Systems and methods for lymph node and lymphatic vessel imaging

Abstract

To provide a system for imaging a lymphatic site.SOLUTION: The system includes a light source 101 for providing infrared radiation having a polarization to a region including at least one lymphatic site of a subject, a sensor 104 configured to sense a reflected portion of the infrared radiation directly reflected from the region and having a polarization opposite to the polarization of the infrared radiation, and a controller in communication with the sensor. The controller is configured to receive information corresponding to the reflected portion of the infrared radiation from the sensor, generate at least one image indicative of at least one lymphatic system site of the subject using the information, and output the at least one image to at least one of a display and / or a memory.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This application is a continuation of U.S. Provisional Application No. 62 / 848,178 (filed May 15, 2019) and This is an application based on the same application No. 62 / 800,674 (filing date: February 4, 2019), The present application claims the benefit of and priority from the following provisional applications: No. 60 / 699,999, filed on Dec. 1, 2003, the entire contents of which are incorporated herein by reference for all purposes.

[0002] This invention was made under grant number P30CA014051 awarded by the National Institutes of Health. This was done with government support. The government has certain rights in this invention. [Background technology]

[0003] Lymph nodes, also known as "lymph glands," are found throughout the human and animal body. Lymph nodes are an integral part of the lymphatic system and are responsible for the protection of the body from disease and infection. The state of the lymph nodes directly reveals the health status of the individual. Swollen lymph nodes can be a sign of bacterial infection, viral infection, cancer, etc. Imaging lymph nodes and checking their condition is important for diagnosing and preventing diseases. and is extremely useful in treatment.

[0004] Currently, there are many imaging modalities available for visualizing and examining lymph nodes. Traditionally, the standard technique has been lymphangiography, which involves administering a radiocontrast agent to the patient. The procedure involves injecting a small amount of fluid into the lymph nodes and using x-rays to visualize the lymph nodes and lymphatic vessels. It causes significant discomfort and uses radioactive agents.

[0005] Recently, computed tomography (CT) and magnetic resonance imaging have become popular methods for lymph node visualization. Cross-sectional imaging modalities, including magnetic resonance imaging (MRI), have become widespread, and lymphography Ultrasound tomography and positron emission tomography (PET) are also useful. These techniques have been shown to allow physicians to identify and Although the condition can be determined with reasonable accuracy, these are general-purpose imaging modalities. Because it is a sedative, its mechanism of action is such that it cannot be detected in lymph nodes without the injection of a special contrast agent. The design does not achieve the best contrast specifically for other organs or tissues. They appear on the image with contrast similar to that of lymph nodes, and sometimes with better contrast than lymph nodes. This can cause problems in lymph node detection and diagnosis. Such general imaging modalities are not only not specific to lymph nodes, but are also fatal in themselves. CT involves exposure to X-rays, and PET uses radioactive drugs, which can be harmful to health. It must be carefully controlled to prevent damage. MRI is expensive equipment and metal Cannot be used on patients with implants. Ultrasound imaging contrast and resolution is low, mainly due to the long imaging wavelength.

[0006] Another common lymph node imaging method in use is the use of blue dye or fluorescent dye. This is a technique in which a dye of one of the following colors is injected into the lymph nodes. The dye is methylene blue, which is actually toxic. The dosage of this dye must be carefully controlled. The fluorescent dye indocyanine green is also used for lymph node imaging. Fluorescent dyes such as indocyanine green and methylene blue are used for The systems used include the FLARE (registered trademark) system, the fluobeam system, The systems are the SPY, FDPM and Photodynamic Eye. Most of these are standalone systems. An image sensor (typically a CCD) is used to capture a visible image (reference image) and a fluorescent image sequentially. or using multiple cameras to capture multiple different spectra simultaneously or sequentially do.

[0007] Dye-based techniques have a number of drawbacks. One drawback is that the dyes can cause irritation in some patients. Another drawback is that side effects may occur in some patients, especially those with kidney complications. However, the leaky lymphatic system can make dye injection techniques unreliable. , Certain dye-based techniques require the invasive application of dye.

[0008] Imaging using multiple cameras to generate multiple images and / or sequential image acquisition In this system, sequential image registration is required. For proper coordination, such image processing must take into account changes in angular coordinates, the distance between the system and the object, and Other types of imaging devices require consideration of the relative motion, the relative position, and both. , in both the red-green-blue channel(s) (RGB) and a single channel of NIR-1 There are special CMOS sensors that can collect light.

[0009] Imaging lymph nodes, including optical speckle imaging and optical coherence tomography There have been several other reports in the academic literature on the use of novel optical techniques to measure However, optical speckle imaging is highly susceptible to motion artifacts. However, optical coherence tomography requires complex equipment and its imaging contrast is poor. is low.

[0010] In summary, given the critical importance of lymph nodes to human health, There are no simple and effective methods for visualizing lymph nodes. is not convenient and is not specific for visualization of lymph nodes unless contrast is injected. Dye-based imaging techniques are generally highly invasive and are not suitable for routine clinical settings. It is incompatible with the conventional imaging equipment. Finally, if there is a new imaging modality that can easily image lymph nodes, It allows doctors to diagnose a patient's health, evaluate the effectiveness of certain treatments, and status an individual's cancer status. This makes it a powerful tool for classifying cancer pages and for many other medical applications. Summary of the Invention

[0011] The following is intended to provide a brief summary of the disclosure and is not intended to be a comprehensive summary of the disclosure. It is not intended to be limiting in scope.

[0012] In one aspect, the present disclosure provides a system for imaging a lymphatic system region. The system applies polarized red light to an area of ​​the subject that includes at least one lymphatic system region. a light source for providing infrared radiation and a polarized light source having a polarized light opposite to that of the infrared radiation reflected directly from the area; a sensor configured to sense a reflected portion of the infrared radiation having a and a controller in communication with the sensor. The controller detects reflected infrared radiation. and receiving information from the sensor corresponding to a portion of the object using the information. generating at least one image showing a lymphatic system region; and displaying the at least one image on a display unit. and / or memory.

[0013] In another aspect, the present disclosure provides a method for imaging lymph nodes or lymphatic vessels in vivo without the use of contrast agents. The present invention provides a method for imaging a subject, the method comprising: using a light source to image a portion of the subject that does not contain a contrast agent; and applying polarized infrared radiation to a region of the body including a lymph node or lymphatic vessel. using a sensor positioned to receive infrared radiation reflected directly from said area. and a reflected portion of the infrared radiation having a polarization opposite to that directly reflected from the region. and detecting a portion of the object that is free of the contrast agent using a reflected portion of the infrared illumination. and generating at least one image showing the lymph node or lymph vessel.

[0014] In yet another aspect, the present disclosure provides a method for imaging lymph nodes or lymphatic vessels without the use of mirrors. The present invention provides a method for imaging a lymph node or lymph node tissue in a subject using a light source. applying infrared radiation to an area including the impeller tube; and reflecting the infrared radiation directly from the area. using a sensor positioned to receive the reflected infrared radiation directly from the area. detecting a reflected portion of the radiation; and detecting a reflected portion of the infrared radiation. generating at least one image showing lymph nodes or lymphatic vessels of the elephant; .

