Open-field handheld fluorescence imaging systems and methods

Abstract

To solve the problem in which, in many applications of imaging systems, such as medical imaging and especially fluorescence medical imaging, it is challenging to achieve even, full field illumination of the imaging field of view, and also to provide a sufficient intensity of illumination to yield a sufficiently strong imaging signal.SOLUTION: An imaging device 10 with an imaging field of view includes at least one illumination port 11 configured to output light for illuminating a target 12; an imaging sensor 13 to detect light traveling along an optical path to the imaging sensor; and a movable window positioned upstream of the sensor with respect to a direction of travel of light along the optical path, where the movable window is configured to move into the optical path in a deployed position for modifying light received from the target.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] References to Related Applications This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 457,690, filed February 10, 2017, entitled "OPEN-FIELD HANDHELD FLUORESCENCE IMAGING SYSTEMS AND METHODS," which is incorporated herein by reference in its entirety.

[0002] This disclosure relates generally to medical illumination and imaging, and more particularly to illumination and imaging of target materials. [Background technology]

[0003] Illumination is a critical component of imaging systems, such as broadband imaging systems with self-contained illumination. In many imaging system applications, such as medical imaging and particularly fluorescence medical imaging, it is challenging to obtain uniform, full-field illumination of the imaging field while providing illumination of sufficient intensity to produce a sufficiently strong imaging signal. Matching the illumination profile to the imaging field is one way to conserve illumination power, while using multiple illumination ports may provide uniform illumination across the field. Existing illumination projections in imaging systems may feature anamorphic projections to match the imaging field, but often feature only a single illumination port and are not configured for close working distances. Single-port illumination systems often result in substantial shadows and poor visibility when illuminating complex shapes, such as human anatomy and other biological materials. Existing designs for open-field surgical imaging and illumination devices minimize shadow areas by using multiple illumination ports, such as a ring light surrounding the imaging optics. However, these designs waste illumination falling outside the field of view and fail to achieve uniform illumination of the field of view across a range of working distances. Summary of the Invention

[0004] According to one embodiment, an imaging device having an imaging field of view may include at least one illumination port configured to output light for illuminating a target, an imaging sensor configured to detect light propagating along an optical path to the imaging sensor, and a first movable window located upstream of the sensor with respect to the direction of propagation of light along the optical path, the first movable window configured to move into the optical path in a deployed position to modify light received from the target.

[0005] In any of these embodiments, the first movable window may be configured to rotate into the optical path when in a deployed position.

[0006] In any of these embodiments, the first movable window may be configured to be displaced into the optical path in a deployed position.

[0007] In any of these embodiments, the first movable window may extend perpendicular to the optical axis in the deployed position.

[0008] In any of these embodiments, the first movable window may be configured to pivot into the optical path in a deployed position.

[0009] In any of these embodiments, the first movable window may be configured to pivot about a first pivot axis that extends perpendicular to the optical axis.

[0010] In any of these embodiments, the first movable window may include a filter.

[0011] In any of these embodiments, the filter may be configured to filter visible light.

[0012] In any of these embodiments, a second movable window may be provided upstream of the imaging sensor with respect to the direction of propagation of light along the optical path, the second movable window being configured to move into the optical path in a deployed position to modify light received from the target.

[0013] In any of these embodiments, the second movable window may be configured to pivot about a second pivot axis that extends perpendicular to the optical axis.

[0014] In any of these embodiments, the first movable window may be configured to pivot about a first pivot axis extending perpendicular to the optical axis, and the first pivot axis and the second pivot axis may be coplanar with a plane extending perpendicular to the optical axis.

[0015] In any of these embodiments, the first movable window and the second movable window may be coupled to a linkage, and the linkage may be configured to move the first pivot window and the second pivot window simultaneously.

[0016] In any of these embodiments, when the first movable window is in the deployed position, the second movable window may be moved out of the light path in a stowed position.

[0017] In any of these embodiments, the image sensor may be displaceable relative to the first movable window.

[0018] In any of these embodiments, the first movable window may extend perpendicular to an optical axis in the deployed position, and the image sensor may be displaceable along the optical axis.

[0019] Any of these embodiments may include a first illumination port and a second illumination port, the first illumination port configured to generate a first illumination distribution at the target, the second illumination port configured to generate a second illumination distribution at the target, the second illumination port spaced apart from the first illumination port, the first and second illumination distributions provided simultaneously to the target and overlapping at the target, and the illumination from the first and second ports matched to the same aspect ratio and field coverage as the imaging field of view.

[0020] In any of these embodiments, the first and second illumination ports may be fixed relative to each other.

[0021] In any of these embodiments, the at least one illumination port may be configured to output visible light and / or excitation light.

[0022] In any of these embodiments, the image sensor may be a single sensor configured to detect light from the target resulting from illumination with visible light and excitation light.

[0023] In any of these embodiments, the image sensor may include a separate sensor configured to detect light from the target resulting from illumination with visible light separately from light resulting from illumination with the excitation light.

[0024] Any of these embodiments may comprise a wavelength dependent aperture upstream of the image sensor, the wavelength dependent aperture being configured to block visible light outside a central region.

[0025] Any of these embodiments may include one or more sensors for detecting the amount of light incident on the device.

[0026] Any of these embodiments may include a control system configured to adjust at least one image acquisition parameter based on output from the one or more sensors.

[0027] In any of these embodiments, the at least one image acquisition parameter may include an exposure duration, an excitation illumination duration, an excitation illumination power, or an imaging sensor gain.

[0028] In any of these embodiments, at least one of the one or more sensors may be configured to detect visible light and near-infrared light.

[0029] In any of these embodiments, at least one of the one or more sensors may be configured to detect near-infrared light.

[0030] Any of these embodiments may include one or more drape sensors configured to detect a drape attached to the device.

[0031] Any of these embodiments may include one or more light emitters for emitting light for detection by the one or more drape sensors.

[0032] In any of these embodiments, the one or more drape sensors may be configured to detect light emitted from the one or more light emitters after the emitted light is reflected from one or more reflective materials in the drape.

[0033] In any of these embodiments, the one or more reflectors may include prisms.

[0034] According to one embodiment, an imaging system may comprise an imaging device according to any of the above-described embodiments, an illumination source for providing illumination to the imaging device, and a processor assembly for receiving imaging data generated by the imaging device.

[0035] According to an embodiment, a method for imaging a target may include illuminating the target with an illuminator of an imaging device, receiving light from the target with an imaging sensor of the imaging device in a first imaging mode, wherein at least some of the light received at the imaging sensor in the first imaging mode includes wavelengths within a first band, switching to a second imaging mode, and while in the second imaging mode, blocking light received from the target with a first movable filter of the imaging device having wavelengths outside a second band from reaching the imaging sensor, wherein at least some of the blocked light includes wavelengths within the first band, and receiving at the imaging sensor the light received from the target with wavelengths within the second band.

[0036] In any of these embodiments, the second band may include near-infrared wavelengths.

[0037] In any of these embodiments, the first band may include visible light wavelengths.

[0038] In any of these embodiments, the method may include detecting a light level at one or more light level sensors of the imaging device while in the second imaging mode, and adjusting one or more of an image sensor signal gain, an illumination pulse duration, an image sensor exposure, and an illumination power based on an output of the one or more light level sensors.

[0039] In any of these embodiments, the method may include detecting a light level at one or more light level sensors of the imaging device while in the first imaging mode, and adjusting one or more of an image sensor signal gain, an illumination pulse duration, an image sensor exposure, and an illumination power based on an output of the one or more light level sensors.

[0040] In any of these embodiments, switching to the second imaging mode may include moving the first movable filter into an optical path along which light from the target propagates to the imaging sensor.

[0041] In any of these embodiments, switching to the second imaging mode may include moving a clear window out of the optical path.

[0042] In any of these embodiments, switching to the second imaging mode may include moving a second movable filter out of the optical path.

[0043] In any of these embodiments, the first imaging mode may be switched to the second imaging mode in response to a user request.

[0044] In any of these embodiments, the user request may include a user input to the imaging device.

[0045] In any of these embodiments, the method may include receiving, while in the second imaging mode, a request from the user to switch to the first imaging mode, and moving the movable filter out of the optical path in response to receiving the request from the user to switch to the first imaging mode.

[0046] In any of these embodiments, the method may include detecting a light level at one or more light level sensors of the imaging device while in the second imaging mode; adjusting one or more of an image sensor signal gain, an illumination pulse duration, an image sensor exposure, and an illumination power based on an output of the one or more light level sensors; and in response to receiving the request from the user to switch to the first imaging mode, ceasing to adjust one or more of an image sensor signal gain, an illumination pulse duration, an image sensor exposure, and an illumination power based on the output of the one or more light level sensors.

[0047] In any of these embodiments, the method may include detecting an object at least partially blocking an illumination beam of the illuminator, and adjusting an illumination power of the illuminator in response to detecting the object.

[0048] According to an embodiment, a kit for imaging an object may include a fluorescent imaging agent and a device of any of the above-described embodiments or a system of any of the above-described embodiments.

[0049] According to certain embodiments, the fluorescent imaging agent may comprise a fluorescent imaging agent used in any of the devices described above, any of the systems described above, any of the methods described above, or any of the kits described above.

[0050] In any of these embodiments, imaging the object may include imaging the object during blood flow imaging, tissue perfusion imaging, lymphatic imaging, or a combination thereof.

[0051] In any of these embodiments, the blood flow imaging, tissue perfusion imaging, and / or lymphatic imaging may include blood flow imaging, tissue perfusion imaging, and / or lymphatic imaging during invasive surgery, minimally invasive surgery, or non-invasive surgery.

[0052] In any of these embodiments, the invasive procedure may include heart-related or reconstructive surgery.

[0053] In any of these embodiments, the heart-related procedure may include coronary artery bypass graft (CABG) surgery.

[0054] In any of these embodiments, the CABG surgery may involve on-pump or off-pump.

[0055] In any of these embodiments, the non-invasive procedure may include wound repair surgery.

[0056] In any of these embodiments, the lymphatic imaging may include identification of lymph nodes, lymphatic drainage, lymphatic mapping, or a combination thereof.

[0057] In any of these embodiments, the lymphatic imaging may relate to the female reproductive system.

[0058] According to some embodiments, a system for imaging a target includes one or more processors, a memory, and one or more programs, wherein the one or more programs are stored in the memory and configured to be executed by the one or more processors, the one or more programs including instructions for: generating an excitation pulse to illuminate the target by activating an excitation light source during a period of time; receiving an ambient light intensity signal from a sensor during a portion of the period when the excitation light source is not activated; exposing an image sensor for a fluorescence exposure time during the excitation pulse; receiving an output from the image sensor; compensating for ambient light based on the ambient light intensity signal; and storing the resulting image in the memory.

[0059] In any of these embodiments, the one or more programs may include instructions for: activating a white light source during the period to generate white light pulses to illuminate the target, wherein the white light pulses do not overlap with the excitation pulse; and exposing the image sensor for a visible exposure time during at least one white light pulse.

[0060] In any of these embodiments, the one or more programs may include instructions for exposing the image sensor for a background exposure time when the target is not illuminated.

[0061] In any of these embodiments, the one or more programs may include instructions for detecting a periodic frequency of the ambient light intensity.

[0062] In any of these embodiments, compensating for ambient light may include setting an image acquisition frame rate equal to a multiple of the periodic frequency prior to exposing the image sensor during the background exposure time and prior to exposing the image sensor during the fluorescence exposure time during the excitation pulse, and forming the resultant image by subtracting image sensor output received during the background exposure time from image sensor output received during the fluorescence exposure time.

[0063] In any of these embodiments, compensating for ambient light may include synthesizing or extracting a complete periodic cycle of ambient light intensity having the detected periodic frequency from one or more received ambient light intensity signals; stretching the ambient light intensity periodic cycle to a duration corresponding to the fluorescent light exposure time; calculating a first accumulated ambient light value corresponding to an area under the curve of ambient light intensity during a background exposure time; calculating a second accumulated ambient light value corresponding to an area under the curve of ambient light intensity during the fluorescent light exposure time; scaling the received image sensor output during the background exposure time and the received image sensor output during the fluorescent light exposure time based on a ratio of the first accumulated ambient light value and the second accumulated ambient light value; and forming the resultant image by subtracting the scaled image sensor output during the background exposure time from the scaled image sensor output during the fluorescent light exposure time.

[0064] In any of these embodiments, the one or more programs may include instructions for receiving an ambient light intensity signal from the sensor during the background exposure time.

[0065] In any of these embodiments, the one or more programs may include instructions for extending the ambient light intensity cycle to the period corresponding to the fluorescent light exposure time.

[0066] According to one embodiment, a method for imaging a target includes, in a system having one or more processors and memory, generating an excitation pulse to illuminate the target by activating an excitation light source; receiving an ambient light intensity signal from a sensor during a portion of the time period when the excitation light source is not activated; exposing an image sensor for a fluorescence exposure time during the excitation pulse; receiving an output from the image sensor; compensating for ambient light based on the ambient light intensity signal; and storing a resulting image in the memory.

[0067] In any of these embodiments, the method may include activating a white light source during the period to generate white light pulses to illuminate the target, wherein the white light pulses do not overlap with the excitation pulses, and exposing the image sensor for a visible exposure time during at least one white light pulse.

[0068] In any of these embodiments, the method may include exposing the image sensor for a background exposure time when the target is not illuminated.

[0069] In any of these embodiments, the method may include detecting a periodic frequency of the ambient light intensity.

[0070] In any of these embodiments, compensating for ambient light may include setting an image acquisition frame rate equal to a multiple of the periodic frequency prior to exposing the image sensor during the background exposure time and prior to exposing the image sensor during the fluorescence exposure time during the excitation pulse, and forming the resultant image by subtracting image sensor output received during the background exposure time from image sensor output received during the fluorescence exposure time.

[0071] In any of these embodiments, compensating for ambient light may include synthesizing or extracting a complete periodic cycle of ambient light intensity having the detected periodic frequency from one or more received ambient light intensity signals; stretching the ambient light intensity periodic cycle to a duration corresponding to the fluorescent light exposure time; calculating a first accumulated ambient light value corresponding to an area under the curve of ambient light intensity during a background exposure time; calculating a second accumulated ambient light value corresponding to an area under the curve of ambient light intensity during the fluorescent light exposure time; scaling the received image sensor output during the background exposure time and the received image sensor output during the fluorescent light exposure time based on a ratio of the first accumulated ambient light value and the second accumulated ambient light value; and forming the resultant image by subtracting the scaled image sensor output during the background exposure time from the scaled image sensor output during the fluorescent light exposure time.

[0072] In any of these embodiments, the method may include receiving an ambient light intensity signal from the sensor during the background exposure time.

[0073] In any of these embodiments, the method may include extending the ambient light intensity period cycle to the period corresponding to the fluorescent light exposure time. [Brief explanation of the drawings]

[0074] The features will become apparent to those skilled in the art from the detailed description of the exemplary embodiments taken in conjunction with the accompanying drawings.

[0075] [Figure 1] FIG. 1 shows a schematic diagram of a system for illumination and imaging, according to an embodiment.

[0076] [Figure 2] 1 shows a schematic diagram of a lighting module according to an embodiment;

[0077] [Figure 3A] 3A and 3B show schematic side and top views, respectively, of an exemplary lens module within a steerable housing, according to an embodiment. [Figure 3B] 3A and 3B show schematic side and top views, respectively, of an exemplary lens module within a steerable housing, according to an embodiment.

[0078] [Figure 4A] FIG. 1 shows a schematic diagram of a linkage for synchronizing focusing of an imaging system and steering of an illumination system, according to an embodiment.

[0079] [Figure 4B] 4B and 4C show bottom and top views, respectively, of a linkage for synchronizing the focusing of an imaging system and the steering of an illumination system, according to an embodiment. [Figure 4C] 4B and 4C show bottom and top views, respectively, of a linkage for synchronizing the focusing of an imaging system and the steering of an illumination system, according to an embodiment.

[0080] [Figure 5A] 5A and 5B show bottom views of the linkage at far and near working distances, respectively, according to an embodiment. [Figure 5B] 5A and 5B show bottom views of the linkage at far and near working distances, respectively, according to an embodiment.

[0081] [Figure 6A] 6A and 6B show perspective top and bottom views of an illumination and imaging system, according to an embodiment. [Figure 6B] 6A and 6B show perspective top and bottom views of an illumination and imaging system, according to an embodiment.

[0082] [Figure 7] 1 shows a housing according to an embodiment.

