present invention;

[0017] Figure 7 A lighting device is shown according to an embodiment of the present invention;

[0018] Figure 8 It shows the use of Figure 7 The reflectivity of a bicolor interface (bicolor mirror) in a lighting device;

[0019] Figure 9 It shows Figure 7 The transmittance of the optical cutting filters included in the lighting equipment;

[0020] Figure 10 It shows Figure 7 Example spectra of the output light of the lighting device in the excitation and emission spectra of IR700, where the optical cut-off filter is removed from the light path;

[0021] Figure 11 It shows Figure 7 Example spectra of the output light of the lighting device in the excitation and emission spectra of IR700, with the optical cut-out filter in the optical path;

[0022] Figure 12 A lighting device is shown according to an embodiment of the present invention;

[0023] Figure 13 A lighting device is shown according to an embodiment of the present invention; and

[0024] Figure 14 A lighting device is shown according to an embodiment of the present invention; and

[0025] Figure 15 Some embodiments of the present invention illustrate a sensor system that can be used in an imaging system. Detailed Implementation

[0026] In the following description, certain embodiments of the invention are given in detail with reference to the accompanying drawings, wherein features of the embodiments may be freely combined with each other unless otherwise described. However, it should be clearly understood that the description of certain embodiments is given by way of example only and is in no way intended to limit the invention to the details disclosed.

[0027] First Embodiment

[0028] According to the first embodiment, the lighting device has at least two light sources:

[0029] - Light source 1 has a peak wavelength of 660nm ≤ λp1 < 699nm. It can be used for both fluorescence imaging and therapeutic purposes. The peak wavelength is shorter than the emission peak wavelength of IR700 (699nm) and shorter than the peak wavelength of "light source 2".

[0030] - Light source 2 has a peak wavelength of 689nm ≤ λp2 < 705nm. It is typically used only for therapeutic purposes. The peak wavelength of light source 2 is greater than the peak wavelength of light source 1. For example, this peak wavelength is at least 5nm larger, preferably at least 10nm larger, and more preferably at least 15nm larger.

[0031] For fluorescence imaging of a scene, only light source 1 is typically used. Therefore, the light from the scene at wavelengths of 700 nm and longer is primarily derived from the fluorescence of IR700.

[0032] In therapeutic applications, both "Light Source 1" and "Light Source 2" are typically turned on to enhance the therapeutic response of PIT. Therefore, compared to illumination using only one light source, the procedure time is reduced, alleviating the burden on patients and medical professionals.

[0033] Light sources 1 and 2 can typically be laser diodes or LEDs. Examples of light source 1 are laser diodes L690-66-60 (obtained from Ushio Opto Semiconductors, Inc.) and MRL-III-690 (see http: / / www.cnilaser.com / red_laser690.htm). An example of light source 2 is a laser diode MLL-FN-698 (see http: / / www.cnilaser.com / Red-Laser-698nm.htm).

[0034] Furthermore, the device may include a third light source 3 for another imaging mode, such as white light imaging. Regarding white light imaging, the third light source 3 emits light such that it is closer to the CIE 1931 white point (x = y = z = 1 / 3) than the light from the first light source. The term "closer to the white point" refers to a shorter Euclidean distance in the xy plane of the CIE 1931 color gamut from the white point x = y = 1 / 3 (ignoring the z-direction). (Coordinate x...) i ,y i The Euclidean distance of the illumination light from the white point in the xy plane is (x i -1 / 3) 2 +(y i -1 / 3) 2 .

[0035] White light imaging is just one example of another imaging mode. Where appropriate, instead of white light imaging (or otherwise), imaging with colored light, or with UV light, or with (far)infrared light (generally: spectral imaging) can be performed.

[0036] Light from two or three light sources is combined using a combiner. For two light sources, one dichroic mirror can be used. For three light sources, two dichroic mirrors can be used. Two dichroic mirrors can be functionally combined within an orthogonal block comprising two dichroic interfaces.

