Systems and methods for lymph node and angiography

By using polarized infrared illumination and detecting reflected light in lymph node imaging, the invasiveness, high cost and insufficient contrast of lymph node imaging in the prior art is solved, and high contrast imaging without contrast agent is achieved.

CN119769992APending Publication Date: 2025-04-08MASSACHUSETTS INST OF TECH
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Patent Information

Application Number
CN202411974617.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2019-05-15
Filing Date
2020-02-04
Publication Date
2025-04-08

AI Technical Summary

Technical Problem

The prior art has problems of invasiveness, high cost and insufficient contrast in lymph node imaging, especially in the absence of contrast injections.

Method used

A system is adopted that includes a light source, a sensor and a controller to generate an image of the lymph node by providing polarized infrared illumination to the lymph node area and using the sensor to detect reflected infrared light. The system does not require contrast agent and lenses and uses low-intensity infrared light.

Benefits of technology

High contrast, non-invasive imaging of lymph nodes without the need for contrast agent is achieved, reducing the cost and health risks of the imaging process.

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Abstract

The present disclosure provides a method for imaging lymph nodes and lymphatic vessels without contrast agents. The method includes providing infrared illumination to a region of a subject having at least one lymphatic component using a light source, detecting a reflected portion of the infrared illumination directly reflected from the region using a sensor located around the region, and generating at least one image indicative of at least one lymphatic component in the subject using the reflected portion of the infrared illumination.
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Description

This application is a divisional application of the application with PCT international application number PCT / US2020 / 016525, international application date February 4, 2020, Chinese national application number 202080027465.X, and titled “Systems and methods for lymph node and vascular imaging”. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on, claims the benefit of, and claims priority to U.S. Provisional Application No. 62 / 848,178, filed on May 15, 2019, and U.S. Provisional Application No. 62 / 800,674, filed on February 4, 2019, the contents of which are incorporated herein by reference in their entirety for all purposes. A note about federally funded research

[0002] This invention was made with government support under Grant P30CA014051 from the National Institutes of Health. The government has certain rights in this invention. Background Art

[0003] Lymph nodes, also known as lymph glands, are oval-shaped organs that are widely found in the human and animal bodies. Lymph nodes are an integral part of the lymphatic system, which is responsible for immune responses to protect the body from disease and infection. The condition of lymph nodes can directly indicate a person's health. Swollen lymph nodes can be a sign of bacterial infection, viral infection, cancer, etc. Examining the condition of lymph nodes by imaging them is very useful for disease diagnosis, prevention, and treatment.

[0004] Currently, there are many imaging modalities used to visualize and examine lymph nodes. Traditionally, the standard method is lymphangiography. Lymphangiography involves injecting a radioactive contrast agent into the patient and using X-rays to visualize the lymph nodes and lymphatic vessels. This procedure is invasive, causes significant discomfort, and involves the use of radiopharmaceuticals.

[0005] In recent years, cross-sectional imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI) have become increasingly popular in the visualization of lymph nodes, replacing lymphangiography. Ultrasound and positron emission tomography (PET) have also proven to be useful. Although the above technologies enable doctors to identify lymph nodes and make reasonably accurate judgments about their condition, they are general imaging modalities and therefore their working mechanisms are not designed to provide optimal contrast for lymph nodes unless a specific contrast agent is injected. As a result, other organs and tissues appear in these images with the same or sometimes even better contrast than lymph nodes, leading to interference with the task of finding and examining lymph nodes. Not only are these general imaging modalities not specific to lymph nodes, but they also have their own serious drawbacks. CT involves X-ray exposure and PET involves radiopharmaceuticals, which require careful control in preventing health hazards. MRI requires expensive equipment and is not compatible with patients with metal implants. Ultrasound provides low imaging contrast and low resolution, mainly because ultrasound waves are long.

[0006] Another common practice for lymph node imaging involves the injection of dye, which is either a blue dye or a fluorescent dye. The most common dye used for lymph node visualization is methylene blue, which is actually toxic. The dosage of this dye must be carefully managed. Indocyanine green (a fluorescent dye) has also been used for lymph node imaging. Systems that utilize fluorescent dyes such as indocyanine green and methylene blue include FLARE TM Most of them use a single image sensor (usually a CCD) to capture the visible image (reference image) and the fluorescent image sequentially, or use multiple cameras to image different spectra simultaneously or sequentially.

[0007] There are many disadvantages to dye-based methods. One disadvantage is that the dye may stimulate a negative reaction in some patients, especially those with renal complications. Another disadvantage is that dye injections may be unreliable due to the leaky nature of the lymphatic system. Additionally, some dye-based methods require invasive application of the dye.

[0008] For imaging systems that produce multiple images using multiple cameras and / or sequential image acquisition, subsequent image registration is required. In order to correctly reconcile the differences in spatial parameters of the multiple images, such image processing must account for changes in angular coordinates, potential relative motion between the system and the subject, or both. Other types of imagers include specialized CMOS sensors that can collect light via (multiple) red-green-blue channels (RGB) as well as a single channel in NIR-1.

[0009] There are also some reports in academic papers on the use of novel optical techniques to image lymph nodes, including optical speckle imaging, optical coherence tomography, etc. However, optical speckle imaging is very susceptible to motion artifacts, and optical coherence tomography involves complex instruments and has poor imaging contrast.

[0010] In summary, there is currently no convenient, efficient method for visualizing lymph nodes, given their critical importance to human health. Cross-sectional imaging methods are inconvenient and untargeted for lymph node visualization unless contrast agents are injected. Dye-based imaging techniques are often highly invasive and incompatible with clinical settings such as routine examinations. A new imaging modality that can conveniently perform highly specific, high-contrast imaging of lymph nodes without the need to inject any imaging contrast agents would be a powerful tool for practicing physicians to examine patient health, assess the effectiveness of a treatment, determine the stage of a person's cancer condition, and many other medical applications. Summary of the invention

[0011] The following content is intended to briefly summarize the present disclosure and is not intended to limit the scope of the present disclosure.

[0012] In one aspect, the present disclosure provides a system for imaging lymphatic components. The system includes a light source configured to provide infrared illumination with polarization to an area of ​​a subject having at least one lymphatic component; a sensor configured to sense a reflected portion of the infrared illumination having a polarization opposite to the polarization of the illumination directly reflected from the area; and a controller in communication with the sensor. The controller is configured to receive information corresponding to the reflected portion of the infrared illumination from the sensor; use the information to generate at least one image indicating the at least one lymphatic component in the subject; and output the at least one image to at least one of a display and / or a memory.

[0013] In another aspect, the present disclosure provides a method for imaging lymph nodes or lymphatic vessels without contrast agents. The method includes providing infrared illumination with polarization to an area in the body of a subject having lymph nodes or lymphatic vessels without contrast agents using a light source; detecting a reflected portion of the infrared illumination directly reflected from the area and having a polarization opposite to the polarization, the reflected portion, using a sensor positioned to receive illumination directly reflected from the area; and generating at least one image indicating lymph nodes or lymphatic vessels without contrast agents in the subject using the reflected portion of the infrared illumination.

[0014] In yet another aspect, the present disclosure provides a method for imaging lymph nodes and lymphatic vessels without a mirror. The method includes providing infrared illumination to an area of ​​a subject having lymph nodes or lymphatic vessels using a light source; detecting a reflected portion of the infrared illumination using a sensor positioned to receive illumination reflected directly from the area; and generating at least one image indicating lymph nodes or lymphatic vessels in the subject using the reflected portion of the infrared illumination.

[0015] In a further aspect, a system for imaging lymphatic components is provided. The system includes a light source configured to provide infrared illumination having a polarization to an area of ​​a subject having at least one lymphatic component; a sensor configured to: sense a reflected portion of the infrared illumination having a polarization opposite to the polarization directly reflected from the area; generate at least one image indicating at least one lymphatic component in the subject based on the reflected portion of the infrared illumination; and output the at least one image to at least one of an external display or an external memory. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 A schematic diagram showing an example of an imaging system according to certain aspects of the present disclosure is shown.

[0017] Figure 2 Another example of an imaging system according to certain aspects of the present disclosure is illustrated.

[0018] Figure 3 A schematic diagram illustrating yet another exemplary embodiment of an imaging system according to certain aspects of the present disclosure is shown.

[0019] Figure 4 It shows that some embodiments of the disclosed subject matter can be used to implement Figure 3 Examples of computing device and interface platform hardware are shown.

[0020] Figure 5 An exemplary flow chart of a process included in an image generation and analysis application is shown.

[0021] Figure 6 An exemplary flow chart of another process included in an image generation and analysis application is shown.

[0022] Fig. 7A The imaging results of the area imaged without using a polarizer are shown.

[0023] Figure 7B The image obtained by using a polarizer is shown in FIG. Fig. 7A Imaging results of the same area.

[0024] Fig. 8A An image of a region of a mouse taken with a standard camera is shown.

[0025] Figure 8B The image was taken using the imaging system before the injection of adjuvant. Fig. 8A Images of regions of mice.

[0026] Figure 8C The image was taken 48 hours after the injection of adjuvant using the imaging system. Fig. 8A Images of regions of mice.

[0027] Fig.9A An image of the mouse region taken with a standard camera is shown.

[0028] Fig. 9B The image was taken using the imaging system before the injection of adjuvant. Fig.9A Images of regions of mice.