[0015] In yet another aspect, a system for imaging a lymphatic system region is provided. The system applies polarized red light to an area of ​​the subject that includes at least one lymphatic system region. The device is provided with a light source for external radiation irradiation and a sensor, and the sensor detects light reflected directly from the area. sensing a reflected portion of the infrared radiation having a polarization opposite to that of the incident infrared radiation; and detecting a small amount of radiation indicative of said at least one lymphatic region of the subject based on a reflected portion of the radiation. and generating at least one image, and displaying the at least one image on an external display and / or an external memory. The device is configured to output the signal to at least one of the input / output ports. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a schematic diagram of an example imaging system in accordance with certain aspects of the present disclosure. [Figure 2] FIG. 1 is a schematic diagram of another example imaging system according to certain aspects of the present disclosure. [Figure 3] FIG. 10 is a schematic diagram of an imaging system according to yet another example embodiment of certain aspects of the present disclosure. [Figure 4] FIG. 4 illustrates example hardware that can be used to implement the computer and interface platform shown in FIG. 3 according to some embodiments of the present disclosure. [Figure 5] 10 is a flowchart of an example of processing included in an image generation and analysis application. [Figure 6] 10 is a flowchart illustrating an example of another process included in an image generation and analysis application. [Figure 7A-B] Figure 7A shows the imaging results of an area photographed without a polarizer, and Figure 7B shows the imaging results of the same area photographed with a polarizer. [Figure 8A-C]Figure 8A shows an image of a region of a mouse taken with a standard camera, Figure 8B shows an image of the region of the mouse in Figure 8A taken with an imaging system before injection of the adjuvant, and Figure 8C shows an image of the region of the mouse in Figure 8A taken with an imaging system 48 hours after injection of the adjuvant. [Figure 9A-C] Figure 9A shows an image of a region of a mouse taken with a standard camera, Figure 9B shows an image of the region of the mouse in Figure 9A taken with an imaging system before injection of the adjuvant, and Figure 9C shows an image of the region of the mouse in Figure 9A taken with an imaging system 48 hours after injection of the adjuvant. [Figures 10A-E] Figure 10A shows an example image taken using an InGaAs camera when an illumination wavelength of 1000 nm is used. Figure 10B shows an example image taken using an InGaAs camera when an illumination wavelength of 1175 nm is used. Figure 10C shows an example image taken using an InGaAs camera when an illumination wavelength of 1250 nm is used. Figure 10D shows an example image taken using an InGaAs camera when an illumination wavelength of 1375 nm is used. Figure 10E shows an example image taken using an InGaAs camera when an illumination wavelength of 1550 nm is used. [Figure 11A-D] Figure 11A shows an image including lymph nodes generated using illumination at a wavelength of 690 nm. Figure 11B shows an image including the lymph nodes of Figure 11A generated using illumination at a wavelength of 730 nm. Figure 11C shows an image including the lymph nodes of Figure 11A generated using illumination at a wavelength of 810 nm. Figure 11D shows an image including the lymph nodes of Figure 11A generated using illumination at wavelengths of 900-950 nm. [Figure 11E-H]Figure 11E is an image including the lymph node of Figure 11A generated using illumination at a wavelength of 1000 nm. Figure 11F is an image including the lymph node of Figure 11A generated using illumination at a wavelength of 1125 nm. Figure 11G is an image including the lymph node of Figure 11A generated using illumination at a wavelength of 1175 nm. Figure 11H is an image including the lymph node of Figure 11A generated using illumination at a wavelength of 1250 nm. [Figure 11I-M] FIG. 11I shows an image including the lymph node of FIG. 11A generated using illumination at a wavelength of 1300 nm. FIG. 11J shows an image including the lymph node of FIG. 11A generated using illumination at a wavelength of 1375 nm. FIG. 11K shows an image including the lymph node of FIG. 11A generated using illumination at a wavelength of 1550 nm. FIG. 11L shows an image including the lymph node of FIG. 11A generated using illumination at a wavelength of 1575 nm. FIG. 11M shows an image including the lymph node of FIG. 11A generated using illumination at a wavelength of 8-10 μm. [Figure 12A-B] Figure 12A shows an image of tissue generated using a conventional camera and ambient visible light, and Figure 12B shows an image of the tissue of Figure 12A generated using the imaging system embodiment of Figure 3. DETAILED DESCRIPTION OF THE INVENTION

[0017] In one example embodiment shown in FIG. 1, an imaging device for imaging lymphatic systems is used. The "lymphatic system site" here refers to a lymph node or The imaging system 100 may include at least one of: An LED light source 101 that emits light of 900 to 1300 nm can be provided. The LED light source 101 may also be referred to as a "light source" 101. The system 100 includes a linear polarizer 107 to generate linearly polarized illumination light 107 (i.e., illumination). 02, and the linear polarizer 102 is mounted on a rotation mount to The linear polarizer 102 may comprise a linear polarizing film. Linearly polarized illumination 107 is directed onto an object of interest 105. The object of interest 105 is shown in FIG. The subject may be a human, as shown, or an animal.

[0018] The light source 101 can be directed towards an in-vivo target region 106 of an object of interest 105. The internal target region 106 is also referred to herein as the "internal region" or "target region." In some embodiments, the target region 106 may be an ex vivo region, such as a portion of tissue. The ex vivo tissue portion may include fat, lymph nodes and / or lymphatic vessels. The lymph nodes and / or lymphatic vessels can be visualized as if this tissue were in vivo. It can be imaged.

[0019] Some light sources, such as certain lasers, are inherently linearly polarized. For light sources that are inherently linearly polarized, a linear polarizer can be used to generate linearly polarized illumination. Therefore, if the light source 101 is inherently linearly polarized, the linear polarizer 1 In other words, the linear polarizer 102 may not be needed in the imaging system. Polarized illumination improves the imaging contrast of this technique. The clear contrast of lymph nodes is shown in Figures 7A-7B. As shown, it can be formed without any polarizers.

[0020] With continued reference to FIG. 1, the imaging system 100 includes a sensor 104. The sensor 104 can detect the illuminated area of ​​the human or animal. The light source is directed toward a target area 106 of an object of interest 105. The imaging system 100 may include another linear polarizer 103. This can be referred to as the "sensor linear polarizer 103." A linear polarizer film may be provided. The sensor linear polarizer 103 is placed in front of the sensor 104. and / or may be positioned between the sensor 104 and the target area 106. It is possible.

[0021] The ideal imaging contrast is from the polarizer 103 in front of the sensor 104 The polarization of the incident light 108 before the sensor 104 is determined by the polarizer 10 3. The incident light is incident on the tissue of the in-vivo region 106. In principle, the linearly polarized radiation 107 may include a portion of the linearly polarized radiation 107 that has interacted with the When reflected from the surface of human or animal skin, most of the radiation remains linearly polarized. The polarization state of polarized light remains unchanged when it bounces directly off the skin surface. Only a small fraction of the light The laser penetrates relatively deep into the biological tissue, which becomes a random scattering medium. The sensor linear polarizer 103 is placed in front of the sensor 104 in the direction of the incident light 108. By placing the sensor linear polarizer 103 perpendicular to the The light emitted from the light source 101 is filtered out and reflected by the surface. Only a portion of the light 107 that interacts with the skin tissue is transmitted. The imaging system 100 performs best when the surface glare (i.e., surface glare) is reduced to a minimum level. In practice, this ideal The contrast is adjusted by adjusting the sensor linear polarization until the overall intensity detected by the sensor 104 is minimized. Either the photon 103 or the linear polarizer 102 in front of the light source 101 is rotated. This minimum overall intensity is the threshold contrast level. The threshold contrast level can be associated with a minimum overall intensity within a given range, e.g. For example, this threshold control may be within 10% of the minimum overall intensity. The polarizer (e.g., sensor linear polarizer 103 or light source 101) The linear polarizer 102 in front of the light source 101 and / or the light source 101 can be adjusted.

[0022] When linearly polarized photons interact with tissue in the target area 106 and undergo scattering, The emitted photons gradually lose their linear polarization. For example, the linear polarization The photon becomes a completely depolarized photon. This completely depolarized photon then passes through sensor 1. The linear polarizer 103 in front of the sensor 104 The polarizer 103 is approximately perpendicular to the linear polarizer 102 in front of the light source 101, so it is completely Only photons with the opposite polarization state are polarized and can be detected by the sensor 104. Only photons that interact with tissue in the target region 106 at greater depths are “selected” for analysis. The image is then "separated" to remove surface glare and unwanted surface features.

[0023] If the wavelength of the light emitted from the light source 101 is made much longer than that of visible light (for example, 1550 nm), m), imaging quality can be further improved. At longer wavelengths, scattering effects Therefore, the required composition to completely depolarize linearly polarized light at longer wavelengths is The thickness of the fabric is much thicker than that of linearly polarized light with shorter wavelengths. Imaging systems such as imaging system 100 are sensitive to short wavelengths (e.g., the visible light spectrum). have a longer wavelength to image deeper tissues better than with a conventional 1000 Hz wavelength Light can be provided to an object (eg, object 105).

[0024] If the light source 101 is a laser that is already linearly polarized without the use of a polarizer, the sensor linearly polarized A threshold contrast level is met by rotating either the photon 103 or the laser itself. The relative orthogonal relationship is important, not the absolute direction of polarization. As long as this orthogonal polarization relationship is satisfied, either the polarizer, the light source, or the sensor can be rotated. By rotating the lens, the optimum contrast can be achieved. The imaging system 100 does not require mirrors and does not require mirrors or other optical components conventional in certain imaging technologies. This eliminates the need for other reflective surfaces, such as those shown in FIG. The cost of constructing the system can be reduced compared to other imaging technologies.

[0025] The present disclosure recognizes that lymph nodes are birefringent, i.e., responsive to polarized light. Lymph nodes and / or lymphatic vessels may contain collagen, which is a complex Furthermore, the tissue surrounding the lymph node, such as the fat (i.e., lipid) layer, is refractive. Generally, the present disclosure provides a method for producing images of lymph nodes and / or lymphatic vessels. to utilize the difference in birefringence between lymph nodes and / or lymphatic vessels and the surrounding tissues to It is recognized that cross-polarized light, i.e., the orthogonal polarization relationships described above, can be utilized. In some embodiments, light source 101 provides illumination at wavelengths between 1200 and 1600 nm. This can be done by measuring the lymph nodes and / or lymphatic vessels contained in the target region 106. This corresponds to one or more absorption peaks of collagen. By using the illuminating wavelength, imaging of lymph nodes and / or lymphatic vessels and surrounding tissues is possible. As mentioned above, increasing the wavelength reduces the scattering effect. The reduction can improve imaging resolution of lymph nodes and / or lymphatic vessels.

[0026] Furthermore, irradiation containing longer wavelength light, particularly light with a wavelength of 1550 nm, can be used to treat target areas 1 It can improve the contrast of lymphatic areas in 06. Generally, lymphatic areas are fatty. Lymph nodes and lymphatic vessels are highly hydrated, whereas fat is very hydrated. The absorption of photons in water occurs at 1550 nm, which is probably why the target area By using light with a wavelength of 1550 nm to illuminate the area 106, the imaging system Contrast of lymph nodes and / or lymphatic vessels in images generated using the TEAM 100 This may improve the visibility of lymph nodes and / or lymphatic vessels. When an image is generated using irradiation light with a wavelength of 1550 nm, lymph nodes and The lymphatic vessels appear dark, while the fat appears light.