[0083] [Figure 8A] 8A and 8B show perspective views of different exemplary positions in which the system can be utilized. [Figure 8B] 8A and 8B show perspective views of different exemplary positions in which the system can be utilized.

[0084] [Figure 9A] 1 illustrates a drape used in the system, according to an embodiment. [Figure 9B] 9B through 9E show perspective, front, top, and side views, respectively, of a draped lens and frame used in the system, according to an embodiment. [Figure 9C] 9B through 9E show perspective, front, top, and side views, respectively, of a draped lens and frame used in the system, according to an embodiment. [Figure 9D] 9B through 9E show perspective, front, top, and side views, respectively, of a draped lens and frame used in the system, according to an embodiment. [Figure 9E] 9B through 9E show perspective, front, top, and side views, respectively, of a draped lens and frame used in the system, according to an embodiment. [Figure 9F] 1 illustrates a draped lens and frame attached to a housing of a system, according to an embodiment. [Figure 9G] 9F shows a cross-sectional view of a draped lens and frame attached to the housing of the system of FIG. 9F.

[0085] [Figure 10A] 10A to 10D show illumination distributions for different illumination configurations. [Figure 10B] 10A to 10D show illumination distributions for different illumination configurations. [Figure 10C] 10A to 10D show illumination distributions for different illumination configurations. [Figure 10D] 10A to 10D show illumination distributions for different illumination configurations.

[0086] [Figure 11A] 1 shows a timing diagram for visible and excitation illumination and image sensor exposure according to an embodiment.

[0087] [Figure 11B] 1 shows a timing diagram for visible and excitation illumination and image sensor exposure according to an embodiment.

[0088] [Figure 11C] 1 shows a timing diagram for visible and excitation illumination and image sensor exposure according to an embodiment.

[0089] [Figure 11D] 1 shows a timing diagram for visible and excitation illumination and image sensor exposure according to an embodiment.

[0090] [Figure 11E] 1 shows a timing diagram for visible and excitation illumination, image sensor exposure, and ambient light measurement, according to an embodiment.

[0091] [Figure 12A] 12A to 12C show pixel layouts and interpolation schemes according to an embodiment. [Figure 12B] 12A to 12C show pixel layouts and interpolation schemes according to an embodiment. [Figure 12C] 12A to 12C show pixel layouts and interpolation schemes according to an embodiment.

[0092] [Figure 13A]13A through 13C show diagrams of an embodiment of the display method output when a target reticle is placed over an area of ​​no fluorescence intensity, an area of ​​high relative normalized fluorescence intensity, and an area of ​​moderate relative normalized fluorescence intensity, respectively. [Figure 13B] 13A through 13C show diagrams of an embodiment of the display method output when a target reticle is placed over an area of ​​no fluorescence intensity, an area of ​​high relative normalized fluorescence intensity, and an area of ​​moderate relative normalized fluorescence intensity, respectively. [Figure 13C] 13A through 13C show diagrams of an embodiment of the display method output when a target reticle is placed over an area of ​​no fluorescence intensity, an area of ​​high relative normalized fluorescence intensity, and an area of ​​moderate relative normalized fluorescence intensity, respectively.

[0093] [Figure 13D] 10 shows an illustration of an embodiment of a display method output including a signal time history plot of normalized fluorescence intensity values ​​on a display.

[0094] [Figure 14] 10 shows a recorded image of an anatomical fluorescence imaging phantom characterizing an embodiment of a display method output showing normalized fluorescence intensity.

[0095] [Figure 15] 2 illustrates an exemplary light source of an exemplary illumination source of the system for illumination shown in FIG. 1.

[0096] [Figure 16] 2 illustrates an exemplary imaging module of the fluorescence imaging system of FIG. 1, the imaging module including a camera module.

[0097] [Figure 17A] FIG. 1 illustrates a perspective top view of an illumination and imaging system, according to an embodiment.

[0098] [Figure 17B]17B shows a schematic side view of a movable filter assembly for illumination and imaging of FIG. 17A, according to an embodiment.

[0099] [Figure 17C] 17C and 17D show a housing according to an embodiment. [Figure 17D] 17C and 17D show a housing according to an embodiment.

[0100] [Figure 17E] 10 illustrates a sensor and light source configuration in a front portion of the housing, according to an embodiment.

[0101] [Figure 18] 1 shows a schematic diagram of components of an illumination and imaging system, according to an embodiment.

[0102] [Figure 19] 1 shows a schematic diagram of a drape detection module, according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0103] Exemplary embodiments are described more fully below with reference to the accompanying drawings, although the exemplary embodiments may be embodied in different forms and should not be construed as limited to those described herein. Rather, these embodiments are provided so that this disclosure will be thorough and will fully convey exemplary implementations to those skilled in the art. Various devices, systems, methods, processors, kits, and imaging agents are described herein. While at least two variations of the devices, systems, methods, processors, kits, and imaging agents are described, other variations may include combinations of aspects of the devices, systems, methods, processors, kits, and imaging agents described herein in any suitable manner, including combinations of all or some of the described aspects.

[0104] Generally, corresponding or like reference numerals will be used throughout the drawings to refer to the same or corresponding parts wherever possible.

[0105] Spatially relative terms, such as "below," "below," "lower," "above," and the like, may be used herein to facilitate the description of the relationship of one element or feature to another element or feature as depicted in the figures. It will be understood that the spatially relative terms are intended to encompass different configurations of the device in use or operation in addition to the configuration depicted in the figures. For example, if the device in the figures were turned over, elements described as "below" or "below" other elements or features would now be positioned "above" those other elements or features. Thus, the exemplary term "below" can encompass both an above and below orientation. The device may be otherwise configured (e.g., rotated 90 degrees or in other orientations), and the spatially relative descriptors used herein may be interpreted accordingly.

[0106] FIG. 1 shows a schematic diagram of an illumination and imaging system 10 according to an embodiment. As shown in FIG. 1, the system 10 may include an illumination module 11, an imaging module 13, and a video processor / illuminator (VPI) 14. The VPI 14 may include an illumination source 15 for providing illumination to the illumination module 11 and a processor assembly 16 for sending control signals and receiving data about light detected by the imaging module 13 from the target 12 illuminated by the light output by the illumination module 11. In one variation, the video processor / illuminator 14 may include a separately housed illumination source 15 and processor assembly 16. In one variation, the video processor / illuminator 14 may include the processor assembly 16, while one or more illumination sources 15 are housed separately within the housing of the illumination module 11. The illumination source 15 may output light in different wavelength ranges, such as white (RGB) light, excitation light for inducing fluorescence in the target 12, or a combination thereof, depending on the characteristics of the object under investigation and the material of the target 12. Light at different wavelength bands may be output by illumination source 15 simultaneously, sequentially, or both. Illumination and imaging system 10 may be used to facilitate medical (e.g., surgical) decision-making, for example, during surgery. Target 12 may be a target having a complex shape, such as a living body containing tissue, anatomical structures, or other objects with contours and shapes that cast shadows when illuminated. VPI 14 may record, process, and display the resulting images and related information.

[0107] FIG. 2 shows a schematic perspective view of the illumination module 11 of FIG. 1 , according to an embodiment. As shown in FIG. 2 , the illumination module 11 may include at least two illumination ports that direct illumination from an illumination source 23, which may be included in the VPI box 14, to, for example, a rectangular target field 24. In some variations, the illumination source 23 may be disposed within the device housing along with the illumination module 11. Each illumination port is for providing illumination onto the target field 24, e.g., with substantial or complete overlap of light at the target material 12 (shown in FIG. 1 ). More than two illumination ports may be used. The illumination distributions are substantially similar and overlap (e.g., substantially or completely) at the target 12, thereby providing uniform illumination of the target 12. Using at least two illumination ports can help reduce shadow effects due to anatomical shapes and aid in providing uniform illumination over the target field 24. Directing illumination from illumination module 11 to rectangular target field 24 (which, in other embodiments, may have a non-rectangular configuration) can match the illumination area to the rectangular imaging field of view (which, in other embodiments, may have a non-rectangular configuration), which can help provide uniform illumination and increase the efficiency of the illumination module by reducing wasted illumination. Matching the illumination field to the imaging field of view also provides a useful indication of the location and extent of the anatomical region currently being imaged. In some variations, illumination from illumination module 11 may be directed to provide uniform illumination of target 12 without matching the illumination area to a rectangular imaging field of view, and rectangular target field 24 of FIG. 2 may be replaced with a non-rectangular target field.

[0108] In some embodiments, light pipes can be used to achieve mixing of illumination light to produce a uniform illumination profile. Light pipe mixing can eliminate the influence of the structure of the light source on the illumination profile, which, if not eliminated, can adversely affect the uniformity of the illumination profile. For example, using light pipes to mix illumination light output from a fiber optic light guide can eliminate the image of the structure of individual optical fibers from the illumination profile. In some embodiments, rectangular light pipes can be used to match the illumination profile to a rectangular imaging field while efficiently utilizing illumination power. In some embodiments, light pipe materials with high refractive indices for both visible and near-infrared light, such as the optical glass material N-SF11, can be used to increase the efficiency of illumination power transmission.

[0109] According to one embodiment, a rectangular light pipe with an aspect ratio that matches the aspect ratio of the imaging field (e.g., both aspect ratios are 16:9) may be used in conjunction with rotationally symmetric illumination optics.

[0110] According to one embodiment, a rectangular light pipe with a different aspect ratio than the imaging field (e.g., a 16:9 imaging field aspect ratio for a square light pipe) may be used in conjunction with a cylindrical illumination optic, which allows one or both dimensions of the rectangular illumination profile to be individually tailored to match the aspect ratio of the imaging field.

[0111] Depending on the desired system requirements for working distance range and illumination uniformity, various approaches can be used to match the illumination to overlap the imaging field of view. For example, applications requiring a wide range of working distances and high illumination uniformity may require the use of dynamically steered illumination optics and / or ports to adequately match the illumination to the imaging field of view, while applications with lower requirements may use fixed illumination optics and / or ports to match the illumination to the field of view.

[0112] In some embodiments, the direction of illumination is adjusted from multiple illumination ports in synchronization with the adjustment of the field of view to steer the illumination field to maintain correspondence with the field of view.

[0113] In some embodiments, a driver may rotate one or more lighting optical elements to steer the lighting.

[0114] In one embodiment, to steer the illumination, a driver may move one or more illumination optical elements perpendicular to the imaging optical axis.

[0115] In some embodiments, one or more illumination optical elements may be configured to provide some distortion to the illumination profile to accommodate inherent distortions of the associated imaging system.

[0116] In certain embodiments, uniform illumination of the imaging field over a specified range of working distances can be achieved with a fixed position and orientation of the illumination optics. The offset distance of the illumination optics from the imaging optical axis, along with the orientation of the illumination optics, may be set to optimize the match between the illumination profile and the imaging field at some working distances within the specified range, while maintaining a substantial match between the illumination profile and the imaging field at other working distances within the specified range.

[0117] As shown in FIG. 2 , each illumination port may include a lens module 20, a connecting cable 22 that connects to an illumination source 23, and a light pipe 21 that matches the large numerical aperture of the connecting cable 22 to the smaller numerical aperture of the lens module 20. The lens module 20 may be steerable, as described in more detail below. In some scenarios, acceptable performance can be achieved without steering. In other words, it may be sufficient for the illumination module and imaging device to provide an illumination field (e.g., provide uniform illumination across the imaging field) with a rectangular form factor (or a non-rectangular configuration) that matches the field of view of an imaging system that uses at least two illumination ports, where each port generates an illumination gradient in the field of view and the sum of the illumination flux at the object plane is approximately the same at each point in the illumination field.

[0118] In some variations, where the illumination light source 23 may be included within the device housing along with the illumination module 11, the connecting cable 22 of FIG. 2 may be replaced by one or more illumination light sources 23. In some variations, the connecting cable 22 and light pipe 21 of FIG. 2 may be replaced by one or more illumination light sources 23. In some variations, the lens module 20 of FIG. 2 may include the illumination light source 23. In some variations, a separate variation of the lens module 20 from FIG. 2 may individually include the white light source and the fluorescence excitation light source of the illumination light source 23. In certain embodiments, three or more lens modules 20 may be configured with a ring of illumination ports, another functionally equivalent configuration of illumination ports, or another configuration including a continuous or non-continuous distribution / arrangement of illumination ports, with each lens module 20 oriented to converge on the imaging field of view and provide uniform illumination therethrough. In some variations, three or more lens modules 20 with a ring of illumination ports may not necessarily constrain illumination to a rectangular field, and the rectangular target field 24 of FIG. 2 may be replaced by a non-rectangular target field, such as a circular / elliptical target field.

[0119] 3A and 3B show side and top views, respectively, of lens module 20. Lens module 20 may include a lens mounted in a steerable lens housing 30. As used herein, a lens is any optical element having optical power, whether implemented by refractive or diffractive elements. For ease of illustration, other elements not essential for understanding, such as a cover surrounding the lens module (see FIG. 2), are not shown.

[0120] In the particular example shown herein, the lenses may include a pair of horizontal-axis cylindrical lenses 31-32 and a pair of vertical-axis cylindrical lenses 33-34. Also shown is a prism element 35 that can align the illumination light to an intended output optical axis. In particular, according to one embodiment, the prism element 35 may correct for angles introduced by the light pipe 21 to make the device more compact. The mounting design of each lens element 31-35 may allow for adjustment of the magnification and focus of the illumination optics. According to this embodiment, the steerable lens housing 30 houses and steers the three cylindrical lenses 31, 33, 34 and the prism lens element 35, e.g., grouped together. This lens example is for illustrative purposes only; the lenses of the lens module 20 may be modified as appropriate.

[0121] In this particular embodiment, the base portion of the steerable housing 30 is pinned about pivot point 36, for example, using pin 46 (see FIG. 6B) inserted through housing bore 37, to a fixed housing frame 90 (see FIG. 6A) and mechanical linkage 40 (see FIGS. 4A-4C), each of which will be described in more detail below, while the lens 32 is rigidly connected to the housing 90 (i.e., not to the housing 30) (see FIG. 6B).

[0122] FIG. 4A is a schematic diagram illustrating the direction of motion provided by the various components of linkage 40. Linkage 40 may include drive cam 41, illumination cams 45a, 45b (one for each illumination port), and imaging cam 43. Drive cam 41 receives input from a user (see FIG. 7) and translates the input into synchronous movement of lens modules 20a, 20b mounted on corresponding illumination cams 45a, 45b via corresponding housings 30 (see FIG. 3B) and pins 46 (see FIG. 6B), and into synchronous movement of imaging lens 51 and imaging sensor 52 (see FIGS. 5A and 5B) mounted on imaging cam 43 via cam follower pins. Here, imaging lens 51 is depicted as a single field lens, although additional and / or alternative lenses may be used to focus light from target 20 onto imaging sensor 52. Each port has its own associated illumination cam 45A or 45B, depicted here as being to the left or right of an input window for receiving light from target 12. Although drive cam 41 is shown here as a plate with a leading edge that extends beyond the rear of lens modules 20a, 20b, drive cam 41 need not be in the form of a plate, but instead may have multiple surfaces for interfacing with and driving more than two lens modules, in which case the leading edge of drive cam 41 and the trailing edges of illumination cams 45a, 45b may be set further back to accommodate the additional lens modules and corresponding illumination cams.

[0123] In particular, movement of drive cam 41 moves imaging cam 43 along the x-axis, which in turn causes imaging cam 43 to move imaging lens 51 and imaging sensor 52 along the z-axis and to move illumination cams 45 a, 45 b, which in turn simultaneously steers corresponding lens modules 20 a, 20 b about corresponding pivot points 36, such that the steering of lens modules 20 a, 20 b is performed synchronously with the positioning of imaging lens 51 and imaging sensor 52 to ensure proper focusing of light from the target onto sensor 52. Alternatively, imaging cam 43 may move only imaging lens 51 along the z-axis, or may move any other combination of imaging optical elements to ensure proper focusing of light from the target onto sensor 52.