[0029] Fig. 9C The image was taken 48 hours after the injection of adjuvant using the imaging system. Fig.9A Images of regions of mice.

[0030] Fig. 10A An exemplary image taken with an InGaAs camera when using an illumination wavelength of 1000 nm is shown.

[0031] Fig. 10B An exemplary image taken with an InGaAs camera when using an illumination wavelength of 1175 nm is shown.

[0032] Fig. 10C An exemplary image taken with an InGaAs camera when using an illumination wavelength of 1250 nm is shown.

[0033] Fig. 10D An exemplary image taken with an InGaAs camera when using an illumination wavelength of 1375 nm is shown.

[0034] Fig.10E An exemplary image taken with an InGaAs camera when using an illumination wavelength of 1550 nm is shown.

[0035] Fig.11A An image including a lymph node generated using 690 nm wavelength illumination is shown.

[0036] Fig. 11B shows the use of 730nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0037] Fig. 11C shows the use of 810nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0038] Fig.11D The image is shown using 900-950nm wavelength illumination. Fig.11A Image of lymph nodes.

[0039] Fig.11E The results are shown using 1000nm wavelength illumination. Fig.11A Image of lymph nodes.

[0040] Fig.11F shows the use of 1125nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0041] Fig.11G shows the use of 1175nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0042] Fig.11H shows the use of 1250nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0043] Fig.11I shows the use of 1300nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0044] Fig.11J shows the use of 1375nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0045] Figure 11K shows the use of 1550nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0046] Fig.11L The figure shows the use of 1575nm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0047] Fig.11M shows the use of 8-10 μm wavelength illumination to generate Fig.11A Image of lymph nodes.

[0048] Fig. 12A An image of tissue generated using a conventional camera and ambient visible light is shown.

[0049] Fig. 12B Shows the use of Figure 3 An embodiment of an imaging system generates Fig. 12A image of the organization. DETAILED DESCRIPTION

[0050] In an exemplary embodiment, Figure 1 As depicted, an imaging system 100 for imaging lymphatic components is provided. As used herein, the lymphatic components may include at least one of lymph nodes or lymphatic vessels. The imaging system 100 may include an LED light source 101 emitting between 900 and 1300 nm as a light source. The LED light source 101 may also be referred to as light source 101. The imaging system 100 may include a linear polarizer 102 mounted on a rotating mount and placed in front of the LED light source 101 to produce linearly polarized light 107 (i.e., illumination). The linear polarizer 102 may include a linear polarizing film. The linearly polarized illumination 107 is directed onto a subject of interest 105, which may be a human (e.g., Figure 1 depicted) or animals.

[0051] The light source 101 can be directed toward an in vivo target region 106 of a subject 105 of interest. The in vivo target region 106 may also be referred to herein as an in vivo region or a target region. In some embodiments, the target region 106 may be an ex vivo region (such as a tissue region). An ex vivo tissue portion may include fat, lymph nodes, and / or lymphatic vessels that may be imaged like a tissue portion in vivo.

[0052] Some light sources, such as certain lasers, are inherently linearly polarized. For these inherently linearly polarized light sources, creating linearly polarized light illumination does not require the use of a linear polarizer. Thus, when light source 101 is inherently linearly polarized, linear polarizer 102 may not be required. In other words, some imaging systems may not include linear polarizer 102. Polarized illumination helps improve imaging contrast of this technique, but is not required. Fig. 7A -B shows that even without any polarizer, clear contrast of the lymph node can be formed.

[0053] Still reference Figure 1 , the imaging system 100 may include a sensor 104, which may be a camera. The sensor 104 is used to visualize an illuminated area on a person or animal. The light source may be directed toward a target area 106 of a subject of interest 105. The imaging system 100 may include another linear polarizer 103, which may be referred to as a sensor linear polarizer 103. The sensor linear polarizer 104 may include a linear polarizing film. The sensor linear polarizer 103 may be placed in front of the sensor 104 and / or between the sensor 104 and the target area 106.

[0054] Ideal imaging contrast can be formed when the polarization of incident light 108 before sensor 104 and polarizer 103 in front of sensor 104 are orthogonal to polarizer 103 in front of sensor 104. The incident light can include a portion of linearly polarized illumination 107 that has interacted with tissue in internal body region 106. In principle, linearly polarized illumination mostly remains linearly polarized when reflected from the surface of human or animal skin. The polarization of linearly polarized light does not change when it bounces directly from the surface of the skin. Only a small portion of the light becomes randomly polarized because it enters relatively deeply into biological tissue, which is a random scattering medium. By placing the sensor linear polarizer 103 in front of the sensor 104 orthogonal to the direction of the incident light 108, the sensor linear polarizer 103 filters the light reflected by the surface of human or animal skin and only allows part of the light 107 emitted from the light source 101 to interact with deeper tissue to pass. When the light reflected from the skin surface (i.e., surface glare) is reduced to a minimum level, the imaging system 100 achieves the best contrast and the deepest penetration depth. In practice, this ideal contrast can be formed by rotating one of the polarizers (the sensor linear polarizer 103 or the linear polarizer 102 in front of the light source 101) until a minimum total intensity detected by the sensor 104 is reached. The minimum total intensity can be associated with a threshold contrast level. The threshold contrast level can be within a predetermined range of the minimum total intensity (such as within 10% of the minimum total intensity), and the polarizer (e.g., the sensor linear polarizer 103 or the linear polarizer 102 in front of the light source 101) and / or the light source 101 can be adjusted until the threshold contrast level is reached at the sensor 104.

[0055] After the linearly polarized photons interact with the tissue in the target area 106 and through scattering, the linearly polarized photons slowly lose their linear polarization. For example, after about ten scattering events, the linearly polarized photons become fully depolarized photons. These fully depolarized photons then reach the sensor linear polarizer 103 in front of the sensor 104. Since the sensor linear polarizer 103 in front of the sensor 104 is approximately orthogonal to the linear polarizer 102 in front of the light source 101, the sensor 104 is only allowed to detect the photons that are now fully depolarized and have the opposite polarization. Therefore, only the photons that interact with the tissue in the target area 106 at a deeper level are "selected" for analysis, and surface glare and unnecessary surface features are removed.

[0056] When the wavelength of light emitted from light source 101 is much longer than visible light (e.g., 1550 nm), the imaging quality can be further improved. Longer wavelengths are associated with smaller scattering effects. Therefore, thicker tissue is required to completely depolarize linearly polarized light with longer wavelengths than linearly polarized light with shorter wavelengths. Therefore, an imaging system (such as imaging system 100) can provide light with longer wavelengths to a subject (e.g., subject 105) to better image deeper tissues than with shorter wavelengths (e.g., wavelengths in the visible spectrum).

[0057] In the case where the light source 101 is a laser that is already linearly polarized and no polarizer is used, the threshold contrast level is met by rotating the sensor linear polarizer 103 or the laser itself. The relative orthogonal relationship is important, while the absolute direction of polarization is not. As long as the orthogonal polarization relationship is met, the best contrast can be achieved by rotating the polarizer, light source, or sensor. Note that Figure 1 The imaging system 100 does not require a mirror and does not require mirrors or other reflective surfaces that are common in some imaging technologies, which can reduce the construction cost compared to other imaging technologies. Figure 1 The cost of the imaging system 100.

[0058] The present disclosure recognizes that lymph nodes are birefringent, i.e., sensitive to polarized light. Lymph nodes and / or lymphatic vessels may contain birefringent collagen. In addition, tissues around lymph nodes (such as fat layers (i.e., lipids)) are generally not birefringent. Therefore, the present disclosure recognizes that cross-polarization (i.e., the above-mentioned orthogonal polarization relationship) can be used to utilize the birefringence difference between lymph nodes and / or lymphatic vessels and surrounding tissues to generate images of lymph nodes and / or lymphatic vessels. In some embodiments, light source 101 can provide illumination with a wavelength of 1200-1600nm, which can correspond to one or more absorption peaks of collagen in the lymph nodes and / or lymphatic vessels included in the target area 106. Therefore, the imaging contrast between lymph nodes and / or lymphatic vessels and surrounding tissues can be improved using an illumination wavelength of 1200-1600nm. As described above, due to the reduction of the scattering effect, longer wavelengths can improve the imaging resolution of lymph nodes and / or lymphatic vessels.

[0059] Additionally, illumination including longer wavelength light, particularly light at a wavelength of 1550 nm, can improve the contrast of lymphatic components in the target region 106. Typically, lymphatic components are surrounded by fat. Lymph nodes and lymphatic vessels have a high water content, while fat has a low water content. Absorption of photons in water occurs at 1550 nm, which may be why illuminating the target region 106 with light at a wavelength of 1550 nm can improve the contrast (and therefore visibility) of lymph nodes and / or lymphatic vessels in images generated using the imaging system 100. When an image is generated using light at a 1550 nm illumination wavelength, lymph nodes and lymphatic vessels appear dark, while fat appears light.