[0027] Furthermore, irradiation containing longer wavelength light, particularly light with a wavelength of 1550 nm, can be used to treat target areas 1 06) can improve the contrast of lymphatic tissue relative to the surrounding blood. Blood has a high water content and a high cell content. Cells are highly scattering and absorb water. Tests have shown that the imaging system 100 detects blood flow in the target region 106. It has been found to produce images in which fluid and / or bleeding is not visible and is not visible when compared to fat. Reducing the visibility of blood and / or bleeding can result in images in which blood and / or bleeding is visible. The advantages of imaging system 100 over other imaging modalities include: The bleeding can be mistaken for a lymph node and is then sampled for analysis. By controlling and / or removing bleeding from the tissue, the pathologist may be able to avoid falsely positive results when diagnosing the patient. This reduces the number of times gender identification is required.

[0028] The imaging system 100 is described above as being applied to an in vivo region of interest. However, it is clear that the imaging system can also be applied to ex vivo tissue samples. For example, the target area 106 may include a tissue packet that may include lymph nodes and fat. This tissue packet is then transferred to the lymph node after the tumor and associated lymph nodes have been identified. It can be harvested from the subject 105 during the node resection. Lymph nodes from fat and all other surrounding tissue contained in the tissue packet during the ocular diagnostic step. Typically, the pathologist will separate the lymph nodes by palpation and visual inspection. However, this method is prone to errors because lymph nodes are transparent and resemble fat. The distance between the two ends of the lymph nodes can be as small as 1 mm, and the location of the lymph nodes The imaging system 100 provides the pathologist with It can be used to visualize lymph nodes and display lymph nodes, allowing the pathologist to target areas. The lymph nodes can be efficiently and accurately extracted from the area 106. A certain number of lymph nodes may be required to diagnose the physical type. The number of lymph nodes can range from 12 to 38. - Allows for a reduction in the number of missed lymph nodes in the target area 106, thereby Your doctor can help you obtain the required number of lymph nodes.

[0029] Another example embodiment of an imaging system 200 is shown in FIG. In the imaging system 200, a halogen lamp that emits continuous light is used as the light source 201. To reduce background caused by direct reflection of wavelengths outside the 900-1300 nm range, Use a long-pass filter with a cutoff wavelength of 900 nm or 1000 nm. The imaging system 200 filters out light of wavelengths shorter than the first order long pass. The first long-pass filter 203 and the second long-pass filter 205 may be provided. The cutoff wavelengths of the pass filter 203 and the second-order long-pass filter 205 are respectively The wavelength can be selected from 900 nm to 1000 nm. A linear polarizer 202 mounted on a screw mount may be included. The light source 201 can be provided with a linear polarizing film. A light source 201 is placed in front of the light source 201 to linearly polarize the light emitted from the light source (e.g., a halogen lamp). The first-order long-pass filter 203 can be placed in the It is placed in front of the light source 201 to filter out as much light as possible below the off-wavelength. It is possible.

[0030] The sensor 204 included in the imaging system 200 is a commercially available ordinary In some embodiments, a silicon camera is used. A holographic camera and / or an InGaAs camera can be used. The sensor linear polarizer 206 is attached to a screw mount. The linear polarizer 206 may comprise a linear polarizing film. A lens (not shown) is also placed in front of 4, and this lens is a telecentric lens. The telecentric lens can be used to measure lymph nodes that are far from the sensor 204. The size of lymph nodes in images generated using the sensor 204, regardless of distance Improve the measurement accuracy of the imaging system 200 by helping to normalize the The primary long-pass filter 203 is used to filter out ambient light or light source 201 (e.g., halogen lamp). ) in front of the sensor 204 to filter out unwanted background from either In some embodiments, the second-order long-pass filter 205 is disposed in the background light, which may contain visible frequencies below the cutoff frequency of the filter 205. Therefore, there is no need to calibrate the sensor 204 for different amounts of ambient and / or background light. By eliminating the need for calibration of the sensor 204, the time it takes to detect lymphatic sites is reduced. and imaging systems requiring calibration of one or more sensors. This makes the imaging system 200 more robust than the conventional system. Both the sensor 204 and the sensor 206 may be either a human or an animal, e.g., as shown in FIG. It is necessary to face the same area of ​​interest as the object being investigated, such as a human 207. The imaging system 200 does not include mirrors and is not a mirror as is conventional in certain imaging technologies. This eliminates the need for mirrors or other reflective surfaces, making it ideal for other imaging systems and and / or other imaging technologies compared to the components that make up the imaging system 200 of FIG. This can reduce strikes.

[0031] In some embodiments, the imaging system 200 is equipped with a controller (not shown). The controller can be connected to a light source such as a laser or LED, or a sensor such as a camera. The controller is coupled to and communicates with the light source and the sensor. The controller controls the power supplied to the light source to make the light source emit red light. The controller may also be configured to cause external radiation to be delivered to the region. Information corresponding to the reflected infrared radiation can also be received from the sensor. The reflected radiation can also be referred to as the "reflected portion" of the original infrared radiation provided by the source. The controller uses the received information to generate at least one signal indicative of a lymph node of interest. It is also possible to generate images of

[0032] Referring now to FIG. 3 in conjunction with FIGS. 1 and 2, an imaging system according to yet another exemplary embodiment is shown. 3 shows a schematic of an imaging system 300. In some embodiments, the imaging system 300 can be roughly the size of a shoebox, making it a benchtop imaging system The imaging system 300 can be implemented using an interface platform 30. 2. The interface platform 302 may include at least one and any other device capable of communicating with the memory, at least one processor, sensors, and light sources (not shown). The interface platform 3 may include a number of connection interfaces. 02 may be configured to execute at least a portion of the image generation and analysis application 304 (e.g., and storing the program in (e.g., one or more memory) and executing (e.g., using the at least one processor). As described below, the interface platform 302 The imaging system 300 may be coupled to and communicate with a computer 334. The computer 334 also stores at least a portion of the image generation and analysis application 304. The interface platform 302 may execute and / or control A computer that receives signals from a laser, laptop computer, desktop computer, or sensor. The controller may be any other device capable of outputting a capture control signal to the light source. For example, a microcontroller such as the Raspberry Pi (registered trademark) 4 Model B In some embodiments, the controller may be a Windows An Intel® processor configured to operate with an operating system It can be a NUC computer.

[0033] The interface platform 302 is provided in the imaging system 300. The illumination generation system 306 may be coupled to and communicate with the illumination generation system 306. The interface platform 302 may include a light source 308. The interface platform 302 can be coupled to and communicate with the light source 3 A control signal can be output to the light source 308 to cause the light source 308 to emit light. In this embodiment, the light source 308 provides the interface platform 302 with appropriate data (e.g., The illumination generation system 306, more specifically, The light source 308 is oriented to provide illumination 314 to a target area 318. This target region 318 can be measured in vivo (e.g., as described in more detail below). , a region contained in a subject 316 such as a patient) or ex vivo. The illumination 314 output from system 306 may also be referred to as "supplied illumination 314." 314 can be infrared radiation. The infrared radiation is in the near infrared range (wavelength 800 to 140 0 nm) and / or light in the short-wave infrared range (wavelength 1400-3000 nm) can.

[0034] The light source 308 may be an LED such as a single LED, a plurality of LEDs such as an LED array, a tungsten Halogen lamps such as ten-halogen lamps, quartz halogen lamps, or hydrogen iodine lamps , laser, or other suitable light source capable of outputting light of one or more predetermined wavelengths. In some embodiments, the light source 308 may include one or more Discrete wavelengths of light, e.g., 1550 nm, 1375 nm, 1300 nm, and / or 80 It is possible to output other wavelengths selected from wavelengths of 0 nm to 1700 nm. For example, The light source 308 may output only light of wavelength 1550 nm. In this form, the light source is a subrange of wavelengths within the range of 800-2000 nm, for example, 1200-1 Outputting one or more discrete frequencies within a wavelength subrange of 600 nm, etc. In some embodiments, the light source 308 emits light in a continuous range of wavelengths, e.g., 900-1300 Hz. 00nm, 1500~1600nm, 1200~1600nm, 1000~1700nm (i.e., near-infrared), and / or other wavelength ranges within 800-2000 nm In some embodiments, light source 308 may be light source 101 of FIG. 1 or light source 101 of FIG. 201. In particular, the light source 308 may be a light source that is irradiated with the surrounding oil as described above. To better contrast lymphatic areas against fat, blood, and / or hemorrhage, It is possible to output light with a longer wavelength, particularly light with a wavelength of 1550 nm. For system 300 to operate properly, light source 308 must emit light within a certain range of wavelengths. Tests have shown that excellent imaging can be achieved using only 1550 nm light. However, the imaging system 300 can also generate appropriate images using multiple wavelengths of light. Some sensors stop responding above 2600 nm. There are sensors, such as certain InGaAs cameras, that can use up to 260 wavelengths of light. Therefore, the imaging system 300 is considered to be 800 to 26 The test can be performed using light with wavelengths in the range of 800 nm. The higher the wavelength of light, for example, 800 to 1700 nm, the better the performance. did not show any.