[0124] FIG. 4B shows a bottom view of linkage 40, and FIG. 4C shows a top view of linkage 40, according to an embodiment. Drive cam 41 may include two drive parts 41a and 41b, and, if steering is included, a third drive part 41c, all depicted here as rigidly attached to form rigid drive cam 41. Similarly, imaging cam 43 may include two imaging parts 43a and 43b. Drive cam 41 receives input from a user (via control surface 62) through first drive part 41a, which moves imaging cam 43 via a cam follower pin in drive part 41b. In turn, imaging cam part 43a moves sensor 52, and imaging cam part 43b moves imaging lens 51. If the linkage includes steering, the third drive part 41c moves the illumination cam parts 45a and 45b to simultaneously steer (rotate) the lens modules 20a, 20b using pins 46 (see FIG. 6B) associated with each of the illumination cam parts 45a and 45b. The pins 46 may be inserted through respective slots 49 in the illumination cams 45a, 45b and corresponding housing holes 37 in the lens modules 20a, 20b. The drive part 41c steers the lens modules 20a, 20b simultaneously so that they both still illuminate the same field of view as each other in the target field of view of the target 12.

[0125] 5A and 5B show bottom views of the linkage combined with lens modules 20a, 20b, imaging field lens 51, and sensor 52 at far and near working distances, respectively, according to an embodiment. As shown in those figures, linkage 40 synchronizes the steering of the illumination source with the focusing of the imaging system at two sample working distance illumination steering settings. Figures 5A-5B show the positions of lens modules 20a, 20b (rotating about pivot pin 37) and lens 51 and sensor 52 (moving along optical axis 55 and along the z-axis of the imaging system) at two focus positions resulting from user input.

[0126] 5A and 5B, to minimize or reduce friction during movement, each member that moves axially within linkage mechanism 40 may be guided by two fixed rolling elements 47 and one spring-biased rolling element 48. Linkage 40 may also include a drive cam input connection point 42.

[0127] 6A and 6B show perspective top and bottom top views of device 10, according to an embodiment. In FIGS. 6A and 6B, illumination module 11 and imaging module 13 are mounted in housing 90, the top of which has been removed for clarity. Also shown is focus drive mechanism 70, which translates movement from user input via drive cam input connection point 42 into movement of drive cam 41.

[0128] 6A, an optical axis 55 of imaging module 13 passes through the center of the imaging module, and lens modules 20a, 20b are disposed symmetrically about imaging optical axis 55. Light to be imaged from target 12 travels along optical axis 55 and is incident on lens 51 and sensor 52. Wavelength-dependent aperture 53 may be provided upstream of lens 51 and may include a smaller central aperture that allows the transmission of all visible light and fluorescent light, e.g., near-infrared (NIR) light, and a larger annular aperture that blocks visible light but allows the transmission of fluorescent light.

[0129] 6B and 4A-4B, pin 46 connects lens module 20 to slot 49 in linkage 40 through housing hole 37 in housing 30. Pivot point pin 44 also connects lens module 20 to chassis 90.

[0130] FIG. 7 illustrates an embodiment of an ergonomic housing 60 that encloses the illumination module 11 and imaging module 13. The ergonomic housing 60 is designed to be held in different usage modes / configurations, such as a pistol-style grip ( FIG. 8A ) for forward imaging in the scanning imaging position, and a vertical grip ( FIG. 8B ) for downward imaging in the top-down imaging position. As shown in FIG. 7 , the housing 60 includes a control surface 62, a grip detail 64, a window frame 68, and a nosepiece 66. The ergonomic housing 60 is connectable to the VPI box 14 via a light guide cable 67 and a data cable 65, through which light is provided to the illumination ports 20 a, 20 b. The data cable 65 carries power, sensor data, and any other (non-optical) connections.

[0131] Control surface 62 includes focus buttons 63a (decrease working distance) and 63b (increase working distance) for controlling linkage 40. Other buttons on control surface 62 may be programmable and may be used for various other functions, such as excitation laser power on / off, display mode selection, white balance for white light imaging, saving screenshots, etc. Alternatively or in addition to the focus buttons, a proximity sensor may be provided on the housing and used to automatically adjust linkage 40.

[0132] As seen in FIG. 8A , when the housing 60 is held with the imaging window facing forward, the thumb rests on the control surface 62, and the fingers of the operator's hand are loosely wrapped around the bottom of the grip detail 64. As seen in FIG. 8B , when the housing 60 is held with the imaging window facing downward, the grip detail 64 is located between the thumb and index finger, and the fingers are wrapped around to access the control buttons and switches on the control surface 62. The grip detail 64 is shaped to provide partial support for the weight of the device on the wrist in a vertical grip. In this case, the housing 60 hangs loosely, eliminating the need to tightly grip the housing 60. Thus, the housing 60 can be operated with one hand in multiple positions. In various other embodiments, the housing 60 may be supported on a support (e.g., a movable support).

[0133] The window frame 68 (see also FIG. 9A) defines different windows of the housing 60. In other words, the window frame 68 defines windows 68a, 68b corresponding to the two lens modules 20a, 20b, and also defines a window 68c that serves as an input window for light from the target that should be incident on the sensor 52.

[0134] 17A-D illustrate an imaging system 300, according to one embodiment. The imaging system 300 may include one or more components of the imaging system 10 of FIG. 1. For example, the imaging system 300 may include the illumination module 11 and the imaging module 13 of the system 10. The system 300 may be used for or in conjunction with any of the methods and processes described herein with respect to the system 10.

[0135] 17A , a perspective top view, imaging system 300 includes two illumination ports 311, an imaging module 313, and a plate 302, each mounted on a frame or chassis (not shown). Light to be imaged from target 12, which may include light from illumination port 311 reflected by target 12 and / or fluorescent light emitted from target 12, travels along optical axis 355 through plate 302 and into imaging module 313, which houses one or more imaging sensors. As described below, imaging module 313 may include movable filters for filtering light entering the imaging module. In some embodiments, imaging module 313 may include one or more wavelength-dependent apertures, including a smaller central aperture that allows transmission of all visible light and fluorescent light, e.g., NIR light, and larger peripheral apertures that block visible light but allow transmission of fluorescent light.

[0136] Each illumination port 311 includes a lens module 320, a connecting cable 322 that connects to the illumination source 23, and a light pipe 321 that matches the large numerical aperture of the connecting cable 322 to the smaller numerical aperture of the lens module 320. The lens module 320 can provide illumination with a rectangular form factor that matches the field of view of the imaging system 300. Each illumination port 311 can generate an illumination gradient so that the total illumination flux in the object plane is reasonably similar at each point in the illumination field, e.g., to provide uniform illumination across the imaging field of view. Each lens module 320 includes one or more lens and / or prism elements to shape and direct the illumination to meet the requirements of the application. For example, two illumination ports 311 are positioned horizontally offset from the center of the optical axis 355 of the imaging system 300, so that a prism can be included in the lens module 320 to direct the beam to the center of the field of view. The degree of directionality can be tailored to a particular application or set of particular applications. For example, in some variations, the degree of orientation is selected so that the beams overlap at a nominal imaging distance of 25 cm. In some variations, the horizontal offset and degree of orientation of the illumination ports 311 are selected so that the beams substantially overlap and substantially cover the field of view over a range of working distances, such as distances of 18-40 cm. In the embodiment shown in FIG. 17A, the illumination ports are fixed relative to the frame. In other embodiments, the illumination ports are steerable according to the principles described above.

[0137] The imaging module 313 includes an image sensor assembly 352 aligned along an optical axis 355, an optical module 351, and a movable filter assembly 330. The image sensor assembly 352, which includes an image sensor and may include one or more lenses, filters, or other optical components, is movable relative to the frame along the optical axis 355 via a focus drive assembly 370. The focus drive assembly 370 includes a lead nut 372 secured to a housing of the image sensor assembly 352. The lead nut 372 is coupled to a lead screw 374 extending from a focus motor 376. The focus motor 376 is secured to the frame and can be actuated back and forth to rotate the lead screw 374, which translates the lead nut 372 along the lead screw axis and moves the image sensor assembly 352 back and forth along the optical axis 355. The lead nut 372 and / or the focus drive assembly 370 may be mounted on a shaft that slides within a mounting on the frame to limit lateral and angular play, for example, using one or more linear ball bearings or bushings. In some embodiments, image sensor assembly 352 may include a single image sensor configured to detect light from the target resulting from illumination with visible light and excitation light. In other embodiments, image sensor assembly 352 may include multiple image sensors. For example, image sensor assembly 352 may include another image sensor configured to detect light from the target resulting from illumination with visible light that is separate from illumination with visible light and excitation light.

[0138] The controller may be used to control the movement of the image sensor assembly 352 for focusing, which may be based on user input. For example, the system 300 may include one or more controls, such as buttons or a touchscreen control, to allow a user to adjust the focus. The user may activate the focus control until the desired focus is achieved, or may input a value related to the desired focus, and the controller may activate the image sensor assembly 352 until the desired focus is achieved. In some embodiments, a magnetic position sensor mounted on the housing of the image sensor assembly 352 detects the position of the image sensor assembly 352 for closed-loop control of the focus drive assembly 370 by the controller. In some embodiments, the controller may use open-loop control of the focus drive assembly 370, for example, by using a stepper motor.

[0139] An optical module 351, located in front of the image sensor assembly 352, is fixed relative to the frame and may include one or more optical components (e.g., lenses, apertures, filters, etc.) to condition light traveling along the optical path before reaching the image sensor. For example, the optical module 351 may include a wavelength-dependent aperture (e.g., similar to aperture 53 in FIG. 6A) that includes a smaller central aperture that allows transmission of all visible light and fluorescent light, e.g., NIR light, and a larger surrounding aperture that blocks visible light but allows transmission of fluorescent light.

[0140] The movable filter assembly 330 is positioned in front of the optical module 351 (upstream relative to the direction of light travel from the target to the image sensor) and includes a first window 334a and a second window 334b, each of which is housed in a bracket (first window bracket 332a and second window bracket 332b, respectively). The first and second windows 334a, 334b ​​can be moved alternately in and out of the optical path. In some embodiments, the first and second windows 334a, 334b ​​can be moved alternately in and out of the optical path via a linkage assembly 336 actuated by a filter motor 338. In some variations, the first and / or second windows can be moved via any combination of motion, including rotation (e.g., on a rotating wheel) and / or translation. One or both of the windows 334a, 334b ​​can include a filter to filter light before it reaches the image sensor. By moving the filter in and out of the optical path, the imaging system 300 can operate in different imaging modes. For example, in some embodiments, one of the windows (e.g., first window 334a) includes a filter to block visible light, while the other window (e.g., second window 334b) includes a clear glass plate that does not block light. By including a blocking filter in the optical path, the imaging system can be operated in a first mode, and by including clear glass in the optical path, the imaging system can be operated in a second mode. When switching modes, one window moves into the optical path and the other window moves out of the optical path. In some embodiments, a visible-light rejection filter that transmits only NIR light between 830 and 900 nm is included in the first window for the fluorescence-only imaging mode, and an anti-reflection coated glass plate that passes all light is included in the second window for use in the second mode. The glass plates ensure the same optical path length regardless of the mode.In some variations, the controller of the system 300 may control the movable filter assembly 330 to change modes in response to, for example, user input.

[0141] 17A, the second window bracket 332b is in a deployed position such that the second window 334b ​​is positioned in the optical path and oriented perpendicular to the optical axis 355. By actuating the filter motor 338, which actuates the linkage assembly 336, the second window bracket 332b and the second window 334b ​​are moved out of the optical path by pivoting about a pivot axis that extends perpendicular to the optical axis 355. Simultaneously, the first window bracket 332a and the first window 334a are moved into the optical path by pivoting about a pivot axis that extends perpendicular to the optical axis 355. In some embodiments, the pivot axis of the first window bracket and the pivot axis of the second window bracket are aligned perpendicularly, and the first and second window brackets and windows are symmetrical to provide matching optical path lengths regardless of mode.

[0142] Linkage assembly 336 is actuated by a filter motor 338, which may be controlled by the system 300's controller. Filter motor 338 rotates filter lead screw 341, moving filter lead nut 342 back and forth. Linkage 344 is pivotally connected at a first end to filter lead nut 342 and at a second end to slider 346a. Pivot link 348a is pivotally connected at one end to slider 346a and at the other end to first window bracket 332a. As shown in FIG. 17B, slider 346b and pivot link 348b (not shown in FIG. 17A) are provided below slider 346a and pivot link 348a to actuate second window bracket 332b.

[0143] The movable filter assembly 330 is shown schematically in FIG. 17B. A filter motor 338, fixed relative to the frame, rotates a filter lead screw 341 clockwise and counterclockwise, causing a filter lead nut 342 to translate forward and backward along the filter lead screw axis. Translation of the filter lead nut 342 causes translation of a slider 346a via a linkage 344. Translation of the slider 346a causes translation of a pivot link 348a. The pivot link 348a is pivotally connected to the first window bracket 332a at a location offset from the center of the first window bracket's pivot connection 349a with the frame. Thus, movement of the pivot link 348a causes rotation of the first window bracket 332a. For example, from the configuration of FIG. 17B, forward translation of the slider 346a (toward the plate 302) rotates the first window bracket 332a 90 degrees out of the optical path.

[0144] Drive linkage 345 is pivotally connected at a first end to linkage 344, pinned to the frame at connection point 345a, and pivotally connected at a second end to slider 346b. Thus, translation of linkage 344 causes rotation of drive linkage 345, which translates slider 346b. Slider 346b is connected to second window bracket 332b via pivot link 348b, which is pivotally connected to second window bracket 332b at a location offset from the center of pivot connection 349b of second window bracket 332b with the frame. Thus, translation of slider 346b causes rotation of second window bracket 332b. From the configuration of FIG. 17B, rearward translation of slider 346b (when slider 346a moves forward) rotates second window bracket 332b 90 degrees into the optical path. One or more sensors may be included to sense the position of one or more of the components of the movable filter assembly 330 to provide feedback to the controller for closed-loop control.

[0145] Plate 302 is a flat plate that seals the housing and protects the illumination and imaging optics. In some embodiments, plate 302 is a single plate of glass. One or more optical components, such as a lens, can be mounted between the glass plate and movable filter assembly 330. In some variations, one or more sensors are positioned behind plate 302 to measure light incident on plate 302. One or more of these sensors can detect ambient light, light reflected from targets, light emitted by targets, and / or light reflected from non-target objects. In some embodiments, a drape detector is included to detect the presence of a drape. The drape detector can include, for example, an infrared emitter and a photodetector that detects infrared light reflected by a drape placed over the imaging system.

[0146] 17C-D show one embodiment of an ergonomic housing 360 enclosing the illumination port 311 and imaging module 313 according to one variation. The ergonomic housing 360 is designed to be held in a pistol grip. The housing 360 may include a control surface 362, a grip 364, a window frame 368, and a nosepiece 366. The ergonomic housing 360 is connectable to the VPI box 14 via a light guide cable 367 and a data cable 365, with light being provided to the illumination port 311 through the light guide cable 367. The data cable 365 carries power, sensor data, and any other (non-optical) connections.

[0147] Control surface 362 includes focus buttons 363a and 363b that control focus drive assembly 370. Other buttons on control surface 362 may be programmable and may be used for various other functions, such as excitation laser power on / off, display mode selection, white balance for white light imaging, saving screenshots, etc. Alternatively or in addition to the focus buttons, a proximity sensor may be provided on the housing and used to automatically adjust focus drive assembly 370.

[0148] Housing 360 can be operated with one hand in a pistol-grip style orientation. In various other embodiments, housing 360 can be supported on a support (e.g., a movable support). In some embodiments, housing 360 can be used in conjunction with a drape, such as drape 80 of FIG. 9A or drape 390 of FIG. 9B.

[0149] In some embodiments, window frame 368 is provided in the front portion of housing 360 in front of plate 302. In other embodiments, window frame 368 is provided in the front portion of housing 360 behind plate 302, with plate 302 providing the exterior surface of the housing. In other embodiments, no frame is provided, and plate 302 provides the exterior surface of the housing. Window frame 368 includes windows 368a, 368b corresponding to the two lens modules 320, and may also include window 368c, which functions as an input window for light from the target that is to enter the image sensor. Window frame 368 may also include one or more windows 369 for sensors provided behind plate 302.

[0150] FIG. 17E illustrates a modified embodiment of a sensor configuration behind plate 302 on the front portion of housing 360. In this embodiment, a central sensor group 391 including one or more sensors 392 is provided to detect reflected illumination light for input to an automatic gain control function, as described below. Also in this embodiment, peripheral sensor groups 393a and 393b, each including one or more sensors 394, are provided to detect reflected illumination light for proximity detection to an imaging target or to detect any objects near the front portion of housing 360, as described below. The source of illumination light for proximity detection may be the main illumination beam or one or more dedicated emitters for proximity detection. Also in this embodiment, one or more sensors 387 and one or more light sources 386 are provided to detect the presence of an installed drape lens, as described below. Also in this embodiment, one or more sensors 395 may be provided to detect ambient room light intensity to facilitate correction of image intensity artifacts resulting from pulsed room light components, as described herein.