[0060] Additionally, illumination including longer wavelength light, particularly light at a 1550 nm wavelength, can improve the contrast of lymphatic components to surrounding blood in the target area 106. Although blood contains a large amount of water, it also contains a large amount of cells. Cells are highly scattering and overwhelm the water absorption effect. In testing, the imaging system 100 has been shown to generate images in which blood and / or hemorrhage in the target area 106 is not visible, even when compared to fat. Suppressing the visibility of blood and / or hemorrhage is an advantage of the imaging system 100 over other imaging modes that generate images with visible blood and / or hemorrhage. Hemorrhage may be mistaken for lymph nodes and then collected for analysis. Suppressing and / or eliminating hemorrhage in images can reduce the number of false positives identified by pathologists when diagnosing patients.

[0061] Although the imaging system 100 has been described as being applied to an in vivo region of a subject, it should be understood that the imaging system can also be applied to an ex vivo tissue sample. For example, the target region 106 can include a tissue bag that can include lymph nodes and fat. During the lymph node resection performed after identifying the tumor and the associated lymph nodes, the tissue bag may have been removed from the subject 105. Then, during the gross dissection step, the lymph nodes may need to be separated from the fat and any other surrounding tissue contained in the tissue bag. Typically, pathologists remove lymph nodes via manual palpation and visual inspection, which is prone to error because lymph nodes are usually translucent and look like fat, the diameter of the lymph nodes may be as small as 1 mm, and the location of the lymph nodes is often unpredictable. The imaging system 100 can be used to visualize the lymph nodes and display the lymph nodes to the pathologist, who can then effectively and accurately remove the lymph nodes from the target region 106. For a particular type of cancer, the cancer tissue may need to check a certain number of lymph nodes. The number of lymph nodes required can be in the range of 12 to 38. Thus, the imaging system 100 may assist the pathologist in obtaining a desired number of lymph nodes by potentially reducing the number of missed lymph nodes in the targeted region 106 .

[0062] exist Figure 2, a diagram of another exemplary embodiment of an imaging system 200 is shown. In this exemplary imaging system 200, a halogen lamp with continuous light illumination is used as a light source 201. In order to reduce the background from direct reflections at wavelengths outside the range of 900-1300nm, a long pass filter with a cutoff wavelength of 900nm or 1000nm is used to filter out light with shorter wavelengths. The imaging system 200 may include a primary long pass filter 203 and a secondary long pass filter 205. Each of the primary long pass filter 203 and the secondary long pass filter 205 may have a cutoff wavelength selected from 900nm to 1000nm (including 900nm and 1000nm). The imaging system 200 may include a linear polarizer 202 on a threaded mount. The linear polarizer 202 may include a linear polarization film. The linear polarizer 202 may be placed in front of the light source 201 to linearly polarize the illumination light from the light source 201 (e.g., a halogen lamp). The main long pass filter 203 may be placed in front of the light source 201 in order to filter out as much light as possible emitted from the light source 201 below the cut-off wavelength.

[0063] A conventional commercial silicon camera is used as the sensor 204 included in the imaging system 200. In some embodiments, a black silicon camera and / or an InGaAs camera may be used as the sensor 204. A sensor linear polarizer 206 is placed in front of the sensor 204 on a threaded mount. The sensor linear polarizer 206 may include a linear polarizing film. A lens (not shown), which may be a telecentric lens, is also placed in front of the sensor 204 to form an image. The telecentric lens may improve the measurement accuracy of the imaging system 200 by helping to normalize the size of the lymph nodes in the image generated using the sensor 204, regardless of how far the lymph nodes are from the sensor 204. A primary long pass filter 203 is also placed in front of the sensor 204 to filter out unwanted background from the ambient light or the light source 201 (e.g., a halogen lamp). In some embodiments, the sensor 204 may not need to be calibrated for different amounts of ambient and / or background light because the secondary long pass filter 205 may eliminate the background light, which may include visible frequencies below the cutoff frequency of the secondary long pass filter 205. Eliminating the need to calibrate sensor 204 can save time in detecting lymphatic components and make imaging system 200 more robust than imaging systems that require calibration of one or more sensors. Both light source 201 and sensor 204 should be pointed toward the subject being studied (whether human or animal (eg, Figure 2 The same region of interest of the person 207)) shown. Note that Figure 2 The imaging system 200 does not include a mirror and does not require a mirror or other reflective surface as is common in some imaging techniques. This can reduce the construction time compared to other imaging systems and / or techniques. Figure 2 The cost of the imaging system 200.

[0064] In some embodiments, a controller (not shown) may be included in the imaging system 200. The controller may be coupled to a light source, such as a laser or LED, and a sensor, such as a camera. The controller may be coupled to and communicate with the light source and the sensor. The controller may be configured to cause the light source to provide infrared illumination to the area by controlling the power supplied to the light source. The controller may also receive information corresponding to the infrared illumination reflected from the subject from the sensor. The reflected infrared illumination may be referred to as a reflected portion of the infrared illumination originally provided by the light source. The controller may also generate at least one image indicating a lymph node within the subject using the received information.

[0065] Reference now Figure 1 and Figure 2 as well as Figure 3 , a schematic diagram of yet another exemplary embodiment of an imaging system 300 is shown. In some embodiments, the imaging system 300 can be approximately the size of a shoebox and can therefore be a desktop imaging device. The imaging system 300 can include an interface platform 302. The interface platform 302 can include at least one memory, at least one processor, and any number of connection interfaces capable of communicating with sensors and light sources (not shown). The interface platform 302 can also store (e.g., in at least one memory) and execute (e.g., using at least one processor) at least a portion of an image generation and analysis application 304. As described below, the interface platform 302 can be coupled to and communicate with a computing device 334 included in the imaging system 300, which can also store and / or execute at least a portion of the image generation and analysis application 304. The interface platform 302 can be a controller, a laptop computer, a desktop computer, or another device capable of receiving signals from a sensor and outputting control signals to a light source. The controller can be a microcontroller, such as a Raspberry Pi 4 Model B. In some embodiments, the controller can be a computer configured to operate using a Windows operating system. computer.

[0066] The interface platform 302 can be coupled to and communicate with an illumination generation system 306 included in the imaging system 300. The illumination generation system 306 can include a light source 308. The interface platform 302 can be coupled to and communicate with the light source 308. The interface platform 302 can output a control signal to the light source 308 so as to cause the light source 308 to provide illumination. In some embodiments, the light source 308 can output appropriate data (e.g., a total existence time of the operation) to the interface platform 302. The illumination generation system 306, and more specifically, the light source 308, can be oriented to provide illumination 314 to a target area 318, which can be in vivo (e.g., included in a subject 316 (such as a patient)) or ex vivo, as further described below. The illumination 314 output by the illumination generation system 306 can be referred to as provided illumination 314. The illumination 314 can be infrared illumination. Infrared illumination may include light in the near infrared range (800-1400 nm wavelength) and / or light in the short wave infrared range (1400-3000 nm wavelength).

[0067] The light source 308 may include at least one of an LED (such as a single LED), a plurality of LEDs (such as an LED array), a halogen lamp (such as a tungsten halogen lamp, a quartz halogen lamp, or a quartz iodine lamp), a laser, or another suitable light source capable of outputting light at one or more predetermined wavelengths. In some embodiments, the light source 308 may output light at one or more discrete wavelengths, such as 1550 nm, 1375 nm, 1300 nm, and / or other wavelengths selected from the range of 800 nm to 1700 nm. For example, the light source 308 may only output light at a wavelength of 1550 nm. In some embodiments, the light source may output one or more discrete frequencies within a sub-range of wavelengths within the range of 800 nm to 2000 nm (such as a sub-range of 1200-1600 nm wavelengths). In some embodiments, the light source 308 may output light in a continuous wavelength range, such as 900-1300 nm, 1500-1600 nm, 1200-1600 nm, 1000-1700 nm (i.e., near infrared), and / or other wavelength ranges within 800-2000 nm. In some embodiments, light source 308 may be Figure 1 Light source 101 or Figure 2The light source 201 of FIG. 308 can output light of a longer wavelength, in particular light of a wavelength of 1550 nm, so as to better contrast the lymphatic components with the surrounding fat, blood and / or hemorrhage as described above. In order for the imaging system 300 to work properly, the light source 308 does not need to emit light of a wavelength range. In tests, excellent imaging has been obtained using only light of a wavelength of 1550 nm. However, the imaging system 300 can use light of multiple wavelengths to perform suitable imaging. It is conceivable that light of wavelengths up to 2600 nm can be used because some sensors (such as some InGaAs cameras) stop responding when they exceed 2600 nm. Therefore, light of a wavelength range of 800-2600 nm can be used in the imaging system 300. In tests, light of wavelengths below 800 nm did not perform as well as light of higher wavelengths (such as 800-1700 nm).

[0068] 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 imaging system 300 may include a polarizer 310. The polarizer 310 may include a linear polarizing film. The polarizer 310 may be mounted and placed in front of the light source 310 to produce linearly polarized light. The polarizer 310 may be mounted on a rotating mount or other suitable mount to allow adjustment of the polarizer 310. Thus, the illumination 314 provided to the target area 318 may be linearly polarized. Polarized illumination may improve imaging contrast in images generated by the imaging system 300, but this is not required. In some embodiments, the polarizer 310 may be Figure 1 Linear polarizer 102 or Figure 2 If light source 308 is an inherently polarizing device, such as certain lasers, polarizer 310 may not be included in imaging system 300. In some embodiments, polarizer 310 may be a circular polarizer.