[0035] In some embodiments, the illumination generation system 306 may include a polarizer 310, such as a linear polarizer. For certain light sources that are not inherently polarized, such as halogen light sources, the image The imaging system 300 can include a polarizer 310. The polarizer 310 is a linearly polarized The polarizer 310 can be used to polarize the light source 3 to produce linearly polarized illumination light. The polarizer 310 can be mounted in front of the polarizer 10 on a rotating mount or The polarizer 310 can be mounted on any other suitable mount that allows adjustment. The illumination 314 delivered to the target area 318 can be linearly polarized. Thus, the imaging contrast of the image produced by imaging system 300 In some embodiments, the polarizer 310 can improve 1 or the linear polarizer 202 of FIG. For devices that are inherently polarized, such as certain lasers, polarizer 310 can be used to image In some embodiments, the polarizer 310 may not be a circular polarizer. It can be a photon.

[0036] In some embodiments, the illumination generation system 306 may include an optical filter 312. The optical filter 312 can be, for example, a cold mirror, a colored glass filter, a heat-cured aluminum filter, or the like. ADC filter or short wavelength light (e.g. visible light) Long-pass filters, such as other suitable filters that attenuate light at wavelengths and pass longer wavelengths (e.g., infrared light) The cutoff wavelength of the long-pass filter should not exceed 800 nm. For example, the cutoff wavelength can be 800 nm, 900 nm, or 100 The optical filter 312 may be set to a cutoff value of 0 nm. In order to filter out as much light as possible below the wavelength, it is placed in front of the light source 308. In some embodiments, the optical filter 312 may be a first order long pass filter as shown in FIG. In some embodiments, the optical filter 312 may be, for example, a hard It may be a bandpass filter such as a coated filter or a colored glass filter. A bandpass filter transmits only light with wavelengths in the range of 800 to 2000 nm. Or it transmits only light of a partial range of wavelengths included in the range of 800 to 2000 nm. For example, a bandpass filter can transmit only light with wavelengths between 900 and 1700 nm. Thus, the radiation 314 delivered to the target area 318 can be long-pass or band-pass filtered. Cut.

[0037] The light source 308, polarizer 310 and / or optical filter 312 may be any of the components shown in FIGS. 1 and / or 2. Physically placing (i.e., positioning) the components relative to one another as shown For example, the respective arrangements of the light source 308 and the polarizer 310 may be the same as those shown in FIG. The arrangement of the light source 101 and the linear polarizer 102 can be the same as that of the light source 101 and the linear polarizer 102. The arrangement of the light source 308, polarizer 310 and optical filter 312 is as shown in FIG. The light source 201, the linear polarizer 202, and the long-pass filter 203 are arranged in the same manner as above. The light source 308 outputs illumination 314, which is transmitted through the polarizer 310. and polarized by polarizer 310 and / or attenuated by optical filter 312. The illumination 314, which may be polarized and / or attenuated, is then directed onto the target area 31. 8.

[0038] As mentioned above, the light source 308, and more generally the illumination generation system 306, is oriented , can be oriented to provide illumination 314 to a target area 318. In an embodiment, the target region 318 may be an in vivo region contained within the subject 316. In these embodiments, the target region 318 may be referred to as an "in vivo region." The elephant 316 can be a human patient. In other embodiments, the target area 318 is In these embodiments, the target area 318 may be an ex vivo area. For example, the target area 318 may be the area targeted for visual diagnostic purposes, as described above. The imaging system 300 can be used to visualize the tissue fragments of an elephant. By visualizing lymphatic tissue, the physician can easily visualize the tissue. This can be done.

[0039] The target area 318 may be provided with at least a portion of the irradiation 314. The target area 318 may include one or more lymphatic sites. can interact with lymphatic sites and surrounding tissues in the target area 318. At least a portion of the supplied illumination 314 can be randomly polarized as described above. At least a portion of the supplied illumination 314 can be reflected as reflected illumination 320. The incident radiation 320 may include light that has interacted with tissue deep within the target region 318. do.

[0040] The interface platform 302 is provided in the imaging system 300. The sensing system 322 may be coupled to and communicate with the sensing system 322. 322 may include sensors 324. The interface platform 302 The sensor 324 can be coupled to and communicate with the reflected illumination 320. and outputting a signal related to the image based on the sensed reflected illumination 320. The interface platform 302 can display images from the sensor 324. A signal can be received that contains information about the image. In some embodiments, this information is stored in a file format such as PNG, JPEG, DICOM (i.e., DIC Images formatted in a predefined image format, such as those contained in an .OM file etc. In some embodiments, the information may include metadata about the image, e.g. It may also include the time the image was taken or the patient associated with the image. In the example, the sensor 324 is a silicon charge-coupled device (CCD) camera with a fluorescent coating. silicon cameras, including silicon or silicon complementary metal oxide semiconductor (CMOS) cameras; Germanium Camera, Germanium Tin-on-Silicon Camera, Black Silicon Camera cameras, such as quantum dot short-wave infrared (SWIR) cameras, and / or InGaAs cameras The InGaAs camera is a nitrogen-cooled InGaAs camera. The sensor 324 may be a mercury cadmium telluride (HgCdTe or MCT) cap. The sensor 324 may include a laser, at least a portion of which may be 800 nm to 2000 nm. and particularly light at or near a wavelength of 1550 nm. It should be noted that the imaging system 300 may include multiple sensors and / or Unlike other systems that may require a camera, only one sensor may be needed (e.g. Silicon camera, etc.).

[0041] The sensing system 322 includes a lens 326 positioned in front of the sensor 324. In some embodiments, for example, the sensor 324 and lens 326 may be a single, off-the-shelf device. If sold as a commercial product, the lens 326 may be integral with the sensor 324. The lens 326 can improve the imaging performance of the sensor 324. For example, the lens 326 The telecentric lens can be used to visualize lymph nodes. Regardless of the distance from the sensor 324, the image generated using the sensor 324 This helps normalize lymph node size in the imaging system 300 measurements. This can improve the accuracy of the measurement.

[0042] In some embodiments, the sensing system 322 may include a piece of ground glass or tissue paper, for example. The optical diffuser 328 may include a lens 326 and a The polarizer 332 may be inserted between the sensing system 32 2. The optical diffuser 328 provides a more uniform reflected illumination 320. The optical diffuser 328 can generate a light pattern with a wide distribution. As a result of the more uniform pattern, the imaging performance of the sensor 324 can be improved.

[0043] In some embodiments, the sensing system 322 is positioned before the sensor 324. An optical filter 330 may be provided. The optical filter 330 may be, for example, a cold mirror. -, color glass filter, heat-cured ADC filter, or short wavelength light (e.g. visible light) Long-pass filters, such as other suitable filters that attenuate light at wavelengths and pass longer wavelengths (e.g., infrared light) The cutoff wavelength of the long-pass filter should not exceed 800 nm. For example, the cutoff wavelength can be 800 nm, 900 nm, or 100 In some embodiments, the optical filter 330 may be This allows the filter to filter out background light that may contain visible frequencies below the cutoff frequency of the filter 330. It may not be necessary to calibrate the sensor 324 for different amounts of edge and / or background light. In some embodiments, the optical filter 330 may be a second-order long-pass filter, as shown in FIG. 205. In some embodiments, the optical filter 330 may be, for example, a hard The filter may be a band-pass filter such as a band filter or a colored glass filter. A pass-through filter is a filter that transmits only light with wavelengths in the range of 800 to 2000 nm. is assumed to transmit only light of a partial range of wavelengths included in the range of 800 to 2000 nm. For example, a bandpass filter can transmit only light with wavelengths between 900 and 1700 nm. Thus, the reflected illumination 320 provided to the sensor 324 may be It can be round-pass filtered or band-pass filtered.

[0044] As mentioned above, the sensing system may include a polarizer 332. The polarizer 332 can be a linear polarizer. In some embodiments, the polarizer 332 is a circular polarizer. The polarizer 332 may be placed in front of the sensor 324. The polarizer 332 may comprise a linear polarizing film. Similar to the polarizer 310 provided in the sensing system 322, the polarizer 332 also The optical axis can be mounted on a transverse mount or other suitable mount that allows adjustment. The components 310 and 332 are rotated as described above to obtain ideal imaging contrast. The polarizer 332 may be adjusted in the same manner as the supplied illumination 314. Any light having a polarization can be removed from the reflected illumination 320. The sensor 324 Light contained in the reflected illumination 320 and having the opposite polarization can be detected as the supplied illumination 314. Cut.

[0045] In some embodiments, the sensor 324 is coupled to and capable of communicating with an external display 372. Alternatively or additionally, the sensor 324 may be located within the imaging system 300 or 300. The memory 374 may be external to the imaging system 300. For example, the memory 374 may be a flash memory provided on a memory card. The sensor 324 may be coupled to an external display 372 and / or a memory 374. In a communicating embodiment, the sensor 324 senses a reflected portion of the supplied illumination 314. , based on the reflected portion of the delivered illumination 314 (i.e., reflected illumination 320) of the target area. and generating at least one image showing all lymphatic components of the region 318. The sensor 324 can display the at least one image on an external display 372 or in a memory 373. 74.