[0151] Sensor 392 can be used to detect reflected light levels to provide input for an automatic gain control (AGC) function (see FIG. 18 ), which can be used to facilitate optimization of illumination and imaging parameters and provide consistent and / or smoothly varying image brightness, even with varying working distances. AGC may also be used to minimize illumination intensity to facilitate optimizing or maximizing image signal-to-noise ratio or to minimize photobleaching. For example, AGC may be used to dynamically adjust image signal gain, illumination pulse duration, exposure, and / or illumination power. The reflected illumination light detected by sensor 392 can include visible light and / or fluorescent excitation light, such as NIR light. In certain embodiments, sensor 392 is sensitive to NIR light but not visible light, such that ambient visible light and white light illumination do not contribute to the light level signal from sensor 392. In some variations, sensor 392 is comprised of a photodiode.

[0152] The reflected light level sensor 392 may be used as an input to the AGC in any imaging mode, including white-light imaging mode and / or multiplexed white-light and fluorescence imaging mode, and may be particularly important in fluorescence-only imaging mode. For example, when operating in fluorescence-only imaging mode, where filter 334a blocks visible light from reaching the image sensor, the reflected white-light luminance image is not recorded, which would otherwise be used as an input to the AGC, while the recorded fluorescence image necessarily excludes reflected fluorescence excitation light (which would otherwise greatly exceed the power of the fluorescence signal) due to the use of a notch filter in the imaging optics. Thus, sensor 392 can provide the only measurement of reflected light. In one variation, operation of the AGC in fluorescence-only imaging mode prioritizes maximizing exposure duration and minimizing gain.

[0153] In some embodiments in which sensor 392 is sensitive to excitation light, to achieve constant image brightness for a given fluorescent sample regardless of working distance, the gain, excitation period (which may be the same as the image sensor exposure time, for example), and instantaneous excitation power can be adjusted as follows: Based on the reflected excitation light E measured by sensor 392, the AGC can adjust the excitation period T, instantaneous excitation power P, and image sensor gain G such that E*T*G=K, where K is a constant based on the desired target brightness. The priority for adjusting T, G, and P can be optimized to minimize noise while limiting the maximum exposure of the tissue to the excitation light.

[0154] In one embodiment, the sensors 392 are arranged so that their detection cones substantially cover the imaging field of view, as shown in Figure 17E. For example, in this embodiment, the sensor group 391 consists of four sensors 392 arranged in a rectangular pattern surrounding the imaging port.

[0155] According to one embodiment, the AGC operates by starting with settings for initial gain g, initial exposure e, and initial illumination power p. User-defined brightness parameters can specify target values, such as a target peak brightness P and a target average brightness M, along with a selection of AGC modes based on peak values, average values, or a balanced combination of both peak and average values.

[0156] During each image acquisition frame, a peak sensor brightness Ps may be calculated based on the peak signal from within sensor 392 during the acquisition period, and an average sensor brightness Ms may be calculated based on the average of the signal from sensor 392 during the period. An adjustment factor F is then calculated based on these values ​​to obtain a target exposure value e t and the target gain value g tFor example, in peak mode F=Pt / Ps, in average mode F=Mt / Ms, and in balance mode F=(1 / 2)(Pt / Ps+Mt / Ms). In one variation, the balance mode may be a weighted combination of sensor signal values, such as a weighted average of Ps and Ms, such as F=(k1*Ps+k2*Ms), where k1 and k2 are constants. In one variation, the constants k1 and k2 may satisfy the constraints k1+k2=1 and 0≦k1≦1. The target exposure is e t =Fe0, and the target gain is g t =Fg0.

[0157] According to one embodiment, the AGC calculates the current exposure e0 and the target exposure e t Adjust the exposure duration (and the corresponding excitation illumination duration) by a step equal to half the value between . The resulting new exposure e l =e0+(e t -e0) / 2. In this way, the exposure is increased to the maximum exposure e max and the minimum exposure e min nor can it be reduced below

[0158] According to one embodiment, the current exposure e0 is equal to the maximum exposure e max and the adjustment factor F is greater than 1, the AGC adjusts the gain to a new gain g l =g0+(g t -g0) / 4. If the current gain is greater than 1 and F is less than 1, the gain is instead adjusted to the new gain g l =g0-(g o -g o (e max / e0)) / 4. Otherwise, the new gain is instead g l = g0.

[0159] According to one embodiment, the excitation power may be adjusted as the lowest adjustment priority.

[0160] Following each AGC cycle, the new values ​​of exposure, gain, and power are treated as the current values ​​for the next AGC cycle.

[0161] The sensor 394 may be used to detect reflected illumination light that falls within the periphery of the illumination beam and reflects off objects located near the front of the housing 360. For example, detection of such nearby objects may be used to trigger a switch to a reduced illumination power setting to reduce possible safety risks due to excessive illumination power being delivered to nearby objects. The reflected illumination light detected by the sensor 394 may include visible light and / or fluorescent excitation light, such as NIR light. In one embodiment, the sensor 394 is sensitive to NIR light but not visible light, such that ambient visible light and white light illumination do not contribute to the detection signal from the sensor 394. In some variations, the sensor 394 comprises a photodiode or a time-of-flight sensor. In some variations, the sensor 394 is positioned to detect objects that fall within the illumination beam but are not within the imaging field of view.

[0162] In some embodiments, a method for imaging a target includes illuminating the target with an illuminator of the imaging system, such as illumination port 311 of imaging system 300, and receiving light from the target with an imaging sensor of the imaging system in a non-restrictive imaging mode. In some embodiments, the light received from the target includes light reflected by the target and light emitted by the target. In some embodiments, the reflected light includes visible light, and the emitted light includes fluorescence from the target. The imaging mode is switched from the non-restrictive imaging mode to a restrictive imaging mode, in which light of wavelengths outside of one or more desired wavelength bands is blocked from reaching the imaging sensor. The light is blocked using a movable filter of the imaging device. Light that passes through the filter is received by the imaging sensor. The imaging mode is switched back to the non-restrictive imaging mode, in which the filter is moved out of the light path so that it no longer blocks light in the light path.

[0163] For example, the system 300 can operate in an unrestricted imaging mode in which the first window 334a is in a deployed position within the optical path. The first window 334a may include a transparent plate that allows all light to pass through it. In this unrestricted imaging mode, the image sensor can receive all or most of the light reaching the first window 334a. Following the principles described above, the system 300 can switch to a restricted imaging mode in which the first window 334a is in a retracted position outside the optical path and the second window 334b ​​is in a deployed position within the optical path. The second window 334b ​​can include a filter that rejects light that is not in a desired wavelength band or set of wavelength bands. For example, the filter can reject all visible light but allow infrared light (e.g., NIR light) to pass. Thus, during the restricted imaging mode, the imaging sensor provides imaging data for only the light that passes through the filter.

[0164] System 300 may be switched to the restricted imaging mode in response to a request, which may be received from a user (e.g., via actuation of one or more buttons on control surface 362) or from an external control system. While the above description refers to restricted and non-restrictive modes, the same principles can be used to switch between the two restricted modes (i.e., some light is blocked in both modes). For example, the system may be switched between the two restricted imaging modes by including a first filter configured to block a first wavelength band or set of wavelength bands and a second filter configured to block a wavelength band or set of wavelength bands different from the first filter.

[0165] In some embodiments, the automatic gain control process described above may be started upon switching to the constrained imaging mode and stopped upon switching to the unconstrained imaging mode (e.g., AGC may be started and stopped automatically by a controller of system 300). In other embodiments, AGC is performed during both the constrained and unconstrained imaging modes.

[0166] As shown in FIG. 9A , the housing 60 of FIG. 7 may be used in conjunction with a drape 80. The drape 80 may be a surgical drape suitable for use during surgery. The drape includes a drape material 81, a drape lens 82, a drape window frame 83 surrounding the drape lens, and an interlocking interface 84 integrated with the drape window frame 83. The drape material 81 is intended to encase the device within the housing 60 and also cover any other items as needed. The drape window frame 83 conforms to the shape of the housing nosepiece 66, such that the drape window frame 83 may be inserted into the housing nosepiece 66 without interfering with the windows 68a-68c. The drape 80 is designed to minimize reflections and image ghosting by ensuring that the drape lens 82 is flush with the imaging and illumination window frame 68, e.g., within 0.5 mm. The drape 80 may employ the interlocking interface 84. It may engage an edge on the inner surface of the housing nosepiece 66 to lock flush therewith. In one variation, the interlock interface 84 may fit into a recess on the inner surface of the housing nosepiece 66.

[0167] One or more interlocking interfaces 84 on the interior or exterior surface of housing nosepiece 66 may be used to ensure a tight fit of draped lens 82 against window frame 68. In the particular embodiment shown, two interfaces 84 are used, one on the top and one on the bottom of draped window frame 83, each engaging the interior surface of housing nosepiece 66.

[0168] According to some variations, feedback may be provided to the user to indicate when the draped lens is properly installed on the housing nosepiece. In one variation, a raised ridge around at least a portion of the draped window frame can provide tactile and / or auditory feedback when pressed onto one or more detent features on the inner surface of the housing nosepiece. In another variation, a raised ridge around at least a portion of the draped window frame can provide tactile and / or auditory feedback when pressed onto one or more detent features on the outer surface of the housing nosepiece. In another variation, one or more interlocking interfaces can provide tactile and / or auditory feedback when pressed into place to engage with the inner surface of the housing nosepiece. In another variation, one or more interlocking interfaces can provide tactile and / or auditory feedback when pressed into place to engage with the outer surface of the housing nosepiece. Additionally or alternatively, the drape detection module may provide feedback to indicate when the draped lens is properly installed, as described below.

[0169] According to one embodiment, the drape may be symmetrical so that it can be rotated 180 degrees about its central axis (e.g., an axis aligned with the imaging optical axis) and still be properly attached to the housing nosepiece both before and after such rotation.

[0170] The drape lens material can include, for example, a transparent polymer material such as polymethyl methacrylate (PMMA), polycarbonate, polyvinyl chloride, or glycol-modified polyethylene terephthalate. In some embodiments, the drape lens material can be selected in part based on having a relatively low refractive index and high optical transmittance in the visible and NIR bands compared to other candidate materials to minimize artifacts caused by reflections at the drape lens and maximize illumination and imaging transmission. For example, a drape lens material such as PMMA can have a refractive index of less than about 1.5 and an optical transmittance of greater than about 92% in the visible and NIR bands. The drape lens and / or drape window frame can be manufactured by injection molding.

[0171] In some variations, the draped lenses may be coated with an anti-reflective coating to reduce imaging and lighting artifacts from reflections on the window.

[0172] 9B-G show an embodiment of a drape 390 comprising a drape lens 380 and a drape window frame 381 used in combination with a drape material (not shown), such as drape material 81 (see FIG. 9A), to cover the housing 360 of FIGS. 17C-D. The drape 390 may be a surgical drape suitable for use during surgery. The drape includes the drape material (not shown), the drape lens 380, a drape window frame 381 surrounding the drape lens, an interlocking interface 384 integrated with the drape window frame 381, and a reflective feature 388. The drape material is intended to encase the device within the housing 360 and also to cover anything else as needed. The drape window frame 381 may conform to the shape of the front portion of the housing 360 so that the drape window frame 381 can be inserted into the front portion of the housing 360. Drape 390 is designed to minimize reflections and image ghosting by ensuring that draped lens 380 is flush with the front surface of housing 360, such as plate 302 in Figures 17A-B, within, for example, 0.5 mm. Drape 390 may use an interlocking interface 384, which may be locked flush with housing 360 by engaging with edge 383 on the inner surface of the front portion thereof.

[0173] In one embodiment, a drape detection module can be provided to detect the attachment of a drape lens onto the housing nosepiece. For example, the drape detection module may use any combination of one or more ultrasonic sensors, inductive sensors, capacitive sensors, optical sensors, light emitters, radio frequency identification chips and antennas, Hall effect sensors, proximity sensors, or electrical contacts to detect the attachment of a drape lens to the housing. In one embodiment, a drape detection light source 386 (see FIG. 17E), such as an LED, can be used to transmit light that is detected by a corresponding sensor 387, such as a photodiode, only when reflected from the installed drape lens. For example, according to one embodiment, the light source 386 can have a narrow emission wavelength band centered around 905 nm, and the sensor 387 can have a narrow wavelength detection band that includes wavelengths around 905 nm. In one embodiment, the light source 386 and sensor 387 are positioned near the front portion of the housing 360 behind the plate 302. In one embodiment, as shown in FIG. 9C , reflective feature 388 is positioned on drape lens 380 in a position aligned with light source 386 and sensor 387, such that light from light source 386 is reflected from one or more interfaces of reflective feature 388 onto sensor 387. For example, according to one embodiment of drape detection module 385 as shown in FIG. 19 , reflective feature 388 can include a triangular prism protruding from the surface of drape lens 380, which can reflect detection light 389 from light source 386 onto sensor 387. For example, reflective feature 388 can reflect detection light 389 using total internal reflection. In one variation, the output from sensor 387 can be provided to a transimpedance amplifier to amplify the drape detection signal. In one variation, light source 386 and sensor 387 can be positioned on the housing nosepiece. In one variation, the intensity of the reflected light signal detected by sensor 387 can be used as feedback to evaluate and adjust the mounting position of drape lens 380 to minimize artifacts caused by misalignment of the drape lens.In some variations, detection of placement of drape lens 380, as indicated by drape detection module 385, can trigger automatic adjustment of lighting and / or imaging parameters, or automatic changes to image processing performed by the processor assembly. For example, the imaging and lighting systems may be calibrated and / or configured to correct for distortion, attenuation, or other effects on lighting and / or imaging caused by placement of drape lens 380.

[0174] According to one embodiment, the process for installing a drape on a housing includes unpacking the drape, installing the drape lens on the housing nosepiece by pushing the drape lens into place until an audible and / or tactile click is heard by the user (indicating that the interlocking interface has engaged with a corresponding ridge in the housing nosepiece), unwinding the drape bag onto the camera, and securing the drape bag along the housing cables at the front and rear of the housing, as needed. To remove the drape from the housing, clips on the drape interlocking interface may be pressed inward to disengage from the ridges and then pulled away from the housing. According to the above process, both installation and removal of the drape lens may be performed with one hand in contact with the drape lens.

[0175] 10A through 10C show typical illumination distributions (fills) relative to a rectangular imaging field (outline) for an illumination ring ( FIG. 10A ), a pair of fixed anamorphic projection illumination sources ( FIG. 10B ), a pair of steered anamorphic projection illumination sources according to an embodiment ( FIG. 10C ), and a steered illumination ring ( FIG. 10D ), shown at working distances of 10 cm (left column), 15 cm (center column), and 20 cm (right column), respectively. FIG. 10A illustrates the use of a ring of illumination ports to minimize shadowing, but does not match the illumination to the imaging field and does not provide uniform illumination at all working distances (e.g., the distribution varies with distance). FIG. 10D illustrates the use of a steering ring of three or more illumination ports to facilitate minimizing shadowing and provide uniform illumination when changing working distances, but does not constrain the illumination to the imaging field, according to one embodiment. FIG. 10B shows an anamorphic projection from two fixed illumination sources (e.g., using an illumination lens configuration featuring a cylindrical lens and a textured diffuser) that is therefore well calibrated for uniform illumination that matches the imaging field of view at a fixed working distance, e.g., 15 cm, but does not have the same uniformity or match at other distances, whether larger or smaller. As noted above, such illumination is often acceptable on its own. FIG. 10C illustrates the ability of an embodiment to maintain good uniform illumination and to better confine illumination to the field of view by steering the illumination as the working distance (and imaging focal point) is changed.

[0176] As mentioned above, the illumination used may include both white light and fluorescent excitation illumination, for example from a laser, to excite NIR light from the target, however, ambient light may interfere with the light from the target.

[0177] 11A shows a timing diagram of white light (RGB) and fluorescence excitation (laser) illumination, and visible (VIS) and NIR fluorescence (FL) imaging sensor exposure configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor. As used herein, a white pulse indicates white light (RGB) illuminating a target, and an excitation pulse indicates laser illuminating a target.

[0178] The exposures of the even (Exp1) and odd (Exp2) sensor pixel rows are shown interleaved with different exposure times, which facilitates the separation of the evaluation of the ambient room light signal components. Such interleaved exposure readout modes are offered in some imaging sensors, such as the "High Dynamic Range Interleaved Read-out" mode offered in the CMOSIS CMV2000 sensor.