[0069] In some embodiments, the illumination generation system 306 may include an optical filter 312. The optical filter 312 may be a long pass filter, such as a cold mirror, a colored glass filter, a thermosetting allyl carbonate diglycol (ADC) filter, or another suitable filter capable of attenuating lower wavelength light (e.g., visible light) and passing higher wavelength light (e.g., infrared light). The long pass filter may have a cut-off wavelength of not less than 800 nm. For example, the cut-off wavelength may be 800 nm, 900 nm, or 1000 nm. The optical filter 312 may be placed in front of the light source 308 to filter out as much light as possible that is emitted from the light source 308 and is below the cut-off wavelength. In some embodiments, the optical filter 312 may be Figure 2The main long pass filter 203 of the target area 318 can be a band pass filter. In some embodiments, the optical filter 312 can be a band pass filter, such as a hard coated filter or a colored glass filter. The band pass filter can only pass the wavelength range within the 800-2000nm window or a sub-range of the 800-2000nm window. For example, the band pass filter can only pass the light of 900-1700nm wavelength. Therefore, the illumination 314 provided to the target area 318 can be long pass filtered or band pass filtered.

[0070] like Figure 1 and / or Figure 2 As shown, light source 308, polarizer 310, and / or optical filter 312 can be physically arranged (i.e., positioned) relative to each other. For example, light source 308 and polarizer 310 can be arranged in a manner similar to light source 101 and linear polarizer 102, respectively, as shown in FIG. Figure 1 As another example, the light source 308, the polarizer 310, and the optical filter 312 may be arranged in a manner similar to the light source 201, the linear polarizer 202, and the long pass filter 203, respectively, as shown in FIG. Figure 2 Light source 308 may output illumination 314, which may pass through and be polarized by polarizer 310 and / or pass through and be attenuated by optical filter 312. Illumination 314, which may be polarized and / or attenuated, may then be provided to a target area 318.

[0071] As described above, the light source 308, and by extension the illumination generation system 306, can be oriented to provide illumination 314 to a target area 318. In some embodiments, the target area 318 can be an in vivo area included in a subject 316. In these embodiments, the target area 318 can be referred to as an in vivo area. The subject 316 can be a human patient. In other embodiments, the target area 318 can be an ex vivo area. In these embodiments, the target area 318 can be referred to as an ex vivo area. For example, as described above, the target area 318 can be a tissue portion removed from a subject for gross dissection purposes. The imaging system 300 can be used to assist in the gross dissection of a tissue portion by visualizing the lymphatic components for the practitioner.

[0072] At least a portion of the illumination 314 can be provided to a target area 318. The target area 318 can include one or more lymphatic components. The provided illumination 314 can interact with the lymphatic components and surrounding tissue in the target area 318. At least a portion of the provided illumination 314 can become randomly polarized as described above. At least a portion of the provided illumination 314 can be reflected as reflected illumination 320. The reflected illumination 320 can include light that has interacted with deep tissue in the target area 318.

[0073] The interface platform 302 may be coupled to and communicate with a sensing system 322 included in the imaging system 300. The sensing system 322 may include a sensor 324. The interface platform 302 may be coupled to and communicate with the sensor 324. The sensor 324 may sense the reflected illumination 320 and output a signal associated with an image based on the sensed reflected illumination 320. The interface platform 302 may receive a signal indicative of an image from the sensor 324. The signal may include information related to the image. In some embodiments, the information may include an image formed in a predetermined image format such as PNG, JPEG, DICOM (i.e., included in a DICOM file), etc. In some embodiments, the information may also include metadata related to the image, such as the time the image was taken or the patient associated with the image. In some embodiments, the sensor 324 may include a camera, such as a silicon camera (including a silicon complementary metal oxide semiconductor (CMOS) camera or a silicon charge coupled device (CCD) camera with a phosphor coating), a germanium camera, a germanium tin on silicon camera, a black silicon camera, a quantum dot short wave infrared (SWIR) camera, and / or an InGaAs camera. The InGaAs camera may be a nitrogen cooled InGaAs camera. The sensor 324 may include a mercury cadmium telluride (HgCdTe or MCT) camera. The sensor 324 may be responsive to light including at least a portion of light in the wavelength range of 800nm-2000nm, particularly wavelengths at or near 1550nm. Note that the imaging system 300 may require only a single sensor (e.g., a silicon camera) compared to other systems that may require multiple sensors and / or cameras.

[0074] The sensing system 322 can include a lens 326 located in front of the sensor 324. In some embodiments, the lens 326 can be integrated with the sensor 324, such as if the sensor 324 and the lens 326 are sold as a single off-the-shelf component. The lens 326 can improve the imaging capabilities of the sensor 324. For example, the lens 326 can be a telecentric lens. The telecentric lens can improve the measurement accuracy of the imaging system 300 by helping to normalize the size of the lymph nodes in the images generated using the sensor 324, regardless of how far the lymph nodes are from the sensor 324.

[0075] In some embodiments, the sensing system 300 may include a light diffuser 328, such as a sheet of frosted glass or tissue paper. The light diffuser 328 may be inserted between the lens 326 and the polarizer 332 included in the sensing system 322. The light diffuser 328 may create a more evenly distributed light pattern in the reflected illumination 320. The light diffuser 328 may improve the imaging capability of the sensor 324 due to the more evenly distributed light pattern.

[0076] In some embodiments, the sensing system 322 may include an optical filter 330 located in front of the sensor 324. The optical filter 330 may be a long pass filter, such as a cold mirror, a colored glass filter, a thermoset ADC filter, or another suitable filter capable of attenuating lower wavelength light (e.g., visible light) and passing higher wavelength light (e.g., infrared light). The long pass filter may have a cut-off wavelength of no less than 800 nm. For example, the cut-off wavelength may be 800 nm, 900 nm, or 1000 nm. In some embodiments, it may not be necessary to calibrate the sensor 324 for different environments and / or amounts of background light because the optical filter 330 may eliminate background light that may include visible frequencies below the cut-off frequency of the optical filter 330. In some embodiments, the optical filter 330 may be a Figure 2 The secondary long pass filter 205 shown. In some embodiments, the optical filter 330 can be a band pass filter, such as a hard coated filter or a colored glass filter. The band pass filter can only pass a wavelength range within a 800-2000nm window, or a sub-range of the 800-2000nm window. For example, the band pass filter can only pass light with a wavelength of 900-1700nm. Therefore, the reflected illumination 320 provided to the sensor 324 can be long pass filtered or band pass filtered.

[0077] As described above, the sensing system may include a polarizer 332. The polarizer 332 may be a linear polarizer. In some embodiments, the polarizer 332 may be a circular polarizer. The polarizer 332 may be placed in front of the sensor 324. The polarizer 332 may include a linear polarizing film. Similar to the polarizer 310 included in the illumination generation system 306, the polarizer 332 included in the sensing system 322 may be mounted on a rotating mount or other suitable mount to allow adjustment. The linear polarizers 310, 332 may be rotated or otherwise adjusted to produce a desired imaging contrast, as described above. The polarizer 332 may remove any light having the same polarization as the provided illumination 314 from the reflected illumination 320. The sensor 324 may detect light included in the reflected illumination 320 having a polarization opposite to the provided illumination 314.

[0078] In some embodiments, the sensor 324 can be coupled to and communicate with an external display 372. Alternatively or in addition, the sensor 324 can be coupled to and communicate with a memory 374, which can be included in the imaging system 300 or outside the imaging system 300. For example, the memory 374 can be a flash memory included in a memory card. In embodiments where the sensor 324 is coupled to and communicates with an external display 372 and / or a memory 374, the sensor 324 can be configured to sense a reflected portion of the provided illumination 314 and generate at least one image indicating any lymphatic component in the target area 318 based on the reflected portion of the provided illumination 314 (i.e., the reflected illumination 320). The sensor 324 can also be configured to output at least one image to at least one of the external display 372 or the memory 374.

[0079] In some embodiments, the light source 308 may not be coupled to a controller or other device, and may only need to be coupled to a power source. In these embodiments, the light source 308 may continuously or semi-continuously provide illumination 314 to the target area 318. In some embodiments, the interface platform 304 may provide power to the light source 308 (i.e., act as a power source). In other embodiments, the light source 308 may receive power from a wall outlet, one or more batteries, or another suitable power source.

[0080] In some embodiments, sensor 324 can be coupled to external display 372 and / or memory 374, and light source can be coupled to power source without coupling to interface platform 304 and / or other suitable devices. Thus, imaging system 300 can be implemented without using a controller or computing device.

[0081] In some embodiments, imaging system 300 may be Class 1, 510(k) exempt, and / or Good Manufacturing Practice (GMP) exempt.

[0082] The imaging system 300 may also include an external display 372 and / or a computing device 334. As described above, the interface platform 302 may be coupled to and in communication with the computing device 334. The imaging system 300 may include a communication network 336. The communication network 336 may facilitate communications between the interface platform 302 and the computing device 334. The interface platform 302 may be coupled to and in communication with the external display 372.

[0083] In some embodiments, the communication network 336 may be any suitable communication network or combination of communication networks. For example, the communication network 336 may include a Wi-Fi network (a Wi-Fi network may include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, etc. that complies with any suitable standard (such as CDMA, GSM, LTE, Advanced LTE, WiMAX, etc.)), a wired network, etc. In some embodiments, the communication network 336 may be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a company or university intranet), any other suitable type of network, or any suitable combination of networks. Figure 3 The communication links shown may each be any suitable communication link or combination of communication links, such as a wired link, a fiber optic link, a Wi-Fi link, a Bluetooth link, a cellular link, etc. In some embodiments, a computing device may implement portions of the image generation and analysis application 304 .