[0037] Figure 3 An embodiment of such lighting equipment is shown. Figure 4 It shows the use of Figure 3 The reflectivity of the bicolor interface of orthogonal blocks in a lighting fixture. For example, from... Figure 3It can be seen that the light from light source 1 and light source 3 are reflected at the corresponding two-color interfaces of the orthogonal block. The light from light source 2 passes through both two-color interfaces. Therefore, in this example, one of the two-color interfaces reflects light near the peak wavelength λp1 of the first light source, and the other two-color interface reflects white light (e.g., in the range of 400nm to 650nm), as shown below. Figure 4 As shown. The reflection bands are usually separated from each other. The dichroic interface transmits light of other wavelengths, such as the peak wavelength λp2 of the second light source and wavelengths near λp2.

[0038] Combined light can be focused by a condenser (such as a convex lens) on an optical connector, which directs the light into an optical fiber to illuminate a scene. For example, the emitting end of the optical fiber can be positioned in the distal rigid end portion of an endoscope to illuminate a scene that is imaged by an imaging device (objective) positioned in the rigid end portion of the endoscope.

[0039] If the lighting equipment is located near the scene to be illuminated, for example, if the lighting equipment is located in the rigid end portion of an endoscope, then the condenser, fiber optic connector, and fiber optic cable can be omitted. Figures 12 to 14 Corresponding examples are provided. In this case, light source 1 and light source 2 are typically LEDs, for example, based on AlGaInP material. Some embodiments include two different types of LEDs. In some embodiments, LED1 may be the same type as LED2, but covered with a filter, which corresponds to the filter described below relative to... Figure 7 The filter is further described below.

[0040] like Figure 12 As shown, the illumination device provided in the rigid distal portion of the endoscope includes only LED1 and LED2 arranged on one or two circuit boards. Alternatively, the illumination device may include other LEDs, such as blue LEDs and blue-violet LEDs, as... Figure 13 As shown. Furthermore, the LED can be covered by a phosphor layer and / or a transparent cap, such as... Figure 14 As shown. Preferably, the phosphor layer has an excitation spectrum such that fluorescence or luminescence is not excited by the light from LED1 or LED2. That is, the phosphor layer is substantially transparent with respect to the light from LED1 and LED2.

[0041] In some embodiments, light from even more light sources with different peak wavelengths can be combined using an appropriate number of bicolor reflective interfaces (n light sources → n-1 bicolor reflective interfaces). Up to four bicolor interfaces can be arranged together in corresponding orthogonal blocks (two bicolor interfaces for reflecting light from the first and second light sources are arranged in a first plane including the propagation direction of the output light, and two bicolor interfaces for reflecting light from the third and fourth light sources are arranged in a second plane including the propagation direction of the output light, wherein the first plane intersects the second plane; typically, the second plane is perpendicular to the first plane).

[0042] An example of such lighting equipment is shown in Figure 6 In. Figure 6 In this configuration, each of the three orthogonal blocks (generally, orthogonal prisms) has two bicolor interfaces. Light from three near-infrared (NIR) sources, NIR1, NIR2, and NIR3, is combined by the first orthogonal block, while the second and third orthogonal blocks combine RGB light (red, green, and blue) and UV light (ultraviolet light), which is output from the first orthogonal block. White light imaging can be achieved using RGB light. UV light (possibly along with green light) can be used to enhance vascular imaging. Figure 6 In this example, the light from the light source is collimated by a corresponding lens before entering the respective orthogonal block. The arrangement of the light sources can be changed if the two-color reflective interface has appropriate reflective properties. For example, some or all of the RGB light sources can be swapped with the positions of the NIR light sources.

[0043] Generally, each light source in a lighting device can be individually controlled. That is, each of them can be turned on and off independently of the other light sources. Furthermore, in some embodiments, the light intensity or emitted color of at least one light source can be controlled independently of the other light sources. Some embodiments include a controller to perform the control.