[0046] In some embodiments, the light source 308 may not be connected to a controller or other device. In this embodiment, the only connection required is a power supply. The source 308 may provide illumination 314 to a target area 318 either continuously or quasi-continuously. In some embodiments, the interface platform 302 may power the light source 308. In other embodiments, the light source 308 can It may be powered from a wall power source, one or more batteries, or other suitable power source.

[0047] In some embodiments, the sensor 324 is coupled to an external display 372 and / or memory 374. and connecting the light source to the interface platform 302 and / or other suitable devices. Therefore, the imaging system 30 can be coupled to a power source without being coupled to a power source. 0 can be implemented without a controller or computing device.

[0048] In some embodiments, the imaging system 300 is Class 1, 510(k) exempt, and and / or Good Manufacturing Practice (GMP) exemptions.

[0049] The imaging system 300 may include the external display 372 and / or computer 334 described above. As mentioned above, the interface platform 302 may The imaging system 300 can be coupled to and communicate with a communication network 334. The communication network 336 may include an interface platform. The interface may facilitate communication between the platform 302 and the computer 334. The platform 302 is capable of coupling to and communicating with an external display 372 .

[0050] In some embodiments, the communication network 336 may be any suitable communication network, or It may be any suitable combination of multiple communication networks. The network 336 may be a Wi-Fi network (one or more wireless routers, a peer-to-peer network (e.g., a Bl Bluetooth (registered trademark) network, etc.), mobile phone network (e.g., CDMA, GSM , LTE, LTE Advanced, WiMAX, or any other suitable standard 3G network, 4G network, etc.), wired network, etc. In some embodiments, the communication network 336 may be a local area network, a wide area network, or a area network, public network (such as the Internet), private or semi-private network privately owned networks (e.g., company or university intranets), or any other suitable type The network may be a network of the same type, or any suitable combination of networks. Each communication link shown in FIG. 3 may be, for example, a wired link, an optical fiber link, or a Wi-Fi link. Any suitable link may be used, such as a WiFi link, a Bluetooth link, a mobile phone link, etc. It may be a communication link or any suitable combination of communication links. In an embodiment, the computer 334 may implement a portion of the image generation and analysis application 304. This can be done.

[0051] Referring now to FIG. 4 in conjunction with FIG. 3, some embodiments of the presently disclosed invention are shown in FIG. can be used to implement the computer 334 and interface platform 302. As shown in FIG. 4, the computer 334 is a processor. 350, a display unit 352, an input unit 354, a communication system 356, and a memory 358. The processor 350 may include a small number of image generation and analysis applications 304. The image generation and analysis application 304 may be implemented in part or in part, for example. A program (e.g., a program stored in memory 358 and called from memory 358) The processor 350 can execute a program, for example, from Any suitable hardware, such as a central processing unit ("CPU"), a graphics processing unit ("GPU"), etc. The processor may be a hardware processor or any suitable combination of processors, The program may include the processes described below.

[0052] In some embodiments, the display 352 may present a graphical user interface. In some embodiments, the display 352 may be a computer monitor, a touchscreen, or a The present invention may be implemented using any suitable display device such as a smartphone, a television set, or the like. In an embodiment, the input 354 of the calculator 334 may include an indicator, a sensor, an actuatable button, or the like. , keyboard, mouse, graphical user interface, touch screen display In some embodiments, the input 354 may include a user (e.g., a A doctor (radiologist, etc.) interacts with a computer 334 (e.g., a communication network 3 36) for interacting with the interface platform 302 It can be said that.

[0053] In some embodiments, the communication system 356 may communicate with other devices via any suitable communication network. Any hardware, firmware and / or software suitable for communicating with the system For example, the communication system 356 may include one or more transmitting and receiving may include a transmitter, one or more communication chips, and / or a chipset, etc. In one specific example, the communication system 356 may include a coaxial connection, a fiber optic connection, an Ethernet connection, or any combination thereof. Connection, USB connection, WiFi (registered trademark) connection, Bluetooth (registered trademark) connection, Hardware, firmware, and / or devices that can be used to establish cellular or other connections In some embodiments, the communication system 356 may include a computer. 334 interfaces (e.g., directly or indirectly via a communication network 336) It is for communicating with the platform 302 .

[0054] In some embodiments, the memory 358 may be configured to, for example, allow the processor 350 to use the display 352 To present the content, the interface is established via communication system(s) 356. to store instructions, values, etc. that can be used to communicate with the base platform 302, etc. The memory 358 may include one or more suitable storage devices. Any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, the memory 358 may include RAM, ROM, EEPROM, One or more flash drives, one or more hard disks, one or more software It may include a solid-state drive, one or more optical drives, etc. In an embodiment, memory 358 is stored in computer 334 (or interface platform 30). 2) storing an encoded computer program for controlling the operation of In some embodiments, the processor 350 may process the content (e.g., user interface interface processor to present the data (interfaces, images, graphics, tables, reports, etc.) 302 to receive content from the interface platform. Execute at least a part of the computer program described above, for example, to transmit the program to the form 302. It can be done.

[0055] As shown in FIG. 4, the interface platform 302 includes a processor 36 0, a display unit 362, an input unit 364, a communication system 366, a memory 368, and a connector In some embodiments, the processor 360 may include an image generator 370. At least a portion of the image generation analysis application 304 may be implemented. The analysis application 304 may be, for example, a program (e.g., stored in memory 358) The processor 360 can execute the program from the program (e.g., a program called from 368). , a central processing unit ("CPU"), a graphics processing unit ( Any suitable hardware processor or processors, such as a Graphics Processing Unit (GPU), The program may include the processes described below. can.

[0056] In some embodiments, the display 362 may present a graphical user interface. In some embodiments, the display 362 may be a computer monitor, a touchscreen, or The display device may comprise any suitable display device such as a monitor, a television, or the like. The input section 364 of the interface platform 302 may include indicators, sensors, Movable buttons, keyboard, mouse, graphical user interface, touchscreen In some embodiments, the input 364 may include a user interface, a screen display, or the like. A user (e.g., a first responder) interacts with the interface platform 302. and interacting with a computer 334 (e.g., via a communications network 336). The computer 334 may be coupled to an external display 372 for communication. The external display unit 372 can provide at least some of the functions of the display unit 352. This can be done.

[0057] As shown in FIG. 4, the interface platform 302 is 66. The communication system 366 may be connected via any suitable communication network. Any hardware, firmware and / or software suitable for communicating with other systems For example, the communication system 366 may include one or more The present invention may include a transceiver, one or more communication chips, and / or a chipset. In one specific example, the communication system 366 may include a coaxial connection, a fiber optic connection, an Ethernet connection, or a Internet connection, USB connection, Wi-Fi (registered trademark), Bluetooth (registered trademark) hardware, firmware, and other software that can be used to establish a connection, cellular connection, etc. In some embodiments, the communication system 366 may include: The interface platform 302 (e.g., directly or via a communication network 336) The communication system 366 is for communicating with the computer 334 (indirectly via the light source). and / or communicate with the sensor 324 to provide at least some of the functionality of the connector 370 This is also possible, as explained below.

[0058] In some embodiments, the memory 368 may be configured to, for example, allow the processor 360 to use the display 362 To present the content, the computer 33 may communicate with the computer 33 via one or more communication systems 366. One or more memory devices that can be used to store instructions, values, etc., that can be used to communicate with 4, etc. The memory 368 may include any suitable volatile memory. , non-volatile memory, storage, or any suitable combination thereof. For example, memory 368 may include RAM, ROM, EEPROM, one or more flash memory devices. drive, one or more hard disks, one or more solid state drives, In some embodiments, the memory 368 may include one or more optical drives, etc. to control the operation of the interface platform 302 (or computer 334). In some embodiments, the computer program may be encoded as In this state, the processor 360 processes the content (e.g., the user interface, graphics , tables, reports, etc.), to receive content from the calculator 334, to the computer 334, etc., It can be executed.

[0059] In some embodiments, the connector 370 may be a wired connection, allowing the light source 3 308 and sensors 324 to communicate with the interface platform 302, This allows (for example, directly via communication system 366 or, for example, via communication network 3 36 or indirectly via a computer 334. Alternatively, the light source 308 and / or the sensor 324 may be connected to (e.g., a connector 370 and / or a communication transmitting information to interface platform 302 (via communication system 366) and / or may receive information from the interface platform 302.

[0060] Referring now to FIG. 5 in conjunction with FIGS. 3 and 4, the image generation and analysis application 304 includes 4 shows a flowchart of an example of a process 400 that may be used. To generate an image of the target area 318, the interface platform 302 and the computer 334 can each perform a part of the process 400. The lymphatic system may include, for example, lymph nodes and / or lymphatic vessels. As such, the target region 318 may be in vivo (e.g., a region contained within the object 316) or in vivo. In some embodiments, the tissue may be collected from a subject. Now, the interface platform 302 can perform the entire process 400. do.