[0084] Reference now Figure 3 as well as Figure 4 , showing that some embodiments of the disclosed subject matter may be used to implement Figure 3 334 and the hardware of the interface platform 302 are shown. Figure 4 As shown, computing device 334 may include processor 350, display 352, input 354, communication system 356, and memory 358. Processor 350 may implement at least a portion of image generation and analysis application 304, which may be executed, for example, from a program (e.g., saved and retrieved from memory 358). Processor 350 may be any suitable hardware processor or combination of processors (such as a central processing unit ("CPU"), graphics processing unit ("GPU"), etc.) that may execute a program, which may include the processes described below.

[0085] In some embodiments, display 352 may present a graphical user interface. In some embodiments, display 352 may be implemented using any suitable display device, such as a computer monitor, a touch screen, a television, etc. In some embodiments, input 354 of computing device 334 may include an indicator, a sensor, an actuatable button, a keyboard, a mouse, a graphical user interface, a touch screen display, etc. In some embodiments, input 354 may allow a user (e.g., a physician, such as a radiologist) to interact with computing device 334 and thereby interact with interface platform 302 (e.g., via communication network 336).

[0086] In some embodiments, the communication system 356 may include any suitable hardware, firmware, and / or software for communicating with other systems via any suitable communication network. For example, the communication system 356 may include one or more transceivers, one or more communication chips and / or chipsets, etc. In a more specific example, the communication system 356 may include hardware, firmware, and / or software that may be used to establish a coaxial connection, a fiber optic connection, an Ethernet connection, a USB connection, a Wi-Fi connection, a Bluetooth connection, a cellular connection, etc. In some embodiments, the communication system 356 allows the computing device 334 to communicate with the interface platform 302 (e.g., directly or indirectly, such as via the communication network 336).

[0087] In some embodiments, memory 358 may include any suitable one or more storage devices that may be used to store instructions, values, etc., which may be used, for example, by processor 350 to present content using display 352, to communicate with interface platform 302 via (multiple) communication systems 356, etc. Memory 358 may include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 358 may include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid-state drives, one or more optical drives, etc. In some embodiments, memory 358 may have a computer program encoded thereon for controlling the operation of computing device 334 (or interface platform 302). In such embodiments, processor 350 may execute at least a portion of the computer program to present content (e.g., images, user interfaces, graphics, tables, reports, etc.), receive content from interface platform 302, send information to interface platform 302, etc.

[0088] like Figure 4 As shown, the interface platform 302 may include a processor 360, a display 362, an input 364, a communication system 366, a memory 368, and a connector 370. In some embodiments, the processor 360 may implement at least a portion of the image generation and analysis application 304, which may be executed from a program (e.g., saved and retrieved from the memory 368), for example. The processor 360 may be any suitable hardware processor or combination of processors (such as a central processing unit ("CPU"), a graphics processing unit ("GPU"), etc.) that may execute a program, which may include the processes described below.

[0089] In some embodiments, display 362 may present a graphical user interface. In some embodiments, display 362 may include any suitable display device, such as a computer monitor, a touch screen, a television, etc. In some embodiments, input 364 of interface platform 302 may include an indicator, a sensor, an actuatable button, a keyboard, a mouse, a graphical user interface, a touch screen display, etc. In some embodiments, input 364 allows a user (e.g., a first responder) to interact with interface platform 302 and thereby interact with computing device 334 (e.g., via communication network 336). Computing device 334 may also be coupled to and communicate with external display 372, which may provide at least some of the functionality of display 352.

[0090] like Figure 4 As shown, the interface platform 302 may include a communication system 366. The communication system 366 may include any suitable hardware, firmware, and / or software for communicating with other systems via any suitable communication network. For example, the communication system 366 may include one or more transceivers, one or more communication chips and / or chipsets, etc. In a more specific example, the communication system 366 may include hardware, firmware, and / or software that can be used to establish a coaxial connection, a fiber optic connection, an Ethernet connection, a USB connection, a Wi-Fi connection, a Bluetooth connection, a cellular connection, etc. In some embodiments, the communication system 366 allows the interface platform 302 to communicate with the computing device 334 (e.g., directly or indirectly, such as via the communication network 336). It is contemplated that the communication system 366 can communicate with the light source and / or sensor 324, and thus provide at least some of the functions of the connector 370, which will be described below.

[0091] In some embodiments, memory 368 may include any suitable one or more storage devices that may be used to store instructions, values, etc., which may be used, for example, by processor 360 to present content using display 362, to communicate with computing device 334 via communication system(s) 366, etc. 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 drives, one or more hard disk drives, one or more solid-state drives, one or more optical drives, etc. In some embodiments, memory 368 may have a computer program encoded thereon for controlling the operation of interface platform 302 (or computing device 334). In such embodiments, processor 360 may execute at least a portion of the computer program to present content (e.g., images, user interfaces, graphics, tables, reports, etc.), receive content from computing device 334, send information to computing device 334, etc.

[0092] In some embodiments, connector 370 can be a wired connection so that light source 308 and sensor 324 can communicate with interface platform 302, and therefore can communicate with computing device 334 (e.g., via communication system 366, and directly or indirectly, such as via communication network 336). Additionally or alternatively, light source 308 and / or sensor 324 can send information to interface platform 302 and / or receive information from interface platform 302 (e.g., using connector 370 and / or communication system 366).

[0093] Reference now Figure 3-4 as well as Figure 5 , an exemplary flow chart of a process 400 included in the image generation and analysis application 304 is shown. In some embodiments, the interface platform 302 and the computing device 334 can each perform a portion of the process 400 to generate an image of the target area 318, which can include lymphatic components, such as lymph nodes and / or lymphatic vessels. As described above, the target area 318 can be in vivo (e.g., included in the subject 316) or ex vivo (e.g., a tissue package removed from the subject). In some embodiments, the interface platform 302 can perform the entire process 400.

[0094] At 402, process 400 may cause light source 308 to provide illumination 314 to target area 318. Target area 318 may include lymphatic components. The provided illumination 314 may pass through polarizer 310 and / or optical filter 312. The provided illumination 314 is then provided to target area 318. At least a portion of the provided illumination 314 may then be reflected toward sensing system 322 as reflected illumination 320, as described above. The reflected illumination 320 may pass through polarizer 332, optical filter 330, light diffuser 328, and / or lens 326 before reaching sensor 324. In some embodiments, if light source 308 continuously or semi-continuously provides illumination 314 to target area 318, process 400 may not require light source 308 to provide illumination. In other words, in some embodiments, process 400 may not implement step 402.

[0095] At 404, process 400 can detect a reflected portion of illumination 314. The reflected portion can be the reflected illumination 320. The reflected portion can be reflected directly from target area 318. Because the reflected portion is reflected directly from target area 318, system 300 does not need to use a mirror or other reflector to redirect the reflected portion toward sensor 324. Process 404 can detect the reflected portion using sensor 324. Detecting the reflected portion of illumination 314 can include receiving a signal from sensor 324 in response to the reflected portion.

[0096] At 406, process 400 may generate at least one image indicating one or more lymphatic components (such as lymph nodes and lymphatic vessels, if present in target area 318) using the reflected portion of illumination 314. Process 400 may generate at least one image based on the signal received from sensor 324 at 404. Process 400 may generate an image based on the signal from sensor 324. In some embodiments, the signal output by sensor 324 may include at least one image indicating lymphatic components. Process 400 may reformat and / or compress at least one image received from sensor. Alternatively, process 400 may store at least one image received from sensor 324 (i.e., in memory 358 and / or memory 368).

[0097] At 408, process 400 can output at least one image to at least one of a display and / or a memory. The display can be display 362, which can be included in interface platform 302, display 352, which can be included in computing device 334, or external display 372. The memory can be memory 368 included in interface platform 302 or memory 358 included in computing device 334. The memory can be memory external to imaging system 300, such as memory included in a remote server.

[0098] Reference now Figure 3-4 as well as Figure 6 , shows an exemplary flow chart of a process 450 included in the image generation and analysis application 304. In some embodiments, the interface platform 302 and the computing device 334 can each perform a portion of the process 450 to train a segmentation machine learning model and / or a classification machine learning model, and use the segmentation machine learning model and / or the classification machine learning model to analyze images generated by the imaging system (e.g., Figure 3 and Figure 4 An image produced by the imaging system 300 in FIG.

[0099] At 452, process 450 may receive training data for a segmentation model. The segmentation model may be a machine learning model, such as a convolutional neural network. The convolutional neural network may include a U network architecture. The training data for the segmentation model may include the original image and the associated segments. The imaging system (such as Figure 1 The imaging system 100, Figure 1 The imaging system 200 or Figure 3The imaging system 300 in the image is used to generate the original image. The segmentation can be an area in the image corresponding to a lymph node or an area where a lymph node is not present. In some embodiments, the segmentation can also include an area corresponding to a lymphatic vessel. Therefore, the segmentation model can be trained to segment the lymph nodes and lymphatic vessels in the image. The segmentation can be determined in advance by a qualified practitioner (such as an oncologist). In some embodiments, the segmentation model can be a predetermined algorithm configured to identify lymph nodes that may not require training.