[0179] Pulsing white light illumination at 80 Hz results in a flashing light frequency that exceeds the frequency perceptible to the human eye or that can trigger epileptic seizures. The visible light image exposure may be, for example, twice as long as the RGB illumination, ensuring overlap between the 60 Hz exposure frame rate and the 80 Hz RGB illumination pulses. The excess ambient light captured during the visible exposure may be ignored, since the intensity of the RGB illumination pulses and the signal from the target 12 is much stronger.

[0180] By setting the NIR fluorescence image exposure times Exp1 and Exp2 to acquire 1 / 2 and 1 / 4 frame periods, respectively, and activating the excitation laser only during the last 1 / 4 frame of every other frame, the even rows (Exp1) record 1 / 4 frame of NIR fluorescence plus 1 / 2 frame of ambient room light, while the odd rows (Exp2) record 1 / 4 frame of NIR fluorescence and 1 / 4 frame of ambient room light. Making these fractional exposures within each visible or NIR fluorescence frame minimizes motion artifacts that would otherwise be introduced into the frame sequence for ambient room light subtraction.

[0181] In such an acquisition design, an estimate of the ambient room light contribution to the image signal can be isolated by subtracting the Exp2 sensor row of the NIR fluorescence image from the Exp1 sensor row (interpolated to match the Exp2 pixel locations), resulting in an estimate of a quarter-frame of ambient room light signal. The estimate of the quarter-frame of ambient room light signal is then subtracted from the Exp2 sensor row of the NIR fluorescence image, resulting in an estimate of the NIR fluorescence signal with the quarter-frame of ambient room light removed. Illumination and exposure control may be performed by VPI box 14.

[0182] In one embodiment, the room light subtraction method described above may be modified to accommodate the use of Bayer pattern color sensors. Figure 12A shows a Bayer pattern arrangement of color sensor pixels, where even and odd sensor rows have different filter arrangements (e.g., no red pixels in the even sensor rows and no blue pixels in the odd sensor rows), so that the ambient light recorded in the even rows would not be a good estimate of the ambient light reaching the odd rows during the same period. However, every individual row contains a green pixel signal, which is also sensitive to NIR fluorescence. By using only the green pixels and performing two-dimensional interpolation from the green pixel signal to other pixel locations, an estimate of the ambient light signal component can be obtained, and thus an estimate of the NIR fluorescence component and the visible light component can be obtained for the NIR light image and the visible light image, respectively.

[0183] To calculate the NIR signal value at a given location, the green pixel values ​​in Exp1 (even rows) and Exp2 (odd rows) near that location need to be calculated, and one or both of those values ​​interpolated. Figure 12B shows an example, where, at a red pixel location, the best estimate of the green value in Exp1 (even rows) is the average of the green values ​​immediately above and below, while the best estimate of the green value in Exp2 (odd rows) is the average of the green values ​​immediately to the left and immediately to the right.

[0184] The following mathematical example is useful in illustrating an embodiment of the ambient room light subtraction method: If A=incident ambient light during a 1 / 4 frame period, and F=incident fluorescent light during a 1 / 4 frame period, then: Exp1=2A+F Exp2=A+F Solving for F, we get F=2*Exp2-Expl

[0185] In the particular example shown in FIG. 11A, the detection period is three frames, with the white light pulse and excitation pulse having the same duration or width but different frequencies, and visible light is detected during two frames, e.g., the first two frames, and fluorescence light is detected during one frame with two different exposure times, e.g., the third or final frame. As shown, the visible light exposure time may be twice the duration of the white light pulse, the first fluorescence exposure time may be equal to the duration of the excitation pulse, and the second fluorescence exposure time may be a pulse, e.g., twice as long as the excitation pulse. Furthermore, the visible light exposure may have a different frequency than the white light pulse. For example, the visible light exposure may not occur with every individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse.

[0186] Below, alternative timing and exposure diagrams are described in which sensors with rows that are all active for a common exposure duration may be used, but a single sensor may still be used to compensate for ambient light. For example, background light may be detected directly by the sensor when the target is not illuminated. Other variations on pulsing, exposure, and detection will be apparent to those skilled in the art.

[0187] Figure 11B shows an alternative timing diagram for white light (RGB) and fluorescence excitation (laser) illumination, as well as visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor. Visible light exposures and fluorescence exposures are shown in sequence, along with exposures for acquiring a background (BG) image signal due to ambient light. As noted above, white light illumination may be pulsed at 80 Hz. Fluorescence excitation illumination may be pulsed at 20 Hz, with the pulse duration or width increased, for example, by twice the white light pulse duration, to allow for longer corresponding fluorescence exposures. When using an imaging sensor with a global shutter, each sensor exposure must end with a readout period at the end of the imaging frame. The exposure for acquiring the ambient light background image signal may occur at the end of the frame, when neither the pulsed white light nor the excitation light is present. As shown in the example of FIG. 11B, if the video is acquired at a frame rate of 60 Hz, a white light illumination pulse width of 1 / 4 frame duration may be used, resulting in a visible light exposure of 1 / 4 frame duration in frames where the end of the white light illumination pulse aligns with the end of the frame.

[0188] The contribution of ambient light may be removed from the fluorescence image by subtracting scaled image signals recorded during one or more background exposures from each fluorescence exposure image. For example, the image signal from a background exposure of ¼ frame duration may be scaled up by a factor of two and subtracted from a subsequent image signal from a fluorescence exposure of ½ frame duration. As another example, both the image signal from a background exposure of ¼ frame duration preceding the image signal from a fluorescence exposure of ½ frame duration and the image signal from a second ¼ frame background exposure following the fluorescence exposure may be subtracted from the fluorescence image signal. Scaling the image signals from the first and second background exposures may include predicting pixel values ​​corresponding to intermediate time points by interpolating pixel values ​​from the first and second exposure time points.

[0189] Using an imaging sensor with a fast readout that allows for higher video frame acquisition rates allows for additional exposure periods to be allocated within the illumination and exposure timing scheme for a given white light pulse frequency. For example, while maintaining the 80 Hz white light illumination pulse described above, using a sensor with a higher video frame acquisition rate, such as 120 Hz, allows for additional white light exposure, ambient background exposure, or fluorescent light exposure within a given period compared to using a slower video frame acquisition rate, such as 60 Hz.

[0190] In the specific example shown in FIG. 11B, the detection period is three frames, the excitation pulse has a width twice that of the white light pulse, the visible light is detected during one frame (e.g., the first frame), the background light is detected during one frame (e.g., the second frame), and the fluorescence is detected during one frame (e.g., the third or last frame). Here, the visible exposure time may be equal to the duration of the white light pulse, the background exposure time may be equal to the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Furthermore, the visible exposure may have a different frequency from the white light pulse. For example, the visible exposure may not occur with every individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the fluorescence exposure may occur only once within a period.

[0191] FIG. 11C shows an alternative timing diagram for white light (RGB) and fluorescence excitation (laser) illumination, as well as visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor with a 120 Hz video frame acquisition rate. An 80 Hz white light pulse frequency may be used, with a white light illumination pulse width of 1 / 2 frame duration, resulting in a 1 / 2 frame duration visible light exposure in the frame where the end of the white light illumination pulse aligns with the end of the frame. Fluorescence excitation illumination is pulsed at 40 Hz, with a pulse duration shown as 1 frame, allowing for a corresponding higher frequency fluorescence exposure. The exposure for acquiring the ambient light background image signal may occur at the end of the frame when there is no pulsed white light or excitation light. For example, as shown in this exemplary embodiment, a 1 / 2 frame duration exposure may occur in the frame between the fluorescence exposure and the next white light exposure.

[0192] In the specific example shown in FIG. 11C, the detection period is three frames, the excitation pulse has a width twice that of the white light pulse, the visible light is detected during one frame (e.g., the second frame), the background light is detected during one frame (e.g., the first frame), and the fluorescence is detected during one frame (e.g., the third or last frame). Here, the visible exposure time may be equal to the duration of the white light pulse, the background exposure time may be equal to the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Furthermore, the visible exposure may have a different frequency than the white light pulse. For example, the visible exposure may not occur with every individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the fluorescence exposure may occur only once within a period.

[0193] Depending on the intensity of the fluorescence excitation light used, there may be safety considerations that limit the duration and frequency of the excitation light pulses. One approach to reducing the applied excitation light intensity is to reduce the duration of the excitation light pulses and the corresponding fluorescence exposure. Additionally or alternatively, the frequency of the excitation light pulses (and corresponding fluorescence exposure) may be reduced, improving ambient light measurement by using the readout period that would otherwise be used for the fluorescence exposure instead for the background exposure.

[0194] Figure 11D shows an alternative timing diagram of white light (RGB) and fluorescence excitation (laser) illumination, as well as visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor with a 120 Hz video frame acquisition rate. An 80 Hz white light pulse frequency may be used, with a white light illumination pulse width of 1 / 2 frame duration, resulting in a visible light exposure of 1 / 2 frame duration in the frame where the end of the white light illumination pulse aligns with the end of the frame. Fluorescence excitation illumination is pulsed at 20 Hz, with a pulse duration shown as 1 frame. Exposure for acquiring an ambient light background image signal may occur at the end of the frame in the absence of pulsed white light or excitation light. For example, as shown in this exemplary embodiment, a background exposure of ½ frame duration may occur in the frame between the fluorescent exposure and the first subsequent white light exposure, and both a first background exposure of 1 frame duration and a second background exposure of ½ frame duration may occur in the frame between the first white light exposure and the second subsequent white light exposure.

[0195] In the specific example shown in FIG. 11D, the detection period is six frames, the excitation pulse is twice as wide as the white light pulse, visible light is detected during two frames (e.g., the second and fifth frames), background light is detected during three frames (e.g., the first, third, and fourth frames), and fluorescence is detected during one frame (e.g., the sixth or last frame). Here, the visible exposure time may be equal to the duration of the white light pulse, the background exposure time may be equal to or twice the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Furthermore, the visible exposure may have a different frequency from the white light pulse. For example, the visible exposure may not occur with every individual white light pulse (e.g., only twice within a period), while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the background exposure may occur three times within a period, with a total duration four times the duration of the white light pulse.

[0196] In some use environments of open field imaging devices, such as those according to various embodiments described herein, ambient room lighting may include pulsed or periodic light rather than continuous light. Such pulsed light components may be due, for example, to interactions between some room light sources and the AC frequency of their power sources. For example, incandescent lamps, some LED lamps, some fluorescent lamps, including fluorescent lamps with low-frequency ballasts, or arc lamps may emit pulsed light when connected to a common 50 Hz or 60 Hz AC mains power supply or other AC power source. The presence of a pulsed light component in the background light signal may introduce distracting image intensity artifacts during acquisition of successive images due to successive exposures receiving different cumulative light intensity contributions from the pulsed light component in the background light; therefore, it may be useful to correct the acquired images to reduce or eliminate such artifacts. Such correction is useful with or without room light subtraction techniques and may include one or more of the following exemplary techniques: detecting the AC frequency of the power supply for the pulsed light component, modifying the image acquisition frame rate, modifying the exposure duration of the fluorescence and / or background light exposure, measuring the pulsed light intensity during periods when device illumination is turned off, synthesizing a completed periodic cycle of the pulsed light intensity, identifying the portion of the periodic cycle of the pulsed light intensity that coincides with the fluorescence and / or background light exposure, calculating a fluorescence accumulated ambient light value F Lacc corresponding to the accumulated ambient light intensity during the fluorescence exposure, calculating a background accumulated ambient light value B Gacc corresponding to the accumulated ambient light intensity during the background exposure, scaling the image intensity of the fluorescence image or the background image based on the ratio of the respective accumulated light values ​​F Lacc and B Gacc, and subtracting the background image from the fluorescence image to output the resulting image.

[0197] In some embodiments, the AC frequency F of the power source for the pulsed light component of the ambient room illumination may be retrieved from device memory, e.g., due to a user setting a known frequency value during device calibration in the environment of use, or may be detected based on measurements by the imaging device. For example, one or more sensors 395 (see FIG. 17E) may be used to measure ambient light intensity during one or more periods when the device white light illumination is turned off and the fluorescence excitation illumination is turned off. In certain embodiments, the one or more sensors 395 may be photodiodes and may have a response similar to that of sensors used for fluorescence imaging, such as a response to visible and NIR light, with an input cone approximating the field of view of the imaging device. As another example, in one variation where an image sensor responsive only to NIR light, or an image sensor with a separate filter in front of the image sensor that blocks visible or other non-NIR light from reaching the sensor, is used for fluorescence imaging, the one or more sensors 395 may be photodiodes responsive only to NIR light.

[0198] The measurement periods by the sensor 395 should be of sufficient duration and number to capture the portion of the pulsed ambient light intensity that constitutes a complete periodic cycle, in combination with successive measurement periods captured over a period of up to about the time between successive fluorescent light exposures, and sufficient that there is at least partial overlap in cycle coverage for successive measurement periods to help synthesize a periodic cycle of pulsed ambient light that may constrain the lower limit of the frequency FAC that can be supported. However, frequency values ​​of FAC below 30 Hz may be impractical for use with indoor lighting because they may induce noticeable and distracting visible light flicker in general use. Because indoor light sources typically have equivalent responses to each of the positive and negative voltage halves of the AC cycle, the frequency of the pulsed light intensity is typically twice the corresponding value of FAC.

[0199] 11E shows an exemplary timing diagram of white light (RGB) and fluorescent excitation (laser) illumination, the period of ambient light measurement by sensor 395, and visible (VIS) and fluorescent (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescent signal and correction for pulsed ambient light intensity with a single sensor. In this embodiment, the frequency of the fluorescent excitation illumination and corresponding fluorescent exposure is 20 Hz, the frequency of the white light illumination is 80 Hz, and the ambient light measurement period is any period during which both the white light illumination and the fluorescent excitation illumination are turned off. The timing scheme shown may enable pulsed ambient light intensity signals corresponding to all practical frequency values ​​for FAC of 30 Hz or greater to be detected based on measurements in the time between successive fluorescent exposures by capturing portions of the pulsed ambient light intensity that constitute a complete periodic cycle with at least partial overlap of cycle coverage for the multiple measurement periods. A simplified pulsed ambient light intensity profile with a frequency of 120 Hz, corresponding to a 60 Hz FAC, is shown here for reference, but the pulsed ambient light correction techniques described herein may be used for any pulsed or periodic ambient light intensity profile. As can be seen, the sample's pulsed ambient light intensity profile results in different cumulative ambient light intensity contributions from the fluorescent exposure and the background exposure, and these differences cannot be explained simply by differences in exposure duration, as these exposures capture different portions of the pulsed ambient light intensity profile. Other pulsed ambient light intensity profiles, such as those with frequencies that are not multiples of the fluorescent exposure frequency, may also generally result in different cumulative ambient light intensity contributions from one fluorescent exposure to the next.

[0200] In some embodiments, the minimum sampling rate within each measurement period for sensor 395 may be set to at least four times the quotient of the maximum expected frequency FAC and the measurement period duty cycle to enable accurate synthesis of a complete pulsed ambient light intensity cycle with a periodic frequency of twice FAC. In some variations, using a higher sensor sampling rate may provide more measurement points in the overlap region and / or support higher possible FAC values. For example, as shown in FIG. 11E, using a sensor sampling rate of at least 480 Hz with a measurement period duty cycle of 50% within an ambient light intensity measurement period can support frequency values ​​for FAC up to 60 Hz and a corresponding pulsed ambient light intensity frequency up to 120 Hz. The partial overlap of cycle coverage allows for the comparison of measurements obtained from multiple measurement periods to detect the frequency F (or the corresponding frequency of the pulsed ambient light intensity), for example, by calculating the frequency F (or the corresponding frequency of the pulsed ambient light intensity) corresponding to the best time alignment, for example, by minimizing a measure of the average error between corresponding measurement points at candidate time alignments of the portions of the periodic cycle captured by the multiple measurement periods. By arranging the portions of the periodic cycle captured by the multiple measurement periods according to the best time alignment, a synthesis of a complete periodic cycle of duration 1 / (2 F) can be obtained. In some variations, a complete periodic cycle may be directly extracted from a single measurement period whose duration is longer than the complete periodic cycle. The synthesis or extraction of a complete periodic cycle allows for the extension / extrapolation of the pulsed ambient light signal beyond the period during which measurements by the sensor 395 were taken.