[0044] For example, if only the first light source is turned on, the lighting device can illuminate the scene to form an image on the imaging surface. Regarding imaging, an imaging apparatus can be used. An imaging apparatus typically includes an objective lens for imaging the scene onto the imaging surface. However, an imaging apparatus is not limited to lens optics; it may include, for example, reflective components (reflective systems).

[0045] Furthermore, in some embodiments, the imaging device includes a filter (excitation light cutting filter), which may be a band filter. In other words, within a wavelength range between 670 nm and 715 nm, the filter allows the fluorescence of IR700 (i.e., wavelength bands in the range greater than 699 nm and less than 715 nm) to pass through and blocks excitation light in the range less than 699 nm. Therefore, the excitation light does not interfere with (or barely interferes with) the fluorescence image. Generally, the filter blocks light below a preset wavelength and allows light above a preset wavelength, which is in the range of 690 nm to 700 nm.

[0046] In addition, such as Figure 5 As shown, the filter allows white light (wavelength less than 650nm) from a third light source to pass through, making the same imaging device usable for both fluorescence imaging illuminated by a first light source and white light imaging illuminated by a third light source.

[0047] Images on the imaging surface can be captured by an image sensor, such as a CMOS array or a CCD array. In some embodiments, images on the imaging surface can be observed directly or via relay optics.

[0048] In some embodiments, the light beam may be split by another dichroic mirror. This other dichroic mirror may reflect fluorescence, allowing the fluorescent image to be observed through the first image sensor, while blocking the other light from the first image sensor. The other dichroic mirror may transmit another light, such as white light (or one of the RGB lights) or UV light, from one or more other light sources. Therefore, due to illumination by the other light, the image can be observed through a second image sensor. Observation can be performed simultaneously on both the first and second image sensors. In some embodiments, instead of the configuration described above, the other dichroic mirror may transmit fluorescence and reflect another light.

[0049] Furthermore, the sensor configuration may include an excitation light cutting filter (such as one described above) to filter the excitation light, particularly when the other dichroic mirror does not include a corresponding filter function. Such a sensor configuration is shown in... Figure 15 In the middle. For clarity purposes, the objective lens and other optical components are from... Figure 15 Omitted. In this case, the excitation light cutter filter allows light with a wavelength at least 20 nm lower than the preset wavelength to pass through. Preferably, the difference is even greater (e.g., 40 nm or even 60 nm), such that almost no excitation light passes through the excitation light cutter filter, while white light (or either RGB light) or UV light passes through the excitation light cutter filter.

[0050] Second Embodiment

[0051] The differences between the second embodiment and the first embodiment are described below. Unless otherwise stated or obvious from the context, the description of the first embodiment also applies to the second embodiment.

[0052] In the second embodiment, as Figure 7 As shown, the lighting device includes only one NIR light source (first light source) having a wavelength λp1 in the range of 660nm ≤ λp1 < 700nm and an emission spectrum that extends beyond 700nm with an intensity of at least 30% of the peak wavelength.

[0053] Furthermore, an optical filter (e.g., a bandpass filter) is located in the optical path between the light source and the output of the lighting device (e.g., between the light source and the optical connector). The bandpass filter is movable, allowing it to be located either within or outside the optical path. The bandpass filter transmits excitation light and substantially blocks light within the wavelength range of the fluorescence emitted by the IR700. For example, the bandpass filter can transmit light with wavelengths shorter than a predetermined wavelength and block light with wavelengths longer than a predetermined wavelength, wherein the predetermined wavelength is in the range of 689 nm and 700 nm.

[0054] To effectively function as a filter, the light intensity of the first light source at a predetermined wavelength is at least 50% of the light intensity at the peak wavelength of the first light source. Preferably, it is at least 65%, or even at least 80%.

[0055] The filter can be moved into or out of the light path by a moving device. The moving device can be, for example, a motor. The motor can be controlled by a controller. The moving device can be, for example, a handle or some other mechanism, allowing the filter to be moved manually. This movement can be, for example, linear or rotary. If the filter moves out of the light path, then the light output from the lighting device includes the light from the light source without passing through any filter that filters out more than 30% of the light intensity of any wavelength in the relevant wavelength range between 680 nm and 720 nm.