[0100] At 454, process 450 can receive training data for a classification model. The classification model can be a machine learning model, such as a recurrent neural network. The classification model can be trained to classify the entire image. The training data for the classification model can include using an imaging system (such as Figure 1 The imaging system 100, Figure 1 The imaging system 200 or Figure 3 The training data may also include a plurality of original images generated by the imaging system 300 in the training data. The training data may also include a plurality of segmented images corresponding to the plurality of original images. The segmented images may be generated by providing the original images to the trained segmentation model. In some embodiments, the training data may include a classification of each segmented lymph node and / or lymphatic vessel. The classification may be malignant or healthy and may be provided by a suitable medical practitioner. In some embodiments, each classification may be associated with the entire original image included in the training data.

[0101] At 456, process 450 can train the segmentation model using the training data for the segmentation model. After the segmentation model is trained at 456, the segmentation model can be referred to as a trained segmentation model.

[0102] At 458, process 450 can train the classification model using training data for the classification model. Based on the training data, the classification model can be trained to identify individual lymphatic components (i.e., lymph nodes and / or lymphatic vessels) as malignant or healthy, or trained to identify the entire image as healthy or malignant. After the classification model is trained at 456, the classification model can be referred to as a trained classification model.

[0103] At 460, process 450 can provide the images to the trained segmentation model. In some embodiments, process 450 can provide any number of images sequentially to the trained segmentation model at 460.

[0104] At 462, process 450 can receive a plurality of segments associated with an image provided to a trained segmentation model. In some embodiments, process 450 can receive, at 460, a plurality of segments for each image provided to a trained segmentation model.

[0105] At 464, process 450 can provide the images to the trained classification model. In some embodiments, process 450 can provide any number of images sequentially to the trained classification model at 464.

[0106] At 466, process 450 can receive a classification of the image provided to the trained classification model. In some embodiments, process 450 can receive a plurality of classifications associated with the plurality of images provided to the trained model at 464.

[0107] At 468, process 450 can output any received (multiple) segmentation and / or (multiple) classification to at least one of a display and / or a memory. The display can be a display 362 that can be included in the interface platform 302, a display 352 that can be included in the computing device 334, or an external display 372. The memory can be a memory 368 included in the interface platform 302 or a memory 358 included in the computing device 334. The memory can be a memory external to the imaging system 300, such as a memory included in a remote server. An external process can perform further analysis on the received segmentation. For example, the segmentation can be used to determine the characteristics of each segmented lymphatic component, including lymph node size, lymph node aspect ratio, lymph node symmetry, lymph node boundary clarity, lymph node curvature and / or lymphatic vessel pattern. The characteristics of each lymphatic component can be further analyzed. In some embodiments, process 450 may output a heat map for each image that identifies distinguishing features in each raw image (and, by extension, lymphatic component), thereby resulting in a classification of each lymphatic component and / or raw image.

[0108] It should be understood that the image generation and analysis application 304 may include Figure 5 The course 400 and Figure 6 In some embodiments, multiple applications may be implemented to perform Figure 5 The course 400 and Figure 6 One or both of processes 450.

[0109] Fig. 7A and Figure 7B Imaging results of an imaging system constructed according to the imaging system described herein are shown. Fig. 7A The imaging results of the area imaged without using a polarizer are shown. Figure 7B The imaging results of the same area when a polarizer is used are shown. Fig. 7A and Figure 7B The region shown includes a lymph node 500. A polarizer improves imaging contrast, but the lymph node can be visualized with or without the use of a polarizer.

[0110] Fig. 8A -C shows an exemplary imaging result of a mouse. The imaging system used includes an LED emitting light around 1200 nm as a light source, and a liquid nitrogen-cooled InGaAs camera as a sensor. Fig. 8A An image of the mouse region taken with a standard camera is shown. Figure 8B An image of a region of a mouse taken using an imaging system prior to injection of adjuvant is shown. Lymph nodes 504 and bladder 508 can be visualized. Figure 8C An image of a region of a mouse taken using an imaging system 48 hours after injection of the adjuvant is shown. Lymph nodes 504 and bladder 508 can be visualized. The results show that within 48 hours after injection of the adjuvant, the size of the lymph nodes 504 increased significantly.

[0111] Fig.9A -C show exemplary imaging results of mice. The imaging system used included a halogen lamp as the light source with a long pass filter to filter the light from the lamp, and a standard silicon camera as the sensor, similar to Figure 2 The imaging system 200 in FIG. Fig.9A An image of the mouse region taken with a standard camera is shown. Fig. 9B Images of mouse regions taken using an imaging system before adjuvant injection are shown. Fig. 9C An image of a region of a mouse taken using an imaging system 48 hours after injection of the adjuvant is shown. The results show that within 48 hours after injection of the adjuvant, the size of lymph nodes, such as lymph node 512, increased significantly. The results are similar in quality to more expensive systems, such as Figure 1 The imaging system 100 shown in FIG. In addition, compared with other imaging systems, the imaging system 100 used to generate Fig. 9B -C's imaging system is more compatible with ambient light.

[0112] Figure 10A-10E The results of imaging lymph nodes using various illumination wavelengths and an InGaAs camera are shown. When an illumination wavelength of 1000 nm is used, the images are taken Fig. 10A When using an illumination wavelength of 1175nm, the image is taken Fig. 10B When using an illumination wavelength of 1250nm, the image is taken Fig. 10C When using an illumination wavelength of 1375nm, the image is taken Fig. 10D When using an illumination wavelength of 1550nm, the image is taken Fig.10E .

[0113] Fig.11A-M shows the imaging results of lymph nodes in an ex vivo porcine mesenteric tissue sample. The lymph nodes were imaged using different illumination wavelengths and sensors included in the imaging system according to an embodiment of the present invention. A single wavelength LED light source was used to generate illumination wavelengths of 690nm and 730nm. A continuous wavelength lamp with a bandpass filter was used to generate an illumination wavelength in the range of 810nm to 1575nm. A continuous wavelength lamp without a bandpass filter was used to generate 8-10μm illumination. Since the sensor used was a thermal camera that was only sensitive to 8-10μm wavelength light, 8-10μm illumination was achieved. For illumination of 690nm and 730nm wavelengths, a silicon camera was used as a sensor. For illumination wavelengths in the range of 810nm to 1575nm, an InGaAs camera was used as a sensor. For all illumination wavelengths, the imaging system was included in orthogonally positioned polarizers. Each of the individual illumination wavelengths represents the most dominant wavelength in the wavelength band.

[0114] For each illumination wavelength, the signal-to-noise ratio is measured to measure the performance of the illumination wavelength. A higher signal-to-noise ratio is preferred because the lymph nodes will stand out more relative to the surrounding tissue.

[0115] Fig.11A An image including lymph nodes generated using 690 nm wavelength illumination is shown. Fig. 11B An image including lymph nodes generated using 730 nm wavelength illumination is shown. Fig. 11C An image including lymph nodes generated using 810 nm wavelength illumination is shown. Fig.11D An image including lymph nodes generated using 900-950 nm wavelength illumination is shown. Fig.11E An image including lymph nodes generated using 1000 nm wavelength illumination is shown. Fig.11F An image including lymph nodes generated using 1125 nm wavelength illumination is shown. Fig.11G An image including lymph nodes generated using 1175 nm wavelength illumination is shown. Fig.11H An image including lymph nodes generated using 1250 nm wavelength illumination is shown. Fig.11I An image including lymph nodes generated using 1300 nm wavelength illumination is shown. Fig.11J An image including lymph nodes generated using 1375 nm wavelength illumination is shown. Figure 11K An image including lymph nodes generated using 1550 nm wavelength illumination is shown. Fig.11L An image including lymph nodes generated using 1575 nm wavelength illumination is shown. Fig.11M An image including lymph nodes generated using 8-10 μm wavelength illumination is shown.

[0116] Table 1 below summarizes the signal-to-noise ratio for each illumination wavelength. The results in Table 1 show that the illumination wavelength of 1550 performed the best, with the highest signal-to-noise ratio of 24. Illumination wavelengths in the range from 1175 to 1375 had comparable performance providing usable performance. Illumination wavelengths at or below 810nm performed much worse than those in the 900-1575nm range. The performance of 8-10um wavelength illumination was significantly lower than that of 1550nm or 1575nm wavelength illumination, indicating that illumination wavelengths significantly above 1575nm may result in degraded performance. Table 1 Illumination wavelength Signal-to-Noise Ratio Corresponding drawings 690nm 4 11A 730nm 2 11B 810nm 3 11C 900--950nm 5 11D 1000nm 9 11E 1125nm 8 11F 1175nm 10 11G 1250nm 12 11H 1300nm 11 11I 1375nm 13 11J 1550nm 20 11K 1575nm 24 11L 8-10μm 8 11M

[0117] Reference now Fig. 12A and Fig. 12B , shows a comparison of images of a lymph node 516 in an ex vivo human tissue sample generated using different imaging techniques. Fig. 12A An image of a lymph node 516 generated using a conventional camera and ambient visible light is shown. Fig. 12B Shows the use of Figure 3 The embodiment of the imaging system 300 generates an image of the lymph node 516. The lymph node 516 is Fig. 12B More clearly visible.