[0201] In some embodiments, the image acquisition frame rate of the imaging device may be set to match a known or detected AC frequency of the power source for the pulsed light component of the ambient room illumination, or a multiple thereof, so that there is an equal contribution from the pulsed light component in each fluorescence exposure of a given duration. To accommodate this image acquisition frame rate setting, corresponding scaling of the frequency of the pulsed white light source, the frequency of the pulsed fluorescence excitation light source, and the frequency of the image exposure may be performed. Also, in embodiments using room light subtraction techniques that include performing a background light exposure, the exposure duration of the background light exposure and the exposure duration of the fluorescence exposure may be set to be equal, so that there is an equal contribution from the pulsed light component in both exposures.

[0202] In some embodiments using a room light subtraction technique that includes performing a background light exposure, the background exposure image intensity and / or the fluorescent exposure image intensity can be scaled based on measurements of the pulsed room light intensity so that the scaled image intensities correspond to equivalent contributions from the pulsed room light. After measuring the pulsed light intensity and synthesizing a complete periodic cycle of pulsed light intensity as described herein, identifying the portion of the periodic cycle of pulsed light intensity that coincides with the fluorescent exposure and the background light exposure may be performed by repeating / extrapolating the periodic cycle as necessary to find the portion that coincides with the time spanned by each corresponding exposure. Next, calculation of a fluorescent accumulated ambient light value F Lacc corresponding to the accumulated ambient light intensity during the fluorescent exposure may be performed by calculating the area under the curve marked by the portion of the periodic cycle of pulsed light intensity for that exposure, and calculation of a background accumulated ambient light value B Gacc corresponding to the accumulated ambient light intensity during the background exposure may be performed by calculating the area under the curve for the portion of the periodic pulsed light intensity that coincides with that exposure. Next, a scaling of the image intensity of the fluorescence image or the background image can be performed based on the ratio of the respective accumulated light values ​​FLacc and BGacc to normalize the scaled image to reflect an equivalent contribution of accumulated ambient light. Following scaling, the ambient light signal can be removed by subtracting the scaled background image from the scaled fluorescence image to generate a corrected fluorescence image that includes a correction for the contribution of pulsed ambient light. In one embodiment, one or the other of the fluorescence image or the background image is scaled by 1.

[0203] In embodiments in which room light subtraction is not employed, the fluorescence exposure image intensities may be scaled based on measurements of the pulsed room light intensity to facilitate reducing image intensity artifacts resulting from the pulsed room light. For example, scaling may be performed based on the ratio of intensities measured for successive fluorescence images.

[0204] To improve the performance of the ambient room light compensation methods described herein, a wavelength-dependent aperture (e.g., element 55 in FIG. 6A ) may be used that includes a smaller central aperture that allows all visible and NIR light to pass through and a larger surrounding aperture that blocks visible light but allows NIR light to pass through. Using such a wavelength-dependent aperture allows a greater proportion of the NIR signal to be collected relative to the visible light signal, thereby improving the performance of image signal subtraction for evaluation and removal of the ambient room light component. The wavelength-dependent aperture may also feature a third, larger aperture that blocks both visible and NIR light and surrounds the other, smaller apertures. By way of example, the wavelength-dependent aperture may comprise a film aperture. A film of a material (e.g., a plastic or glass film) that blocks visible light but allows NIR light to pass through has a central aperture (e.g., a hole) that allows both visible and NIR light to pass through. Such a film aperture may include a material that blocks visible light through reflection and / or a material that blocks visible light through absorption. As another example, the wavelength-dependent aperture may comprise a dichroic aperture formed by masked thin-film deposition on a single substrate. A thin film that allows visible and NIR light to pass through may be formed in a smaller central aperture, and a second thin film that blocks visible light but allows NIR light to pass through may be formed in a larger surrounding aperture. The aperture sizes of the smaller central aperture and the larger surrounding aperture of the wavelength-dependent aperture may be set so that the depth of field for visible light and the depth of field for NIR light are substantially similar when captured by the imaging system. One or more wavelength-dependent filters may be positioned at different locations throughout the device, optimizing for rejection of visible signals and passage of NIR signals. For example, such a wavelength-dependent filter may be positioned immediately before lens 51. As another example, one or more wavelength-dependent filters may be positioned at the pupil plane of the imaging lens.

[0205] It may be convenient to display a target reticle around the region within the field of view being imaged and calculate and display the normalized fluorescence intensity within that region, for example, to more easily compare the fluorescence signals in different regions. Normalizing the measured fluorescence intensity values ​​allows for meaningful comparison of multiple images and corresponding values. To correct for variations in the measured fluorescence intensity due to working distance (e.g., the distance between the anatomical structure being imaged and the imaging system), the normalized fluorescence intensity value may be based on the ratio between the measured fluorescence intensity value and the reflected light value within the target reticle region.

[0206] A numerical representation of the normalized fluorescence intensity values ​​within the target reticle region may be displayed in or near the image frame, allowing for easier comparison of values ​​when the target reticle is oriented at different locations on the anatomical structure being imaged. For example, the numerical representation may be the average of the normalized fluorescence intensity values ​​across all image pixels within the target reticle region.

[0207] Additionally or alternatively, a time history plot of numerical representations of normalized fluorescence intensity values ​​within the target reticle region may be displayed in or near the image frame, making it easier to compare values ​​when the target reticle is directed to different locations on the anatomical structure being imaged, or to the same location over a series of time points. Such a time history plot can further assist a user in assessing the fluorescence profile at the imaged tissue surface by scanning across the anatomical region of interest and viewing the relative normalized fluorescence intensity profile plot.

[0208] FIG. 13A shows a diagram of a sample display output from an embodiment of the display method. A target reticle 125 is positioned over a region 122 of the anatomical structure 120 being imaged that has no fluorescence intensity, and a numerical representation 126 of the fluorescence intensity is displayed near the target reticle 125. FIG. 13B shows another diagram of a sample display output. The target reticle 125 is positioned over a region 124 of high relative normalized fluorescence intensity, showing a corresponding numerical representation 126 of the relatively high fluorescence intensity. FIG. 13C shows another diagram of a sample display output. The target reticle 125 is positioned over a region 124 of medium relative normalized fluorescence intensity, showing a corresponding numerical representation 126 of the relatively medium fluorescence intensity. FIG. 13D shows a diagram of a sample display output. The target reticle 125 is positioned over a region 124 of medium relative normalized fluorescence intensity, showing a time history plot 128 of the numerical representation of the normalized fluorescence intensity. This plot 128 is consistent with sequential imaging of regions of zero relative normalized fluorescence intensity, regions of high relative normalized fluorescence intensity, and regions of moderate relative normalized fluorescence intensity. Alternatively or in addition to displaying a numerical representation and / or history plot on the target, a display area associated with the target reticle, for example on the device itself or other display, may display this information.

[0209] 14 shows a recorded image of an anatomical fluorescence imaging phantom featuring an embodiment of a display method output displaying normalized fluorescence intensity. In particular, a target 110 is illuminated with excitation light according to an embodiment, and a target reticle 115 is positioned over a region 112 of fluorescence intensity. A numerical representation of the target reticle 115 is displayed in a region 116 associated with the target reticle 115. A time history plot 118 of the numerical representation of the normalized fluorescence intensity resulting from imaging different positions of the reticle 115 may also be displayed.

[0210] Normalization of measured fluorescence intensity values ​​may additionally or alternatively be performed on a pixel-by-pixel basis for an entire acquired fluorescence image or series of images, which can facilitate providing consistent and / or smoothly varying image brightness, even when changing working distances. To correct for variations in measured fluorescence intensity due to working distance (e.g., the distance between the anatomical structure being imaged and the imaging system), the normalized fluorescence intensity value for each pixel in an acquired fluorescence image may be based on the ratio between the measured fluorescence intensity value of that pixel and the reflected light value or a component of the reflected light value of the same pixel in an acquired reflected light image. In certain embodiments, the reflected light image used for such normalization is a white-light image formed from reflection of visible white-light illumination. For example, in embodiments in which a color image sensor is used to acquire the reflected light images, an overall brightness value or a combination of one or more color channel intensities detected for each pixel from the color image sensor may be used.

[0211] Such display methods and / or normalization techniques for measured intensity values, such as any of those described herein, may be useful in a variety of fluorescence imaging systems, including endoscopic or laparoscopic fluorescence imaging systems, open-field fluorescence imaging systems, and combinations thereof. Such normalization and display of fluorescence intensity values ​​may facilitate quantitative comparison of relative fluorescence intensities between image data from different time points within an imaging session. In combination with appropriately standardized fluorescent agent administration and imaging protocols and standardized calibration of the imaging device, such normalization and display of fluorescence intensity values ​​may further facilitate quantitative comparison of relative fluorescence intensities between image data from different imaging sessions. example Fluorescence medical imaging system for acquiring image data

[0212] In one embodiment, a system for illuminating and imaging an object (also referred to in one embodiment as a device) may be used in conjunction with or as a component of a medical imaging system, such as a fluorescence medical imaging system for acquiring fluorescence medical imaging data. An example of such a fluorescence medical imaging system is fluorescence imaging system 10, shown schematically in FIG. 1. In this embodiment, fluorescence imaging system 10 is configured to acquire a time series of fluorescence signal intensity data (e.g., images, video) that acquires passage of a fluorescent imaging agent through tissue.

[0213] Fluorescence imaging system 10 (FIG. 1) includes an illumination source 15 and illumination module 11 that illuminates tissue of interest to stimulate fluorescent emission from a fluorescent imaging agent 17 in the tissue of interest (e.g., in blood), an imaging module 13 configured to acquire a time series of fluorescent images from the fluorescent emission, and a processor assembly 16 configured to use the acquired time series of fluorescent images (fluorescent signal intensity data) in accordance with various embodiments described herein.

[0214] In various embodiments, illumination source 15 ( FIG. 1 ) comprises, for example, light source 200 ( FIG. 15 ), which includes a fluorescence excitation source configured to generate excitation light having an intensity and wavelength suitable for exciting fluorescent imaging agent 17. Light source 200 of FIG. 15 includes laser diode 202 (which may include, for example, one or more fiber-coupled diode lasers) configured to provide excitation light for exciting fluorescent imaging agent 17 (not shown). Examples of other sources of excitation light that may be used in various embodiments include one or more LEDs, arc lamps, or other illumination technologies of sufficient intensity and suitable wavelength to excite fluorescent imaging agent 17 in tissue (e.g., blood). For example, excitation of fluorescent imaging agent 17 in blood (wherein the fluorescent imaging agent 17 is a fluorescent dye with near-infrared excitation characteristics) may be performed using one or more 793 nm, conduction-cooled, single-bar, fiber-coupled laser diode modules available from DILAS Diode Laser Co., Germany.

[0215] In various embodiments, the light output from the light source 200 of FIG. 15 may be projected through an optical element (e.g., one or more optical elements) to shape and direct the output used to illuminate the tissue region of interest. The shaping optics may include one or more lenses, light guides, and / or diffractive elements to achieve a flat field across substantially the entire field of view of the imaging module 13. In certain embodiments, the fluorescence excitation source is selected to emit at a wavelength near the maximum absorption of the fluorescent imaging agent 17 (e.g., ICG). For example, with reference to the embodiment of the light source 200 of FIG. 15, the output 204 from the laser diode 202 passes through one or more converging lenses 206 and then through a homogenizing light pipe 208, such as a light pipe commonly available from Newport Corporation, USA. Finally, the light passes through an optical diffractive element 214 (e.g., one or more optical diffusers), such as a ground-glass diffractive element available from Newport Corporation, USA. Power for the laser diode 202 itself may be provided by, for example, a high-current laser driver available from Lumina Power Inc., USA. The laser may optionally be operated in a pulsed mode during the image acquisition process. In this embodiment, an optical sensor, such as a solid-state photodiode 212, is integrated into the light source 200 to sample the illumination intensity generated by the light source 200 via scattering and diffuse reflection from various optical elements. In various embodiments, an additional illumination source may be used to provide guidance when aligning and positioning the module over the region of interest. In various embodiments, at least one of the components of the light source 200 shown in FIG. 15 may comprise the illumination source 15 and / or may comprise the illumination module 11.

[0216] Referring again to FIG. 1 , in various embodiments, imaging module 13 may be a component of, for example, fluorescence imaging system 10 and may be configured to acquire a time series of fluorescence images (e.g., video) from the fluorescence emission from fluorescent imaging agent 17. Referring to FIG. 16 , an exemplary embodiment of imaging module 13 is shown, comprising camera module 250. As shown in FIG. 16 , camera module 250 may acquire images of fluorescence emission 252 from fluorescent imaging agent 17 within tissue (e.g., blood) (not shown) by using a system of imaging optics (e.g., front element 254, rejection filter 256, dichroic 260, and rear element 262) to focus the fluorescence emission onto image sensor assembly 264, which includes at least one two-dimensional solid-state image sensor. Rejection filter 256 may be, for example, a notch filter used to reject a wavelength band corresponding to the excitation light. Dichroic 260 may be, for example, a dichroic mirror used to selectively pass a subset of the incoming light wavelength spectrum and redirect the remaining wavelengths away from the light path for rejection or toward a separate image sensor. The solid-state image sensor may be a charge-coupled device (CCD), CMOS sensor, CID, or similar two-dimensional sensor technology. The electrical charge resulting from the optical signal converted by image sensor assembly 264 is converted into an electronic video signal, including both digital and analog video signals, by appropriate readout and amplification electronics within camera module 250.

[0217] According to one embodiment, an excitation wavelength of about 800 nm + / - 10 nm and an emission wavelength of >820 nm are used with NIR compatible optics for ICG fluorescence imaging. Those skilled in the art will appreciate that other excitation and emission wavelengths may be used for other imaging agents.

[0218] Returning to FIG. 1, in various embodiments, processor assembly 16 includes, for example: A processor module (not shown) configured to perform various processing operations, including executing instructions carried on a computer-readable medium, that cause one or more of the systems described herein to perform the methods and techniques described herein. A data storage module (not shown) for recording and retaining data from the operations and, in one embodiment, for retaining instructions executable by the processor module, the instructions for implementing the methods and techniques disclosed herein.

[0219] In various embodiments, the processor module includes any computer or computing means, such as a tablet, laptop, desktop, network computer, or dedicated stand-alone microprocessor. Inputs may be obtained, for example, from the image sensor 264 of the camera module 250 shown in FIG. 16, from the solid-state photodiode of the light source 200 of FIG. 15, or from external control hardware such as a footswitch or remote control. Outputs are provided to a laser diode driver and optical aligner. In various embodiments, the processor assembly 16 (FIG. 1) may include a data storage module with the ability to store a time series of input data (e.g., image data) in a tangible, non-transitory, computer-readable medium, such as internal memory (e.g., hard disk or flash memory), thereby enabling data recording and processing. In various embodiments, the processor module may include an internal clock, which allows control of various elements and ensures proper timing of illumination and sensor shutters. In various other embodiments, the processor module may provide a graphical display of user inputs and outputs. The fluorescence imaging system may optionally include a video display (not shown). The video display may display images as they are being acquired or in playback after they have been recorded, or may further visualize data generated at various stages of the method as described above.

[0220] In operation, and with continued reference to the exemplary embodiments of FIGS. 1, 15, and 16, a subject is placed in an imaging position such that the subject's anatomical area of ​​interest is located under both the illumination module 11 and the imaging module 13. As a result, a substantially uniform illumination field is generated across substantially the entire region of interest. In various embodiments, an image of the area of ​​interest may be acquired for background subtraction prior to administering the fluorescent imaging agent 17 to the subject. For example, to do this, an operator of the fluorescent imaging system 10 of FIG. 1 may initiate acquisition of a time series (e.g., video) of fluorescent images by depressing a remote switch or foot control or via a keyboard (not shown) connected to the processor assembly 16. This turns on the illumination source 15, and the processor assembly 16 begins recording the fluorescent image data provided by the image acquisition assembly 13. It will be appreciated that, instead of the pulsed mode described above, in certain embodiments, the illumination source 15 may comprise a radiation source that is continuously on during the image acquisition sequence. When operating in pulsed mode, the image sensor 264 of the camera module 250 (FIG. 16) is synchronized to collect fluorescent radiation following a laser pulse generated by the diode laser 202 of the light source 200 (FIG. 15). In this manner, maximum fluorescent radiation intensity is recorded and the signal-to-noise ratio is optimized. In this embodiment, the fluorescent imaging agent 17 is administered to the subject and transported to the area of ​​interest via the arterial flow. Acquisition of a time series of fluorescent images is initiated, for example, immediately after administration of the fluorescent imaging agent 17, and a time series of fluorescent images from substantially the entire area of ​​interest is acquired throughout the inflow of the fluorescent imaging agent 17. Fluorescent radiation from the area of ​​interest is collected by the collection optics of the camera module 250. Residual ambient excitation light and reflected excitation light are attenuated by subsequent optical elements of the camera module 250 (e.g., optical element 256 of FIG. 16, which may be a filter). As a result, fluorescent radiation can be acquired by the image sensor assembly 264 with minimal interference with light from other sources.