[0056] If the bandpass filter is in the optical path, then a light source can be used for imaging because the light corresponding to fluorescence from that source is largely blocked. If the bandpass filter is not in the optical path, then the light source can be used for high-power therapy.

[0057] like Figure 7 As shown, the lighting device of the second embodiment may additionally (optionally) include a second light source (e.g., a white light source). The second light source corresponds to the third light source of the first embodiment and can be used, for example, for white light imaging. The light from the first light source (which, when inserted into the light path, has been filtered by a movable filter) and the light from the second light source can be combined by a dichroic reflective surface (e.g., a dichroic mirror). Figure 8An example of the reflectivity of a dichroic reflective surface is shown, where the light from a first light source near the peak wavelength λp (also schematically shown in...) Figure 8 The light from the white light source should be reflected and the white light from the white light source should pass through the dichroic reflective surface. In this case, the reflection spectrum also includes at least a portion of the spectrum of the first light source, which can be cut by a movable filter.

[0058] Figure 9 An example of the transmission spectrum of a movable filter is shown. The filter only transmits light in the lower wavelength range of the first light source. Figure 9 In some cases, only light with wavelengths lower than the peak wavelength of the first light source is transmitted. However, this is not mandatory. The transmission band can be set such that enough light to excite the fluorescence of the IR700 is transmitted while a sufficient majority of the larger wavelengths (corresponding to the fluorescence) are blocked.

[0059] Figure 10 It shows in Figure 1 The image shows an example of the excitation and emission spectra of the IR700 emitted by the first light source of the second embodiment (black squares). In this case, the spectrum of the light from the first light source substantially corresponds to the peak of the excitation spectrum of the IR700. Therefore, the light from the first light source effectively excites the fluorescence of the IR700. A high energy dose can be deposited in the tissue.

[0060] In comparison, Figure 11 It shows in Figure 1 The excitation and emission spectra of the IR700 are shown, along with the spectrum of light from the first light source (black squares) filtered by a movable filter. In this example, the emitted light at a larger wavelength (greater than approximately 695 nm) is cut off. Therefore, this light still excites the fluorescence of the IR700, but hardly interferes with the fluorescence generated by the IR700.

[0061] The imaging device of the second embodiment may be the same as the imaging device of the first embodiment. Additionally, the illumination device of the second embodiment may include other light sources that emit wavelengths different from the first light source, such as one or more RGB light sources, UV light sources, or (far)IR light sources, similar to... Figure 6 The lighting equipment shown.

[0062] According to some embodiments of the invention, the illumination device may be arranged in an external housing (light source housing or processor system). Light from the external housing may be guided from the proximal end of the endoscope to the distal end of the endoscope via one or more optical fibers to illuminate the object space of an imaging device (e.g., an objective lens) arranged at the distal end of the endoscope. However, the illumination system may be arranged in the control body, the endoscope connector, or even alternatively in the distal end of the endoscope.

[0063] In some embodiments, optical fibers and optics (e.g., optical connectors) can be considered as part of the output portion of a lighting device, with the optics used to guide light from the lighting device into the optical fiber. In these embodiments, the impact on the light output from the orthogonal block can be considered when designing the light source and combiner (such as a bicolor reflective interface).

[0064] Some embodiments of the invention include a combination of a master endoscope and a daughter endoscope. Such a combination can be used to access narrow and peripheral areas or organs, such as the bronchus. In this case, the master endoscope functions as a conventional endoscope. The daughter endoscope is guided through the working channel of the master endoscope. That is, the daughter endoscope is significantly narrower than the master endoscope.

[0065] The light output from the external housing (light source housing) can be split into the main mirror and the daughter mirror at an appropriate ratio by a beam splitter, so that both the main mirror and the daughter mirror illuminate the corresponding scene with the same light. The beam splitter can be part of the optical connector of the light source housing.