[0118] The present disclosure provides various embodiments of imaging systems, each of which provides a set of advantages over other imaging systems. One advantage is that the imaging system is completely non-invasive and non-labeling. This advantage makes the provided imaging system stand out from the common technologies based on methylene blue, indocyanine green and other injectable dyes. The imaging system does not require injection or operation (e.g., cutting operation) to achieve high imaging contrast of lymph nodes. It should also be noted that the lymph nodes are in the body when imaged by the imaging system, which is different from other imaging systems that require the removal of lymph nodes and / or surrounding tissue from the subject to perform lymph node imaging.

[0119] Another advantage of the imaging system provided herein is that safety is improved compared with other imaging modes. The system uses only very low-intensity infrared light. The images shown in the figures listed in this document are taken only under 1mW light power illumination, which is one thousandth of the prescribed exposure limit. This advantage makes the disclosed imaging system stand out relative to CT, PET and other imaging systems that inherently cause health hazards to patients. The present disclosure describes an optical method for conveniently visualizing lymph nodes without any injection. The method uses illumination light between 800-1700nm and a sensor capable of detecting the wavelength range or a part of the wavelength range. The imaging system can utilize illumination light to detect lymph nodes using the intrinsic absorption spectrum of lymph nodes. Using illumination light with a wavelength between 800-1700nm, especially a wavelength of 1550nm, the imaging system generates an image showing that lymph nodes naturally protrude from their surrounding tissues (including fat, blood and / or hemorrhage), as described above. The image contrast of lymph nodes can be improved by the implementation of polarizers; however, they are not necessary for this method. The present disclosure provides systems and methods to non-invasively visualize lymph nodes and can be a powerful tool for health screening, disease prevention, diagnosis, and treatment.

[0120] Certain embodiments of the imaging system provided by the present invention can also be constructed economically. For example, similar to Figure 2 The construction cost of an embodiment of the imaging system 200 may be less than $100. Therefore, the construction cost of some lymph node imaging systems is much cheaper than any of the cross-sectional imaging modes. The prices of CT, MRI, ultrasound and PET instruments range from tens of thousands of dollars to millions of dollars. The economy of these provided imaging systems will help to produce a much greater impact in clinical settings. These imaging systems can be used by medical practitioners and even ordinary consumers to perform routine health examinations, track disease recurrence, etc. In addition, unlike the cross-sectional mode, the wavelength range of the disclosed imaging system is specific to natural lymph nodes and lymphatic vessels (that is, lymph nodes and lymphatic vessels without any external injection). Even imaging systems including relatively more expensive components (e.g., InGaAs cameras used as sensors) can still be constructed more economically than at least some of the cross-sectional modes described above.

[0121] It should be understood that Figure 6 The above steps of the process may be performed or carried out in any order or sequence, not limited to the order and sequence shown and described in the figures. Figure 5 and Figure 6 Some of the above steps of the process may be performed substantially simultaneously or in parallel where appropriate to reduce delays and processing time.

[0122] In some embodiments, aspects of the present disclosure (including computerized implementations of methods) may be implemented as systems, methods, apparatus, or articles of manufacture that use standard programming or engineering techniques to generate software, which may be firmware, hardware, or any combination thereof, for controlling a processor device, a computer (e.g., a processor device operatively coupled to a memory), or another electronic operating controller to implement the various aspects described in detail herein. Accordingly, for example, embodiments of the present invention may be implemented as an instruction set tangibly implemented on a non-transitory computer-readable medium, such that a processor device can implement instructions based on reading instructions from the computer-readable medium. Some embodiments of the present invention may include (or utilize) devices, such as automated devices, special-purpose or general-purpose computers including various computer hardware, software, firmware, etc., consistent with the discussion below.

[0123] As used herein, the term "article of manufacture" is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non-transient signal), or medium (e.g., non-transient medium). For example, computer-readable media may include, but are not limited to, magnetic storage devices (e.g., hard disks, floppy disks, magnetic tapes, etc.), optical disks (e.g., compact disks (CDs), digital versatile disks (DVDs), etc.), smart cards, and flash memory devices (e.g., cards, sticks, etc.). In addition, it will be understood that a carrier wave may be employed to carry computer-readable electronic data, such as those used in sending and receiving e-mail or accessing a network such as the Internet or a local area network (LAN). Those skilled in the art will recognize that many modifications may be made to these configurations without departing from the scope and spirit of the claimed subject matter.

[0124] Certain operations of the methods according to the present invention or certain operations of the systems that perform those methods may be schematically represented in the accompanying drawings or discussed separately herein. Unless otherwise specified or limited, the representation of specific operations in a specific spatial order in the accompanying drawings does not necessarily require that these operations be performed in a specific order corresponding to the specific spatial order. Correspondingly, certain operations represented in the accompanying drawings or disclosed separately herein may be performed in a manner suitable for a specific embodiment of the present disclosure, in an order different from the order explicitly explained or described. Further, in some embodiments, certain operations may be performed in parallel, including by dedicated parallel processing devices, or by separate computing devices configured to interact as part of a larger system.

[0125] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms "component", "system", "module", etc. may be intended to cover part or all of a computer-related system including hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer may be a component. One or more components (or systems, modules, etc.) may reside within an executing process or thread, may be located on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, etc.).

[0126] As used herein, the terms "controller" and "processor" include any device capable of executing a computer program, or may include any device that is configured to perform the functions described. For example, this may include a processor, a microcontroller, a field programmable gate array, a programmable logic controller, etc.

[0127] The discussion herein is presented for those skilled in the art to make and use embodiments of the present invention. Various modifications to the illustrated embodiments will be very obvious to those skilled in the art, and the general principles herein may be applied to other embodiments and applications without departing from embodiments of the present invention. Therefore, embodiments of the present invention are not intended to be limited to the illustrated embodiments, but should conform to the maximum scope consistent with the principles and features disclosed herein. Detailed description is read with reference to the accompanying drawings, wherein the same elements in different drawings have the same reference numerals. The drawings, which may not necessarily be drawn to scale, depict selected embodiments and may not be intended to limit the scope of embodiments of the present invention. Those skilled in the art will recognize that the embodiments provided herein have many useful alternatives and fall within the scope of embodiments of the present invention.

[0128] Therefore, as described above, systems and methods are provided for visualizing lymphatic components using near infrared (800-1400nm) and / or short wave infrared (1400-3000nm). For example, illumination between 800-1700nm can be used. For some applications, an illumination wavelength between 1500-1600nm (such as 1550nm) can be advantageous for imaging lymphatic components. In one embodiment, only illumination with a wavelength of 1550nm can be used.

[0129] The systems and methods described herein provide near infrared and / or short infrared imaging techniques using one or more near infrared or short wave infrared light sources and sensors. The imaging system can work with a polarizer. A polarizer can be placed in front of (multiple) light sources (also referred to as (multiple) optical sources), and another polarizer can be placed in front of (multiple) sensors. The rotation angle between the two polarizers can be adjusted to minimize direct reflections from human or animal skin and optimize visualization of lymphatic components. In some configurations, it may not be necessary to use a polarizer in front of (multiple) light sources, and the imaging system can work without a polarizer in front of (multiple) light sources. Some light sources emit linearly polarized light due to their inherent working mechanism without a polarizer. Therefore, polarizers help to improve the contrast of lymphatic components; however, they are not required. Lymphatic components can still be visualized without any polarizer or polarization modification, especially when the illumination wavelength is between 800-1700nm and the sensor is ready to detect light in this wavelength range.

[0130] In one aspect, the present disclosure provides a lymphatic component imaging system. The system includes a light source configured to provide infrared illumination to an area of ​​a subject having at least one lymphatic component; a sensor configured to sense a reflected portion of the infrared illumination directly reflected from the area; and a controller in communication with the light source and the sensor and configured to cause the light source to provide infrared illumination to the area, receive information corresponding to the reflected portion of the infrared illumination from the sensor, and generate at least one image indicating at least one lymphatic component in the subject using the information.

[0131] The system may be configured to generate at least one image indicating at least one lymph component without reference light. The system may be configured to generate at least one image indicating at least one lymph component without information from ambient light around the sensor. In the system, the light source may include a laser. In the system, the light source may include a light emitting diode. The system may further include a long pass or band pass filter, which is arranged between the area and the light source and has a cut-off wavelength of not less than 800nm. In the system, the sensor may include at least one of a silicon camera, an InGaAs camera, and a black silicon camera. The system may further include a polarizer arranged between the area and the sensor. The system may not include a contrast agent, and at least one lymph component may include a lymph node or a lymphatic vessel. In the system, the infrared illumination may have an illumination wavelength of 800-1700nm.

[0132] In another aspect, the present disclosure provides a method for imaging lymphatic components without contrast agents. The method includes providing infrared illumination to a region within a subject having lymphatic components using a light source, detecting a reflected portion of the infrared illumination directly reflected from the region using a sensor located about the region, and generating at least one image indicating lymphatic components in the subject using the reflected portion of the infrared illumination.

[0133] In the method, the infrared illumination may have an illumination wavelength of 800-2000 nm. In the method, the infrared illumination may be provided without the use of a polarizer. The method may further include rotating the polarizer in front of the sensor until the sensor detects a minimum total intensity. In the method, the infrared illumination may have an optical power of no more than 1 mW. The method may further include positioning a polarizer between the area and the sensor, and arranging the polarizer to be approximately orthogonal to the infrared illumination directly reflected from the area. The method may further include adjusting at least one of the polarizer and the light source until a threshold contrast level is reached at the sensor.