[0061] At 402, the process 400 causes a light source 308 to provide illumination 314 to a target area 318. The target area 318 can include lymphatic system areas. The illumination 314 can be transmitted through a polarizer 310 and / or an optical filter 312. Afterwards, the delivered radiation 314 is delivered to the target area 318. At least a portion of the reflected radiation is reflected back towards the sensing system 322 as described above. 20. Before the reflected illumination 320 reaches the sensor 324, it passes through a polarizer 332. , passing through the optical filter 330, the optical diffuser 328, and / or the lens 326. In some embodiments, the light source 308 may provide continuous illumination 314 to the target area 318. If the illumination is provided continuously or quasi-continuously, the process 400 requires the light source 308 to provide illumination. In other words, in some embodiments, process 400 may not perform step 402. It is possible that there is no

[0062] At 404 , the process 400 can detect the reflected portion of the illumination 314 . This reflected portion can be reflected illumination 320. The reflected portion can be reflected back to the target. The reflected light may be reflected directly from the target area 318. Since the light is reflected directly from the region 318, the system 300 There is no need to use a mirror or other reflector to redirect the light toward the sensor 324. The process 404 can detect the reflected portion using the sensor 324. The detection of the reflected portion of the beam is accomplished by receiving a signal from the sensor 324 in response to the reflected portion. and

[0063] At 406, one or more lymph nodes, such as lymphatic vessels, are located in the target region 318. If phosphorus sites are present, process 400 uses a reflected portion of illumination 314 to At least one image showing the pathological region can be generated. generating at least one image based on signals received from the sensor 324; The process 400 can generate an image based on the signal from the sensor 324. In some embodiments, the signal output from the sensor 324 may include at least one signal indicative of a lymphatic system location. The process 400 may include at least one image received from the sensor. A single image may be format converted and / or compressed. Alternatively, process 400 storing said at least one image as received from the sensor 324; (i.e., stored in memory 358 and / or memory 368).

[0064] At 408, the process 400 stores the at least one image on a display and / or memory. The display unit can output to at least one of the interface platform. A display unit 362 that can be provided in the room 302, a display unit 363 that can be provided in the arithmetic unit 334, The memory can be the display unit 352, or the external display unit 372. The memory 368 provided in the platform 302 or the memory 334 provided in the computer 334 58. The memory may be external to the imaging system 300, e.g. It may be a memory provided on a remote server, or the like.

[0065] 3 and 4, and FIG. 6, the image generation and analysis application 304 includes 4 shows a flowchart of an example of a process 450 that includes the segmentation. To train annotation and / or classification machine learning models and Using the segmentation and / or classification machine learning models developed generated by an imaging system (such as imaging system 300 of FIGS. 3 and 4). To analyze the generated images, an interface platform 302 and a computer 334 can each perform a part of process 450.

[0066] At 452, the process 450 receives training data for a segmentation model. The segmentation model can be, for example, a convolutional neural network. Convolutional neural networks can be used as machine learning models. This training for segmentation models can include The training data may include raw images and associated segments. For example, the imaging system 100 of FIG. 1, the imaging system 200 of FIG. 2, or the imaging system 200 of FIG. 3 can be generated using an imaging system such as imaging system 300 The segments are areas of the image that correspond to lymph nodes or areas where lymph nodes are absent. In some embodiments, the segments may include regions corresponding to lymphatic vessels. Therefore, the segmentation model can segment lymph nodes and lymphatic vessels in the image. Segments can be trained to provide a range of training, for example, for oncologists. In some embodiments, the segmentation The model can be a predetermined algorithm for identifying lymph nodes, and this algorithm The program may require no training.

[0067] At 454, the process 450 can receive training data for the classification model. The classification model can be a machine learning model, such as a recurrent neural network. A classification model can be trained to classify an entire image. The training data for the imaging system 100 of FIG. 1 and the imaging system 2 of FIG. using an imaging system such as the imaging system 200 or the imaging system 300 of FIG. The training data can include a large number of raw images generated by the above-mentioned method. It can contain multiple images that have been segmented accordingly. The processed images are then processed by inputting the raw images into a trained segmentation model. In some embodiments, the training data may be generated by segmenting This classification may include classification of lymph nodes and / or lymphatic vessels as malignant or benign. In some embodiments, each A classification can be associated with each raw image in the training data as a whole.

[0068] At 456, the process 450 uses the training data for the segmentation model to A segmentation model can be trained. After training the model, this segmentation model is called a "trained segmentation" It can be called a "model."

[0069] At 458, the process 450 trains the classification model using the training data for the classification model. Depending on the training data, individual lymphatic regions (i.e., lymph nodes and and / or lymphatic vessels) are malignant or benign, or Training a classification model to identify whether an entire sample is benign or malignant After training the classification model in 458, this classification model is called a "trained classification model." It can be called a "model."

[0070] At 460, the process 450 inputs the image into the trained segmentation model. In some embodiments, the process 450 may include a number of trained images at 460. These can then be sequentially input into the segmentation model.

[0071] At 462, the process 450 performs a segmentation analysis on the image input to the trained segmentation model. In some embodiments, the process may receive multiple segments associated with the 450 is used to calculate the number of images input to the trained segmentation model. Each can receive multiple segments.

[0072] At 464, the process 450 can input the image into the trained classification model. In some embodiments, process 450 passes any number of images to a trained classification model at 464. You can input sequentially.

[0073] At 466, the process 450 receives the classification of the image input to the trained classification model. In some embodiments, the process 450 may include, at 464, A plurality of classifications associated with a plurality of input images may be received.

[0074] At 468, the process 450 processes any received segment(s) and and / or the classification(s) are also stored in at least one of the display and / or memory. The display unit can be provided in the interface platform 302. a display unit 362 that can display the image, a display unit 352 that can be provided in the computer 334, or an external display The memory may be provided in the interface platform 302. The memory 368 may be provided in the processor 334, or the memory 358 may be provided in the processor 334. The memory may be an imaging memory, such as a memory provided on a remote server. The external process may store the received segment in a memory external to the system 300. For example, the segments can be used to The characteristics of the treated lymphatic system can be identified, including lymph node subtypes. size, lymph node aspect ratio, lymph node symmetry, lymph node boundary clarity, lymph node curvature, and The characteristics of each lymphatic region require further analysis. In some embodiments, process 450 may include: Distinguishing features within each raw image from which image classification is performed (and by extension lymphatic system regions) It is possible to output a heat map for each image that identifies the differences (distinctions).

[0075] The image generation and analysis application 304 performs the process 400 in FIG. 5 and the process 450 in FIG. 6. It will be appreciated that in some embodiments, the process of FIG. 6. Multiple applications may be used to perform one or both of the processes 400 and 450 of FIG. It is possible to implement

[0076] 7A and 7B are images constructed using the imaging system described herein. The imaging results of the imaging system are shown in Figure 7A. Figure 7B shows the results of imaging the area imaged using a polarizer. The areas shown in Figures 7A and 7B are lymph nodes. 500. Polarizers improve imaging contrast, but lymph nodes are not polarized. It can be visualized with or without children.

[0077] 8A to 8C show examples of mouse imaging results. The system is equipped with an LED that emits light of around 1200 nm as a light source and is cooled by liquid nitrogen. The sensor is an InGaAs camera. Figure 8A is taken using a standard camera. Figure 8B shows an image of the area of ​​the mouse imaged before the adjuvant was injected. Images of the area of ​​the mouse taken using the system are shown. Figure 8C shows the image taken 48 hours after the injection of the adjuvant. Images of the area of ​​the mouse taken using the imaging system are shown. These results suggest that the adjuvant can be administered intravenously for 4 hours after injection. It can be seen that the size of lymph node 504 has increased significantly after 8 hours.

[0078] 9A to 9C show examples of mouse imaging results. The system filters the light from the lamp, similar to the imaging system 200 of FIG. It is equipped with a halogen lamp as a light source along with a long-pass filter for The sensor is a standard silicon camera. Figure 9B shows an image of the area of ​​the mouse imaged before the adjuvant was injected. Figure 9C shows an image of the area of ​​the mouse taken using the system. Images of the mouse region taken using an imaging system 48 hours after injection. These results show that 48 hours after the injection of the adjuvant, lymph nodes 51 It can be seen that the size of the second-order lymph nodes is significantly increased. The quality is comparable to that of more expensive systems, such as the imaging system 100 shown in FIG. Furthermore, the imaging system used to generate Figures 9B-9C is It is more compatible with ambient light than other imaging systems.

[0079] 10A-10E show images of lymph nodes using various illumination wavelengths and an InGaAs camera. Figure 10A shows the results of imaging using an illumination wavelength of 1000 nm. Figure 10B was taken using an illumination wavelength of 1175 nm. Figure 10C was taken using an illumination wavelength of 1250 nm. 10A and 10B were taken using an illumination wavelength of 1375 nm. The images were taken using an irradiation wavelength of 100 nm.

[0080] Figures 11A-11M show the results of lymph node imaging of an ex vivo porcine mesenteric tissue sample. The lymph node is visualized using a number of different illumination wavelengths and the imaging system of the present invention. The image was taken using a sensor installed in the camera. The irradiation wavelength ranged from 690 nm to 730 nm. A lamp was used to generate irradiation wavelengths ranging from 810 nm to 1575 nm. An unfiltered continuous wave lamp was used to generate 8-10 μm illumination. The reason for achieving this was that the sensor used only detects light with a wavelength of 8 to 10 μm. For irradiation with wavelengths of 690 nm to 730 nm, silicon A camera was used as a sensor. For illumination with wavelengths ranging from 810 nm to 1575 nm. used an InGaAs camera as the sensor. The system was equipped with orthogonally arranged polarizers. Each individual illumination wavelength was measured in a wavelength band. is the most dominant wavelength of

[0081] For each illumination wavelength, the signal-to-noise ratio was measured to measure the performance of the illumination wavelength. A higher signal-to-noise ratio is advantageous because it makes the lymph nodes stand out more against the surrounding tissue.