[0066] An endoscope including an illumination device may be an axisless (e.g., rigid or flexible block) capsule endoscope, or an endoscope including an axis (e.g., rigid or flexible block) and a rigid distal portion. The rigid distal portion may be directly or indirectly connected to the axis via an angled segment. The endoscope may be adapted for insertion into a lumen of the human body.

[0067] In some embodiments, the lighting device and, possibly the imaging device, may be used externally, so that they are not arranged in the endoscope.

Claims

1. A lighting device for outputting light, the lighting device comprising: A first light source is configured to emit first light at a first peak wavelength within a first range of 660 nm to 699 nm; A second light source is configured to emit second light at a second peak wavelength within a second range of 689 nm to 705 nm; wherein... The second peak wavelength is at least 5 nm larger than the first peak wavelength; The second light source is configured to be turned on and off independently of the first light source; The lighting device is configured to output the first light as the output light when the second light source is off, and to output both the first light and the second light as the output light when the second light source is on.

2. The lighting device according to claim 1, further comprising: A first combiner is configured to combine the first light from the first light source and the second light from the second light source to output the output light.

3. The lighting device according to claim 2, further comprising: A white light source, configured to emit white light; A white light combiner is configured to combine the white light from the white light source, such that the output light includes the white light; wherein... The white light source is configured to be independent of the first light source, and to be turned on and off independently of the second light source in the case that the lighting device includes the second light source.

4. The lighting device according to claim 3, wherein, The white light combiner is integrated with the first combiner.

5. The lighting device according to any one of claims 2 to 4, wherein, The first combiner includes at least one dichroic mirror, the at least one dichroic mirror having at least one dichroic reflective interface.

6. An imaging system, comprising: The lighting device according to claim 5, and An imaging device configured to image the scene on a first imaging surface when the scene is illuminated by the output light of the lighting device.

7. The imaging system according to claim 6, wherein, The imaging device includes An excitation light cutting filter is configured to block light with a wavelength smaller than a preset wavelength from the scene light, preventing such light from reaching the first imaging surface; and the excitation light cutting filter is configured to transmit light with a wavelength greater than the preset wavelength from the scene light, allowing such light to reach the first imaging surface. The preset wavelength is in the range between 690nm and 700nm.

8. The imaging system according to claim 6, further comprising: A first image sensor is disposed on the first imaging surface.

9. The imaging system according to claim 8, further comprising: Another dichroic mirror is configured to divide light from the scene such that light from the scene having a wavelength greater than a preset wavelength reaches the first imaging surface, and another light having a wavelength shorter than a minimum wavelength reaches a second imaging surface different from the first imaging surface. A second image sensor is disposed at the second imaging surface; and wherein... The imaging device includes an excitation light cutting filter configured to transmit light having a wavelength smaller than the minimum wavelength; and The minimum wavelength is at least 20 nm smaller than the preset wavelength.

10. An endoscope, comprising The lighting device according to any one of claims 1 to 5, and A rigid distal end portion, wherein the rigid distal end portion is disposed at the distal end of the endoscope; wherein, The rigid end portion of the endoscope is configured to output the output light from the illumination device.

11. The endoscope according to claim 10, wherein, The rigid end portion includes the lighting device.

12. The endoscope according to claim 10, further comprising: An optical fiber, configured to transmit the output light of the lighting device to the rigid end portion; wherein... The lighting device is located at the proximal end of the endoscope or on the outside of the endoscope.

13. An endoscope, comprising The imaging system according to any one of claims 6 to 9, and A rigid distal end portion, wherein the rigid distal end portion is disposed at the distal end of the endoscope; wherein, The rigid end portion of the endoscope is configured to output the output light from the illumination device.

14. The endoscope according to claim 13, wherein, The rigid end portion includes the lighting device.

15. The endoscope according to claim 13, further comprising: An optical fiber, configured to transmit the output light of the lighting device to the rigid end portion; wherein... The lighting device is located at the proximal end of the endoscope or on the outside of the endoscope.

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