[0134] In yet another aspect, the present disclosure provides a method for imaging lymphatic components without a mirror. The method includes providing infrared illumination to an area of ​​a subject having lymphatic components using a light source, detecting a reflected portion of the infrared illumination directly reflected from the area using a sensor located around the area, and generating at least one image indicating lymphatic components in the subject using the reflected portion of the infrared illumination. In the method, the infrared illumination can have an illumination wavelength of 800-2000nm. In the method, the infrared illumination can be provided without using a polarizer.

[0135] Although the present invention has been described in considerable detail with reference to certain embodiments, it will be appreciated by those skilled in the art that the present invention may be implemented by embodiments other than those described, which are presented for purposes of illustration and not limitation. Accordingly, the scope of the appended claims should not be limited to the description of the embodiments contained herein.

Claims

1. A method for imaging biological tissue, the method comprising: providing infrared illumination from a light source to a region of a subject having biological tissue, the biological tissue comprising a first tissue region and a second tissue region, wherein the first tissue region has a first water content level and the second tissue region has a second water content level lower than the first water content level, wherein the infrared illumination has an illumination wavelength of 1500-1700 nm; sensing, by a sensor, a first reflected portion of the infrared illumination and a second reflected portion of the infrared illumination, wherein the first reflected portion of the infrared illumination is reflected from the first tissue portion and has a first intensity, and wherein the second reflected portion of the infrared illumination is reflected from the second tissue portion and has a second intensity that is higher than the first intensity; as well as receiving, by a controller in communication with the sensor, from the sensor information corresponding to the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination; generating, by the controller, at least one image of the at least one biological tissue in the subject by using the information, wherein the at least one image distinguishes the first tissue region from the second tissue region; as well as The at least one image is output by the controller to at least one of a display and / or a memory.

2. The method according to claim 1, characterized in that: The at least one image is generated without reference light.

3. The method according to claim 1, characterized in that: The at least one image is generated without information from ambient light surrounding the sensor.

4. The method according to claim 1, characterized in that: The light source includes a laser.

5. The method according to claim 1, characterized in that: The light source includes a light emitting diode.

6. The method of claim 1, further comprising filtering the infrared illumination by arranging a long pass filter or a band pass filter between the region and the light source, wherein the long pass filter or the band pass filter has a cut-off wavelength of not less than 800 nm.

7. The method according to claim 1, characterized in that: The sensor includes at least one of a silicon camera, an InGaAs camera, and a black silicon camera.

8. The method according to claim 1, characterized in that The sensor includes at least one of a germanium camera, a germanium tin on silicon camera, a quantum dot short-wave infrared camera, or a mercury cadmium telluride camera.

9. The method of claim 1, further comprising polarizing the infrared illumination via a first polarizer such that the infrared illumination incident on the biological tissue has a first polarization.

10. The method of claim 9, further comprising polarizing the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination by a second polarizer so that the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination incident on the sensor have a second polarization opposite to the first polarization.

11. The method according to claim 1, characterized in that: The biological tissue does not contain a contrast agent.

12. The method according to claim 1, characterized in that: The first tissue region includes lymphatic tissue and the second tissue region includes adipose tissue.

13. The method according to claim 1, characterized in that: The first tissue region has a first absorption at 1550 nm and the second tissue region has a second absorption at 1550 nm, wherein the first absorption is higher than the second absorption.

14. The method according to claim 1, characterized in that: The infrared illumination has an illumination wavelength of 1300 nm.

15. The method according to claim 1, characterized in that: The infrared lighting has an optical power no greater than 1 mW.

16. A system for imaging biological tissue, the system comprising: a light source configured to provide infrared illumination to a region of a subject having biological tissue, the biological tissue comprising a first tissue region and a second tissue region, wherein the first tissue region has a first water content level and the second tissue region has a second water content level lower than the first water content level, wherein the infrared illumination has an illumination wavelength of 1500-1700 nm; a sensor configured to sense a first reflected portion of the infrared illumination and a second reflected portion of the infrared illumination, wherein the first reflected portion of the infrared illumination is reflected from the first tissue portion and has a first intensity, and wherein the second reflected portion of the infrared illumination is reflected from the second tissue portion and has a second intensity that is higher than the first intensity; as well as a controller in communication with the sensor and configured to: receiving, from the sensor, information corresponding to the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination; generating at least one image of the at least one biological tissue in the subject using the information, wherein the at least one image distinguishes the first tissue region from the second tissue region; as well as The at least one image is output to at least one of a display and / or a memory.

17. The system of claim 16, further comprising a first polarizer disposed between the light source and the biological tissue and configured to polarize the infrared illumination such that the infrared illumination incident on the biological tissue has a first polarization.

18. The system of claim 17, further comprising a second polarizer disposed between the biological tissue and the sensor and configured to polarize the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination so that the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination incident on the sensor have a second polarization opposite to the first polarization.

19. A method for imaging biological tissue, the method comprising: providing infrared illumination from a light source to a region of a subject having biological tissue, the biological tissue comprising a first tissue region and a second tissue region, wherein the first tissue region has a first water content level and the second tissue region has a second water content level lower than the first water content level, wherein the infrared illumination has an illumination wavelength of 1000-2600 nm; sensing, by a sensor, a first reflected portion of the infrared illumination and a second reflected portion of the infrared illumination, wherein the first reflected portion of the infrared illumination is reflected from the first tissue portion and has a first intensity, and wherein the second reflected portion of the infrared illumination is reflected from the second tissue portion and has a second intensity that is higher than the first intensity; as well as receiving, by a controller in communication with the sensor, from the sensor information corresponding to the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination; generating, by the controller, at least one image of the at least one biological tissue in the subject by using the information, wherein the at least one image distinguishes the first tissue region from the second tissue region; as well as outputting, by the controller, the at least one image to at least one of a display and / or a memory; The biological tissue does not contain a contrast agent.

20. The method of claim 19, wherein: The at least one image is generated without reference light.

21. The method of claim 19, wherein: The at least one image is generated without information from ambient light surrounding the sensor.

22. The method of claim 19, wherein: The light source includes a laser.

23. The method of claim 19, wherein: The light source includes a light emitting diode.

24. The method of claim 19, further comprising filtering the infrared illumination by disposing a long pass filter or a band pass filter between the region and the light source, wherein the long pass filter or the band pass filter has a cut-off wavelength of not less than 800 nm.

25. The method of claim 19, wherein: The sensor includes at least one of a silicon camera, an InGaAs camera, and a black silicon camera.

26. The method of claim 19, wherein: The sensor includes at least one of a germanium camera, a germanium tin on silicon camera, a quantum dot short-wave infrared camera, or a mercury cadmium telluride camera.

27. The method of claim 19, further comprising polarizing the infrared illumination via a first polarizer such that the infrared illumination incident on the biological tissue has a first polarization.

28. The method of claim 27, further comprising polarizing the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination by a second polarizer so that the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination incident on the sensor have a second polarization opposite to the first polarization.

29. The method of claim 19, wherein: The biological tissue does not contain a contrast agent.

30. The method of claim 19, wherein: The first tissue region includes lymphatic tissue and the second tissue region includes adipose tissue.

31. The method of claim 19, wherein: The first tissue region has a first absorption at 1550 nm and the second tissue region has a second absorption at 1550 nm, wherein the first absorption is higher than the second absorption.

32. The method of claim 19, wherein: The infrared illumination has an illumination wavelength of 1000-1700 nm.

33. The method of claim 19, wherein: The infrared illumination has an illumination wavelength of 1300 nm.

34. The method of claim 19, wherein: The infrared lighting has an optical power no greater than 1 mW.

35. A system for imaging biological tissue, the system comprising: a light source configured to provide infrared illumination to a region of a subject having biological tissue, the biological tissue comprising a first tissue region and a second tissue region, wherein the first tissue region has a first water content level and the second tissue region has a second water content level lower than the first water content level, wherein the infrared illumination has an illumination wavelength of 1000-2600 nm; a sensor configured to sense a first reflected portion of the infrared illumination and a second reflected portion of the infrared illumination, wherein the first reflected portion of the infrared illumination is reflected from the first tissue portion and has a first intensity, and wherein the second reflected portion of the infrared illumination is reflected from the second tissue portion and has a second intensity that is higher than the first intensity; as well as a controller in communication with the sensor and configured to: receiving, from the sensor, information corresponding to the first reflective portion of the infrared illumination and the second reflective portion of the infrared illumination; generating at least one image of the at least one biological tissue in the subject using the information, wherein the at least one image distinguishes the first tissue region from the second tissue region; as well as outputting the at least one image to at least one of a display and / or a memory; The biological tissue does not contain a contrast agent.

36. The system of claim 35, further comprising a first polarizer disposed between the light source and the biological tissue and configured to polarize the infrared illumination such that the infrared illumination incident on the biological tissue has a first polarization.

37. The system of claim 36, further comprising a second polarizer disposed between the biological tissue and the sensor and configured to polarize the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination so that the first reflected portion of the infrared illumination and the second reflected portion of the infrared illumination incident on the sensor have a second polarization opposite to the first polarization.