[0221] In various embodiments, the processor is in communication with or is a component of the imaging system. Program code means or other computer-readable instructions according to various embodiments may be written in and / or stored in any suitable programming language and may be provided to the processor in many forms, including, but not limited to, information permanently stored on a non-writable storage medium (e.g., a read-only memory device such as a ROM or CD-ROM disk), information reversibly stored on a writable storage medium (e.g., a hard drive), information passed to the processor via a transitory medium (e.g., a signal), or information conveyed to the processor over a communications medium, such as a local area network, a public network such as the Internet, or any type of medium suitable for carrying electronic instructions. In various embodiments, tangible non-transitory computer-readable media includes all computer-readable media. In some embodiments, the computer-readable instructions for performing one or more of the methods or techniques described herein may be stored solely on a non-transitory computer-readable medium.

[0222] In some embodiments, the illumination and imaging system may be a component of a medical imaging system, such as the fluorescence medical imaging system 10, that acquires medical imaging data. In embodiments in which the illumination and imaging system is a component of an imaging system, such as the fluorescence imaging system described above, the light source, illumination module, imaging module, and processor of the medical imaging system may function as the camera assembly and processor of the illumination and imaging system. Those skilled in the art will understand that imaging systems other than fluorescence imaging systems may be employed for use in illumination and / or imaging systems such as those described above, depending on the type of imaging to be performed. Exemplary Imaging Agents Used in Generating Image Data

[0223] According to one embodiment, in a fluorescent medical imaging application, the imaging agent is a fluorescent imaging agent, such as indocyanine green (ICG) dye. When ICG is administered to a subject, it binds to blood proteins and circulates with the blood through tissues. The fluorescent imaging agent (e.g., ICG) may be administered to a subject as a bolus (e.g., into a vein or artery) at a concentration suitable for imaging. In this case, the bolus circulates through the vascular system and passes through the capillary system. In other embodiments in which multiple fluorescent imaging agents are used, such agents may be administered simultaneously (e.g., in a single bolus) or sequentially (e.g., in separate boluses). In one embodiment, the fluorescent imaging agent may be administered via a catheter. In one embodiment, the fluorescent imaging agent may be administered to a subject within one hour prior to making a measurement of signal intensity resulting from the fluorescent imaging agent. For example, the fluorescent imaging agent may be administered to a subject within 30 minutes prior to making the measurement. In yet another embodiment, the fluorescent imaging agent may be administered at least 30 seconds prior to making the measurement. In yet another embodiment, the fluorescent imaging agent may be administered simultaneously with making the measurement.

[0224] According to certain embodiments, the fluorescent imaging agent may be administered at various concentrations to achieve a desired circulating blood concentration. For example, in embodiments where the fluorescent imaging agent is ICG, it may be administered at a concentration of about 2.5 mg / mL to achieve a circulating blood concentration of about 5 μM to about 10 μM. In various embodiments, the upper concentration limit for administering the fluorescent imaging agent is the concentration at which the fluorescent imaging agent becomes clinically toxic in the circulation, and the lower concentration limit is the limit of the device for acquiring signal intensity data resulting from the fluorescent imaging agent circulating with the blood to detect the fluorescent imaging agent. In various other embodiments, the upper concentration limit for administering the fluorescent imaging agent is the concentration at which the fluorescent imaging agent becomes self-deactivated. For example, the circulating concentration of ICG may range from about 2 μM to about 10 mM. Thus, in certain aspects, a method includes administering an imaging agent (e.g., a fluorescent imaging agent) to a subject and acquiring signal intensity data (e.g., video) before processing the signal intensity data according to various embodiments. In other aspects, a method may exclude administering an imaging agent to a subject.

[0225] According to certain embodiments, suitable fluorescent imaging agents used to generate fluorescent image data in fluorescent imaging applications are those that are circulatable with blood (e.g., fluorescent dyes that circulate with blood components such as lipoproteins and blood plasma serum), that pass through the vasculature of tissues (i.e., large blood vessels and capillaries), and that generate signal intensity upon exposure to appropriate light energy (e.g., excitation light energy and absorption energy). In various embodiments, the fluorescent imaging agent includes a fluorescent dye, an analog thereof, a derivative thereof, or a combination thereof. The fluorescent dye includes a non-toxic fluorescent dye. In certain embodiments, the fluorescent dye optimally fluoresces in the near-infrared spectrum. In certain embodiments, the fluorescent dye is or includes a tricarbocyanine dye. In certain embodiments, the fluorescent dye is or includes indocyanine green (ICG), methylene blue, or a combination thereof. In other embodiments, the fluorescent dye is or includes fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, orthophthalaldehyde, fluorescamine, rose bengal, trypan blue, fluorogold, or a combination thereof, excitable using the appropriate excitation light wavelength for each dye. In certain embodiments, analogs or derivatives of fluorescent dyes may be used. For example, fluorescent dye analogs or derivatives include fluorescent dyes that have been chemically altered but that retain the ability to fluoresce when exposed to light energy of the appropriate wavelength.

[0226] In various embodiments, the fluorescent imaging agent may be provided as a lyophilized powder, solid, or liquid. In some embodiments, the fluorescent imaging agent may be provided in a vial (e.g., a sterile vial), which may allow for reconstitution at the appropriate concentration by preparing a sterile fluid with a sterile syringe. Reconstitution may be performed using a suitable carrier or diluent. For example, the fluorescent imaging agent may be reconstituted with an aqueous diluent immediately prior to administration. In various embodiments, any diluent or carrier that will maintain the fluorescent imaging agent in solution may be used. As an example, ICG can be reconstituted with water. In some embodiments, once the fluorescent imaging agent is reconstituted, it may be mixed with additional diluents and carriers. In some embodiments, the fluorescent imaging agent may be conjugated to other molecules (e.g., proteins, peptides, amino acids, synthetic polymers, sugars, etc.) to enhance, for example, solubility, stability, imaging properties, or a combination thereof. Additional buffers may be added, including trisaminomethane, HCl, NaOH, phosphate buffer, and / or HEPES.

[0227] Those skilled in the art will appreciate that although fluorescent imaging agents are described in detail above, other imaging agents may be used in connection with the systems, methods and techniques described herein, depending on the optical imaging modality.

[0228] In some variations, the fluorescent imaging agents used in combination with the methods, systems, and kits described herein may be used for blood flow imaging, tissue perfusion imaging, lymphatic imaging, or a combination thereof, which may be performed during invasive, minimally invasive, non-invasive, or a combination thereof. Examples of invasive procedures that may involve blood flow and tissue perfusion include cardiac-related procedures (e.g., CABG on-pump or off-pump) and reconstructive surgery. Examples of non-invasive or minimally invasive procedures include the treatment and / or management of wounds (e.g., chronic wounds such as pressure ulcers). In this regard, for example, changes in wound size (e.g., diameter, area) over time, as well as changes in tissue perfusion within and / or around the wound, may be tracked over time using the methods and systems. Examples of lymphatic imaging include identification of lymph nodes, lymphatic drainage, lymphatic mapping, or a combination thereof. In some variations, such lymphatic imaging may relate to the female reproductive system (e.g., uterus, cervix, vulva).

[0229] In embodiments involving cardiac or any vascular application, the imaging agent (e.g., ICG alone or in combination with other imaging agents) may be injected intravenously. For example, the imaging agent may be infused intravenously through a central venous line, bypass pump, and / or cardioplegia line, and / or other vascular system to flush and / or perfuse the coronary vasculature, capillaries, and / or grafts. ICG may be administered to vascular grafts or other vasculature as a dilute ICG / blood / saline solution, such that the final concentration of ICG in the coronary arteries or other vasculature (depending on the application) is approximately the same as or lower than that resulting from an injection of approximately 2.5 mg (i.e., 1 ml of 2.5 mg / ml) into the central line or bypass pump. ICG may be prepared, for example, by dissolving 25 mg of solid in 10 ml of sterile aqueous solvent, which may be provided together with the ICG by the manufacturer. One milliliter of ICG solution may be mixed with 500 ml of sterile saline (e.g., by injecting 1 ml of ICG into a 500 ml saline bag). Thirty milliliters of the dilute ICG / saline solution may be added to 10 ml of the subject's blood. The blood may be obtained aseptically from a central arterial line or a bypass pump. ICG in the blood binds to plasma proteins, helping to prevent leakage from the blood vessels. Mixing of the ICG and blood may be performed using standard sterile techniques within a sterile surgical field. For each graft, 10 ml of the ICG / saline / blood mixture may be administered. Instead of administering ICG by injection through the graft wall with a needle, ICG may be administered with a syringe attached to the (open) proximal end of the graft. When the graft is implanted, the surgeon routinely attaches an adapter to the proximal end of the graft. In this case, prior to making the first anastomosis, a saline-filled syringe is attached, the distal end of the graft is closed, and saline is injected into the graft, applying pressure to the graft, thereby assessing the integrity of the conduit (e.g., for leaks, side branches, etc.) In other aspects, the methods, doses, or combinations thereof described herein in connection with cardiac imaging may be used in any vasculature and / or tissue perfusion imaging application.

[0230] Lymphatic mapping is an important part of effective surgical staging for cancers that spread through the lymphatic system (e.g., breast, gastric, and gynecological cancers). Removal of multiple lymph nodes from a particular lymphatic basin can cause significant complications, including acute or chronic lymphedema, paresthesia, and / or seroma formation. Indeed, if a sentinel lymph node is negative for metastasis, the surrounding lymph nodes are also often negative. Identification of tumor-draining lymph nodes (LNs) has become an important step for staging cancers that spread through the lymphatic system, for example, in breast cancer surgery. LN mapping involves using dyes and / or radiotracers to identify LNs for either biopsy or resection and for subsequent pathological evaluation of metastases. The goal of lymphadenectomy during surgical staging is to identify and remove LNs at high risk for local spread of cancer. Sentinel lymph node (SLN) mapping has emerged as an effective surgical strategy in the treatment of breast cancer. It is generally based on the following concept: metastasis (spread of cancer to the axillary LNs), if present, must be located in the SLN, which is defined in the art as the first LN or group of lymph nodes to which cancer cells from the primary tumor have most likely spread. If an SLN is negative for metastasis, the surrounding second and third LNs should also be negative. The main advantage of SLN mapping is that it reduces the number of subjects who undergo traditional partial or complete lymphadenectomy and therefore suffer from associated conditions such as lymphedema and lymphocysts.

[0231] The current standard of care for SLN mapping involves the injection of a tracer to identify lymphatic pathways from the primary tumor. The tracer used may be a radioisotope (e.g., technetium-99 or Tc-99m) for intraoperative localization with a gamma probe. Radioactive tracer techniques (known as scintigraphy) are limited to hospitals with access to radioisotopes, require the involvement of a nuclear physicist, and do not provide real-time visual guidance. A colored dye, isosulfan blue, has also been used, but this dye cannot be seen through skin or fatty tissue. In addition, blue stains can appear as chest tattoos that remain for several months, and subdermal injections can cause skin necrosis. Rarely, allergic reactions, including anaphylaxis, have been reported. Severe anaphylactic reactions have occurred (in approximately 2% of patients) after isosulfan blue injection. Symptoms include dyspnea, shock, angioedema, hives, and itching. Reactions are more likely in patients with a history of bronchial asthma and in patients with allergies or drug reactions to triphenylmethane dyes. Isosulfan blue is known to interfere with measurements of oxygen saturation by pulse oximetry and methemoglobin by gas analyzers. Use of isosulfan blue may cause transient or long-term blue staining (tattooing).

[0232] In contrast, fluorescence imaging according to various embodiments used in SLN visualization and mapping facilitates direct intraoperative real-time visual identification of LNs and / or afferent lymphatic channels, facilitates high-resolution optical real-time guidance through skin and adipose tissue, and facilitates visualization of blood flow, tissue perfusion, or a combination thereof.

[0233] In some embodiments, visualization and / or classification of lymph nodes during fluorescence imaging may be based on imaging with one or more imaging agents, which may further be based on visualization and / or classification with a gamma probe (e.g., technetium Tc-99m, a clear, colorless aqueous solution that is injected around the areola according to standard practice), other conventionally used colored imaging agents (isosulfan blue), and / or other evaluations, such as histology. For example, a subject's chest may be injected with two doses of approximately 1% isosulfan blue (for comparison) and two doses of an ICG solution having a concentration of approximately 2.5 mg / ml. The injection of isosulfan blue may precede the injection of ICG, or vice versa. For example, an anesthetized subject may be injected with 0.4 ml (0.2 ml at each site) of isosulfan blue in the periareolar area of ​​the chest using a TB syringe and a 30G needle. For the right breast, the subject may be injected at the 12 o'clock and 9 o'clock positions, and for the left breast, the subject may be injected at the 12 o'clock and 3 o'clock positions. The total dose of intradermal injection of isosulfan blue for each breast may be approximately 4.0 mg (0.4 ml of a 1% solution: 10 mg / ml). In another exemplary embodiment, a subject may first receive an ICG injection followed by isosulfan blue (for comparison). One 25 mg ICG vial may be reconstituted with 10 ml of sterile water for injection to create a 2.5 mg / ml solution immediately prior to ICG administration. For example, using a TB syringe and a 30G needle, a subject may be injected with approximately 0.1 ml (0.05 ml at each site) of ICG in the area around the areola of each breast (injections may be made at the 12 and 9 o'clock positions for the right breast, and at the 12 and 3 o'clock positions for the left breast). The total dose of intradermal injection of ICG for each breast may be approximately 0.25 mg (0.1 ml of a 2.5 mg / ml solution) per breast. ICG may be injected at a rate of, for example, 5 to 10 seconds per injection. When ICG is injected intradermally, due to the protein-binding properties of ICG, it is rapidly absorbed by the lymph and travels through the ducts to the LNs.In some embodiments, ICG may be provided in the form of a sterile, lyophilized powder containing 25 mg of ICG with less than 5% sodium iodide. ICG may be packaged with an aqueous solvent consisting of sterile water for injection, which is used to reconstitute the ICG. In some embodiments, the ICG dose (mg) for sentinel lymphatic mapping of breast cancer ranges from about 0.5 mg to about 10 mg, depending on the route of administration. In some embodiments, the ICG dose may be about 0.6 mg to about 0.75 mg, about 0.75 mg to about 5 mg, or about 5 mg to about 10 mg. The route of administration may be, for example, subdermal, intradermal (e.g., the area around the areola), under the areola, in the skin overlying the tumor, intradermal in the areola closest to the tumor, subdermal within the areola, intradermal above the tumor, around the areola over the entire breast, or a combination thereof. NIR fluorescence-positive LNs (e.g., using ICG) may be represented, for example, as black-and-white NIR fluorescence images and / or as fully or partially color (white light) images, fully or partially unsaturated white light images, enhanced color images, overlays (e.g., fluorescence with other images), composite images (e.g., fluorescence incorporated into other images) that may have various colors, levels of unsaturation, or ranges of color to highlight / visualize predetermined features of interest. Images may be further processed for further visualization and / or other analysis (e.g., quantification). Lymph nodes and lymphatic vessels may be visualized (e.g., intraoperatively, in real time) using fluorescence imaging systems and methods according to various embodiments of ICG and SLNs alone or ICG and SLNs combined with a gamma probe (Tc-99m) in accordance with the American Society of Breast Surgeons (ASBrS) practice standards for SLN biopsy of breast cancer patients. Fluorescence imaging of the LN may begin by tracing the lymphatic channels from the injection site to the axillary LN. Once a visual image of the LN is identified, LN mapping and LN identification may be performed through the incised skin, and LN mapping may be performed until an ICG-visualized lymph node is identified.For comparison, mapping with isosulfan blue may be performed until "blue" lymph nodes are identified. LNs identified with ICG alone or in combination with other imaging techniques (e.g., isosulfan blue and / or TC-99m) may be labeled for resection. Subjects may have various stages of breast cancer (e.g., IA, IB, IIA).