[0082] Figure 11A shows an image containing lymph nodes generated using illumination at a wavelength of 690 nm. Figure 11B shows an image containing lymph nodes generated using illumination at a wavelength of 730 nm. Figure 11C shows an image containing lymph nodes generated using illumination at a wavelength of 810 nm. Figure 11 shows an image containing lymph nodes generated using irradiation with wavelengths of 900-950 nm. E shows an image containing lymph nodes generated using illumination at a wavelength of 1000 nm. Figure 11G shows an image containing lymph nodes generated using illumination at a wavelength of 1125 nm. Figure 11H shows an image containing lymph nodes generated using illumination at a wavelength of 1175 nm. Figure 11I shows an image containing lymph nodes generated using illumination at a wavelength of 1250 nm. Figure 11J shows an image containing lymph nodes generated using 1300 nm illumination. Figure 11K shows an image containing lymph nodes generated using 1375 nm illumination. Figure 11L shows an image containing lymph nodes generated using 550 nm illumination. Figure 11M shows an image containing lymph nodes generated using 75 nm illumination. Images containing lymph nodes generated using 0 μm illumination are shown.

[0083] Table 1 below summarizes the signal-to-noise ratio for each irradiation wavelength. The signal-to-noise ratio of 1550 was 24, which was the highest, and it was found to have the best performance. The irradiating wavelength range of 1175 to 1375 also shows similar performance and is useful for The performance of irradiation wavelengths below 810 nm was 900-1575 The 8-10 μm wavelength irradiation was significantly worse than the 1550 nm wavelength range. This results in significantly worse performance than illumination at 1 m or 1575 nm, which is This suggests that performance may degrade significantly above 575 nm. [Table 1]

[0084] 12A and 12B, a number of different imaging techniques were used to generate A comparison of lymph node 516 images from ex vivo human tissue samples is shown in Figure 1. 2A shows an image of a lymph node 516 generated using a conventional camera and ambient visible light. FIG. 12B shows a phosphorescent image generated using the imaging system 300 of one embodiment of FIG. 12B shows an image of lymph node 516. Lymph node 516 is much more clearly visualized in FIG. 12B. There are.

[0085] The present disclosure provides various implementations, each offering a series of advantages over other imaging systems. One advantage of the imaging system is that the imaging system The advantages of the present invention are that it is entirely non-invasive and label-free. The imaging system used is for methylene blue, indocyanine green, and other injection colors. This imaging system is superior to conventional element-based techniques. To achieve high imaging contrast of lymph nodes, injection or surgery (e.g., open surgery) ) is not required. When performing imaging using the imaging system, It is necessary to obtain lymph nodes and / or surrounding tissue from the subject in order to perform lymph node imaging. Unlike some other imaging systems, the lymph nodes are in vivo.

[0086] Another advantage of the imaging system provided herein is that it is The system has improved safety compared to conventional modalities. Only infrared light is used. The images shown in the figures of this application were illuminated with only 1 mW of optical power. The optical power is within the exposure limits set by regulations. This advantage makes the imaging system disclosed in this application more reliable than CT, PET, and other similar imaging methods. and outstanding performance over other imaging systems that may inherently pose health hazards to patients. In this application, a method for easily visualizing lymph nodes without any injection is used. This optical method uses irradiation light of 800 to 1700 nm and This imaging system uses a sensor that can detect all or part of the lymph nodes. The absorption spectrum of the substance can be utilized to irradiate light for detecting lymph nodes. By using irradiation light with a wavelength of 800 to 1700 nm, especially irradiation light with a wavelength of 1550 nm, The imaging system may be configured to capture the image from surrounding tissue, including fat, blood, and / or hemorrhage, as described above. Images can be generated that show lymph nodes in their natural state. The trust can be improved by implementing a polarizer, but a polarizer is not required for this method. The present disclosure provides systems and methods for non-invasively visualizing lymph nodes. It will provide a powerful tool for population health screening, disease prevention, diagnosis and treatment. It is possible.

[0087] Certain embodiments of the imaging system provided by the present disclosure are economical to configure and For example, an embodiment such as the imaging system 200 of FIG. The cost of constructing a lymph node imaging system can be less than $100. The imaging system is more affordable than any other multimodality imaging modality. CT, MRI, ultrasound and PET equipment can cost anywhere from tens of thousands to millions of US dollars. The reasonableness of the imaging system provided in this application is a key factor in clinical practice. Such an imaging system helps to have a much greater impact on floor installations. It may be used by doctors or ordinary consumers to conduct regular health checks, track disease recurrence, etc. Moreover, unlike cross-sectional modalities, the imaging system disclosed herein The wavelength range is determined based on the natural lymph nodes and lymphatic vessels (i.e., lymph nodes without any external injections). Relatively expensive components (e.g., used as sensors) are specific to the lymph nodes or lymphatic vessels. Even imaging systems equipped with InGaAs cameras (such as those used in imaging imaging), There is room for more economical construction of at least some of the ties.

[0088] The order or sequence of performing or executing the above-described steps of the process of FIG. 6 is not shown in the drawings. The present invention should not be construed as being limited to the order or sequence shown or described. Also, some of the above steps of the process of Figures 5 and 6 may be implemented to reduce delay or processing time. and therefore may, where appropriate, be carried out or performed substantially simultaneously or in parallel. There are things that can be done or implemented.

[0089] In some embodiments, aspects of the present disclosure, including computer implementations of methods, , standard programming or engineering techniques for creating software The present invention can be embodied as a system, method, apparatus, or product using the processing device, computer (e.g., a processing unit operatively coupled to a memory), or and controlling other electronically operated controllers to implement the aspects described in detail herein. This may be firmware, hardware, or any combination thereof for Thus, for example, embodiments of the present invention may be implemented such that a processing device may store non-transitory computer-readable media. the computer-readable medium so that the instructions can be executed upon reading the instructions from the medium. The present invention can be embodied as a set of such instructions specifically implemented in a Embodiments may include automation equipment, various computer hardware, and the like consistent with the description below. Special-purpose or general-purpose computers and other devices, including hardware, software, firmware, etc. Chairs may be provided (or used).

[0090] The term "product" as used herein includes any computer-readable device, carrier (e.g., a computer program accessible from a medium (e.g., a non-transitory signal) or medium (e.g., a non-transitory medium) For example, computer-readable media includes magnetic storage media. Devices (e.g. hard disks, floppy disks, magnetic tapes, etc.), optical disks (e.g. For example, compact discs (CDs), digital versatile discs (DVDs), smart cards, This may include flash memory devices (e.g. cards, sticks, etc.) In addition, sending and receiving e-mails or using the internet or It is used to access networks such as local area networks (LANs). using a carrier wave to carry computer-readable electronic data, such as electronic data It should be understood that a person skilled in the art would understand the scope and concept of the invention as set forth in the claims. Numerous modifications to the above arrangements may be realized without departing from the spirit thereof.

[0091] Specific operations of the method of the present invention or of the system for implementing the method are shown in the drawings. It may be generally represented or otherwise generally described in this application. Unless otherwise stated or limited, drawings of specific operations set forth in a specific spatial sequence. The representation in the Therefore, the invention may not be required to perform the operations shown in the drawings or otherwise described in this application. The particular operations disclosed in the aspects may be used as appropriate in specific embodiments of the invention. For example, the steps may be performed in an order different from that explicitly illustrated or described. In some embodiments, the processing may be performed by dedicated parallel processing devices or as part of a larger system. A specific operation can be performed in parallel by multiple separate computers configured to perform the same operation. be.

[0092] With respect to computer implementations, unless otherwise stated or limited, the term "component" as used herein Terms such as "system" and "module" refer to hardware, software, and Any combination of hardware and software, or computer-related items including running software It may be intended to encompass part or all of the system. For example, Components include processors, processes being executed (or executable) by processors, objects, , executable, thread of execution, computer program, or computer This is a non-exhaustive list of possible applications that can be run on a computer. Both applications and computers can be "components." One or more components (or system, module, etc.) can exist within a process or thread of execution. It can be located locally on one computer and can be shared across two or more computers or may be distributed to other processing units or may be integrated into other components (or systems, modules, etc.) can be included in the

[0093] As used herein, the terms "controller" and "processor" refer to a computer program. Any device capable of performing or configured to perform the functions described herein. This includes any device that can contain logic gates. For example, a processor, a microcomputer, controller, field programmable gate array, programmable logic controller It can include la etc.

[0094] The present disclosure is presented to enable one of ordinary skill in the art to make and use embodiments of the present invention. Those skilled in the art will readily be able to introduce various improvements to the embodiments described herein. The general principles of this application may be applied to other embodiments without departing from the scope of the invention. The embodiments and applications of the present invention are also applicable to the present invention. It is not intended to be limited to the embodiments shown, but rather to encompass the principles disclosed herein. The present invention should be accorded the broadest scope consistent with the principles and features of the present invention. In the drawings, like elements in different views are numbered like. The figures, which are not necessarily to scale, depict selected embodiments and are not intended to be limiting unless otherwise specified. It is not intended to limit the scope of the embodiments of the invention. The example embodiments provided in the application have many useful alternative aspects, which may also be used to implement the present invention. It can be recognized that this falls within the scope of the present invention.

[0095] In this way, as described above, in the present application, near infrared (800 to 1400 nm) and / or This system uses short-wave infrared light (1400-3000 nm) to visualize lymphatic systems. For example, irradiation of 800 to 1700 nm can be used. In some applications, radiation with wavelengths of 1500-1600 nm, e.g., 1550 nm, is used for In one embodiment, 15 Only wavelengths of 50 nm wavelength are used.

[0096] The systems and methods described herein may utilize one or more near-infrared or short-wave infrared radiation. Near-infrared and / or short-wave infrared imaging techniques are provided that use a light source and a sensor. The imaging system can operate in conjunction with a polarizer. The polarizer (one or more ) can be placed in front of the light source and an additional sensor in front of the sensor(s). A polarizer can be placed to minimize direct reflections on the skin of humans or animals and reduce phosphorescence. The rotation angles of the two polarizers can be adjusted to optimize visualization of the polarized region. In some embodiments, the use of a polarizer in front of the light source(s) is not required. The imaging system may include a polarizer in front of the light source(s). Some light sources have inherent operation without a polarizer. Some emit linearly polarized light due to the mechanism. Useful for improving contrast, but not essential. The lymphatic system can be visualized without any polarization modification, especially when the irradiation wavelength is 80 0 to 1700 nm, and if the sensor can detect light in this wavelength range, such visualization is possible. It is Noh.

[0097] In one aspect, the present disclosure provides a lymphatic system imaging system, comprising: a light source for applying infrared radiation to an area of ​​the subject that includes at least one lymphatic system site; configured to sense a reflected portion of the infrared radiation reflected directly from said region. and a controller in communication with the light source and the sensor. The laser causes a light source to provide infrared radiation to the region and responds to a reflected portion of the infrared radiation. receiving information from the sensor and using the information to determine the at least one lymphatic system portion of the subject; The device is configured to generate at least one image indicative of the position.

[0098] The system may include a system for detecting the at least one lymphatic system region without using a reference light. The system can be configured to generate one image at a time. The at least one image showing the at least one lymphatic system region without information from light. In the system, the light source may comprise a laser. In the system, the light source may comprise a light emitting diode. A long-pass or band-pass filter placed between the region and the light source. A long-pass filter or band-pass filter with a cutoff wavelength not less than 800 nm is provided. In the system, the sensors are a silicon camera, an InGaAs camera, and and a black silicon camera. The system may further include a polarizer disposed between the region and the sensor. The at least one lymphatic site may be a lymph node or The system uses infrared radiation from 800 to 1700 nm. The wavelength of the light may be irradiated.

[0099] In another aspect, the present disclosure provides a method for imaging lymphatic systems without the use of contrast agents. The method includes using a light source to illuminate a region of a subject's body that includes a lymphatic system. A step of irradiating infrared light and detecting the presence of a substance in the area using sensors arranged around the area. detecting a reflected portion of the infrared radiation reflected directly from the target; generating at least one image indicative of the lymphatic system region of interest using the acquired portion. It has a group and a.

[0100] In the method, the infrared radiation can have an irradiation wavelength of 800 to 2000 nm. In this method, infrared irradiation can be performed without using a polarizer. The method may further comprise rotating a polarizer in front of the sensor until the overall intensity detected is minimized. In the method, the optical power of the infrared radiation may not exceed 1 mW. The method further includes positioning a polarizer between the region and a sensor, and detecting light reflected directly from the region. The polarizer can be positioned substantially perpendicular to the infrared radiation being emitted. The polarizer and the light source are polarized until a threshold contrast level is reached at the sensor. At least one can be adjusted.

[0101] In yet another aspect, the present disclosure provides a method for imaging lymphatic systems without the use of mirrors. The method includes using a light source to illuminate an area of ​​a subject that includes a lymphatic system region. and detecting the amount of radiation from the area using sensors located around the area. detecting a reflected portion of the directly reflected infrared radiation; generating at least one image showing the lymphatic system region of the subject using the extracted portion; In the method, the infrared radiation has an irradiation wavelength of 800 to 2000 nm. In the method, the infrared irradiation can be carried out without using a polarizer.

[0102] Although the present invention has been described in considerable detail with reference to specific embodiments, those skilled in the art will appreciate that the present invention may be modified for illustrative purposes only. It will be apparent that the present invention may be practiced in other embodiments than those set forth herein. This illustrative embodiment is not intended to be limiting. The scope of the claims should not be limited to the description of the embodiments contained in this application.

Claims

1. 1. A system for imaging a lymphatic system region, comprising: A region of the subject that includes at least one lymphatic system region is irradiated with polarized infrared light. a light source for the infrared radiation reflected directly from the region and having a polarization opposite to that of the infrared radiation; a sensor configured to sense the reflected portion of the a controller in communication with the sensor; It is equipped with The controller receiving information from the sensor corresponding to the reflected portion of the infrared radiation; using said information to determine at least one lymphatic site indicative of said at least one lymphatic site of said subject; Generate one image, outputting the at least one image to at least one of a display unit and / or a memory; R A system configured as follows.

2. The controller is configured to determine the at least one lymphatic system region without using a reference light. configured to generate at least one image; The system of claim 1 .

3. The controller may determine the at least one sensor without information from ambient light around the sensor. and generating the at least one image showing one lymphatic system region. The system of claim 1 .

4. the light source comprises a laser; The system of claim 1 .

5. the light source comprises a light emitting diode; The system of claim 1 .

6. a long-pass filter or a band-pass filter disposed between the region and the light source; It also has The cutoff wavelength of the long-pass filter or band-pass filter is less than 800 nm. Not The system of claim 1 .

7. The sensor may be a silicon camera, an InGaAs camera, or a black silicon camera. Contains at least one of The system of claim 1 .

8. The sensor may be a germanium camera, a germanium tin-on-silicon camera, a quantum At least one of a dot shortwave infrared camera or a mercury cadmium telluride camera include, The system of claim 1 .

9. further comprising a polarizer disposed between the region and the sensor. The system of claim 1 .

10. the at least one lymphatic site is free of contrast agent; The at least one lymphatic site includes at least one of a lymph node or a lymphatic vessel. include, The system of claim 1 .

11. The infrared radiation has an irradiation wavelength of 800 to 1700 nm. The system of claim 1 .

12. The infrared radiation has an irradiation wavelength of 1000 to 1700 nm. The system of claim 1 .

13. The infrared radiation has an irradiation wavelength of 1500 to 1700 nm. The system of claim 1 .

14. The infrared radiation has an irradiation wavelength of 800 to 1700 nm. The system of claim 1 .

15. The infrared radiation has an irradiation wavelength of 1000 to 2600 nm. The system of claim 1 .

16. A method for in vivo imaging of lymph nodes or lymphatic vessels without the use of contrast agents, 、 A light source is used to focus the contrast agent-free lymph node or lymphatic vessel in the subject's in vivo region. irradiating the object with polarized infrared light; a sensor positioned to receive said infrared radiation reflected directly from said area; and reflecting the infrared radiation having a polarization opposite to that of the reflected infrared radiation directly reflected from the region. detecting the portion of the image; The reflected portion of the infrared radiation is used to measure the phosphorus-free contrast agent of the subject. generating at least one image indicative of a node or said lymphatic vessel; A method comprising:

17. The infrared radiation has an irradiation wavelength of 800 to 2000 nm.

17. The method of claim 16.

18. The infrared irradiation is carried out without using a polarizer.

18. The method of claim 17.

19. A polarizer is placed in front of the sensor until the overall intensity detected by the sensor is minimized. and rotating the 17. The method of claim 16.

20. the optical power of said infrared radiation does not exceed 1 mW; 17. The method of claim 16.

21. moreover, positioning a polarizer between the region and the sensor; The polarizer is oriented substantially perpendicular to the infrared radiation reflected directly from the region. Place, 17. The method of claim 16.

22. Further, the polarizer and the and adjusting at least one of the light source.

22. The method of claim 21.

23. 1. A method for imaging lymph nodes or lymphatic vessels without the use of mirrors, comprising: A step of irradiating an area of ​​a subject containing lymph nodes or lymphatic vessels with infrared light using a light source. Pu and, a sensor positioned to receive said infrared radiation reflected directly from said area; detecting a reflected portion of said infrared radiation that is reflected directly from said area using said infrared radiation; Pu and, The reflected portion of the infrared radiation is used to measure the lymph nodes or lymph nodes of the subject. generating at least one image indicative of the valve; A method comprising:

24. The infrared radiation has an irradiation wavelength of 800 to 2000 nm.

24. The method of claim 23.

25. The infrared irradiation is carried out without using a polarizer.

25. The method of claim 24.

26. 1. A system for imaging a lymphatic system region, comprising: A region of the subject that includes at least one lymphatic system region is irradiated with polarized infrared light. a light source for A sensor, It is equipped with The sensor The reflected infrared radiation having a polarization opposite to that directly reflected from the region. Sensing a part of it, based on the reflected portion of the infrared illumination, generating at least one image showing the lymphatic system region; The at least one image is displayed on at least one of an external display and / or an external memory. Output to A system configured as follows.

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