[0234] In some embodiments, for example, in gynecological cancers (e.g., uterine, endometrial, vulvar, and cervical malignancies), ICG may be administered intercellularly for visualization of lymph nodes, lymphatic channels, or a combination thereof. When injected intercellularly, ICG's protein-binding properties allow it to be rapidly absorbed by the lymph and transported through the ducts to the SLN. ICG may be provided for injection in the form of a sterile, lyophilized powder containing 25 mg ICG (e.g., 25 mg / vial) with less than 5% sodium iodide. The ICG may then be reconstituted with commercially available water for injection (sterile) before use. According to one embodiment, a vial containing 25 mg of ICG was reconstituted with 20 ml of water for injection to obtain a 1.25 mg / ml solution. To obtain a total dose of 5 mg of ICG per subject, subjects are injected with a total of 4 ml of this 1.25 mg / ml solution (4 x 1 ml injections). The cervix may also be injected four (4) times (for comparison purposes) with 1 ml of a 1% 10 mg / ml solution of isosulfan blue, for a total dose of 40 mg. Injections may be administered while the subject is under anesthesia in the operating room. In certain embodiments, the ICG dose (mg) for sentinel lymph node detection and / or mapping of gynecological cancers ranges from about 0.1 mg to about 5 mg, depending on the route of administration. In certain embodiments, the ICG dose may be about 0.1 mg to about 0.75 mg, about 0.75 mg to about 1.5 mg, about 1.5 mg to about 2.5 mg, or about 2.5 mg to about 5 mg. The route of administration may be, for example, cervical injection, vulvar peritumoral injection, hysteroscopic endometrial injection, or a combination thereof. To minimize spillage of isosulfan blue or ICG that may interfere with the mapping procedure when the LNs are excised, mapping may be performed on one hemipelvic site, with both isosulfan blue and ICG mapping performed before the LNs are excised. LN mapping for clinical stage I endometrial cancer may be performed according to the NCCN Guidelines for Uterine Neoplasia, SLN Algorithm for Surgical Staging of Endometrial Cancer, and SLN mapping for clinical stage I cervical cancer may be performed according to the NCCN Guidelines for Cervical Neoplasia, Surgery / SLN Mapping Algorithm for Early Stage Cervical Cancer.Therefore, identification of LNs may be based on ICG fluorescence imaging alone, or in combination with colorimetric dyes (isosulfan blue) and / or radiotracers, or by co-administration of colorimetric dyes (isosulfan blue) and / or radiotracers.

[0235] Lymph node visualization may be qualitative and / or quantitative. Such visualization may include, for example, lymph node detection, detection rate, and anatomical distribution of lymph nodes. Lymph node visualization according to various embodiments may be used alone or in combination with other variables (e.g., vital signs, height, weight, demographics, surgical predictors, relevant medical history and underlying conditions, tissue visualization and / or evaluation, Tc-99m visualization and / or evaluation, concomitant therapies). Follow-up visits may occur on the day of discharge and at a later date (e.g., one month).

[0236] Lymph contains high levels of proteins, and ICG can therefore bind to endogenous proteins upon entering the lymphatic system. Fluorescence imaging (e.g., ICG imaging) for lymphatic mapping, when used in accordance with the methods and systems described herein, offers the following exemplary advantages: a high signal-to-background ratio (or tumor-to-background ratio) due to the lack of significant autofluorescence in NIR; real-time visualization features of lymphatic mapping; tissue determination (i.e., structural visualization); rapid excretion and disappearance after entering the vasculature; and avoidance of non-ionizing radiation. Furthermore, NIR imaging has superior tissue penetration (approximately 5 to 10 mm of tissue) compared to visible light (1 to 3 mm of tissue). For example, the use of ICG also facilitates visualization through the peritoneum overlying para-aortic lymph nodes. While tissue fluorescence is observable with NIR light for extended periods, it is not visible with visible light, and therefore does not affect the pathological evaluation or treatment of LNs. Furthermore, fluorescence is easier to detect during surgery than blue lymph node staining (isosulfan blue). In other aspects, the methods, doses, or combinations thereof described herein in connection with lymphatic imaging may be used in any vasculature and / or tissue perfusion imaging application.

[0237] Tissue perfusion is related to the microcirculatory blood flow per unit tissue volume, which provides oxygen and nutrients to the capillary bed of the perfused tissue and removes waste products from it. Tissue perfusion is a phenomenon related to but distinct from blood flow within blood vessels. Quantifying blood flow through blood vessels may be expressed in terms that define flow (i.e., volume / time) or in terms that define speed (i.e., distance / time). Tissue blood perfusion defines the movement of blood through capillaries, such as arterioles, tubules, and venules, within a tissue volume. Quantifying tissue blood perfusion is expressed in terms of blood flow through tissue, i.e., volume / time / tissue volume (or tissue mass). Perfusion is related to nutrient vessels (e.g., capillaries), which include vessels associated with the exchange of metabolites between blood and tissue, rather than larger-diameter non-nutrient vessels. In some embodiments, quantifying the target tissue may involve calculating or determining a parameter or quantity related to the target tissue, such as rate, size, volume, time, distance / time, and / or volume / time, and / or change, which may relate to any one or more of the aforementioned parameters or quantities. However, compared to blood movement through larger diameter vessels, blood movement through individual capillaries can be highly irregular. This is primarily due to vasomotion, where spontaneous oscillations in vascular pulses manifest as pulsations in the movement of red blood cells.

[0238] In summary, one or more embodiments can provide a flat illumination field and match the illumination field to a target imaging field while accommodating changes in working distance, thereby enabling accurate quantitative imaging applications. The imaging element that focuses light from the target onto the sensor may be moved synchronously with steering the illumination field. Additionally or alternatively, a drape may be used to ensure a tight fit between the draped lens and the device's window frame. Additionally or alternatively, one or more embodiments can subtract ambient light from the light to be imaged by using a single sensor and controlled timing of illumination and exposure or detection. Additionally or alternatively, one or more embodiments may enable display of normalized fluorescence intensity measured within the target reticle area of ​​the image frame.

[0239] In contrast, if an illumination and imaging device does not align illumination with the target imaging field of view or does not provide a flat, i.e., uniform, or substantially uniform, illumination and image quality will suffer. A non-uniform illumination field can cause disturbing and inaccurate imaging artifacts, especially when used at various working distances in handheld imaging devices. Additionally, excess light outside the imaging field of view can reduce the efficiency of the device and can be a nuisance to the user when positioning the device.

[0240] The methods and processes described herein may be performed by a computer, processor, manager, or controller, or by code or instructions executed in hardware or other circuitry. Having described in detail the algorithms underlying the methods (or the operation of a computer, processor, or controller), the code or instructions for implementing the operations of the method embodiments may transform a computer, processor, or controller into a dedicated processor for performing the methods described herein.

[0241] Other embodiments may also include a computer-readable medium, such as a non-transitory computer-readable medium, for carrying the code or instructions described above. The computer-readable medium may be a volatile or non-volatile memory or other storage device, which may be removably or permanently coupled to a computer, processor, or controller that executes the code or instructions to perform the method embodiments described herein.

[0242] One or more embodiments are directed to an illumination module for use in an imaging system having an imaging field of view for imaging a target, the illumination module including a first illumination port configured to illuminate the target by outputting a first light beam having a first illumination distribution at the target, and a second illumination port configured to illuminate the target by outputting a second light beam having a second illumination distribution at the target, wherein the second illumination distribution is substantially similar to the first illumination distribution at the target, the second illumination port is spaced apart from the first illumination port, the first and second illumination distributions are provided simultaneously to the target and overlap at the target, and the illumination from the first and second ports may be matched to the same aspect ratio and field coverage as the imaging field of view.

[0243] The light from the first and second illumination ports may overlap to provide uniform illumination on the target field of view.

[0244] The lighting module may include a steering driver for simultaneously steering the first and second lighting ports through different fields of view.

[0245] Each of the first and second illumination ports may include a lens module having at least one fixed lens, a steerable housing, and at least one lens attached to the steerable housing, the steerable housing in communication with the steering driver.

[0246] The lighting module may include a housing that houses the first and second lighting ports and the steering driver.

[0247] The housing may be a handheld housing and may include a control surface including an activation device for controlling the steering driver.

[0248] Each of the first and second illumination distributions may be a rectangular illumination distribution.

[0249] Each of the first and second illumination ports may include a lens module having two sets of cylindrical lenses.

[0250] The first and second illumination ports may be symmetrically offset from a midline of a long dimension of the rectangular illumination distribution.

[0251] One or more embodiments are directed to an imaging device having an imaging field of view, the imaging device including: a first illumination port configured to illuminate the target by outputting a first light having a first illumination distribution at the target; a second illumination port configured to illuminate the target by outputting a second light having a second illumination distribution at the target, the second illumination distribution being substantially similar to the first illumination distribution at the target; the second illumination port being spaced apart from the first illumination port; the first and second illumination distributions being presented to the target simultaneously and overlapping at the target; and the illumination from the first and second ports being matched to the same aspect ratio and field of view as the imaging field of view; and a sensor configured to detect light from the target.

[0252] The imaging device may include a housing that houses the first and second illumination ports and the sensor.

[0253] The imaging device may include a steering driver for simultaneously steering the first and second illumination ports through different fields of view.

[0254] The imaging device may include an imaging element that focuses light onto the sensor, the steering driver being for moving the imaging element in synchronization with steering of the first and second illumination ports.

[0255] The steering driver may be within the housing, and the housing may include a control surface including an activation device for controlling the steering driver.

[0256] The housing may have a handheld housing with a form factor that allows one hand to control the control surface and control illumination of the target from multiple orientations.

[0257] The imaging device may include an illumination source that outputs light to the first and second illumination ports, the illumination source being external to the housing.

[0258] The illumination source may output visible light and / or excitation light to the first and second illumination ports.

[0259] The sensor may be a single sensor for detecting light from the target produced by illumination with visible light and excitation light.

[0260] The imaging device may include a wavelength-dependent aperture upstream of the sensor, the wavelength-dependent aperture blocking visible light outside a central region.

[0261] The imaging device may include a video processor box outside the housing.

[0262] The illumination source may be integrated into the video processor box.

[0263] One or more embodiments are directed to a method of interrogating a target, the method including simultaneously illuminating the target with a first light output having a first illumination distribution at the target and a second light output having a second illumination distribution at the target, the second illumination distribution being substantially similar to the first illumination distribution, the first and second illumination distributions overlapping at the target, and the illumination on the target matched to the same aspect ratio and field coverage as an imaging field of view.

[0264] The method may include simultaneously steering the first and second light outputs through different fields of view.

[0265] The method may include receiving light from the target and focusing the light onto a sensor with an imaging element, the imaging element being moved synchronously with the simultaneous steering of the first and second light outputs.

[0266] One or more embodiments are directed to a drape for use with an imaging device, the drape including a barrier material encasing the imaging device, a drape window frame defining an opening in the barrier material, a drape lens within the opening in the barrier material, and an interface integral with the drape window frame that secures the drape lens to the window frame of the imaging device.

[0267] The drape may be insertable into the window frame of the imaging device.

[0268] The interface may include two clamps symmetrically mounted on opposite sides of the drape window frame.

[0269] The two clamps are at the top and bottom of the drape window frame.

[0270] One or more embodiments are directed to a processor for imaging a target, the processor generating excitation pulses to illuminate the target by activating an excitation light source within a time period, generating white pulses to illuminate the target by activating a white light source such that the white pulses do not overlap with the excitation pulses and such that the white pulses are generated at least twice within the time period, exposing an image sensor for a fluorescent exposure time during the excitation pulses, exposing the image sensor for a visible exposure time during at least one white pulse, detecting output from the image sensor, correcting for ambient light, and outputting the resulting image.

[0271] To compensate for ambient light, the processor may expose a first set of sensor pixel rows of the image sensor for a percentage of the fluorescent light exposure time for the first set of sensor pixel rows and expose a second set of sensor pixel rows of the image sensor for the entire fluorescent light exposure time, the first and second sets being for detecting at least one different color.

[0272] The certain ratio may be 1 / 2.

[0273] The processor may determine the fluorescent signal F using the following formula: F=2*Exp2-Exp1 where Exp1 is the signal output during said fraction of the fluorescence exposure time and Exp2 is the signal output during said entire fluorescence exposure time.

[0274] The fraction of the exposure time may be equal to the width of the excitation pulse.

[0275] The visible light exposure time may be longer than the width of the at least one white pulse.

[0276] The visible exposure time may be for one white pulse within the period.

[0277] The visible exposure time may be for two white pulses within the period.

[0278] To compensate for ambient light, the processor may expose the image sensor for a background exposure time if the target is not illuminated at least once within the period.

[0279] One or more embodiments are directed to a method for imaging a target, the method including generating an excitation pulse to illuminate the target within a time period, generating a white pulse to illuminate the target such that the white pulse does not overlap with the excitation pulse and such that the white pulse is generated at least twice within the time period, exposing an image sensor for a fluorescent exposure time during the excitation pulse, exposing the image sensor for a visible exposure time during at least one white pulse, detecting an output from the image sensor, correcting for ambient light, and outputting a resulting image.

[0280] Compensating for ambient light may include exposing a first set of sensor pixel rows of the image sensor for a percentage of the fluorescent light exposure time and exposing a second set of sensor pixel rows of the image sensor for the entire fluorescent light exposure time, the first and second sets being for detecting at least one different color.

[0281] Compensating for ambient light may include exposing the image sensor for a background exposure time if the target is not illuminated at least once within the period of time.

[0282] Generating the excitation pulse may include providing uniform anamorphic illumination to the target.

[0283] Providing uniform, anamorphic illumination to the target includes overlapping illumination from at least two illumination ports.

[0284] One or more embodiments are directed to a method for displaying fluorescence intensity in an image, the method including displaying a target reticle covering an area of ​​the image, calculating a normalized fluorescence intensity within the target reticle, and displaying the normalized fluorescence intensity in a display area associated with the target.

[0285] The display area may be projected onto the target.

[0286] The normalized fluorescence intensity may comprise a single numerical value and / or a historical plot of the normalized fluorescence intensity.

[0287] One or more embodiments are directed to a kit including an illumination module including at least two illumination ports spaced apart from one another, where first and second illumination distributions are simultaneously provided to a target and overlap at the target, and an imaging module including a sensor for detecting light from the target.

[0288] The kit may include a housing that encloses the illumination module and the imaging module.

[0289] One or more embodiments are directed to fluorescent imaging agents for use in, for example, the imaging devices and methods described herein. In one or more embodiments, the use may include blood flow imaging, tissue perfusion imaging, lymphatic imaging, or a combination thereof, which may occur during invasive surgery, minimally invasive surgery, non-invasive surgery, or a combination thereof. The fluorescent agent may be included in a kit described herein.

[0290] In one or more embodiments, the invasive procedure may include cardiac or reconstructive surgery. The cardiac procedure may include coronary artery bypass graft (CABG) surgery, which may be on-pump and / or off-pump.

[0291] In one or more embodiments, the minimally invasive or non-invasive surgery may include wound repair surgery.

[0292] In one or more embodiments, the lymphatic imaging may include identification of lymph nodes, lymphatic drainage, lymphatic mapping, or a combination thereof. The lymphatic imaging may relate to the female reproductive system.

[0293] Although exemplary embodiments have been disclosed herein and specific terms have been used, they are used and should be construed as such in a general and descriptive manner only, and not for purposes of limitation. In certain instances, as would be apparent to one of ordinary skill in the art as of the filing of this application, features, characteristics, and / or elements described in connection with particular embodiments may be used alone or in combination with features, characteristics, and / or elements described in connection with other embodiments, unless otherwise specified. Accordingly, it will be apparent to one of ordinary skill in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the present invention as defined below.

[0294] While the present disclosure has been described in connection with various detailed embodiments, it is not intended to be limited to the details shown, as various modifications and structural changes can be made without departing from the scope of the present disclosure. Various changes in the form, component arrangement, step, detail, and sequence of operations of the described embodiments can be made, and other embodiments of the present disclosure can be made, which will be apparent to those skilled in the art having access to this disclosure, without departing from the scope of the present disclosure. Accordingly, it is intended that the appended claims will cover such modifications and embodiments as fall within the scope of the present disclosure. For purposes of brevity and clarity, features have been described herein as part of the same or different embodiments. However, it will be understood that the scope of the present disclosure includes embodiments having all or any combination of the described features. The terms "for example" and "such as," and their grammatical equivalents, unless expressly stated otherwise, are to be understood as followed by the phrase "and without limitation." As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

Claims

[Claim 1] The invention described in the specification and drawings.

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